indian pharmacopoeia 2010

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Authenticity Certificate

Book Number:0676 .,

IP 2010

Indian Pharmacopoela-2010Apublicatibn of the

Indian Pharmacopoeia Co~mlsslonMinistry ofHealth &Family Welfare

Government ofIndia

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INDIAN PHARMACOPOEIA 2010

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DIOPOEI

2010

IRP

Volume I

~Ul'lit

Government of IndiaMinistry of Health & Family Welfare

Published byTHE INDIAN PHARMACOPOEIA' COMMISSION

GHAZIABAD'

2010, Indian Pharmacopoeia CommissionApplication for reproduction should be made toThe Secretary-cum-Scientific DirectorINDIAN PHARMACOPOEIA COMMISSIONSector-23, Raj Nagar,Ghaziabad-201002, IndiaTel: (91-120)-2783401Fax: (91-120)-2783311Website: www.ipc.gov.inE.mail: [email protected]

ISBN 81-903436-6-1 (VoU)ISBN 81-903436-9-6 (Set)

Sixth Edition (6.0)Effective from 1st September, 2010

On behalfof

Designed, produced & published by

Printed at

Government of IndiaMinistry of Health & Family Welfare

The Indian Pharmacopoeia CommissionIndian Pharmacopoeia LaboratoryGovt. of India, Ministry of Health & Family WelfareSector 23, Raj Nagar, Ghaziabad-201 002

National Institute of Science Communication AndInformation Resources (NISCAIR)Council ofScientific & Industrial ResearchPusa Gate, Dr. K.S. Krishnan Marg, New Delhi-110 012

Price per set: InlandForeign

Rs 20,000$ 900 590

ISBN 81-903436-6-1 ISBN 81-903436-9-6

],"190 343664 ],"190 343695 I01> 06>

Notices

Legal NoticesIn India, under the Drugs and Cosmetics Act 1940, the currentedition of Indian Pharmacopoeia is a book of standards fordrugs included therein and the standards as included in theIndian Pharmacopoeia would be official. Also, in several otherlaws of India, the Indian Pharmacopoeia is recognised as thestandard book. It is expedient that enquiry be made in eachcase in order to ensure that the provisions of any such law arebeing complied with. In general, the Drugs and CosmeticsAct, 1940, the Narcotic Drugs and Psychotropic SubstancesAct, 1985, the Poisons Act, 1919 and the rules framedthereunder should be consulted. These statutes empower theGovernment agencies to enforce the law using this compen-dium. The monographs of the Indian Pharmacopoeia shouldbe read subject to the restriction imposed by those laws whichare applicable.If considered necessary, the standards included in IndianPharmacopoeia can be amended and the Secretary-cum-

v

Scientific Director is authorised to issue such amendments.Whenever such amendments are issued, the IndianPharmacopoeia would be deemed to have been amendedaccordingly.

Patents and Trade MarksIn the Indian Pharmacopoeia, certain drugs and preparationshave been included notwithstanding the existence of actualor potential rights in any part of the world. In so far as suchsubstances are protected by Letters Patent their inclusion inthe Indian Pharmacopoeia neither conveys, nor implies, licenceto manufacture without due permission, authority, or licencefrom the person or persons in whom such rights exist.

The titles given under the individual monographs are publicproperty. These titles cannot be patented as trade marks andno person is permitted to patent any trade mark devising theroot of these titles.

PrefaceThe sixth edition of the Indian Pharmacopoeia (IP 2010) ispublished by the Indian Pharmacopoeia Commission (IPC) onbehalfof the Government ofIndia, Ministry ofHealth & FamilyWelfare. The Indian Pharmacopoeia (IP) is published infulfilment of the requirements of the Drugs and CosmeticsAct, 1940 and Rules thereunder. It prescribes the standardsfor drugs produced and/or marketed in India and thuscontributes in the control and assurance of the quality of themedicines. The standards of this pharmacopoeia areauthoritative and legally enforceable. It intends to help in thelicensing of manufacturing, inspection and distribution ofmedicines. IP is published in continuing pursuit of the missionof IPC to improve the health of the people through ensuringthe quality, safety and efficacy ofmedicines. The Commission

-hasbeenreceiving significantinputs fromregulatory, industrialhouses, academic institutions, national laboratories, individualscientists and others. Publication of IP at regular and shorterintervals is one of the main mandates of the Commission.Indian Pharmacopoeia contains procedures for analysis andspecifications for the determination of quality ofpharmaceutical substances, excipients and dosage forms. IPmonograph for an official substance or preparation includesthe article's defInition, description, identifIcation, packaging,storage, specifIcations, impurities, assay and specifIc tests,one or more analyticru. procedures for each test, acceptancecriteria, other requirements etc.

The history of the IP began in the year 1833 when a Committeeof the East India Company's Dispensary recommended thepublication of a Pharmacopoeia, and Bengal Pharmacopoeiaand General Conspectus of Medicinal Plants was publishedin 1844, which mainly listed most of the commonly usedindigenous remedies. This was followed by IP 1868, whichcovered both the drugs of British Pharmacopoeia (BP) 1867and indigenous drugs used in India, with a Supplementpublished in 1869 incorporating the vernacular names ofindigenous drugs and plants. However, from 1885 the BP wasmade official in India. A Drugs Enquiry Committee appointedin 1927 by the government recommended the publication of aNational Pharmacopoeia.

After independence, the Indian Pharmacopoeia Committee wasconstituted in 1948, for publication of IP as its main function,which published the IP in 1955, followed by a Supplement in1960. This Pharmacopoeia contained both western andtraditional system drugs commonly used in India, and thesame policy continued while preparing the Pharrriacopoeia ofIndia 1966 and its Supplement 1975. There had been aphenomenal growth and development of the Indian Pharmaindustry since independence, especially from early 1970 bothin the range ofActive Pharmaceutical Ingredients (APIs) and

the dosage forms produced. This had totally transformed theprofile of the Indian Pharmaceuticals market. Indian Pharmaindustry had emerged as one of the important global supplierof pharmaceutical products, both to the developed anddeveloping countries. These developments posed majorchallenges for the IP to reflect the quality standards of themarketed drugs, which the subsequent editions of IP tried toaddress.In view of these rapid advances, it was decided to publish anew edition of the Pharmacopoeia and its Addenda at regularand shorter intervals for which the Indian PharmacopoeiaCommittee was reconstituted in 1978. In the Pharmacopoeiaof India 1985, its Addenda 1989 and 1991, inclusion oftraditional system of drugs were limited. However, most of the

. new drugs manufactured and/or marketed were included, whileonly those herbal drugs which had defInitive quality controlstandards had got place in it. In view of the continuing rapidincrease in the range of drugs produced in India, the IP 1996,its Addendum 2000, Supplement 2000 for Veterinary Productsand Addenda 2002 were published. The Addendum 2005 waspublished by the IPC which included a large number ofantiretroviral drugs, and raw plants commonly used in makingmedicinal products not covered by any other pharmacopoeiasand attracted much global attention. The IP Committee decidedto delete the obsolete or less used product monographs andadded monographs based on the therapeutic merit, medicalneed and extent of use of such articles in the country.The Indian Pharmacopoeia Commission has been establishedin year 2005. It provided systematic approach and practicesfor publication of IP 2007 with focus on those drugs andformulations that cover the National Health Care Programmesand the National Essential Medicines. It containedmonographs on antiretroviral, anticancer, antituberculosis andherbal drugs. It further emphasized on biological monographssuch as Vaccines, Immunosera for Human use, Blood products,Biotechnological and Veterinary (Biological and non-biological) preparations. Addendum 2008 to the IP 2007 waspublished which had taken care of the Amendments to IP 2007and also incorporated 72 new monographs.The sixth edition of Indian Pharmacopoeia is published inaccordance with the principles and designed plan decided bythe ScientifIc Body of the IPC. To establish transparency insetting standards for this edition, the contents of newmonographs, revised appendices and other informations havebeen publicized on the website of the IPC, besides followingconventional approach of obtaining comments. The feedbackand inputs were reviewed by the relevant Expert Committee toensure the feasibility and practicability of the standards andmethods revised. The principle of "openness, justice and

vii

PREFACE IP 2010

Indian Phannacopoeia Commission (!PC

Scientific Body approves item for the !P

1Ft; Scientific Staffliaisons nnd reviewitems

fairness" is kept in mind during compiling and editing thecontents of this edition.

Public Review and Comment Process for StandardsDevelopment related to this edition of the IndianPharmacopoeia have given special attention to incorporatecomments from stakeholders. The methodology adopted isappended below:

of the requirements of monographs, appendices and testingprotocols by introducing advanced technology. The contentsof Appendices are by and large revised in consonance withthose adopted internationally. The monographs of specialrelevance diseases of this region have been given specialattention.

(i) The interpretationofamonographmustbein accordancewith all the general requirements, testing methods, textsand notices pertaining to it, in the IP.

(ii) A product is not ofstandard quality unless it complieswith all the requirements of the monograph.

The IP 2010 incorporates 287 new monographs consisting ofAPIs, excipients, dosage forms and herbal products etc. It ishoped that this edition would play a significant role inimproving the quality of medicines which in tum promotepublic health and accelerate the growth and development ofPharma Sector.

In addition, emphasis has been put to bring out harmonisationin Appendices to establish a sound connection betweenindividual monographs and the relevant appendices, so astomake this edition precise and well structured. Number ofMonographs and Appendices are expanded further toincorporate the latest technological advancement andregulatory compliance. Constant efforts have been made tounify the National Drug Standards and to bring them in linewith the In~ernational Standards progressively, by addition ofmonographs ofnew drUgs and adopting current methodology.

This is the sixth edition of the Indian Pharmacopoeia. Itcomprises of three volumes. Each volume has got differentfeatures.

Volume I: Notices; Preface; About Indian PharmacopoeiaCommission; Acknowledgements; Introduction;General Chapters and Reference Data.

Volumell: General Notices; Dosage Forms (GeneralMonographs); Drug Substances, Dosage Formsand Pharmaceutical Aids (A to M).

Volume Ill: General Notices; Drug Substances, DosageForms and Pharmaceutical Aids (N to Z);Vaccines and Immunosera for Human Use; Herbsand Herbal Products; Blood and Blood-relatedProducts; Biotechnology Products; VeterinaryProducts and Index.

