'"W-h#

Hosted by:

Faculty of Pharmacy I Faculty of Dentistry |Faculty of Medicine I

Faculty of Public Health I School of NursingUniversity of Jember, lndonesia

gvlcnSangun $ercrasi$rlenxju Insan$arytasi

ISBN: 978-602-60569-3-1

a

I

I

IIt

,,

II

i

PROCEEDING

1" ICMHS

1 st lnternational Conference

on lVledicine and Health Sciences

lnterpro nal Collaboration to Achievesusta le Development Goals (SDGs)

M^';ft'"",:ki:l:-"I- lndonesia

I1

l

{

!

I

EDITORS

Ari Satia Nugraha, SF., GDipSc., Msc-res, Ph.D., Apt.Lusia Oktora RKS, S.F., M.Sc., Apt.lka Puspita Dewi, S.Farm., M.Biomed., Apt.Afifah Machclaurin, S.Farm., M.Sc., Apt.Antonius Nugraha Widhi. Pratama, S.Farm., MPH., Apt.

11

CONFERENCE COMMITTEE

Steering CommitteeDrs. Moh. Hasan., Ph.D (Rector ofUniversity of Jember)Drs. Zulfikar, Ph.D (Vice Rector forAcademic Affairs University of Jember)Prof Drs Bambang Kuswandi, M.Sc., PhD

drg. Rahardyan Parnaaji, M.Kes., Sp.Pros.

dr. Enny Suswati, M.Kes.

lrma Prasetyowati, SKM., M.Kes.

Ns. Lantin Su listyorini, S.Kep.,M.Kep.

Organizing CommitteeChairmainLestyo Wulandari, S.Si., M.Farm., Apt.SecretaryEndah Puspitasari, S.Farm., M.Sc., Apt.TreasurerYuni Retnaningtyas, S.Si., M.Si., Apt.Nia Kristiningrum, M.Farm., Apt.

Secretariat, Publication, andSponsorshipDivisionEka Deddy lrawan, S.Si., M.Sc., Apt.dr. Cicih Komariah Sp.M.

Anita Dewi Moelyaningrum, S.KM., M.Kes.

drg. Ayu Mas Hartini, Sp.PM.

Ns. Emi Wuri W., M.Kep., Sp.KepJ.

Event DivisionDiana Holidah, S.F., M.Farm., Apt.DR. drg. I Dewa Ayu Susilowati, M.Kes.

dr. Hairrudin, M.Kes.DR. Farida Wahyuningtyas, SKM., M.Kes.

Ns. Wantiya, S.Kep., M.Kep.

dr. Ancah Caesarina Novi M., Ph.D.

Scientific Division (Editors)Ari Satia Nugraha, SF., GDipSc., MSc-res,

Ph.D., Apt.Lusia Oktora RKS, S.F., M.Sc., Apt.lka Puspita Dewi, S.Farm., M.Biomed., Apt.Afifah Machclaurin, S.Farm., M.Sc., Apt.Antonius Nugraha Widhi. Pratama,S.Farm., MPH., Apt.Dr. drg. Masniari Novita, M.Kes.

dr. Rini Riyanti, Sp.PK.

Yunus Ariyanto, S.KM., M.Kes

Ns. Achmad Rifa'i, M.S.

Logistic DivisionDwi Nurahmanto, S.Farm., M.Sc., Apt.

111

CONTENT

PREFACE ..,.........t

EDrTORS........

PHARMACY.............

.

iii

iv

................... 1

................ 20

.......'..'.... 31

............ 35

sp.) ON WISTAR STRAIN WHITE MALE RATS WITH GLUCOSE PRELoAD 74

ANTIBACTERIAL AND ANTIBIOFILM POTENTIAL OF ETHANOLIC EXTRACT FROM BINTAROFLOWER (Cerbera odollam) AGAINST Staphylococcus aureus ATCC 6538.............................. 17

STRUCTURE MODtFtCAT|ON AND MOLECULAR MODELTNG OF 1_(BENZOYLOXY)UREADERIVATIVES AS ANTICANCER DRUG CANDIDATES..

