formulation and evaluation of darifenacin extended release matrix tablets

FORMULATION AND EVALUATION OF DARIFENACIN EXTENDED RELEASE MATRIX TABLETS

1. INTRODUCTION1

Oral route is the most oldest and convenient route for the administration of

therapeutic agents because of low cost of therapy and ease of administration leads to higher

level of patient compliance. Approximately 50% of the drug delivery systems available in the

market are oral drug delivery systems and historically too, oral drug administration has been

the predominant route for drug delivery. It does not pose the sterility problem and minimal

risk of damage at the site of administration.

During the past three decades, numerous oral delivery systems have been

developed to act as drug reservoirs from which the active substance can be released over a

defined period of time at a predetermined and controlled rate. The oral controlled release

formulation have been developed for those drug that are easily absorbed from the

gastrointestinal tract (GIT) and have a short half-life are eliminated quickly from the blood

circulation. As these will release the drug slowly into the GIT and maintain a constant drug

concentration in the plasma for a longer period of time. In oral controlled drug delivery the

amount of drug release is constantly predetermined and these constant releases of drug provide

a constant blood plasma level of the drug for optimal therapeutic response. The oral

controlled drug delivery has many advantages to conventional drug delivery.

The ideal and most important objectives of drug delivery are spatial placement and

temporal delivery of the drug. Spatial placement relates to targeting a drug to a specific organ

or tissue, while temporal delivery refers to controlling the rate of drug delivery to the target

tissue. An appropriately designed sustained release drug delivery system can be a major advance

towards solving issues related to spatial placement and temporal delivery. The bulk of research

has been directed at oral dosage forms that satisfy the temporal aspect of drug delivery, but

many of the newer approaches under investigation may allow special placement as well.

The potential problems associated with conventional (multiple dosages) delivery are:

NARASARAOPET INSTITUTE OF PHARMACEUTICAL SCIENCES


• If the dosing is not appropriate according to the biological half-life of the drug, the

concentration of drug level in blood may result in large "Peaks" and "Valleys".

• For example, drugs with short half-lives require frequent dosing to maintain constant

therapeutic levels.

• The drug blood level may not be within the therapeutic range at sufficiently early

times, an important consideration for certain disease states.

• Patient noncompliance with the multiple-dosing regimen can result in failure of the

conventional approach.

Frequently these problems are significant enough to make drug therapy with

conventional dosage forms less desirable than sustained release drug therapy.

This fact, coupled with the intrinsic inability of conventional dosage forms to achieve spatial

placement, is a compelling motive for investigation of sustained-release drug delivery

systems.

2.EXTENDED RELEASE SYSTEM:2



Extended release drug delivery system achieves a slow release of the drug over an

extended period of time or the drug is absorbed over a longer period of time. Extended

release dosage form initially releases an adequate amount of drug to bring about the

necessary blood concentration (loading dose, DL) for the desired therapeutic response and

therefore, further amount of drug is released at a controlled rate (maintenance dose, DM) to

maintain the said blood levels for some desirable period of time.

The sustained release, sustained action, prolonged action, controlled release, extended

action, timed release, depot and respiratory dosage forms are terms used to identify drug

delivery system that are designed to achieve a prolonged therapeutic effect by continuously

releasing medication over an extended period of time after administration of a single dose.

Extended release formulation is an important program for new drug research and

development to meet several unmet clinical needs. There are several reasons for

attractiveness of these dosage forms viz. provides increase bioavailability of drug product,

reduction in the frequency of administration to prolong duration of effective blood levels,

Reduces the fluctuation of peak trough concentration and side effects and possibly improves

the specific distribution of the drug.

2.1. Objectives of Extended Release Drug Delivery System:

Every noval drug delivery system had a rationale for developing the dosage form

likewise, ERDDS also having some objectives that are discussed below:

2.2. Suitable Drug Candidate for Extended Release Drug Delivery System

The drugs that have to be formulated as a ERDDS should meet following parameters.

• It should be orally effective and stable in GIT medium.