The Standards prescribed in the Indian Pharmacopoeia areto establish the compliance with regulatory requirements onan article. The criteria to be adhered to are:

No further revision needed

!PC Scientific Staffcompile andanalyse comments

Public comments received

812.-lj

g~"'11]'"'-""'7."""';~ . 1IIndian PhannacopoeiaI~

Expert Committees review commentsand respond to the Scientific

StaffLiaisons

Items displayed on the website and mailedsepamtely for public .review

Further revisionneeded

Comments andresponses displayed on ---1\1Io-

website/mailed

The IPC Secretariat and Indian Pharmacopoeia Laboratory(IPL) staff, with the support of different advisory ExpertCommittee and Expert Members of the Scientific Body haveexamined the suitability of the standards. In order to make IP2010 user friendly, the existing formatting pattern has beensuitably revised. The standards prescribed in this edition areencouraged to adhere with the concept of harmonization,keeping in view the technological status for manufacture andanalysis of drugs and pharmaceuticals in the country withoutcompromising with the quality of the products. It strives toupdate the existing monographs as well as incorporating thenew monographs of drug substances based on clinical use ofmedicines in India and improving their test protocols. The IP2010 has been considerably revised and improved in respect

viii

Indian Pharmacopoeia Commission

Chairman(ex-officio)

The Indian Pharmacopoeia Commission (!PC) has been formedas an autonomous institution under the Ministry of Healthand Family Welfare's Resolution bearing even no. dated 06thMay, 2008 published in the Official Gazette, the Governmentof India. It is a three-tier structure comprising of the GeneralBody of 25 members, Governing Body of 13 members andScientific Body of 15-23 members from differentrelated scientificfields. The Secretary, Ministry of Health and Family Welfare,is the Chairman and the Chairman-Scientific Body is the Co-Chairman of the Commission. The Secretary-cum-ScientificDirector is the Chief Scientific and Executive Officer of theCommission.

IPC-Structure

The primary responsibility of the Scientific Body is to provideguidelines for Standards development related to the IndianPharmacopoeia with the assistance of its Expert Committees.

The Indian Pharmacopoeia is published in continuing pursuitof the Mission, Vision and Objectives of the IPC.

MissionTo promote public health in India by bringing out authoritativeand officially accepted standard for quality ofdrugs includingactive pharmaceutical ingredients, excipients and dosageforms, used by health professionals, patients and consumers.

VISion

To take note of the different levels of sophistication inanalytical testing/ instrumentation available while framingthe monographs.To accelerate the process ofpreparation, certification anddistribution of IP Reference Substances, including therelated substances, impurities and degradation products.To collaborate with pharmacopoeia like the Ph Eur, BP,USP, JP, ChP and International Pharmacopoeia with a viewto harmonizing with global standards.To review existing monographs periodically with a viewto deleting obsolete ones and amending those requiringupgrading /revision.To organize educational programs and research activitiesfor spreading and establishing awareness on the needand scope of quality standards for drugs and relatedarticles /materials.To publish the National Formulary of India for updatingmedical practitioners and health professionals.

The Governing BodyThe composition of the Governing Body is given below:

The Secretary (Health & Family Welfare)Government ofIndiaMinistry of Health & Family WelfareNirman BhawanNew Delhi-1I0011.(Ms. K. SujathaRao)

Co-Chairman Dr. NityaAnandEx-Director, Central Drug Research InstituteB-62, Nirala NagarLucknow-226 020.

To promote the highest standards of drugs for use in humanand animals within practical limits ofthe technologies availablefor manufacture and analysis.

ObjectivesTo develop comprehensive monographs for drugs to beincluded in the Indian Pharmacopoeia, including activepharmaceutical ingredients, pharmaceutical aids anddosage forms as well as medical devices, and to keepthem updated by revision on a regular basis.To develop monographs for herbal drugs, both raw drugsand extracts/formulations therefrom.To accord priority to monographs of drugs included inthe National Essential Medicines List and their dosageforms.

ix

Member(ex-officio)

Member(ex-officio)

Member(ex-officio)

The Additional SecretaryMinistry of Health & Family WelfareNirman BhawanNew Delhi-lIO OIl.(Mr. V. Venkatachalam)The Additional Secretary & Finance AdvisorMinistry ofHealth & Family WelfareNirman BhawanNew Delhi -110011.(Mr. Naved Masood)The Joint Secretary (Drugs)Ministry ofHealth & Family Welfare,Nirman BhawanNew Delhi-lIO OIl.(Mr. Vineet Chaudhary)

INDIAN PHARMACOPOEIA COMMISSION IP 2010

The General BodyThe composition of the General Body is as follows:Chairman The Secretary (Health & Family Welfare)(ex-officio) Government ofIndia

Ministry ofHealth &Family WelfareNirrnan BhawanNew Delhi-l10011.(Ms. K. SujathaRao)

The Additional Secretary & Finance AdvisorMinistry ofHealth & Family WelfareNirrnan BhawanNew Delhi -110 OIl.(Mr. Naved Masood)The Joint Secretary (Drugs)Ministry of Health & Family Welfare,Niiman BhawanNew Delhi-l10 011.(Mr. Vineet Chaudhary)

Joint SecretaryDepartment ofPharmaceuticalsMinistry ofChemicals and FertilizersShastri BhawanNew Delhi(Mr. Arun Jha)The Drugs Controller General (1)Directorate General ofHealth ServicesFDA Bhawan, Kotla Road,New Delhi.(Dr. Surinder Singh)The DirectorNational Institute of BiologicalsB-62, Institutional AreaNoida-201307(Dr. Jyotna Sokhey)Dr. Kiran Mazumdar ShawC&MD, BioconLimited20th KM, Hosur RoadElectronics City, P.O., Hebbagodi,Bangalore-560 100

Professor B. SureshPresident, Pharmacy Council of IndiaCombined Councils' BuildingKotla Road, Aiwan-E-Ghalib MargPostBox No. 7020New Delhi-l10002.

Co-Chairman Dr. NityaAnandEx-DirectorCentral Drug Research InstituteB-62, NiralaNagarLucknow-226020.

The Additional SecretaryMinistry of Health & FamilyWelfareNirrnan BhawanNewDelhi-1100ll.(Mr. V. Venkatachalam)

Member(ex-officio)

Member(ex-officio)

Member(ex-officio)

Member(ex-officio)

Member(ex-officio)

Member

Member(ex-officio)

Member

Joint SecretaryDepartment ofPharmaceuticalsMinistry ofChemicals and FertilizersShastri BhawaiJ., New Delhi(Mr. Arun Jha)The Drugs Controller General (1),Directorate General ofHealth ServicesFDA Bhawan, KotlaRoadNew Delhi.(Dr. Surinder Singh)The Director (Drugs)Ministry ofHealth& Family WelfareNirrnan BhawanNew Delhi-1100ll.(Mr. Sanjay Prasad)The DirectorNational Institute of BiologicalsB-62, Institutional AreaNoida-201307(Dr. Jyotna Sokhey)Dr. Kiran Mazumdar Shaw.C&MD, Biocon Limited20th KM, Hosur RoadElectronics City, P.O., HebbagodiBangalore-560 100Professor B. SureshPresident, Pharmacy Council of IndiaCombined Councils' BuildingKotla Road, Aiwan-E-Ghalib MargPost Box No. 7020New Delhi-l10002.Mr. Prafull D. ShethE-256, Greater Kailash-INew Delhi-110048.The Secretary-cum-Scientific DirectorIndian Pharmacopoeia CommissionSector-23, RajnagarGhaziabad-201002(Dr. G N. Singh)

Member

Member(ex-officio)

MemberSecretary(ex-officio)

Member(ex-officio)

Member(ex-officio)

Member(ex-officio)

Member

Member

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IP2010 INDIAN PHARMACOPOEIA COMMISSION

The SecretaryIndian PharmaceuticalAlliance (IPA)Mumbai(Mr. D. G. Shah)

Dr. Parthajyoti GogoiDirector-in-ChargeRegional Drugs Testing Laboratory (RDTL)Khana Para, Panjabari, Six mileGuwahati-781 037.Dr. Prem K. GuptaEx-Drugs Controller (I)House No. 95 DDA FlatsPocket 'B' , Sukhdev VillarNew Delhi-ll0 025.Prof. Y. K. GuptaHead, Department ofPharmacology,All India Institute of Medical SciencesAnsari NagarNew Delhi-110 029.

Member(ex-officio)

The Secretary-cum-Scientific DirectorIndian Pharmacopoeia CommissionSector-23, RajnagarGhaziabad-201002.(Dr. G. N. Singh)

The Scientific Body

MemberSecretary(ex-officio)

Member

The list below includes those members who served during theperiodChairman Dr. Nitya Anand

Ex-DirectorCentral Drug Research InstituteB-62, NiralaNagarLucknow-226 020.Mr. VinodAroraVice-President (pharma Research)Ranbaxy Research LaboratoriesPlot No. 20, Sector 18, Udyog ViharIndustrial AreaGurgaon-122 001.Dr. T. G. ChandrashekharVice-President, Global Quality & Analytical

Research,Ranbaxy Research Laboratories,Plot No. 20, Sector 18, Udyog Vihar Ind. AreaGurgaon-122 001.Dr. Manish GangradeHead -Analytical Development Lab.CIPLA LimitedL.B.S. Marg, V:tkhroli (yV)Mumbai-400 083.

Member

Member

Member

Member

Member

Mr. Prafull D. ShethE-256, Greater Kailash-INew Delhi-l10048.The DirectorCentral Drugs Laboratory3, Kyd StreetKolkata(Mr. p. K. Guha)From Regulatory BodiesCentral Drugs Standard Control OrganisationDirectorate General ofHealth Services,Nirman BhawanNew Delhi-ll0011.(Mr. N.C. Dhawan)Dr. C. AdithanThe Director-ProfessorDepartment ofPharmacologyJawaharlal Institute of Postgraduate Medical

Education and ResearchPondicherry-605 006.Commissioners in-charge ofDrug Control

Administration, Andhra PradeshCommissioners in-charge ofDrug Control

Administration, SikkimCommissioners in-charge ofDrug Control

Administration, GujaratCommissioners in-charge ofDrug Control

Administration, Uttar PradeshCommissioners in-charge ofDrug Control

Administration, Himachal Pradesh

The DirectorNational Institute of Pharmaceutical Education

and Research (NIPER)Sector 67, SAS NagarMohali-160062.

.(Vacant)The PresidentIndian Drug Manufacturers Association

(IDMA)102-B,PoonamChambers, 'NWmg'Dr. Annie Besant Road, WodiMumbai-400018.(Mr.N. R. Munjal)The PresidentOrganization of Pharmaceutical Producers of

India (OPP!)(Mr. Ranga Iyer)

Member(ex-officio)

Member(ex-officio)

Member

Member(ex-officio)Member(ex-officio)Member(ex-officio)Member(ex-officio)Member(ex-officio)Member(ex-officio)

Member

Member(ex-officio)

Member(ex-officio)

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INDIAN PHARMACOPOEIA COMMISSION IP 2010

Executive CommitteeDr Nitya Anand, Mr. P. D. Sheth, Dr. Surinder Singh andDr. G N. Singh.

Member

Member

Member

Member

Member

Member

Member

Member

Professor V. K. KapoorEx-Dean and Chairman, Pharmaceutical

Sciences, Punjab University1743, Pushpae Complex, Sector 49 BChandigarh-160 047.

Dr. Anand Kumar553, 7th Main Road, Sadashivanagar,Bangalore-560080.

Dr. D. B. Anantha NarayanaDirector, Technical Regulatory South AsiaFood, Home & Personal CareHindustan Unilever Limited, Research Centre64, Main Road, WhitefiledBangalore- 560 066.