CHARACTERIZATION AND THE RELEASE TEST OF ANTI-AGING TRETINOIN IN NANOEMULSIONUSING OLIVE OIL.......

EFFECT OF PARTICLE SIZE AND SURFACE CHARGE ON THE UPTAKE AND IMMUNE RESPONSEOF OVALBUMIN.ALGINATE MICROSPHERES

ANTIHYPE RCHOLESTE ROLEM lC EFFECT OF Arcangelisia flava STEM EXTRACT tNHYPERLIPIDEMIC RATS........

GREEN TEA EXTRACT EFFECT ON BLOOD GLUCOSE LEVEL AND LIVER HISTOPATHOLOGY IND|ABETTC MtCE ...........

TH REE-WAVELENGTH SPECTROPHOTOM ETRIC M ETHOD VALI DATION FOR DETERM INATIONOF PREDNISONE TABLET CONTAINING COLORING DYES .... 39

TNFLUENCE OF OLETC ACtD ON THE tN VTTRO PENETRATTON OF DTCLOFENAC SODTUM GEL [3ANTIOXIDANT ACTIVITY OF METHANOL EXTRACTS FROM THE STEM BARK OF MANGROVEPLANT Rhizophora mucronata............ 47

PHYTOCHEMICAL AND ANTIOXIDANT ACItVtTy of MANGROVE pLANT Soneratia sp. ........... 51

EFFECT OF SOLID LIPID NANOPARTICLE (SLN) AND NANO STRUCTURE LIPID CARRIER (NLC)SYSTEM ON ANTIOXIDANT STABILITY OF TOMATO EXTRACT (LtptD: CETyL ALCOHOL ANDlsoPRoPYL MYRTSTATE)...... ....................... 55

EFFECTIVENESS OF BINTARO (Cerberra odollam Gaertn.) LEAF ETHANOLTC EXTRACTAGAINST Staphylococcus aureus I N-VITRO BtOFILM FORMATION 59

lY

CONFERENCE COMMITTEE

coNTENT..........

COMMUNITY PHARMACISTS' COUNSELLING SKILLS ON OVER.THE-COUNTER (OTC)

M EDTCATTONS ....................2

FORMULATION AND OPTIMIZATION OF CAFFEINE NANOEMULSION USING FACTORIALDESTGN STUDY.. .................. 6

EFFECI OF COMBINATION SODIUM ALGINATE-GELATN 7% : 2% CONTENT tNCHARACIERISTIC AND ANTI M ICROBIAL ACTIVITY OF PROBIOTIC MICROSPHERES Lactobacillusacidophilus....... ................ 10

ANTIDIABETIC ACTIVIW OF POWDER AND ETHANOLTC EXTRACT OF ANTLTON (Myrmeleon

ttr """ "'

2m"""" Nluc'IHl Nt vt^Hlsv lo IIU:l^ls oNV tl^l'l Nnuls l9l NllMrlg Nolrvllossv

ztr """"" ltl^trfv 6-dhrrA NorlrsrHNr He nouHl ulf NVI l-svlu8 Jo slsvrsvllt l sll€lHNlNDI8nUOXOO ONV elldas snlrl 'ezrqJoqtuex eurnrrnl lO NOtjVNtgtAOl flISlgUlNAS

'Al-lv^o]

IN:iltvd OI Norl\flru Nr l-tr]vno rfl^Urs luvfHl'lvlH lo srf,rdsv rH1 lo slsAlvNv NV

0tr" " " Af,Nl9rU Urs^rr]Vl-rdSOH IONV€IOS Nl A8V8 NUO8 A IN iOvtxlHdsv lHt_ or vtsd^\flf,rrud rur^ls'rvNurrvt^ clr\n3u lvHr suol-fvl lo sls^lvNv

9Zr""" " "'sfNltlvd ltul_vtcldNI Vr rHj_SV lO Al-tUlAlS lHl 0NV NOrrVZrlrSNrS Nl9UlllVOUlV NlsMrls NOll-Vl3oSSV

TZT'ullNlf, Hr'lv:tH lINnNNol Nol9lu ulSt llfNt suolrvi )stu lt8vHtcot^ H9nouHl Hf,vouddv rNltAl9vNVtA NolsNlluld^H