• Drugs that have short half-life, ideally a drug with half life in the range of 2 – 4 hrs makes

a good candidate for formulation into ER dosage forms eg. Captopril, Salbutamol

sulphate.

• The dose of the drug should be less than 0.5g as the oral route is suitable for drugs given

in dose as high as 1.0g eg. Metronidazole.



• Therapeutic range of the drug must be high. A drug for ERDDS should have therapeutic

range wide enough such that variations in the release do not result in concentration

beyond the minimum toxic levels.

2.3. Merits of Extended Release Drug Delivery System:

• The extended release formulations may maintain therapeutic concentrations over

prolonged periods.

• avoids the high blood concentration.

• Reduce the toxicity by slowing drug absorption.

• Minimize the local and systemic side effects.

• Improvement in treatment efficacy.

• Minimize drug accumulation with chronic dosing.

• Improvement of the ability to provide special effects.

• Enhancement of activity duration for short half life drugs.

2.4. Demerits of Extended Release Drug Delivery System:

• In case of acute toxicity, prompt termination of therapy is not possible.

• Less flexibility in adjusting doses and dosage regimens.

• Risk of dose dumping upon fast release of drug.

• High cost of preparation.

• The release rates are affected by various factors such as, food and the rate transit through

the gut.

• The larger size of extended release products may cause difficulties in ingestion or transit

through gut.

3. Matrix System 3



A polymer and active ingredient are mixed to form a homogenous mixture called as matrix

system. The matrix system is often used for a controlled drug release from a pharmaceutical

dosage form; it is used for delay and control release of the drug that is dissolved or dispersed

in a resistant support. To define matrix, it is necessary to know the characteristics that

differentiate it from other controlled release dosage forms:

• The chemical nature of support (generally formed by polymeric net)

• The physical state of drug (dispersed under molecular or particulate form or both)

• The matrix shape and alteration in volume as a function of time.

• The route of administration (oral administration remains the most widely used but

other route are adaptable)

• The release kinetic model.

Advantages of Matrix System :

The interest awakened by matrix system in last few years is completely justified in

view of its major advantages. Among these, the following stand out:

• With proper control of manufacturing process, reproducible release profiles are

possible.

• There is no risk of "dumping" a large part of dose, as the structure makes the

immediate release of a small amount of active principle unavoidable.

• Their capacity to incorporate active principle is large, which suits them to

deliver large dosag

4. Principle of Modified Drug Release4



Either of the following two principles can modify drug release:

Barrier principle

In this method the retardant material is imposed between the drug and elution

medium. Drug release is by diffusion of the drug through the barrier and or erosion of the

barrier or permeation of the barrier by moisture.

Embedded matrix

In this drug is dispersed or embedded in a matrix of retardant material that may be

encapsulated in particulate form or compressed into tablet. Drug release occurs by

permeation of water leaching extraction or diffusion of drug from the matrix and erosion of

matrix material.

5.Mechanisms of Drug Release from Matrix5



6. Advantages of Hydrophilic Matrix Tablets6

1. With proper control of the manufacturing process, reproducible release profiles are

possible. The variability associated with them is slightly less than that

characterizing coated release form.

2. Structure allows an immediate release of small amount of active principle and

furthermore there is no risk of dose dumping.

3. Their capacity to incorporate active principle is large, which suits them to deliver

large doses.

4. The manufacturing processes are notably simple. Tablet formulation can be done via

direct compression or by wet granulation techniques.

5. Large varieties of non expensive gelling agents are approved for oral use by the

competent official organization.

6. The safety margin of high-potency drugs can be increased.

7. The drug release from hydrophilic matrices show a typical time dependent profile

i.e decreased drug release with time because of increased diffusion path length.



7. OVER ACTIVE BLADDER7

Overactive bladder (OAB) is a syndrome characterised by urinary urgency, with or

without urgency urinary incontinence(UUI) usually with frequency and nocturia, in the

absence of causative infection or pathologic conditions and suggestive of underlying detrusor

overactivity (phasic increases in detrusor pressure).