Dr. Vmay G NayakPresident, Tech. OperationsWatson Pharma Pvt. Ltd.2011301, HOD Building Corporate Enclave"B" Wmg, 100 Link Road, ChakalaAndheri (E)Mumbai-400 009

Dr.S.N.PalExecutive DirectorHSCCE-6(A), Sector-1Noida-201301.

Professor P. Rama RaoFormer DirectorNational Institute of Pharmaceutical Education


Mr. Prafull D. ShethE-256, Greater Kailash-INew Delhi-110 048.

Dr. P. G. ShrotriyaChiefExecutive, Elite Pharma Consultants11/302 Sea Woods, NRI Complex, NerulNavi Mumbai-400 706.

Member

Member

Invitee

Invitee

Invitee

Invitee

MemberSecretary(Ex-officio)

Dr. V. A. SrinivasanResearch DirectorIndian Immunologicals Ltd.Gachibowli PostHyderabad-500032.

Dr. R. SridharanVice PresidentCorporate Quality Assurance-APILupin Limited159, CST Road, Kalina, Santacruz(E)Mumbai-400 098.

Dr. P. V. VenugopalPharmaceutical Consultant to the World BankA-II, Sarvodaya Enclave,New Delhi-110 017.

Mr. Gidy AsraniPresident, Pharmacon,3, Salmona Ville, NorthAvenue,Santa Cruze,Mumbai-400054.

Dr. B. R. JagashettyDrugs Controller for the State of KarnatakaOffice of the Drugs Controller (Karnataka)Post Bag No. 5377, Palace RoadBangalore-560 001.

Mr. S. S. VenkatakrishnanDrugs Controller (Retd), Kerala12/548, Dhanya Sree, Vrindavanam GardensKodunganoor,Thiruvananthapuram-695 013.

Dr. G N. SinghSecretary-cum-Scientific DirectorIndian Pharmacopoeia CommissionSector-23, RajnagarGhaziabad-201 002.

Member

Member

Professor Saranjit SinghProfessor and HeadDepartment of Pharmaceutical AnalysisNational Institute of Pharmaceutical Education


Mr. J. L. Sipahimalani10-C, Ananta, R. Patel LaneMumbai-400 026.

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Expert CommitteesExpert Committee onAnti-Retroviral DrugsDr. Manish Gangrade (Chair), Mr. Anwar, Dr. Pnimod Dalvi ,Mr. Antony Raj Gomes and Dr. Hemant Kumar.Expert Committee on Anti-Tuberculosis/AntiAsthmaDrngsDr. Vmay G Nayak (Chair), Mr. Satyawan Hatte, Prof. SaranjitSingh and Dr. Prashant Dikshit.

IP 2010

Expert Committee on Blood and Blood ProductsDr. Prem K. Gupta (Chair), Dr. Zareen Bharucha, Dr. KabitaChatterjee and Mr. Kapil Bhargava.Expert Committee on Clinical Medicine and PharmacologyProf. Y. K. Gupta (Chair), Prof. Praveen Agrawal, Dr. SridharDwivedi and Prof. G. C. Khilnani

Expert Committee on InformationTechnologyDr. Parthajyoti Gogoi (Chair), Dr. A. Ramkishan, Mr. Daara B.Patel, Mr. Milid Joshi, Mr. B. K. Sharma and Dr. Sanjay Singh.Expert Committee on Devices and DiagnosticsDr. S. N. Pal (Chair), Dr. G. S. Bhuvaneshwar, Sh. M. Mitra andProf. Alok Ray.

Expert Committee on Drng Nomenclature and MedicinalagentsProfessor V. K. Kapoor (Chair), Dr. D. Roy and Mr. SanjeevKumar Garg.

Expert Committee on GeneralAnalytical MethodsMr. 1. L. Sipahimalani (Chair), Mr. Shantanu Chobhe, Dr. Y. K.S. Rathore, Dr. R. A. Singh and Mr. R. Sridharan.

Expert Committee on General Policies and PlanningMr. Prafull D. Sheth (Chair), Mr. S. D. Jog, Mr. Vijay Kshirsagar,Dr. Shailesh Nagarsenker, Prof. Y. Madhusudan Rao and Mr.B. N. Thakore.

Expert Committee on Herbal Products and CrudeDrugsDr. D. B. Anantha Narayana (Chair), Dr. AmitAgarwal, Dr. C.K. Katiyar, Mr. Ramakant Haralakha and Dr. George Patani.

Expert Committee on Parenteral ProductsDr. P. G. Sbrotriya (Chair), Dr. Manish Gangrade, Mr. Satish. R.Kulkarni, Mr. Ashok Modi, Dr. A. Prasad and Mr. R. R.Tuljapurkar. .Expert Committee on Pharmaceutical Dosage FormsMr. Vinod Arora (Chair), Prof. Arvind K Bansal,Dr. Kisan B. Chaudhari, Prof. Roop K. Khar, Dr. Praful R. Naikand Dr Kona Subrahmanya Srinivas.

Expert CommitteeonVaccines and OtherBiologicalProductsDr. V. A. Srinivasan (Chair), Dr. Arun Bharadwaj, Dr. S. S.Jadhav, Dr. Surinder Singh, Dr. Rishendra Verma and Dr. J. M.Kataria.

INDIAN PHARMACOPOEIA COMMISSION

IPC SecretariatScientific and administrative support with inputs to the ExpertCommittees have been extended by the following alongwithother staff of the IPC.

Secretary-com-Scientific Director, IPC

Dr. G. N. Singh

Research & DevelopmentDivision

The major activities related to formatting, reviewing andliaisons for Standards Development have performed byfollowing:Dr. Raman Mohan Singh, Dr. S. C. Mathur, Dr. Dinesh Kr.Sharma, Mr. Pawan Kr. Saini, Mrs. Veenu Tyagi, Mr. GauravPathak, Mr. Deepak Duggal, Mr. Alok Yadav, Mr. MunendraKr. Poonia and Km. Anu Somvanshi.

Pharmacology & Microbiology Division

The matters related to biologicals are taken care of byfollowing:Dr. Jai Prakash, Dr. V. Kalaiselvan, Dr. NishantA. Dafale, Mr.Alok Sharma, Mr. Manoj Kr. Pandey, Mrs. Puja Rajput, Mr.Piyush Kumar, Mr. S. Prabil, Mrs. M. Kalaivani and Mr. MuneshBindal.

Pharmaceutical Chemistry Division

The team contributed on works related other than biologicalmonographs:Dr. Anil Kumar Teotia, Dr. Robin Kumar, Ms. SangeetaBhatnagar, Mr. SatyaPrakashTyagi, Ms. Sreeja P. V., Dr. AshishBhatnagar, Mr. Shishir Pratap Singh, Ms. Nidhi Dubey andMrs. Neelam Upadhyaya Misbra.Publication DivisionThe issues related to publication, sales and marketing arebeing looked after by following:Mr. K. K. Singh, Mr. B. D. Sharma, Mr. S. K. Talwar and Mrs.Anjali Sharma.Administrative and Miscellaneous SupportAdministrative and miscellaneous support have been providedby following:Mr. Chandan Kumar, Mr. ManishJain, Mr. R. C. Saxena, Mr. Y.K. Kush, Mr. Udai Pal, Mr. I. J. S. Oberoi, Ms. Renu Kapoor,Mr. Satyaveer Singh and Mr. Rajendra Kumar Sharma.

xiii

INDIAN PHARMACOPOEIA COMMISSION IF 2010

Other ParticipantsParticipants other than those mentioned above who assisted in the work relating to preparation of this edition are given below:Dr. S. S. Agrawal Ms. Smita AinapureMs. Geeta Amin Mr. Navneet AnandMr. Arun Kumar Bana Mr. Manoj BansalMr. G S. Bedi Dr. Jaideep BhaduriDr. BeenaBhatt Dr. Juggnu BhattMr. 1. P. Chauby Dr. Vijay ChauhanProfessor P. C. Dandiya Dr. Manish DareMr. ChandrakantDhakrak Mr. N. C. DhawanMs. M. M. Doshi Mrs. Celine D'souzaProf. Brijesh Chandra Gautam Mrs. Aboli GirenaMr. Sanjay Gupta Dr. S. K. GuptaDr. R. K. Jadhav Mr. R. S. JadhavMr. NileshJha Dr. Sadhna JoglekarMr. Piyush Joshi Ms. Surekha V. JoshiMr. R. C. Juneja Dr. Prasad V. KanitkarMr. Srinivasrao Katari Dr. Sreedhar KhandavaliDr. Sabine Kopp Mr. H. G. KoshiaMr. Vijay Kshirsagar Mr. Arvind KukretyMr. Dinesh Kumar Mr. Gajendra KumarMr. Naveen Kumar Mr. Sanjay KumarDr. Dharmendra Kushwah Mr. Sanjit Singh LambaMrs. Arona Mane Mr. Amit MandalMr. Harashad P. Mehta Mr. Jigar MehtaMs. Hiranmayee Mishra Dr. S. K. MishraMr. N. R. Munjal Mr. B. MurliMr. Shailesh Nagarsenker Mr. NagarkarMr. Atul Kr. Nasa Mr. S. L. NasaMr. 1. N. Oza Mr. Ananthakrishna PadiyaMr. Keshor Pant Mr. Ganish PatilMs. Sushma Patil Mr. V. N. PhatakMr. Rajan R. Pol Mr. A. K. PradhanMr. Shiv Prasad Mr. Sanjay PriolkarMr. R. Raghuram Mr. Sunil RajMr. G. Ramakrshna Dr. R. RamkrishnanMr. DeepakRanch Mr. B. R. S. RaoMs. Catherine Raphael Mrs. Nivedita N. RautMr. Narayana Reddy Dr. T. Venkat ReddyMr. Samir Sangitrao Mr. Pardha SaradhiMr. Malchand Sehgal Mr. B. R. ShahMr. Atul Sharma Mr. Hemant Kumar SharmaMr. S. K. Sharma Dr. Vandana ShindeMr. D. K. Shringi Mr. Ajay SinghMr. Krishnendu Singh Ms. Madhu Utam SinghMr. Krishnendu Singha Mr. Naresh SoniMr. M. R. Shyam Sundar Dr. Ashish SutharMr. SajiThomas Dr. P. TiwariDr. G Trimurtulu Dr. S. TripathiDr. SurenderTyagi Dr. N. UdupaDr. A. 1. Viadya Dr. VaidyaMr. Sanjeev Wadhwa Mr. C. R. Wani