9II(dtem (r) elelnrrn8un eu8rl) yy99111'11 SNVIV)CNV ( laa/v\S 't snleunl snloaseqd) )OIVU) OUO) iO ll-l'lvnD CNV A-tlSNlO NllIOUd

ZITcvotrud rsolnrS Hr_rM srvu srvt^ uvlstM lo ll^r] rsofnr9 00018lsvlulSc 01 ulcMod sclls I elerlrnur euouuv lo If,vuIxl lt'loNvHll lo lf,llll80I"" " """" " NlglINV VS83V srsolnrraqnl unuapeqocA6l Jo N6ltll6lud ld6ltdl1"gl-E

,OT" " " "stlvu1xl('l srsuaurs etglau4) VII S1O1UVA JO llt1tlfv AUOt_tgtHNt lsv6ts6lntg-lc OUI-1A Nt

r00T""" " """ " "tZ6SZlf,lVsnaJne snrrorol!qdels SCUVMO1 (lCAHlClVUVlntD Ul)Nt'l-SSOUI HItM l.l-ItVdVAXOUCAH

rNrAoS- NVSOTHf) rN\fldrAr rNOs V Nl NIIVXO]jOUdll rO AVSSV 'lvl80u3ltA '

96"sSAVlt rrriol vf rsvuv cNV vISnSou lo lrvuur ll'loNvHl-lt lNt Al-tAU_3V INVOtXOt-LNV CNV t-NtrNOf ll'lONlHd '1V101 lo NollvNllAUlflo

z6 'N9rsrO rVrUOlJVl A8 l-ll€Vl TOIUOIHf,OUCAH WrZVll-]lC JO tAl]-sls IAISIHCVOf nW-9N|IVO'H SV rsolnllll l^Hlr ONV 'rOdOsUVl rO NOllVZltAlldo CNV NOl.l-\nnNUOl

LAOOOJ'IVNI]IO]W SV NIVIN\Nd CNV VNVNV8

ca" " " " """ "'lvMHlVd ltlot-dodvNON VIA SlNll llll UllNVf, SlSSlUddnS DVUIXI ll'lONVHll SlAVll e^elJ etstla8ue:rv

T8U]3NVf, IVf,IAU]] HII/VI

slNlttvd NvrsrNocNr Nl lll'l Jo ll-llvnD No ldvurrotArHf lsv€ Nll\fldsll lo lfvdt/\ll" " " ""ooHrltA ftdH 9Nlsn sdlHf, o1v10d 6L""

Nt sts^'tvNv st-t oNV ooHlltA Slufxor 9Nlsn sllllflxor lclN\fllufv Jo lonls ofl'lls Nl

sL""

oL""

cllv f tNotvn - Wnt3tvl Nrlvlsv^Uolv lo'lvrs^Uf,ol......

]UVf, ''IVf, IlN]]VIAUVHd NI UOIAVH]8 S,.LSI]VIAUVHd

NO S9nUC NolldlU3SlUd Nl llOOtA S,lf,lAU,ls luvf 'lvf,lln3f,vt^UvHd Jo lf,NlnlJNl lHr

99"NOtlVtrNlUlll lc0NV NO|IVUSlltOUd Sll_llodlcvlud lvu No slAV3l lLue'l erloluln eurn2en9 lollvulxr f,r'roNVHll lo sNollJVUr u\nod-rnrs cNV u\nod-NoN lo llllll AUollSlHNl

29 " " """""" " " " I1vu1x1 ullvM]vlld ul^ oll l.l'llsou oNV rlvul-xl'toNVHrr rv3-t llllol vlt8vuv ro NollvNl€t^of All^llf,v lNVClxoll-NV lo ACnrs

CORRELATION OF CD4 WITH TOTAL LYMPHOCYTE COUNTS IN HIV PATIENTS

DENTISTRY...........

Determinants of HIV/AIDS Awareness and Knowledge in Tanah Papua, lndonesia """""" 149

THE ABILITY OF ANTI-INFLAMMATORY JATROPHA CURCAS LEAF EXTRACT AT COX'2

EXPRESSION ON MONOCYTES WERE EXPOSED LPS 1-54

... t45

... 148

NOVEL METHOD THYROID HORMONE MEASUREMENT ...."....