Urgency, is defined as the sudden compelling desire to urinate, a sensation that is difficult to

defer. UUI is urinary leakage associated with urgency. Some women may have both stress

urinary incontinence and UUI, and this is called mixed urinary incontinence. Urinary

frequency is defined as voiding 8 or more times in a 24-hour period. Nocturia is defined as

the need to wake 1 or more times per night to void.

Treatment of OAB is aimed at reducing the debilitating symptoms in order to improve the

overall the quality of life in affected patients and Anticholinergic agents that target the

muscarinic receptors in the bladder (antimuscarinic agents) are the medical treatment of

choice because they reduce the contractility of the detrusor muscle.

7.1 CAUSES:

Overactive bladder is typically caused by spasms of the muscles of the bladder,

resulting in an urge to urinate (hence, urge incontinence). Overactive bladder is primarily a

problem of the nerves and muscles of the bladder. Detrusor is one of the major muscles of the

bladder. Its contraction in response to filling of the bladder by urine is one the steps in the

normal process of urination. The contraction and relaxation of the detrusor muscle is

regulated by the nervous system. Approximately 300 cc of urine in the bladder can signal the

nervous to trigger muscles of the bladder to coordinate urination. Voluntary control of the

sphincter muscles at the opening of the bladder can hold the urine in the bladder for longer.

Up to 600 cc of urine can be contained in a normal adult bladder.

Overactive bladder typically results from inappropriate contraction of the detrusor muscle

regardless of the amount of urine.



There are also some causes of overactive bladder and urge incontinence with a normal

nervous system. For example, urinary tract infection, bladder stones, or bladder tumors can

cause also cause overactivity of the detrusor muscle, leading to overactive bladder.

8.TREATMENT OF OAB

Anticholinergics inhibit the binding of acetylcholine to the muscarinic receptor in

the detrusor, thereby suppressing involuntary bladder contractions. They are associated with

an increase in bladder volume voided, as well as a decrease in micturition frequency and

sensation of urgency.

Muscarinic antagonists are the drugs that bind with muscarinic cholinergic receptors but

do not activate them, thus preventing access to acetylcholine; examples include atropine,

scopolamine, propantheline, and pirenzepine. Muscarinic Receptor antagonists are often

referred to as parasympatholytic because they selectively block the effects of parasympathetic

nerve activity.



9. LITERTURE REVIEW9

1.Darifenacin hydrobromide sustained-release tablet and preparation method –Chuangxin

pharmaceuticals RES AND DEV CO LTD:This invention belongs to medicine technology field

specifically relates to a darifenacin hydrobromide slow release tablet and preparation method thereof

the invention claims a darifenacin hydrobromide slow release tablet adopts the new retardant

carbomer relative to the existing technology high expression processing method of a half of the

retarding agent dosage of carbomer of occupying the preparation by weight 1%- 5% ~ it can achieve

the same as the exterior of the releasing speed and biological utilization degree; New method of a

retarding agent dosage of is greatly reduced it can greatly reduce the material the using amount of the

technique is simple controllability is good the efficiency is improved the production cost is reduced

greatly.

2.K.P.Sampath Kumar et al., (2012), reviewed recent trends in scope and opportunities of

control release oral drug delivery systems. Many of new therapeutics under development are

large molecules such as peptides, proteins, oligonucleotides, and vaccines. Their physical,

chemical, and biopharmaceutical attributes distinct from small molecule drugs demand novel

controlled release technologies to diminish barriers for oral delivery, such as instability in GI

tract and poor absorption. Those unmet technology needs create great opportunities for

research, development, and innovation. It is optimistic that breakthroughs in controlled oral

delivery for water-insoluble drugs and biopharmaceuticals will have a significant impact on

pharmaceutical and biotechnology industry. This article examines several aspects in oral drug

delivery requiring implementation of novel ideas to improve oral drug delivery systems. Drug

Delivery is a burgeoning field that represents one of the major research and development

focus areas of pharmaceutical industry today, with new drug delivery system sales exceeding

10 billion dollars per year.