Mr. Ajit Mr. Intkhab AlamDr. P. V. Appaji Mr. Saurabh AroraMr. D. Baneljee Dr. SumantBaukhandiDr. R. S. Bhakuni Mr. Sameer BhargavaDr. L. H. Bhonsle Mr. Faquir ChandMr. S. N. Chavan Mr. Kisan B. ChoudhariDr. Satish R. Desai Mr. Praduya DeshmukhDr. Chintan S. Dholakia Mr. Rajendra DobriyalMr. K. S. Dubal Mr. Mahendra DurgavaleDr. Bala Gopalnair Mr. Prasun GuhaMr. D. S. Gupte Mr. Ranga IyerDr. D. C. Jain Dr. RaviJainMr. Dharmin Joshi Ms. Neeta Joshi'Mr. Venkat Josti Mr. Grish JunejaMs. Ishani Kapila Mr. Anhinav KapoorDr. Praveen Khullar Prof. (Dr.) Chandrakant KokateMr. J. C. Koshti Dr. S. V. KotbagiMr. Satish Kukrety Mr. A. V. KulkarniDr. Hemnalini Kumar Dr. Jitendra KumarDr. (Mrs.) Rachna Kumria Dr. S. P. KuraniMr. Praful Lahorkar Mr. MahendranMr. Ragho G. Manjrekar Mr. Mangesh A. MantriMr. Y. M. Mehta Professor B. MishraMr. A. P. Mohan Mr. S. M. MuddaDr. Kiran Muzumdar Mr. Sunil S. NadkameMr. Subhash Nair Dr. S. NatarajanDr. SurendraNath Mr. S. M. NazarMr. Manish Paliwal Mr. Satish PandyaMr. Hemal Patel Mrs. Jyoti PatilMr. Vmay Pathak Mrs. Sheetal S. PiseDr. am Prakash Dr. A. L. PrasadMr. N. K. Pushpakaran Dr. Upendra S. QuenimDr. R. Rajan Mr. K. V. G. K. RajuMr. A. B. Ramtake Mr. Ani! RanaMr. Ramesh Raghavendra Rao Dr. D. Venkateshwara RaoMr. K. Nityananda Reddy Mr. M. Narayana ReddyMr. Vijay Kumar Reddy Mr. Siddharth SanghviDr. M. N. Saraf Mr. Pratap SataparaMr. Lalit Shah Ms. Meenu ShankarMr. Karnlakar Sharma Dr. Naresh Kumar SharmaDr. H. G. Shivakumar Ms. ShivaniMr. Amaljit Singh Mr. Charan SinghMr. Rishi Kant Singh Dr. Rahul SinghDr. Jyotish Srivastava Ms. RashIDi SrivastavaDr. A. K. Tahlan Mr. TarnMr. Prashant Tiwari Mr. Vmay TiwariMr. B. V. Trivedi Mr. C. R. TrivediMr. S. V. Veerramani Mr. D. K. VedMr. Vmod Mr. Mone VJDr. S. S. Yadav

xiv

Acknowledgements

In preparing the sixth edition of the Indian Pharmacopoeia2010, the British Pharmacopoeia, the EUropean Pharmacopoeia,the United States Pharmacopoeia, the National Formulary, theInternational Pharmacopoeia, the Chinese Pharmacopoeia, thePharmacopoeia ofJapan, the Pharmaceutical Codex, the MerckIndex and the standards published by the Bureau of IndianStandards have been taken into consideration. The IndianPharmacopoeia Commission expresses its thanks to theCommissions, Committees, Conventions and otherorganizations under whose authority these publications havebeen issued. At the same time, the Commission wishes tostate that if some errors have inadvertently crept into thepresent compilation with regard to the statements ofquantitiesor strengths or making quotations, such mistakes are in noway attributable to any of the publications mentioned aboveor to the authorities issuing them.

Specialists from various organisations in India and abroadhave rendered their support. These include the IndianPharmacopoeia Laboratory, Ghaziabad; Central DrugsLaboratory, Kolkata; Central Drugs Testing Laboratory,Chennai; Central Research Institute, Kasauli; Central DrugsLaboratory, Kasauli; All India Institute of Medical Sciences,New Delhi; Indian Veterinary Research Institute, Izatnagar;Indian Immunological Ltd., Hyderabad; Organisation ofPharmaceutical Producers of India (OPPI), Mumbai; BeePharma Laboratories, Mumbai; Ranbaxy ResearchLaboratories, Gurgaon; Baxter (India) Pvt. Ltd., Gurgaon;Central Institute of Medicinal & Aromatic Plants, Lucknow;Cipla Ltd., Mumbai; Arbro Pharmaceutical Ltd., New Delhi;Hindustan Unilever Ltd., Mumbai; Natural Remedies Pvt. Ltd.,Bangalore; Torrent Research Centre, Ahmedabad and theWorld Health Organization (WHO), Geneva.The assistance provided by the Indian Drug ManufacturersAssociation (lDMA), Mumbai, specially through its TechnicalSub-Committees, its Secretary-General and President inarranging meetings and in enhancing visibility of the IP fromtime to time is noteworthy.

Special mention is being made of the permission granted at thetime ofpreparing the preceding edition by the Controller ofHerMajesty's Stationery Office (HMSO), London for reproductionof Infra-red Reference Spectra of certain drug substances fromthe British Pharmacopoeia. Infra-red Reference Spectraofothercompounds have been drawn by Ranbaxy Laboratories Ltd.,Gutgaon; Arbro Pharmaceuticals Ltd., New Delhi; UnichemLaboratories, Mumbai; Torrent Research Centre, Ahemdabad;

xv

Ma.cleods Pharmaceuticals, Mumbai and the IndianPharmacopoeia Laboratory, Ghaziabad from reference materialsgraciously made available by a number of pharmaceuticalmanufacturers in the country.

The co-operation extended by the United StatesPharmacopoeia Convention, USA, the British PharmacopoeiaCommission, the European Pharmacopoeia Commission andthe Industry in incorporating new features in this edition isgratefully acknowledged.

The structural formulae of the organic molecules forming thesubject matter of the monographs of the drug substanceswere drawn with the support provided by NIPER, Mohali.Professor V. K. Kapoor along with his associate Mr. SanjeevGarg under overa.ll supervision of Dr. Nitya Anand have putin remarkable efforts for ensuring the accuracy of the structuresand the chemical names; the Commission acknowledges theirvaluable contribution in this respect.

The Commission is greatly indebted to the members of theScientific Body. and the experts from the industry for theirvaluable and enthusiastic assistance in preparing this edition.The scientific inputs by way of the co"operation and co-ordination of a high order is deeply appreciated.

Dr NityaAnand, Chairman, Scientific Body of IP Commissionis a source of immense inspiration and in his personal capacitymotivated one and a.ll in their efforts to give of their best forthe creation of this compendium. The Commission is indebtedto him.

The Commission expresses its gratitude to Mr. DebasishPanda, Joint Secretary (HR) and Mr. Vineet Chaudhary, JointSecretary (R) for their interest shown on this publication.Special thanks to Dr. Surinder Singh, Drugs Controller General(I) for his unstinting support provided during different phasesof its updating.

The facility provided by Mr. Chandru Sahani of Clenzaids forcontainerization of Reference Substances by means ofIFPRESS is highly appreciated.The Commission wishes to record its deep appreciation of theinputs by the staff of the National Institute of ScienceCommunication and Information Resources (NISCAIR),particularly Mr. Shiv Kumar Marhkan, Mr. Kaushal Kishore,Smt. Supriya Gupta, Mr. I. K. Sehgal, Mr. Davinder Kapoor,Mr. A.K. Brahrni and Mr. Malkhan Singh in successfullybringing out this publication.

The sixth edition of the Indian Pharmacopoeia,fP 2010, is dedicated to the memory of

Late Shri R. S. fyer for his unforgettable,invaluable guidance and help to the

fPC for preparation of fP.

xvi

Introduction.This new edition of the Indian Pharmacopoeia entitled 6thedition (Indian Pharmacopoeia 2010) is published by the IndianPharmacopoeia Commission (IPC) in accordance with a planand completed through the untiring efforts of its members,Secretariat and Laboratory over a period of about two years.It supersedes the 2007 edition but any monograph of the earlieredition that does not figure in this edition continues to beofficial as stipulated in the Second Schedule of the Drugs andCosmetics Act, 1940.

PresentationThe Indian Pharmacopoeia 2010 is presented in three volumes.Volume I contains the Notices, Preface, the Structure of theIPC, Acknowledgements, Introduction, and the GeneralChapters. Volume II contains the General Notice, GeneralMonographs on Dosage Forms, Monographs on drugsubstances, dosage forms and pharmaceutical aids (A to M).Volume ill contains Monographs on drug substances, dosageforms and pharmaceutical aids (N to Z) followed byMonographs on Vaccines and Immunosera for Human use,Herbs and Herbal products, Blood and blood-related products,Biotechnology products and Veterinary products.

The scope of the Pharmacopoeia has been extended to includeproducts of biotechnology, indigenous herbs and herbalproducts, veterinary vaccines and additional antiretroviraldrugs and formulations, inclusive of commonly used fixed-dose combinations. Standards for new drugs and drugs usedunder National Health Programmes are added and thedrugs as well as their formulations not in use nowadays areomitted from this edition. The number of monographs ofExcipients, Anticancer drugs, Herbal products andAntiretroviral drugs have been increased in this edition.Monographs of Vaccines and Immunosera are also upgradedin view of development of latest technology in the field. Anew chapter on Liposomal products and a monograph ofLiposomal Amphotericin B injection is an added advantage inview of latest technology adopted for drug delivery. Achapter on NMR is incorporated in Appendices. Thechapter on microbial contamination is also updated to agreat extent to harmonise with prevailing international

.requirements.

FonnatIn an effort to make the pharmacopoeia more user-friendly,design of the texts of the monographs and of the test methodsare kept same. Cross-referencing has been avoided to makeeach monograph complete in itself thus making it convenientto the analyst.

Basis ofPharmacopoeial RequirementsAs in the past, this compendium provides a publicly availablestatement concerning the quality of a product that can beexpected and demonstrated at any time throughout theaccepted shelf-life of the article. The standards laid downrepresent the minimum with which the article must complyand it is inculcate on the manufacturer to ensure that thearticle is manufactured in accordance with the GoodManufacturing Practices (GMPs). It is essential thatsufficiently stringent limits are applied at the time ofrelease ofa batch of a drug substance or drug product so that thepharmacopoeial standards are met until its expiry date whenstored under the storage conditions specified.Itmust be noted that a valid interpretation of any requirementof the Pharmacopoeia should be done in the context of themonograph as a whole, the relevant general monograph, whereappropriate, the specified tests and methods of analysisincluding any reference to the relevant General Notices.Familiarity with the General Notices will facilitate the correctapplication of the requirements.

ChangesKeeping in view the essential requirement under the Drugsand Cosmetics Act, 1940 and Rules thereunder in theinformation on category of a drug, dosage and usual availablestrengths of dosage forms has been re-kept in this edition.General chemical tests for identification ofan article have beenalmost eliminated and the more specific infrared and ultravioletspectrophotometric tests have been given emphasis. Theconcept of relying on publishedinfrared spectra as a basisforidentification has been continued,The use of chromatographic methods has been greatlyextended to cope with the need for more specificity in assaysand in particular, in assessing the nature and extent ofimpurities in drug substances and drug products. Most of theexisting Assays and Related substances tests are upgradedby liquid chromatography method in view to have morespecificity and to harmonise with other InternationalPharmacopoeias.The test for pyrogens involving the use of animals has beenvirtually eliminated. The test for bacterialendotoxinsintroduced in the previous edition is now applicable to moreitems. The test for abnormal toxicity is now confined to certainvaccines.