ROBUSTA COFFEE BEANS INCREASE LEVELS OF TNF- o AS A RESPONSE TO Streptococcus

mutans 762

THE LEVE6 OF TNF-A lN GINGIVAL CREVICULAR FLUID (GCF) OF OSING TRIBE WOMEN WITH

OCCLUSAL DISHARMONY...,...,......

Effects of Robusta Coffee Bean Extract (Coffea robusta) on the Viability of Neutrophils

Exposed by Porphyromonas gingivalis.........' ...... 169

ROBUSTA COFFEE BEANS DECREASE OF INFLAMMATION IN DENTAL CARIES""......".......'' 173

The Progressive Low Chronic lnflammation on OralTissues ln Elderly

DENTAL CARIES IN PREGNANT WOMEN WHO VISITED POSYANDU OF SEVERAL PUBLIC

HEALTH CENTERS IN JEMBER 782

Role of Che moattractant Chemokine (SDF-1/CXCR4) ln Bone Marrow Niche " " " " " " ' 185

Establishment of a Rat Model of Temporomandibular Joint Osteoarthritis using lntraarticular

........................ 158

................ 165

................ L77

lnjection of Complete Freund's Adjuvant.......

PUBLIC HEALTH

RECIPROCAL DETERMINISM "DAKOCAN" CHALLENGE EFFORTS TO REDUCE HIV AND AIDS

CASES IN JEMBER DISTRICT....... . 195

IRON TABLETS DISTRIBUTION OF PREGNANT WOMAN IN THE DISTRICT AND CITY OF EAST

JAVA PROVINCE..... 200

RISK MANAGEMENT OF DUE TO EXPOSURE TO PESTICIDE POISONING FOR TOBACCO

FARMERS IN THE JEMBER DISTRICT..

AN OVERVIEW OF MOTHER KNOWLEDGE AFTER GIVING BIRTH ABOUT EXCLUSIVE

BREASTFEEDING ...... ........ 208

D|SASTER PREPAREDNESS AT PUBLIC HEALTH CENTER (PHC) BY SCORING ANALYSIS OF

GENERAL ASPECTS, HEALTH CARE, SURVEILLANCE, ENVIRONMENTAL SANITATION AND

..... 190

.....794

............204

...........272LOGISTICS

INDEPENDENT FAMILY PLANNING IN RURALAND URBAN AREAS GRESIK DISTRICT .....,."...71.5

UNMET NEED FOR FAMILY PLANNING ON ELIGIBLE COUPLE IN INDONESIA: 2OO7 IDHS DATA

ANALYSIS ........219

shells That Have been Polluted by lead around Youtefa Bay in Jayapura City That Have

Potential Risk Of Non Carcinogenik.'...'. ........

DESIGN AND IMPLEMENTATION DIARRHEAL SURVEILANCE REPORT INFORMATION SYSTEM

WITH WATERFALL METHOD IN HEALTH DEVELOPMENT OF JEMBER......"...

........................ 223

\t

227

LOCAL WISDOM OF JEMBER COMMUNITY IN REDUCING CYANOGENIC LEVELS TO LOWER

URINE THIOCYANATE LEVELS 229

UNDERWEIGHT AND MORBIDITY STATUS AMONG UNDER FIVE YEARS CHILDREN IN

suRABAYA..............

CONDOM USE AMONG EXIT CLIENTS OF FEMALE SEXUAL WORKERS FOR PREVENTION

HIV/AIDS IN MAKASSAR 237

THE SOCIAL SUPPORT AND PREVALENCE EMESIS GRAVIDARIUM ON PREGNANT MOTHER IN

TRIMESTER I AT PUSKESMAS KEMBARAN I BANYUMAS REGENCY...............,..,..,..,..,............247

NURSING.. 245

We need a bigger bomb: a community attempt on fighting dengue fever in a suburban

Su ra baya, lndonesia

) ?4.