3.Madhusudhan Pogula et al., (2010), reviewed on Extended Release Formulation. Oral

Extended release drug delivery medication will continue to account for the largest share of

drug delivery systems. Hence, in this work to formulate tablets in order to avoid the first pass

metabolism and increase the bioavailability. Hence in this work an attempt was made to

formulate extended release system in order to achieve plasma concentration profile up to 24

hrs. The extended release formulations are the type of formulations which will improves the

therapeutic index of drug concentration. These formulations make the drug available over



extended time period after oral administration. The extended release product will optimize

therapeutic effect and safety of a drug at the same time improving the patient convenience

and compliance.

4.Harnish Patel et al., (2011), reviewed on Matrix Type Drug Delivery System. Matrix

system are favoured because of their simplicity, patient compliance etc, than traditional drug

delivery (TDS) which have many drawbacks like repeated administration, fluctuation in

blood concentration level etc. Developing oral sustained release matrix tablet with constant

release rate has always been a challenge to the pharmaceutical technologist. Most of drugs, if

not formulated properly, may readily release the drug at a faster rate, and are likely to

produce toxic concentration of the drug on oral administration. Hydrophilic polymers have

become product of choice as an important ingredient for formulating sustained release

formulations.

5.Ranjani et al., to develop model extended-release matrix tablet formulations for

metoprolol tartarate(100mg) sufficiently sensitive for regulatory policy development on

scale-up and post approval changes for modified release dosage forms. Several grades and

levels of Methocel K4M, K15M, K100M filler binders were studied. Three granulation

process were evaluated direct compression, fluid-bed or high-shear granulation. At a fixed

polymer level, drug release from the higher viscosity grades (K100LV). The study led to the

choice of MethocelK100V as the hydrophilic matrix polymer and fluid-bed granulation as the

process choice for further evaluation of critical and non-critical formulation and processing

variables.

Maria et al.,67 the potential value of hydroxyl propylmethyl cellulose mixture as gelling

agents, and to investigate relationship between gelling agent viscosity and the kinetics of drug

release from such tablets. Experiments were carried out with MethocelRK100M. trials were

carried out with atenolol tablets made with 40% and 80% gelling agents. A negative

relationship was observed between the Higuchi constant for each tablet type and the apparent

viscosity of the corresponding gelling agent in aqueous dispersion.

Tahara et al.,68 Application of model-independent and model analysis for the investigation of

drug solubility on its release rate from hydroxyl propyl methyl cellulose sustained release



tablets. Both in the model-independent and model analyses, the relationship obtained between

drug solubility and release characteristic were similar.

.

Basak et al.,69 formulation and release behaviour of sustained release ambroxyl

hydrochloride HPMC matrix tablets and sustained release behaviour of the fabricated tablets

was investigated. The most successful of the study exhibited drug release pattern very close

to theoretical release profile. The mechanism of the drug release from diffusion coupled

erosion.

Hyun park et al.,71 prepared for on extended-release tablet using chitosan/carbopol

interpolymer complex(Ipc), the chitosan/carbopol Ipc as characterized by FT-IR and turbidity

measurements. The turbidity measurement revealed the complexation ratio of Ipc between

chitosan/carbopol. The drug release profile from this tablet was similar to that from the

HPMC tablet and showed at pH – independent release profile.

Rajin et al.721 preparation of extended release formulation of glipizide based on osmotic

technology as developed and evaluated. Drug release as found to be affected by the level of

solubility modifier in the core formulation. Glipizide release was inversely proportional to the

membrane weight gain of the membrane. Drug release from the developed formulations was

independent of pH and agitational intensity but dependent on the osmotic pressure of the

release media. The number of pores in the membrane form where the drug release occurred.

The number of pored were directly proportional to the initial level of pore former in the

membrane.

Srinivas et al.,73 to prepare glipizide matrix transdermal systems using the combination of

ethyl cellulose polyvinylpyrrolidone and Eudragit RL-100/ Eudragit RS-100. The systems

were evaluated for various in vitro and in vivo parameters. Drug content of the patches as

found to be more than 98%. Variations in drug permeation profiles were observed among

various formulations. The drug-polymer interaction results suggested no interaction between

drug and polymers. The in vivo results revealed that the patches successfully prevented the

serve hypoglycemia in the initial hours and they were also effective in chronic application.