General ChaptersVolume I is devoted mainly to test methods that are applicableto all the articles ofthe pharmacopoeia and general information

xvii

INTRODUCTION ( IP 2010

pertaining to the quality requirements ofmedicinal substances.It also includes reference data such as reference spectra,typical chromatograms etc. The test methods reflect thesophistication ofanalytical methodology and instru.riJ.entation.

Analytical methods are, in general, in. harmony with thoseadopted internationally for monitoring the quality of drugs.The steps taken for harmonization have been initiated by theneed to cope with the increasing demand for drugsmanufactured in the country to meet globally acceptedstandards.

The trend towards controlling the microbial quality of allmedicinal products has been recognized and the requirementregarding limits of bacterial contamination even of productsfor oral administrationand topiCal application so that adequatecontrols are exercised by manufacturers by the adoption ofGMPs has been continued.

The chapter on Vaccines: General requirements has beenupdated. Minor corrections have been made in the appendicesentitled Tests onChicken flocks free from specified pathogensfor the production and quality control ofvaccines and Generalprovisions: Avian viral vaccines- Tests for extraneous agentsin seed lot. The peptide mapping test for Inactivated HepatitisB Vaccine has been deleted. Wherever appropriate, othercorrections have also been incorporated and overallpresentation improved.

In view of considering the microbiological quality, the wholemicrobiological general chapter' comprising of effectivenessof antimicrobi!l1 preservatives, microbial contamination innonsterile products and microbiological quality ofraw material,dosage forms, herbs, processed herbs and herbal productshave been extensively revised. For the fIrst time in this chapterthe analysis of strain Shigella boydii has been introducedwhich is possibly not available in other Pharmacopoeias. Theaddition of this strain Shigella boydii is essential as itis acute dysentry causing strain of tropical region of ourcountry.

The chapter on biotechnology derived therapeutic productshas been fully revised. Special emphasis has been given onmonoclonal antibodies Antisera.

MonographsThe General Monographs for dosage forms of activepharmaceutical ingredients (APIs) are grouped together atthe beginning of Volume II. They are followed by themonographs for the APIs, pharmaceutical aids and individualdosage forms, all in alphabetical order. Monographs for otherarticles of a special nature such as vaccines and irnmunoserafor human use, herbs and herbal products, blood and bloodrelated. products, biotechnology products and veterinaryproducts are given in separate sections in Volume m.

A list of287 new monographs items not included in the 2007. edition ofthe Indian Pharmacopoeia and its addendum 2008but added in this edition is given below:

AdmissionsMonographs on drug substances, dosage forms andpharmaceutictl1 aidsAcepromazine MaleateAllantoinAluminium Magnesium SilicateS-Amlodipine BesylateS-Amlodipine TabletsLiposomal Amphotericin B InjectionAnastrozoleAnastrozole TabletsAnhydrous LactoseArtesunateAtazanavir SulphateAtazanavir CapsulesBenzoic Acid SolutionBetamethasone DipropionateBetamethasone CreamBetamethasone LotionBetamethasone OintmentBifonazoleBifonazole CreamBumetanideBumetanideInjectionBumetanide Oral solutionBumetanide TabletsButylparabe~Calcium Chloride InjectionCapecitabineCapecitabine TabletsCefamandole NafateCefamandole InjectionCetrimide CreamCetyl PalmitateChlorothiazideChlorothiazide Oral SuspensionChlorothiazide TabletsChymotrypsinCilastatin SodiumClindamycin HydrochlorideClindamycin Capsules

xviii

rIP20IO

Codeine Phosphate~"Cyproterone.A~Cyproterone TabletsDaunorubidnHydrochlOti(ie.Daunorubicin Injectiori "

Dexch1~eMa1eateDexchlorphenirattUrie0i'iU Sblutibtl "Dexchlorpheniramine TabletsDextropropoxyphene HydfoclIJBrldeDextropropoxyphene CilI'sUlesDextropropoxypheAANilP~~DiacereinDiacerein CapsulesDiazoxideDiazoxide TabletsDicloxacillin Sodimn 'Dicloxacillin Capsules

.. Dicloxacillin Oral SuspensiollDiethanolamineDihydroergocristine Mesyl~~" ,;Dihydroergota1pin~ .MesylateDimethiconeDisopyramide

Disopyramide~ulesDisopyramide Phospha~~apsulesDisopyramide Phosphate Sustailled~"

release C~ulesDivalproex Sustained-release Tab~tsDocetaxel Trihydrat~".Docetaxel InjectionDomperidoneDoxofyllineDoxofylline TabletsEnoxaparin SodiumEnoxaparinInj~tr ,",Escitalhpratn OXalateEscitalopram TabletsEstradiol and Norethisterone TatiletsEtodolacEtodolac Caps~esEtodolac Table~FamotidineFamotidine Tablets

INTRODUCTION

Felodipine Lansopt'8ZC)le Sustained-releaseFelodipine.8UstaiDed~Tablets CapsulesFenbendazole LecithinFenofibrate Levosalbutamol SulphateFentanyl LineIlDlid .Fentanyl Citrate Linezolid TabletsFentanyl Injection Losartan PotassiumandAmlodipineFinasteride TabletsFinasteride Tablets ~;e~imn aJldFluconazole Hydrochlorothiazide Tablets

Maleic AcidFluconazole Capsules Malic AcidFluconazole Tablets, MaltitolFlUCytosine Liquid MaltitolJ:lucytosine Capsules MaltodextrinFlUCytosine Oral SuspensionFlucytosine Tablets Mefloq,t.tine HYdrochlQride

Meloxicam Oral SuspensionFluorescein InjeetionFlutamide Menthol and Benzoin Itlhalat,ion

Flutamide Capsules M~ir~a~~:OChlOlideSustained-FumaricAcid Methadone LinctusGefitinib Metronidazole Sterile SuspensionGefitinib Tablets MiconazoleGemifloxacin Mesylate'" Microcrystalline Cellulose andGemifloxacinTablets CarboxymethylcelfuloSe'SodttimGliclazide MisoprostolGliclazideTablets Mometasone FuroateGJimepiride"" Mometasone AqueousNasalSpiayGlimepiride 'Tablets Motnetasone Crea.ntHomatropine MethylbrotBide MometasOOe OintilielltHomatropine MetIlylbrofuide 1ablets"". Montelukast SodiumHyoscyamine SUlphate"" Montelukast TabletsHyoscyamine Injection :.,~~ ---Mycophenolate MofetilHyoscyamine Oral sottition' Mycophenolate Mofetil CapsulesHyoscyamine Tablets Myristic AcidIbuprofen Cream Naloxone HydrochlOrideIbuprofen Gel Naloxone Injection 'Imatinib Mesylate Naltrexone HydrochlorideImatinib CilPsules Naltrexone Tablets

. Indi}pamideTabfets . /' NaproxenIsobutane Napl'oxell Oral Sospe1t~ionIsopropyl Myristate Naproxe~ SupposttofiesLactulose NilProxen Sustairt~-release TabletsLamotrigine SUStititied-release Tablets Naproxen Tai>letsLansoprazole Neotame

INTRODUCTION

Ondansetron Orally DisintegratingTablets

Ondansetron Oral SolutionPantoprazole SodiumPantoprazole Sustained-release TabletsPerphenazinePerphenazine TabletsPhenoxyethanolPhenylpropanolamine HydrochloridePhenytoinPhenytoin CapsulesPhenytoin Oral SuspensionPimozidePimozide TabletsPiperacillinPiperacillin Intravenous InfusionPoloxamersPolyoxyl35 Castor OilPolyoxyl40 Hydrogenated Castor OilPotassium SorbatePravastatin SodiumPravastatin TabletsPraziquantelPraziquantel TabletsPrednisolone AcetatePregabalinPregabalin CapsulesPregelatinised StarchProgesterone Injectable S~spensionPromazine TabletsPropanePropionic AcidPropofolPropofol InjectionProtriptyline HydrochlorideProtriptyline TabletsPyrimethamine TabletsQuiniodochlor CreamQuiniodochlor OintmentQuiniodochlor and Hydrocortisone

CreamQuiniodochlor and Hydrocortisone

OintmentRamipril and Hydrochlorothiazide

Tablets

RibavirinRibavirin Inhalation SolutionSerratiopeptidaseSerratiopeptidase TabletsSildena:fil CitrateSildenafIl TabletsSimvastatinSimvastatin TabletsSorbitan OleateSucraloseSumatriptanSumatriptan InjectionTelmisartanTelmisartan TabletsTemozolomideTemozolomide CapsulesTerazosin HydrochlorideThiocolchicosideThiocolchicoside CapsulesTicarcillin and Clavulanic Acid

InjectionTolazamideTolazamide TabletsTolnaftateTolnaftate CreamTolnaftate GelTolnaftate Topical PowderTolnaftate Topical SolutionTolterodine TartrateTramadol HydrochlorideTramadol CapsulesTrandolaprilTrandolapril TabletsTravoprostTravoprost Eye dropsTributyl CitrateTrichloromonofluoromethaneTriethyl CitrateTrimetazidine HydrochlorideValproate InjectionValproic AcidValproic Acid CapsulesValproic Acid Oral SolutionValsartan

xx

IP 2010

Valsartan TabletsValsartan and Hydrochlorothiazide

TabletsVancomycin HydrochlorideVancomycin CapsulesVancomycin Intravenous InfusionVancomycin Oral SolutionXanthanGumZoledronic AcidZoledronic Acid InjectionHerbal MonographsAmla Juice PowderAJ.juna Dry ExtractAshwagandha Dry ExtractBelladonna TinctureBhibhitakiAqueous ExtractBrahmiExtractCoconut OilColeus Dry ExtractCorianderOilGarcinia Aqueous ExtractHaridra Dry ExtractHaritaki ExtractHaritaki Aqueous ExtractIpecac TinctureLavangMethiNeemSarpagandha PowderSarpagandha TabletsSunthi ExtractTulasi Dry ExtractVasaka Extract

Veterinary MonographsInfectious Bursal Disease Vaccine,

LiveInfectious Chicken Aneamia Vaccine,

InactivatedInfectious Chicken Aneamia Vaccine,

LiveMarek's Disease Vaccine, LiveReo Virus Vaccine, InactivatedReo Vrrus Vaccine, Live

IF 2010

Salmonella Vaccine, InactivatedSterile Diluent for Live Vaccines

Monographs upgradedMonographs ondrug substances,dosageforms and phannacentical aidsAcarboseAciclovirAdrenaline InjectionAlprazolamAlprazolam TabletsAminophyllineAminophylline InjectionAminophylline TabletsAmitriptyline HydrochlorideAmodiaquine TabletsArginineArteetherArtemetherArtemesininAtorvastatin CalciumAzithromycinAzithromycin Oral SuspensionAzithromycin TabletsBacitracinBacitracin ZincBenzyl alcoholBromhexine HydrochlorideBromhexine TabletsBromocriptine MesylateBromocriptine CapsulesBromocriptine TabletsBisacodylBisacodyl TabletsBuprenorphine HydrochlorideBenzhexol HydrochlorideCalcium Gluconate TabletsCalcium LevulinateCalcium StearateCaptoprilCitric AcidCitric Acid MonohydrateCellulose Acetate PhthalateClofazimine Capsules