,.,.....,.......'.,'.,..,246

APPLICATION OF STANDART NURSING LANGUAGE (NANDA, NOC. NIC) USING SOCIAL MEDIA:

INSTAGRAM@ TO INCREASE INFORMATION SEEKING BEHAVIOUR AND MOTIVATION OF

NURSING STUDENT..... .......250

THE EFFECT OF ONION (Allium ascalonicum L.) COMPRES TOWARD BODY TEMPERATURE OF

CHILDREN WITH HIPERTERMIA IN BOUGENVILLE ROOM DR. HARYOTO LUMAJANG HOSPITAL

.......253

ACHIEVEMENT OF BLOOD PRESSURE TARGET WITH MEDICATION ADHERENCE AND SODIUM

CONSUM PTION IN SAIFUL ANWAR GENERAL HOSPITAL OUTPATIENT CLIN IC... ....,.,,..,........251

EFFECT OF INSTRUCTIONAL VIDEO OF SPLINTING PROCEDURE TO NURSING STUDENTS

spLtNTtNG SKTLL (PREHOSPTTAL SETTING).... ......................261

THE CORRELATION BETWEEN NURSE PERFORMANCE & THE LEVEL OF JAMKESMAS PATIENT

SATISFACTION IN DAHLIA II WARD, NGUDI WALUYO WLINGI HOSPITAL ........266

How To Maintain High Quality Cardiopulmonary Resuscitation ln Adults: Literature Review270

SMOKING BEHAVIOUR AMONG MIDDLE AND LATE ADOLESCENTS IN A SUB DISTRICI OF

MALANG DISTRICT, EAST JAVA, IN DONESI4............ 275

THE DIFFERENCES DECLINE BREAST ENGORGEMENT CONDUCTED CONVENTIONAL METHODS

(BREAST MASSAGE) WITH HERB YEAST-KATU.. 282

v11

INFLUENCE OF OLEIC ACID ON THE IN VITRO PENETRATION

OF DICLOFENAC SODIUM GEL1't Lidya Ameliana, Faculty of Pharmacy, Jember University

Kalimantan 1st street No 2, Jember, lndonesia, 50121, lidyaameliana @yahoo.co.id2nd Esti Hendradi, 3'd Mochammad Yuwono, Faculty of Pharmacy,

Airlangga U n iversity, Surabaya, lndonesia

hydrophilic properties. ln general, the skin is morepermeable to the material which has a partitioncoefficient (P) in octanol-water between L0-1000(Michniac-Kohn et al., 2005).

Oleic acid enhances the penetration of drugs intothe skin by increasing the fluidity of the stratumcorneum lipids through the establishment ofchannels (water channels) (Fang, et al , 2003)

This study aimed to know the influence of OleicAcid (OA) in several concentrations (1%,3% and5%) as penetration enhancer on the in vitropenetration of topical DS gel. Furthermore, thephysical properties of the topical preparation(organoleptic, pH and viscosity), and DS penetrationpercutaneously through rat skin Then observedthat in spite of DS assay and penetrate through therat skin at certain intervals and observed by means

of HPLC.

MATERIALS AND METHODS

MaterialsDiclofenac sodium was obtained as a gift sample

from PT. Kimia Farma, Carbopol 940, Propyleneglycol, Triethanolamine, Potassium Chloride,

Constituents concentration (%)

FO F1 F2 F3

7 L 1 1

0.6 0.6 0.6 0.6DS

30 30 30

Oleic acid 3 5

Distilled water to 100 100 100 100

Carbopol 940Triethanolamine qs qs qs qs

Propylene glycol 30

temperature for 24 h study prior to use.Table 1. composition (% w/w) of DS gels

Evaluation of GelsVisuol oppeoronce

The prepared gels were visually inspected forconsistency, color, and transparency.pH of the gels

The pH of gel was determined after diluting and

dispersing it in distilled water (10% Uv). All themeasurements were made in triplicate and mean

calculated.