10.AIM OF THE STUDY

The aim of the present study is to develop a robust formulation of anti muscarinic

drug as an extended release matrix tablets. The polymers like HPMC K4M, HPMC K15M

and HPMC K100M, Metalose 60 SH-50 and Xanthum gum were used as extended release

polymer to retard the drug release. The invitro release pattern of final formulation was

compared with the innovator.

OBJECTIVE

The overall objective of the work is as follows

• To formulate and evaluate extended release Darifenacin hydrobromide by using

various rate controlling polymers.

• To study the drug release profiles of the dosage form and to develop an optimized

dosage form with better dissolution profile.

• To study the drug release profiles of formulations and To compare their drug-release

profile with the innovator.

• To determine the best fit dissolution profile for dosage form.

• To study the stability of dosage form.



11. PLAN OF WORK

• Literature review

• Procurement of API and Excipients

• Preformulation Studies:

• API Characterization

• Drug Excipient Compatibility Studies

• FTIR Studies

• Formulation of Darifenacin Hydrobromide extended release matrix tablets by using

various drug: polymer ratios.

• Precompression Characterization

• Bulk Density

• Tapped Density

• Compressibility Index

• Hausner’s Ratio

• Angle of Repose

• Postcompression Characterisation

• Weight Variation

• Hardness

• Friability

• Uniformity of drug content



• In vitro dissolution studies

• Comparision of drug release profile

• Study of Drug release kinetics

• Stability studies of the optimized formulation



12. DRUG PROFILE10-11

• Name of Drug : Darifenacin hydrobromide

• Chemical Name : (S)-2-{1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]-3-

pyrrolidinyl}-2,2-diphenylacetamide hydrobromide

• Formula : C28H30N2O2.HBr.

• Molecular Weight : 507.47 Daltons

• Structure:

Appearance : White to almost white, crystalline powder

Solubility : Soluble in dichloromethane, sparingly soluble in ethanol, practically

insoluble in water

Storage : Store in a cool, dry place. Store in a tightly closed conatiner

Stability : Stable under normal temperature & pressure

Melting point : 229°C

Pka (25oC) : 9.2

Loss On Drying : Not more than 1.0%

Pharmacological Class: Genitourinary antispasmodic agent; an Antimuscarinic agent.

Therapeutic Category: Symptomatic treatment of urge incontinence and/or increased

urinary frequency and urgency as may occur in adult patients with overactive bladder

syndrome.



Mechanism of Action: Darifenacin has greater affinity for the M3 receptor than for

the other known muscarinic receptors (9- and 12-fold greater

affinity for M3 compared to M1 and M5, respectively, and

59-fold greater affinity for M3 compared to both M2 and

M4). M3 receptors are involved in contraction of human

bladder and gastrointestinal smooth muscle, saliva

production, and iris sphincter function

Figure 5. Representing mechanism of antimuscarinic drug.

Pharmacokinetics

Absorption: Bioavailability of approximately 15% and 19% after 7.5 mg and 15 mg daily

doses at steady state. Maximum plasma levels are reached approximately 7

hours after administration of the prolonged-release tablets and steady-state

plasma levels are achieved by the sixth day of administration.

Distribution: 98% of darifenacin are bound to plasma proteins; steady-state volume of

distribution (Vss) is estimated to be 163 litres

Metabolism: By CYP3A4 and CYP2D6;

Three main metabolic routes:



• Monohydroxylation in the dihydrobenzofuran ring,

• Dihydrobenzofuran ring opening and

• N-dealkylation of the pyrrolidine nitrogen

Elimination: Approx. 60% urine; 40% faeces.

Clearance: 40 L/h.

Half life: 4-6 hours

Pharmacodynamics

• Drug interactions:

• Metabolized principally by CYP2D6 and CYP3A4.May inhibit CYP2D6 and

CYP3A4; not expected to inhibit CYP1A2 and CYP2C9.

Side effects:

• Adverse drug effects such as dry mouth, constipation and abnormal vision may be

mediated through effects on M3 receptors in these organs. Urinary retention, gastric

retention, or uncontrolled angle-closure glaucoma or risk of these conditions.