CarbimazoleCarvedilol TabletsCefadroxilCrospovidoneCefuroxime InjectionCefaclor Oral suspensionCefadroxil CapsulesCefotaxime SodiumCefazolin SodiumCefiximeCinnarizineCefaperazone SodiumCefazolin InjectionCimetidine TabletsCephalexinCetostearyl AlcoholCetyl AlcoholCarbimazole TabletsCefadroxil TabletsChlordiazepoxideCisplatinClopidogrel BisulphateClopidogrel TabletsClotrimazoleCreamCresol with Soap SolutionCytarabineDanazolDanazol CapsulesDesferrioxamine MesylateDesferrioxamine InjectionDexamethasone Sodium phosphateDextromethorphan HydrobromideDibutyl PhthalateDicyclomine InjectionDigoxinDisodium EdetateDiphenhydramine HydrochlorideErythromycin EstolateEsomeprazole Magnesium TrihydrateEsomeprazole TabletsEthambutol HydrochlorideFerrous GluconateFerrous SulphateDried Ferrous Sulphate

xxi

INTRODUCTION

Fexofenadine HydrochlorideFluocinolone AcetonideFluorescein InjectionFolic AcidFrusemideFrusemideInjectionFrusemide TabletsGallamine TriethiodideGallamine InjectionGentamycin SulphateGlibenclamideGlibenclamide TabletsGuaiphenesinHeparin SodiumHeparin InjectionIbuprofenIbuprofen TabletsImipenemImipenem and Cilastatin InjectionIsoxsuprine HydrochlorideKetarnine HydrochlorideKetamine InjectionKetonazoleKetonazole TabletsKetoprofenKetoprofen CapsulesLactoseLevamisole TabletsLevocitrizine HydrochlorideLevocetirizine TabletsLevofloxacin TabletsMagnesium StearateMagnesium TrisilicateMannitolMannitol InjectionMebendazoleMebendazole TabletsMegestrol AcetateMercaptopurineMethotrexate InjectionMethylergometrine TabletsMetronidazoleMetronidazole TabletsMetronidazole InjectionMorphine Sulphate

INTRODUCTION

Mosapride Citrate DihydrateNaphazoline NitrateNebivolol HydrochlorideNebivolol TabletsNefedipine Sustained- release TabletsNiclosamideNiclosamide TabletsNitrazeparnNitrazeparn TabletsNitrofurazoneNorethisteroneNoscapineNystatinOfloxacinOlanzapineOmeprazoleOndansetron TabletsOxytocinOxytocin InjectionOxytocin Nasal SolutionPhenobarbitonePhenobarbitone SodiumParacetarnolParacetarnol TabletsDiluted Pentaerythritol TetranitratePentamidine IsethionatePentamidine InjectionPethidine HydrochloridePethidine InjectionPhenolphthaleinPhenylbutazonePiracetarnPiroxicarnPolysorbate 20Polysorbate 80Potassium IodidePovidonePrednisolonePropranolol HydrochloridePropranolol InjectionPropranolol TabletsPseudoephedrine HydrochloridePyrantel ParnoateQuetiapine FumarateQuinine Dihydrochloride Injection

Rabeprazole TabletsRiboflavine Sodium PhosphateRitonavir TabletsSalbutarnolSalbutarnol SulphateSalbutarnol InjectionSalmeterol and Fluticasone Propionate

Powder for Inhalation.

SecnidazoleSodiumAlginateSorbitolSoritol Solution (70 per cent)

(Crystallizing)Soritol Solution (70 per cent) (Non-

crystallizing)SpironolactoneSpironolactone TabletsSodium FusidateSodium Fusidate CapsulesSodium PropylparabenSodium MethylparabenMethylparabenPropylparabenStearyl AlcoholSucroseSulphacetamide SodiumSulphacetamide Eye dropsTalcTerbutaline TabletsTheophyllineTheophylline TabletsThiamine HydrochlorideThiamine NitrateTenofovir and Emtricitabine TabletsTerbutaline SulphateThiotepaTopirarnate TabletsVerapamil HydrochlorideVerapamil TabletsVessopressin InjectionVincristine SulphateVmcristine InjectionXylometazoline HydrochlorideWarfarin SodiumWarfarin Sodium ClatharateZidovudine Tablets

xxii

IF 2010

Monographs on Vaccines for HumanUse

Diphtheria and Tetanus Vaccine(Adsorbed) for Adults andAdolescents

Diphtheria, Tetanus and PertussisVaccine (Adsorbed)

Diphtheria, Tetanus, Pertussis (WholeCell), Hepatitis B (rDNA) andHaemophilus Type b ConjugateVaccine (Adsorbed)

Hepatitis B Vaccine (rDNA)Measles, Mumps and Rubella Vaccine

(Live)Tetanus Vaccine (Adsorbed)

Monographs on Vaccines for VeterinaryUseAvian Infectious Bronchitis Vaccine,

InactivatedAvian Infectious Bronchitis Vaccine,

LiveAvian Spirochaetosis VaccineEgg Drop Syndrome'76 (Adenovirus)

Vaccine, InactivatedFoot-and-Mouth Disease Vaccine,

InactivatedFowl Cholera Vaccine, InactivatedFowl Pox Vaccine, LiveInclusion Body Hepatitis (IBH)

Vaccine, InactivatedInfectious Avian Encephalomyelitis

Vaccine, LiveInfectious Bursal Disease Vaccine,

InactivatedInfectious Coryza VaccinePeste Des Petits Ruminants Vaccine,

LiveRanikhet Disease Vaccine, InactivatedRanikhet Disease Vaccine, Live

(Lentogenic Strain)Ranikhet Disease Vaccine, Live

(Mesogenic Strain)

Monographs onVeterinary Diagnostics

Avian Mycoplasma AntigenSalmonellaPullorumAntigen

IP 2010

Changed Titles ofMonographsFrom 'Leptospira Veterinary Vaccine,

Inactivated' to ' Canine LeptospirosisVaccine, Inactivated'

From 'Avian Pleuropneumonia LiveAntigen'to ' Avian MycoplasmaAntigen'

From 'Salmonella Pullorum ColouredAntigen'to'SalmonellaPullorumAntigen'

OmissionsAdenineAluminium SulphateAnalginAnalgin TabletsButylated HydroxyanisoleCaramelCyclopropaneDeslanosideDeslanoside InjectionDibutyl Phthalate

Emetine HydrochlorideEmetine InjectionEphedrineErythromycin EstolateErythromycin Estolate TabletsFusidic Acid Oral Solution2- Deoxy- D- GlucoseProtamine Zinc Insulin InjectionLanatoside CLanatoside C TabletsLaryngotracheitis Vaccine, LiveMenadioneMethdilazine HydrochlorideMethdilazine TabletsOxyphenbutazoneOxyphenbutazone TabletsPhenindamineTartrmePhenindamine TabletsPhenylbutazonePhenylbutazone TabletsPropantheline BromidePropantheline Tablets

xxiii

INTRODUCTION

SodiumAurothiomalateSodiumAurothiomalate InjectionSodium CromoglycateSodium Cromoglycate Powder for

InhalationSodium Fusidate CapsulesPrepared StoraxSulphadimethoxineSulphadimethoxine TabletsSulphadimidine

. Sulphadimidine SodiumSUlphadimidineInjectionSulphadimidine TabletsSulphafurazoleSulphafurazole TabletsSulphaleneSulphaphenazoleSulphaphenazole TabletsSulphobromophthalein SodiumSulphobromophthalein Sodium

Injection

INDIANPHARMACOPOEIA

2010

Volume I


CONTENTS

VOLUME INoticesPrefaceIndianPhannacopoeiaCommissionAcknowledgementsIntroduction

General Chapters

VOLUMEllGeneral NoticesGeneralMonographs on Dosage FormsMonographs on Drug substances, Dosage forms and

Pharmaceutical aids Monographs Ato M

VOLUME illGeneral NoticesMonographs on Drug substances, Dosage forms and

Pharmaceutical aids Monographs N to ZMonographs on Vaccines and Irninunosera for Human UseMonographs on Herbs and Herbal ProductsMonographs on Blood and Blood-related ProductsMonographs on Biotechnology ProductsMonographs onVeterinary ProductsIndex

3

v

vn

ix

xv

XVll

7

711719

755

1729

1737234524632555259126192755

NoticesPrefaceIndianPharmacopoeiaCommissionAclmowledgementsIntroduction

General Chapters

Volume ICONTENTS

5

v

viiix.

xv

xvii

7

GENERAL CHAPTERS

1. General Notices2. Test Methods

2.1. Apparatus

2.2. BiologicalMethods2.3. Chemical Methods2.4. Physical and PhysicochemicalMethods2.5. PharmaceuticalMethods2.6. Tests on Herbal Products2.7. Tests on Vaccines2.8. Tests on Blood and Blood-related Products

3. Reference Data4. Reagents and Solutions5. General Tests6. Containers7. Tables

7

917

192569

105185199203235253557637681699


1. GENERAL NOTICES

General StatementsNameOfficial and OfficialArticlesOfficial StandardsAdded SubstancesAlternativeMethods

Meanings ofTermsProvisions Applicable to Monographs and TestMethods

Expression ofContentsExpression ofConcentrationsAbbreviated StatementsWeights and Measures

MonographsGeneral Monographs

ProductionManufacture ofDrug ProductsExcipients

IndividualMonographsTItlesChemicalFormulaeAtomic and MolecularWeightsDefinitionStatement ofContentCategoryDoseUsual StrengthDescriptionSolubilityTestMethodsIdentification

9

1. GENERAL NOTICES

1111111111

11121212121213131313131313131313131414141414141414

LGENERAL NOTICES

Tests andAssaysTestsOtherTestsLimitsQuantitiesApparatusReagents and SolutionsIndicatorsReference SubstancesTestsAnimalsCalculation ofResultsStorageStorage ContainersLabelling

10


1414151515151515151515161616

IP 2010

General Notices

General StatementsThe General Notices provide the basic guidelines for theinterpretation and application of the standards, tests, assays,and other specifications of the Indian Pharmacopoeia (IP), aswell as to the statements made in the monographs and othertexts of the Pharmacopoeia.

A monograph is to be constructed in accordance with anygeneral monograph or notice or any appendix, note or otherexplanatory material that is contained in this Pharmacopoeiaand that is applicable to that monograph. All statementscontained in the monograph, except where a specific generalnotice indicates otherwise and with the exceptions givenhereafter, constitute standards for the official articles. An articleis not ofpharmacopoeial quality unless it complies with all ofthe requirements stated.

Exceptions to the General Notices do exist, and where theydo, the wording in the individual monograph or an appendixtakes precedence and specifically indicates directions or theintent. Thus, the specific wording of standards, tests, assaysand other specifications is binding wherever deviations fromthe General Notices exist. Likewise, where there is no specificmention to the contrary, the General Notices apply.