13

INTRODUCTION

Diclofenac sodium (DS) is a nonsteroidalantiinflammatory drugs (NsAIDs), that inhibitscyclooxygenase-2 enzyme (COx-2). lt has first pass

metabolism by 40-50%, because of its shortbiological half-life, the drug has to be given

frequently (Ganiswara,2005). Dose of DS in gel is 1%

(Sweetman, 2007). ln peroral use, it may cause therisk of gastrointestinal bleeding, cardiovascular,hypersensitivity reactions and disorders of thecentral nervous (Katzung, 2002, Chuasuwan, et al.,

2008).Ds does not penetrate well through skin and cannotreach the effective concentration at the site ofaction after transdermal application (Mohammed,

2001; Ozguney, et al., 2006). DS partition coefficientin n-octanol-buffer aqua (log P) was 1.1 (Chuasuwan,

2008). Lipophilic nature of the stratum corneum and

the hydrophilic nature of the underlying tissuesshowed that the drug will penetrate the skin shouldhave an optimal balance between the Iipophilic and

Potasium Phosphate Dibasic, Sodium Phosphate

Dibasic, Sodium chloride, Glacial Acetic Acid p.a,

Methanol p.a, distilled water, distilled water pro

HPLC

lnstrumentsUV Visible Spectrophotometer Hitachi UV1800, HPLC

Shimadzu, Dissolution Tester Pharmeq, diffusion cell,pH meter Denver, Viscometer Rion W-04E, filterholder, Millipore Membrane Filters 0,45lrm,Preparation of Topical Formulation

cel was prepared with Carbopol 94O,

triethanolamine, propylene glycol, oleic acid and

distilled water (Table 1) using 2 mixtures. Mixture I

was obtained by dispersing Carbopol 940 in a

mixture of distilled water and neutralized by theaddition of trietha nola m ine. Mixture ll was obtainedby dissolving Ds in a mixture of propylene glycol and

distilled water. After complete hydration of Carbopol

940, mixture ll was added drop by drop to mixture I

by stirring manually. Oleic acid was added to mixtureby stirring manually. The resulting gel stored at room

L

Viscosity DeterrrlinationGel viscosity measurements were evaluated using aviscosimeter Rion VT-04. All viscosity measurementswere performed in triplicate and mean calculatedDrug Content UniformityA series of working standard solution containing(0.4-15.3 rc/ml )of DS were prepared. A 20 [l a

liquot of the solution was injected on to the columnin a duplicate and the chromatograms wererecordedExactly 0.25 g gel was completely dispersed in

distilled water to make final volume 25 mL bysubjecting it to stirring for 5 min. The dispersion wasthan filtered to remove the undissolved residue.Exactly 1 mL of the filtrate was diluted to 10 mL. Anunloaded gel was also subjected to a similardetermination to observe the effect of excipients onthe absorbance. Using the standard curve of DS indistilled water, the drug content in gel was finallyestimated by HPLC.

ln Vitro penetration studiesThe abdominal hair of male Wistar rats, weighing130-140 g was removed carefully, without damagingthe underlying skin, using clippers Full-thickness skin

was excised from the abdomen under etheranesthesia.(Hadgraft and Ridout, 1987; Miller et al.,

1993). Adhering subcutaneous fat phases weredisposed from the dermal surface. The samples werethen allowed to diffusion cell, with the stratumcorneum facing the donor separate into two phases

and the concentration of DS in compartment.Dspenetration rates through rat skin were measuredusing a system of Dissolution Tester-diffusion cells.

with an available diffusion area of 1.77 cmr. ln thisstudy, 500 ml of phosphate buffer saline (PBS)

solution (pH 7.4) was used as the receptor mediumand 2 g of the test gel was placed on the donor side.The receptor medium was kept at 37 oC and stirredat 50 rpm. At predetermined time intervals, 5-mlsamples were taken from the receptorcompartment, for an 8-h period, and replaced by thesame volume of fresh PBS to maintain a constantvolume. DS was determined by HPLC. DS steady-state flux, J, was estimated from the slope of thestraight line portion of the cumulative amount ofdrug absorbed against time profiles.Analytical procedure

The amount of DS in permeation samples wasdetermined using HPLC apparatus (Shimadzu).

Elution was carried out at room temperature with a

mobile phase consisting of methanol-water (9:1,v/v)adjusted to pH 2.2 with glacial acetic acid; the flow-rate was 1 ml /min. Detection was at 276 nm.