Recommended Dose:

• The recommended starting dose is 7.5 mg daily. After 2 weeks of starting therapy,

patients should be reassessed. For those patients requiring greater symptom relief, the

dose may be increased to 15 mg daily, based on individual response.



13.EXCIPIENT PROFILE12

• Dibasic calcium phosphate

• Hypromellose (hydroxypropyl methylcellulose).

• Xanthan gum

• Magnesium stearate

13.1 DIBASIC CALCIUM PHOSPHATE

Table 1. Excipient profile of dibasic calcium phosphate

Synonyms

A TAB; calcium monohydrogen phosphate; calcium

orthophosphate, Di-Cafos AN, Dicalcium

orthophosphate; E34 1; Emcompress Anhydrous;

Fujicalin; phosphoric acid calcium salt (1 : 1); secondary

calcium phosphate.-

Description

Anhydrous dibasic calcium phosphate is a white,

odorless,tasteless powder or crystalline solid. It occurs as

triclinic crystals.

Functional Category Tablet and capsule diluent.

Solubility: Practically insoluble in ether, ethanol and water; soluble

in dilute acids.

Safety:

Widely used in oral pharmaceutical products, food

products, and toothpastes and is generally regarded as a

relatively nontoxic and nonirritant material.

Applications:used both as an excipient and as a source of calcium in

nutritional supplements.



13.2 HYPROMELLOSE

Table2. Excipient profile of hypromellose

Synonyms Benecel, HPMC, Methocel, Hydroxy propyl methyl

cellulose

Description White or creamy white fibrous or granular, odorless,

tasteless powder.

Functional categories Coating agent, film former, rate controlling polymer for

sustained release, stabilizing agent, suspending agent,

viscosity builder.

Solubility Soluble in cold water, forming a viscous colloidal

solution, practically insoluble in mixtures of ethanol and

dichloromethane, mixtures of alcohol and water

Applications High viscosity grades may be used to retard the release of

drugs from a matrix at levels of 10-80%w/w in tablets

and capsules .

13.3 XANTHUM GUM

Table3. Excipient profile of xanthum gum

Synonyms Corn sugar gum; E415; Grindsted; Keldent; Keltrol;

polysaccharide B-1459; Rhodicare S; Rhodigel; Vanzan NF;

xanthani gummi;Xantural.

Description Xanthan gum occurs as a cream- or white-colored, odorless,

freeflowing, fine powder.

Functional

categories

Gelling agent; stabilizing agent; suspending agent; sustained-

release agent; viscosity-increasing agent.

Solubility Practically insoluble in ethanol and ether; soluble incold or

warm water.

Applications Xanthan gum is widely used in oral and topical



pharmaceutical formulations, cosmetics, and foods as a

suspending and stabilizing agent.

Although primarily used as a suspending agent, xanthan gum

has also been used to prepare sustained-release matrix tablets.

13.4 MAGNESIUM STEARATE

Magnesium Stearate is a fine, white, precipitated or milled, impalpable powder of

low bulk density, having a faint, characteristic odor and taste. The powder is greasy to touch

and easily adheres to the skin. The USPNF XVII describes magnesium stearate as a

compound of magnesium with a mixture of solid organic acids obtained from fats and

consists chiefly of variable proportions of magnesium stearate and magnesium palmitate.

Table4.Excipient profile of magnesium stearate

Synonyms Stearic acid magnesium salt, magnesium octadecanoate

Description

It is A fine, white, precipitated or milled, impalpable powder of

low bulk density, having a faint odor of stearic acid & a

characteristic taste.

Functional

CategoriesTablets & Capsule lubricant.

SolubilityIt is insoluble in water, ethanol & ether. Slightly soluble in warm

benzene & warm ethanol.

Applications

It is widely used in cosmetics, food & pharmaceutical

formulations. It is primarily used as a lubricant in capsule &

Tablets at concentration between 0.25-5.0 percent.