Name. The full name or title of this book, including addendathereto, is Indian Pharmacopoeia 2010, abbreviated to IP 2010.In the texts, the term "Pharmacopoeia" or "IP" withoutqualification means the Indian Pharmacopoeia 2010 and anyaddenda thereto.

Official and Official Articles. The word 'official' whereverused in this Pharmacopoeia or with reference thereto, issynonymous. with 'pharmacopoeial', with 'IP' and with'compendial'. The designation IP in conjunction with theofficial title on the label of an article is an indication that thearticle purports to comply with IP standards.

The following terms are used where the articles for whichmonographs are provided are to be distinguished.

An official substance is a single drug or a drug entity or apharmaceutical aid for which the monograph title includes noindication of the nature of a dosage form.

An official preparation is a drug product (dosageform) and isthe finished or partially finished preparation or product of oneor more official substances formulated for use on the patient.

An article is an item for which a monograph is provided,whether an official substance or an official preparation.

Official Standards. The requirements stated in themonographs apply to articles that are intended for medicinal

11

1. GENERAL NOTICES

use but not necessarily to articles that may be sold under thesame name for other purposes.The active pharmaceutical ingredients (drug substances),excipients (pharmaceutical aids), pharmaceutical preparations(dosage forms) and other articles described in the monographsare intended for human and veterinary use (unless explicitlyrestricted to one of these uses).The requirements given in the monographs are not framed toprovide against all possible impurities, contaminants oradulterants; they provide appropriate limitation of potentialimpurities only.A preparation must comply throughout the shelf-life assignedto it by the manufacturer; for opened or broached containersthe maximum period of validity for use may sometimes bestated in the individual monograph. Nevertheless, theresponsibility for assigning the period of validity shall bewith the manufacturer.Added Substances. An official substance, as distinguishedfrom an official preparation, contains no added substancesexcept when specifically permitted in the individual monograph.Unless otherwise specified in the individual monograph, orelsewhere in the General Notices, suitable substances may beadded to an official preparation to enhance its stability,usefulness or elegance, or to facilitate its preparation. Suchauxiliary substances shall be harmless in the amounts used,shall not exceed the minimum quantity required to providetheir intended effect, shall not impair the therapeutic efficacyor the bioavailability or safety of the preparation and shall notinterfere with the tests and assays prescribed for determiningcompliance with the official standards. Particular care shouldbe taken to ensure that such substances are free from harmfulorganisms. The freedom to the manufacturers to add auxiliarysubstances imposes on them the responsibility of satisfyingthe licensing authorities on the purpose of the addition andthe innocuity of such substances. .Alternative Methods. The tests and assays described are theofficial methods upon which the standards of thePharmacopoeia are based. Alternative methods of analysismay be used for control purposes, provided that the methodsused are shown to give results of equivalent accuracy andenable an unequivocal decision to be made as to whethercompliance with the standards of the monographs would beachieved if the official methods were used. Automatedprocedures utilising the same basic chemistry as the testprocedures given in the monograph may also be used todetermine compliance. Such alternative or automatedprocedures must be validated.In the event of doubt or dispute, the methods of analysis ofthe Pharmacopoeia are alone authoritative and only the resultobtained by the procedure given in this Pharmacopoeia isconclusive.

1. GENERAL NOTICES

Meanings ofTermsAlcohol. The term "alcohol" without qualification meansethanol (95 per cent). Other dilutions of ethanol are indicatedby the term "ethanol" or "alcohol" followed by a statement ofthe percentage by volume of ethanol (CZH60) required.Desiccator. A tightly-closed container of suitable size anddesign that maintains an atmosphere of low moisture contentby means of silica gel or phosphorus pentoxideor othersuitable desiccant.

Drying and igriition to constant weight. Two consecutiveweighings after the drying or igniting operations do not differby more than 0.5 mg, the second weighing following anadditional period of drying or of ignition respectivelyappropriate to the nature and quantity of the residue.

Ethanol. The term "ethanol" without qu!Pification meansanhydrous ethanol or absolute alcohol.

Filtration. Unless otherwise stated,fJltration is the passing ofa liquid through a suitable fJlter paper or equivalent deviceuntil the fJltrate is clear.

FresWy prepared. Made not more than 24 hours before it isissued for' use. '

Label. Any printed packing material, including package insertsthat provide information on the article~Negligible. A quantity not exceeding 0.50 mg. .Solntion. Where the name of the solvent is not stated,"solution" implies a solution in water. The water used complieswith the requirements of the monograph on Purified Water.The term 'distilled water' indicates Purified Water prepared bydistillation.

Temperature. The symbol '0' used without qualificationindicates the use of the Celsius thermometric scale.

Water. Ifthe tenn is used without qualification it means PurifiedWater of the Pharmacopoeia. The term 'distilled water'indicates Purified Water prepared by distillation.

Water-bath. A bath of boiling water unless water at anothertemperature is indicated. Other methods of heating may beused provided the required temperature is approximatelymaintained but not exceeded.

ProvisionsApplicable To Monographs and TestMethods,"

Expression of Contents. Where the content of a substance isdefined, the expression "per cent" is used according tocircumstances with OI~e of two meanings:

per cent w/w (percentage, weight in weight) expressingthe number of grams of substance in 100 grams of [malproduct,

12

IF 2010

per cent v/v (percentage, volume in volume) expressingthe number ofmillilitres of substance in 100 millilitres offinal product.

The expression "parts per million" refers to the weight inweight, unless otherwise stated.

Where the content of a substance is expressed in terms of thechemical formula for that substance an upper limit exceeding100 per cent may be stated. Suchan upper limit applies to theresult of the assay calculated in terms of the equivalent contentof the specified chemical formula. For example, the statement'contains not less than 99.0 per cent and not more than 101.0per cent of C7H60 Z implies that the result of the assay is notless than 99.0 per cent and not more thfUl 101.0 per cent,calculated in terms of the equivalent content of C7H60 Z,Where the result of an assay or test is required to be calculatedwith reference to the dried, anhydrous, ignited substance, orthe substance free from solvent, the determination of loss ondrying, water content, loss on ignition, content of the specifiedsolvent, respectively is carried out by the method prescribedin the relevant test in the monograph.

Expression ofConcentrations. The following expressions inaddition to the ones 'given under Expression of Content arealso used:'

per cent w/v (percentage, weight in volume) expressingthe number of grams of substance in 100 millilitres ofproduct

per cent v/w (percentage, volume in weight) ~xpressingthe number of inmilitres of substance in 100 grams ofproduct.

Usually, the strength of solutions of solids in liquids isexpressed as percentage weight in volume, ofliquidsin liquidsas percentage volume in volume, of solids in semi-solid bases(e.g. creams) and of gases in liquids as percentage weight inweight. '

When the concentration of a solution is expressedas,parts ofdissolved substance in parts of solution, it means parts byweight (g) ofa solid in parts by volume (rnl) ofthe [mal solution;as parts by weight (g) ofa' gas in parts by weight (g) of thefinal solution.

When the concentration of a solution is expressed in molaritydesignated by the symbol M preceded by a number, it denotesthe number ofmoles of the stated solute contained in sufficientPurified Water (unless otherwise stated) to produce 1 litre ofsolution.

Abbreviated Statements. Incomplete sentences are employedin parts of the monographs for directDess and brevity (forexample, Iodine Value. Not more than ; Relative Density........to ) Where the tests are abbreviated, it is to beunderstood that the test method referred to in brackets

IP 2010

provides the method to be followed and that the valuesspecified are the applicable limits.

Weights and Measures. The metric system of weights andmeasures is employed in the Pharmacopoeia. All measures arerequired to be graduated at 25 and all measurements in testsand assays, unless otherwise stated, are to be made at thattemperature. Graduated glass apparatus used in analyticaloperations shall comply with the requirements stated inChapter 2.1.6 .

Monographs

General Monographs

General monographs on dosage forms include requirementsof general application and apply to all preparations within thescope of the Introduction section of the general monograph,except where a preamble limits the application. Therequirements are not necessarily comprehensive for a givenspecific preparation; additional requirements may sometimesbe given in the individual monograph for it.

Production. Statements given under the heading Productionrelate to particular aspects of the manufacturing process andare not necessarily comprehensive. However, they aremandatory instructions to manufacturers. Theymay relate,for example, to source materials, to the manufacturing processand its validation and control, to any in-process testing thatis to be carried out by the manufacturer on the final producteither on selected batches or on each batch prior to release.All this cannot beverified on a sample of the final product byan independent analyst. It is for the licensing authority toverify that the instructions have been followed.

The absence of a section on Production does not imply thatattention to features such as those given above is not required.An article described in a monograph of the Pharmacopoeia isto be manufactured in accordance with the principles of goodmanufacturing practice and in accordance with therequirements of the Drugs and Cosmetics Rules, 1945. Thegeneral principles applicable to the manufacture and qualityassurance of drugs and preparations meant for human useapply equally to veterinary products as well.

Manufacture of Drug Products. The opening definitivestatement in certain monographs for drug products is given interms of the active ingredient(s) only. Any ingredient(s) otherthan those included in the statement, must comply with thegeneral notice on Excipients and the product must conform tothe Pharmacopoeial requirements.

Official preparations are prepared only from ingredients thatcomply with the requirements of the pharmacopoeialmonographs for those individual ingredients for whichmonographs are provided.

13

1. GENERAL NOTICES

Excipients. Any substance added in preparing an officialpreparation shall be innocuous, shall have no adverse influencein the therapeutic efficacy of the active ingredients and shallnot interfere with the tests and assays of the Pharmacopoeia.Care should be taken to ensure that such substances are freefrom harmful organisms.