RESULTS AND DISCUSSIONS

Evaluations of GelsVisuoldppedtunce

The prepared gels consistency, color, smell, andtransparency are reported in Table 2

Table 2. Visual appearances of SD Gels

visual appearancesFor-mula Color Trans-

parencyConsistency

0 White Yes

1 Emulgel Yellowish white No

2 Emulgel Ye lowish white No

3 Emulgel Ye lowish white No

pH Determinotion

The transport of DS across the abdominal rat skinwas investigated from a DS gel dosage form. The pH

value of the vehicle, the drug solubility in the vehicleand the viscosity of the gel are three importantfactors to consider !n the evaluation of drugpenetration from a gel dosage form across the skin(Ho et al., 1994). Therefore, carbopol gels wereadjusted to pH 7 to minimize any pH effect. Oleicacid is acidic and has a pH of 4.4 ( Rowe , 2005) . On

the addition of oleic acid at a concentration of 5 %

pH value becomes smaller than the other formulasV i sco s ity Dete rm i n o t io n

The viscosity of the gel matrix may play an importantrole in controlling the release of the drug into thereceptor compartment when the drug diffusionthrough the gel matrix is a rate determining step.However, formulations as they are contents OA

caused a decrease in the viscosity. The viscosity ofthe gel without OA (F0) was the highest, whereasthat of the gel containing 5% OA was the lowest,because the amount of water used to swell Carbopoldecrease with the addition of OA, so it become less

swelling. The pH and viscosity readings are reportedin Table 3.Drug Content UniformityCalibration curyes were constructed in the range ofconcentrations of 0.4 - 15.3 |.rg/ml for DS. The linearregression equation obtained was y = 42971.13x +

481.72, wilh a correlation coefficient ( r) = 0.9998.The calibration curve are presented in Fig 1.

Table 3. and Viscosity of DS gels

Formula pHrsD Viscosity (dPaslt SD

FO 7,10 !O,O3 723,33 ! 2,89F1 7,10 !O,O1 706,27 ! 2,89

F2 7,02 !0,08 97 ,33 ! 2,52

44

F3 6,69 r 0,04 78,33 ! 2,89

Gel

Fi&re 1. Calibration curve ot diclofenac sodium by HPLC

analysis

Table 4. Orut Content Uniformity

Formula Drug Content (%) t 5D EsD (%)

FO 95.29 I 0.91 0.95

F1 94.4a r O.32 0.3 3

F2 97.76 !0,77 0.73

F3 96.36 r 0.94 0.98

It was observed that the drug content of all formulaswas fulfilled the requirement, between 80-110% andRSD less than 6%

Figure 3, Mean maximum fluxes obtained from thepenetration of diclofenac sodium from abdomen rat skin

(n=3)

ln the formula 1 and 2 , which were DS penetration

more higher than the formula 0 and 3, contained OA

7% and 3 % in the DS gel. oA helped DS penetration

into the skin. Mechanism of OA as penetration

enhancers was increasing the fluidity of the stratumcorneum Iipids through the water channels (Fang, etal ,2003), so that the DS permeation was moreeasier to penetrate the stratum corneum In theformula 3 contains OA 5% caused skin morelipophilic, Ds will be retained longer on the skin and

it was difficult to penetrate the stratum corneum. ln

the formula 0, DS largely dissolved in a gel matrix

containing propylene glycol. lmproved solubility ofthe active ingredient in the gel matrix \rvas usually

followed by a decrease in partition coefficient, so,

the ability of DS to penetrate the stratum corneumwas also decrease (Arellano et al , 1998).

coNcr-u5roNThe results presented in this article showed, thepenetration enhancer astion of OA in thepenetration of DS across abdomen rat skin fromcarbopol gels was increasing the fluidity of thestratum corneum lipids through the water channels.

carbopol gels contained oA 1% and 3% provide thesimilar penetration flux and more higher than OA 0%

and 5%.