14. MATERIALS AND EQUIPMENT

The following are the list of materials and equipments used in developing the formulation:

Table 5. List of Materials Used

S. No. Material Name of supplier

1. Darifenacin Hydrobromide Shasun Chemicals and Drugs Ltd

2. Dibasic Calcium phosphate Signet chemicals Ltd.

3. HPMC K4M Colorcon

4. HPMC K15M Colorcon

5. HPMC K100 Colorcon

6. Metalose 60 sh 50 Signet Chemicals Ltd.

6 Xanthum Gum Signet Chemicals Ltd

7. Magnesium stearate Signet chemicals Ltd.

Table6.List of Equipments

s.no Name of the Instrument Manufacturer

1 Electronic weighing balance Sartorious precision balance

2 pH meter Thermo Lab

3 Tablet hardness tester Pharmatron tablet tester 8m

4 Digital Vernier callipers Fischer scientific

5 Friability Tester usp Electrolab

6 Bulk and Tapped Density Apparatus USP Electrolab

7 Coating machine Neocota

8 Sieve Shaker Retsch

9 dissolution apparatus USP I (basket) Electro lab

10 Uv_visible Spectrometer Shimadzu

11 FTIR spectrophotometer Bruker

12 HPLC Agilant

13 Stability Chamber 25˚C/75%RH,40˚C/75%RH Thermo Lab

14 Octagonal Blender Rimet kalveka



15. List of ingredients used for the Extendeded release Darifenacin Hydrobromide matrix

tablet :

INGREDIENTS USES

Darifenacin Hydrobromide Antispasmodic

Di-BasicCalciumPhosphate(A-Tab) Diluent

Methocel K 4 M Matrix polymer and binder



HPMC Matrix polymer and binder

Xanthan Gum Binder

Magnesium Stearate Lubrient



16. REFERENCES

• Clive G Wilson and Patrick J Crowley. "Controlled Release in Oral Drug Delivery".

• Modi S A, Gaikwad P D, Bankar V H, Pawar S P, Sustained release drug delivery system:

A review, International Journal of Pharma. Research and Development, 2011, 02(12),

147-59.

• Chien Y W, "Novel Drug Delivery System", Marcel Dekker, New York, 2nd edition,

Revised and Expanded, Vol II, 1992, 139-140.

• Aulton M E. "Hand Book of Pharmaceutics", ELBS with Churchill Livingstone, Hong Kong,

2001, 291-295.

• Brahmankar D M and Sunil B Jaiswal. "Biopharmaceutics and Pharmacokinetics",

Vallabh Prakashan, 1st edition, 1995, 347-371.

• Pogula M, Nazeer S, Extended release formulation, International Journal of Pharmacy

and Technology, 2010, 02(04), 625-84.

• Increased warning time with Darifenacin: a new concept in the management of urinary

urgency Cardozo, Linda Dexon Andria, The journal of urology,173(4),p.1214-1218,Apr

2005.

• Darifenacin-Pharmacology and clinical usage. Steers,William D-urologic clinics of NA

33(4),p.475-482,Nov 2006.

• Increased warning time with Darifenacin: a new concept in the management of urinary

urgency Cardozo, Linda Dexon Andria, The journal of urology,173(4),p.1214-1218,Apr

2005.

• The clinical Pharmacokinetics of Darifenacin Andry, clinical pharmacokinetics,

45(4),p.325-350,Jan 2006.

• International Union of Pharmacology. XVII. Classification of Muscarinic Acety choline

Receptors. Malcolm p. Caulfield and Nigel J.M.Birdsall B. Dept of Pharmacology

(M.P.C), University of Dundee, Scotland and division of Physical Bio chemistry

(N.J.M.B)

• Koichiro Tahara, Ken Yamamoto, Toshiaki Nishihata. Application of Model-independent

and model analysis for the investigation of effect of drug solubility on its Release rate

from Hydroxypropyl Methylcellulose Sustained Release Tablets.I.J.Pharm. 1996;133:17-

27.


formulation and evaluation of darifenacin extended release matrix tablets

Documents

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reproducible release profiles

fold greater affinity

retarding agent dosage

conventional dosage forms

binder matrix polymer

incorporate active principle

urinary urgency cardozo