Individual Monographs

Drug products that are the subject of an individual monographare also required to comply with the te~ts givenin the generalmonographs.Titles. The main title for a drug substance is the InternationalNon-proprietary Name (INN) approved by the World HealthOrganization. Subsidiary names and synonyms have also beengiven in some cases; where included, they have the samesignificance as the main title.The main titles of drug products are the ones commonlyrecognised in practice. Synonyms drawn from the full non-proprietary name of the active ingredient or ingredients havealso been.given. Where, however, a product contains one orthe other ofdifferent salts of an active molecule, the main titleis based on the full name of the active ingredient. For example;Chloroquine Phosphate Tablets and ChloroquineSulphateTablets.Chemical Fonnulae. When the chemical structure ofan officialsubstance is known or generally.accepted, the graphic. andmolecular formulae are normally given at the beginning of themonograph for information. This information refers to thechemically pure substance and is not to be regarded. as anindication of the purity of the official material. Elsewhere, instatement of purity and strength and in descriptions ofprocesses of assay, it will be evident from the context that theformulae denote the chemically pure substances.Where the absolute stereochemical configuration is specified,the International Union of Pure and Applied Chemistry(IUPAC) RlS and E/Z systems of designation have been used.If the substance is an enantiomer of unknown absolutestereochemistry, the sign of the optical rotation, as determinedin the solvent and under the conditions specified in. themonograph, has been attached to the systematic name. Anindication of sign ofrotation has also been given where this isincorporated in a trivial name that appears on an IUPACpreferred list.Atomic and Molecular Weights. The atomic weight ormolecular weight is shown, as and when appropriate at thetop right hand corner of the monograph. The atomic andmolecular weights and graphic formulae do not constituteanalytical standards for the substances described.DefInition. The opening statement of a monograph is onethat constitutes an official definition of the substance,preparation or other article that is the subject of the

1. GENERAL NOTICES

monograph. In certain monographs for pharmaceuticalpreparations the statement is given in terms of the principalillgredient(s).In monographs on vegetable drugs, the defInition indicateswhether the subject of the monograph is, for example, thewhole drug or the drug in powdered form.Certain pharmaceutical substances and other articles aredefined by reference to a particular method ofmanufacture. Astatement that a substance or article is prepared or obtainedby a certain method constitutes part of the official defInitionand implies that other methods are not permitted. A statementthat a substance may be prepared or obtained by a. certainmethod, however, indicates that this is one possible methodand does not imply that other methods are not permissible.Statement of content. The limits of content stated are thosedetermined by the method described under Assay.Category. The statement of category is provided forinformation and is indicative of the medical or pharmaceuticalbasis for recognition in the Pharmacopoeia. It generallyrepresents an application of the best known pharmacologicalaction of the article or of its active ingredient. In the case ofpharmaceutical aids it may indicate the more common usageof the article. The statement is not intended to limit in any waythe choice or use of the article nor to indicate that it has noother activity or use.Dose. Doses mentioned in the Pharmacopoeia are intendedmerely for general guidance and represent, unless otherwisestated, the average range of quantities which are generallyregarded'as suitable for adults when administered by mouth.They are not to be regarded as binding upon the prescribers.The medical practitioner will exercise his own judgment andact on his own responsibility in respect of the amount of anytherapeutic agent he may prescribe or administer or thefrequency of its administration. If it is usual to administer adrug by a method other than by mouth, the single dose suitablefor that method of administration is mentioned. In the case ofsome preparations notes have been given below the statementof doses to show the approximate quantities of activeingredients contained in the maximal doses as information forthe prescriber.Usual Strength. The statement on the usual strength(s) of apreparation given in the individual monograph indicates thestrength(s) usually marketed for information of the pharmacistand the medical practitioner. It does not imply that a strengthother than the one(s) mentioned in the individual monographmeeting all the prescribed requirements cannot bemanufactured and marketed with the approval of theappropriate authority.Description. The statements under the heading Descriptionare not to be interpreted. in a strict sense and are not to beregarded as official requirements.

IF 2010

Solubility.Statements on solubility are given in Chapter2.4.26and are intended as information on the approximate solubilityat a temperature between15 and 30, unless otherwise~tated,and are not to be considered as official requirements. However,a test for solubility. stated in a mpnograph',constitutes part ofthe 'standards for the substance that is the subject of thatmonograph.

TestMethods

References to general methods of testing are indicated by testmethod numbers in brackets immediately after the heading ofthe test or at the end of the text.

Identification. The tests given under the heading IdentifIcationare not necessarily sufficient to establish absolute proof ofidentity. They provide a means of verifying that the identityof the material under examination is in accordance with thelabel on the container.

, In certain monographs alternative series ofidentifIcation testsare given; compliance with either one or the other set of testsis adequate to verify the identity of the article. '

When tests for infrared absorption are applied to materialextracted from formulated preparations, strict concordancewith the specifIed reference spectrum may not always bepossible, but nevertheless a close resemblance betwe.en thespectrum of the extracted material and the specifIed referencespectrum should be achieved.

Tests and Assays

The tests and assays are the official methods upon which thestandards of the Pharmacopoeia depend. The requirementsare not framed to take into account all possible impurities. It isnot to be presumed, for example, that an impurity that is notdetectable by means of the prescribed tests is tolerated.Material found to contain such an impurity is not ofpharmacopoeial quality if the nature or amount of the impurityfound is incompatible with gOQd pharmaceutical practice.Pharmacopoeial methods and limits should be used merely ascompliance requirements and not as requirements to guaranteetotal quality assurance. Tests and assays are prescribed forthe minimum sample available on which the attributes of thearticle should be measured. Assurance of quality must beensured by the manufacturer by the use of statistically validsampling and testing programmes.

Tests. Unless otherwise stated, the assays and tests are carriedout at a temperature between 20 and 30.

Where it is directed that an analytical operation is to be carriedout 'in subdued light', precautions should be taken to avoidexposure to direct sunlight or other strong light. Where aprocedure is directed to be performed 'protected from light'precautions should be taken to exclude actinic light by the

14

IP 2010

use oflow-actinic glassware, working in a dark room or similarprocedures.

For preparations other than those of fixed strength, thequantity to be taken for a test or an assay is usually expressedin terms of the active ingredient. This means that the quantityof the active ingredient expected to be present and the quantityof the preparation to be taken are calculated from the strengthstated on the label.Other Tests. In the monographs on dosage forms and certainpreparations, under the sub-heading 'Other tests' it is statedthat the article complies with the tests stated under the generalmonograph of the relevant dosage form or preparation. Detailsof such tests are provided in the general monographs.Limits. The limits given are based on data obtained in normalanalytical practice. They take into account normal analyticalerrors, of acceptable variations in manufacture and ofdeterioration to an extent that is acceptable. No furthertolerances are to be applied to the limits for determining whetheror not the article under examination complies with therequirements of the monograph.

Quantities. Unless otherwise stated, the quantities to be takenfor assays, limit tests and other tests are of the substanceunder examination.In tests with numerical limits and assays, the quantity statedto be taken for testing is approximate. The amount actuallyused, which may deviate by not more than 10 per cent fromthat stated, is accurately weighed or measured and the resultof analysis is calculated from this exact quantity. In tests wherethe limit is not numerical but usually depends uponcomparison with the behaviour of a reference in the sameconditions, the stated quantity is taken for testing. Reagentsare used in the prescribed amounts.

Quantities are weighed or measured with an accuracycommensurate with the indicated degree of precision. Forweighings, the precision is plus or minus 5 units after the lastfigure stated. For example, 0.25 g is to be interpreted as 0.245g to 0.255 g. For the measurement of volumes, if the figureafter the decimal point is a zero or ends in a zero, e.g. 10.0mI or0.50 mI, the volume is measured using a pipette, a volumetricflask or a burette, as appropriate; in other cases, a graduatedmeasuring cylinder or a graduated pipette may be used.Volumes stated in microlitres are measured using a micropipetteor microsyringe.

The term 'transfer' is used generally to indicate a quantitativeoperation.

Apparatus. Measuring and weighing devices and otherapparatus are described in the chapter entitled 'Apparatus forTests and Assays' . A specification for a definite size or typeof container or apparatus in a test or assay is given merely asa recommendation.

15

1. GENERAL NOTICES

Unless otherwise stated, comparative tests are carried outusing identical tubes of colourless, transparent, neutral glasswith a flat base, commonly known as Nessler cylinders.Reagents and Solutions. The reagents required for the testsand assays of the Pharmacopoeia are defined in the variouschapters showing their nature, degree of purity and thestrengths of the solutions to be made from them. Therequirements set out are not intended to imply that the materialsare suitable for use in medicine; reagents not covered bymonographs in the pharmacopoeia shall not be claimed to beof IP quality.The term 'analytical reagent grade of commerce' implies thatthe chemical is of a high degree ofpurity wherein the limits ofvarious impurities are known. Where it is directed to use a'general laboratory reagent grade ofcommerce' it is intendedthat a chemically pure grade material, not necessarily requiredto be tested for limiting or absence of certain impurities, is tobe used.Indicators. Where the use of an indicator solution is mentionedin an assay or test, approximately 0.1 mI of the solution shallbe added, unless otherwise directed.Reference Substances. Certain monographs require the useof a chemical reference substance or a biological referencepreparation or a reference spectrum These are authenticspecimens chosen and verified on the basis of their suitabilityfor intended use as prescribed in the Pharmacopoeia and arenot necessarily suitable in other circumstances.IP Reference Substances, abbreviated to IPRS (and referredto as RS in the individual monographs) are issued by theIndian Pharmacopoeia Commission (lPC). They are the officialstandards to be used in cases of arbitration. SecondaryStandards (Working Standards) may be used for routineanalysis, provided they are standardized at regular intervalsagainst the Reference SubstancesBiological Reference Substances, also abbreviated to IPRSand Standard Preparations of antibiotics are issued byagencies authorised by the IPC. They are standardized againstthe International Standards and Reference Preparationsestablished by the World Health Organization (WHO). Thepotency of these preparations is expressed in InternationalUnits.Reference spectra are published by the IPC and they areaccompanied by information concerning the conditions usedfor sample preparation and recording of the spectra.Test Animals. Unless otherwise directed, animals used in atest or an assay shall be healthy and are drawn from a uniformstock, and have not previously been treated with any materialthat will interfere with the test or the assay.Calculation of Results. In determining compliance with anumerical limit in assay or test, the result should be calculated

1. GENERAL NOTICES

to one decimal place more than the significant figures statedand then rounded up or down as follows: if the last figurecalculated is 5 to 9, the preceding figure is increased by 1; if itis 4 orless, the preceding figure is left unchanged.

.Storage. Statements under the side-heading Storage constitutenon-mandatory advice. The articles of the Pharmacopoeia areto be stored under conditions that prevent contamination and,as far as possible, deterioration. Precautions that should betaken in relation to the effects of the atmosphere, moisture,heat and light are indicated, where appropriate, in the individualmonograph.

Specific directions are given in some monographs with respectto the temperatures at which Pharmacopoeial articles shouldbe stored, where it is considered that usage at a lower orhigher temperature may produce undesirable results. Thestorage conditions are defmed by the following terms:

Store in a dry, well-ventilated place ata temperature notexceeding 30Store in a refrigerator (2 to 8). Do not freezeStore in a freezer (-2 to -18)Store in a deep freezer (Below -18)

Storage conditions not related to temperature are indicated inthe following terms:

Store protected from lightStore protected from light and moisture

IP 2010

Where no specific storage directions or limitations are givenin the monograph or by the manufacturer, it is to be understoodthat the storage conditions includ~ protection from moisture,freezing and excessiveheat (any temperature above 40).Storage Containers. The requirements, guidance andinformation on containers for pharmaceutical use are given inthe chapter entitled Containers (6.1)In general, an article should be packed in a well-closedcontainer i.e. one that protects the contents from contaminationby extraneous solids, liquids or vapours and from loss of thearticle under normal conditions of handling and storage.Where, additionally, loss or deterioration of the article fromeffervescence, deliquescence or eyaporation under normalconditions of storage is likely, the container must be capableof being tightly closed, and re-closed'after use.In certain cases, special requirements of pack have beenindicated in some monographs under Storage, .usingexpressions that have been defmed in chapter 6.1.Labelling. The labelling of drugs and pharmaceuticals isgoverned by the Drugs and Cosmetics Rules, 1945. Thestatements that are given in the monographs under the side-heading 'Labelling' are not comprehensive. Only those thatare necessary. to demonstrate compliance or otherwise withthe monograph have been given and they are mandatory. Forexample, in the monograph on Betamethasone Sodium Tabletsthe labelling st

indian pharmacopoeia 2010

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