REFERENCES

1. Arellano, A., Santoyo, S., Martin, C., Ygartua, P.,

lnfluence of Propylene Glycol and lsopropylMyristate on The ln Vitro Percutaneous

Penetration of Diclofenac Sodium from Carbopol

Gels. Europeon Journol of PhormoceuticolScience, No.7, p. 129-135 (1998)

2. Chuasuwan, 8., Binjesoh, V., Polli, J.E., zhang, H.,

Amidon, G.1., Junginger, H.E., Midha, K.K., Shah,

V.P., Stavchansky, S., Dressman, J.8., Barends,

D.M. Biowaiver Monographs for lmmediateRelease Solid oral Dosage Forms: Diclofenac

10.@ 15.00

ga c@.r.noi (!!r'nl.]

i-tuE-!"0I*j

00

30

e

Bt!

IrII

,15

The drug content uniformity of all formula arereported in Table 4.

ln Yrtro penetration studies

with respect to drug permeation through the skin

from vehicles, a drug should first diffuse out fromthe vehicle to the skin. Thus, the influence of OA onthe penetration of DS from the carbopol gels

through abdomen rat skin was examined. Thepenetration profiles of DS from these gels throughthe abdomen rat skin are presented in Fig. 2. Thepenetration profiles of F1(OA 1%) was almost similarto that from the gel F2 (OA 3%), but F2 has thehigher penetration flux of DS. F3(OA 5%) has morelower penetration flux of DS than F1 and F2. F0 (OA

0%) has the lowest fluxes. The mean maximumfluxes obtained from the penetration of Ds fromabdomen rat skin are presented in Fig.3.

Figure 2, Penetration profiles showing the effect ofdifferent grades of Oleic acid on the penetration of

diclofenac sodium

i:r

..!

Sodium and Diclofenac Potassium. .lournol olPho rmoceuticol Sciences.p.l-13.(2008)

3. Fang, J.Y., Hwang, T.1., Fang, C.l. ln vitro and inviyo evaluations of the efficacy and safety ofskin permeation enhancers using flurbiprofen as

a model. lnternotionol Journol ofPho rm oceutics.255(L-2): 153-165 (2003)

4. Ganiswara, S.G. Formdkologi ddn Teropi, Edisi 4,Bagian Farmakologi FKUI, Jakarta, hal. 218(200s)

5. Hadgraft, 1., Ridout, G., Development of modelmembranes for the percutaneousmeasurements. l. lsopropyl myristate. /rt. J.

Phorm., 749-75617987],6. Ho, H.-O., Huang, F.-C., Sokoloski, T.D., Sheu,

M.T., The influence of cosolvents on the in vitropercutaneous penetration of diclofenac sodiumfrom a gel system. J. Pharm. Pharmacol.636-642.1L994).

7. Katzung. B.G. .Basic ond ClinicalPhormdcology.lOth ed, New York:Mc Graw Hill Companies(Electronic version) (2007)

8. Michniac-Kohn, B,8., Wertz, P.W., Al-Khalili, M.,Meidan, V.M. Skin: Physiology and Penetration

Pathways. /n; Rosen, M.R., Delivery SystemHandbook for Personol Core ond CosmeticProducts-Technology, Applicotions, ondFormuldtions. New York: William Andrew,lnc.p.95(2005)

9. Mohammed, F.A. Topical PermeationCharacteristics of Diclofenac Sodium from Na

CMC Gels in Comparison with Conventional Gel

Formulations. Drug Development dnd lndustriqlPhormocy,Vol2l, No.11, p. 1083-1097 (2001)

10. Ozguney, 1.S., Karasulu, H.Y., Kantarci G., Sozer,S., Guneri, T., Erthan, G.Transdermal Delivery ofDiclofenac Sodium Through Rat Skin FromVarious Formulation. AAPS PhormoceuticolScie nces o nd Technology, No.7, V ol.4(2006l

11. Rowe, CR., Sheskey, J.P., Owen, 5.C. Hqndbookof Phormoceuticol Excipient, Fifth edition,London : American Pharmaceutical Association,p. 777-tt4, 624-626 (2006l

12. Sweetman SC (Edl. Mortindole 35: The CompleteDrug Reference. London: Pharmaceutical Press,(Electronic version) (2007)

.16