DEVELOPMENT OF MELOXICAM TRANSDERMAL MATRIX TYPE PATCH USING POLYVINYLPYRROLIDONE, HYDROXYPROPYL METHYCELLULOSE, AND ETHYL CELLULOSE COMBINATION

.f.{s%s

K#pffiffi

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Drug

Deiivery Systems:

From

Drug-Discovery,

Pre-formulaticn,

Formulation and Technological Approaches

for

Poorly Soluble Drugs and Protein

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i::r'r,:tr* ',t: .: :l- !

The

l"t

lnternational

conference

on

Pharmaceutics

&

Pharmaceutical

Sciences

Proceedings

ISBN : 97 8-5A2-72333-0-0

(Letter of National ISBN Agency No' 4L27lE'slp/03'2015 Date 18 March 2015)

1st edition Proceeding Published bY:

Faculty of Pharmacy Universitas Airlangga Surabaya, lndonesia

Address:

Kampus B Jl. Dharmawangsa Dalam Surabaya 60286

Phone +62315033710

Fax +62 31 5020514

Website : www.icpps2014.com or wwwff'u na i r'ac'id Email: icppinfo@gmail.com

rsBN 1?A-t0e-?e333-0-tl

PREFACE

From Chairman

It

is

our

pleasure

to

present you

the

proceedings

of

The Lst lnternational Conference on Pharmaceutics and Pharmaceutical Sciences (ICPPS) organized by The Faculty

of

Pharmacy

Universitas Airlangga Surabaya lndonesia.

The proceeding was produced based on papers and posters presented at The

1st

lnternational

Conference on Pharmaceutics and Pharmaceutical Sciences (ICPPS), held in Surabaya, lndonesia, 14-15November2014.

The proceeding clearly reflects broad interest, from the participants that coming from all around the world.

The papeJ$presented were pharmaceutics and biopharmaceutics; requirements on howto evaluate molecufp!

in

discovery and their appropriateness

for

selection as potential candidate; their

development

in

context

of

challenges and benefits, together

with

associated time and cost implications and also requirements to progress through pre-clinical and clinical.

ln this an opportunity, lwould like to express my appreciation to the editorialteam of the proceeding who have been working hard to review manuscripts, and making the first edition of this proceeding

be possible.

I would like also

to

thanks

to

all invited speakers and presenters who participated in The 1st

lnternational Conference

on

Pharmaceutics and Pharmaceutical Sciences (ICPPS) and your contribution to this proceeding.

Finally,

I

hope this proceeding _{will give contribution}

to

the Pharmaceutics and Pharmaceutical

Sciences research.

Chairman,

COMMITTEE

Advisor Chairman

Editor

n ,rtn

Committee:

: Dean

of

Faculty

of

Pharmacy Universitas Airlangga : Dra. Esti Hendradi,

M'Si"

Ph'D' APt'

: Dr.

Wouter

U. Hinrichs (Netherlands) Prof. Kozo TakaYama (JaPan)

Dr. Srinivas

Mutalik

(lndia)

or.

ttuttakorn

Baisaeng {Thailand) Prof. Dr.

WidiiSoeratri'

DEA (lndonesia)

Prof. Dr.

Widji

Soeratri, DEA' APt' Prof. Dr. Siswandono, MS'' APt' Prof .Dr. Tutuk Budiati' MS'' APt'

Prof. Dr.

rer'nat'

Muhammad Yuwono' MS''

Apt'

Drs. Hadi Poerwono, MSc''Ph'D' APt'

Drs. Marcellino Rudyanto' MSi'' Ph'D'

Apt'

Drs. Bambang Widjaja, M'Si' APt'

Drs. SugiYartono, MS, APt' Dra.Tutiek Purwanti, MSi' APt' Dra.Tristiana Erawati, MSi' APt' Dra.Retno Sari, MSc, APt'

Dra.Dewi lsadiartuti, MSi' APt' Dra.Noorma Rosita, MSi' APt'

Dr. DwiSetyawan, SSi, MSi" APt'

Or.

ni"tt.

Primaharinastiti' SSi' MSi'

Apt'

Dewi

MelaniHariyadi'

SSi'

M'Phil''

Ph'D'

Apt'

HelmY Yusuf, SSi, MSc'' Ph'D' APt'

Dr. rer. nat. wtaria l-ucia Rrdhani Dwi Lestari' SS|'MPharmSci''

Apt-tvt"lanny lka Sulistyowati' SFarm' M'Sc'

Apt'

Febri Annuryanti, SFarm'M'Sc'

Apt'

-

'

M. Faris Adrianto, MFarm' APt'

TABLE ofCONTENT Preface

from

Chairman

Committee

... ii

Table

of

Contents

....--..--..--.

...

iii

Author

lndex

...

iii

AUTHQR INDEX

COMPARISON OF SODIUM STARCH GLYCOLATE AND CROSSCARMELLOSE SODIUM AS SUPERDISINTEGRANT IN MEFENAMIC ACID FAST DISINTEGRATING TABLET

Adeltrudis Adelsa D, Oktavia Eka Puspita, Amalia Ayuningtyas, Marulita lsadora ,...,... 1

STUDY EXPRESSION OF HUMAN ERYTHROPOIETIN EXPRESSSION IN MAMMALIAN CELL

Adi Santoso, Popi Hadiwisnuwardhani, Yana Rubiana, Yulaika Romadhani, Endah Puji Septisetyani, Dyaningtyas D.P. Putri

ANTIOXIDANT STABILITY ASSAY OF ALPHA TOCOPHERYL ACETATE IN SOL]D LIPlD NANOPARTICLE SYSTEM (LlPlD BASE BEESWAX AND MONOSTEARIC GLISERYL 50:50)

Anggie Widhi, Noorma Rosita, Widji Soeratri ...

A BIOACTIVE BOVINE HYDROXYAPATITE4ELATIN IMPLANT FOR IN VITRO GENTAMIC]N RELEASE

Aniek Setiya Budiatin, M. Zainuddin, Junaidi Khotib, Diah Himawati ... 13

EFFECT OF COMPARISON SURFACTANTAND COSURFACTANT IN WATER/OIL MICROEMULSION IN RELEASE OF OVALBUMIN Microemulsion Water/Oilwith Surfactant (Span 8O-Tween 80) :

C-osurfactant (Ethanol) _=5:L,6:!, and 7:1)

Anisa Rizki Amalia, Riesta Primaharinastiti, Esti Hendradi

...,...,

... 18

ANALYSIS OF MYCOLIC ACIDS CLEAVAGE PRODUCT OF Mycobacterium tuberculosis BY GAS

CHROMATOGRAPHY-FLAM E IONIZATION DETECTOR

Asri Darmawati, Deby Kusumaningrum, lsnaeni, Muhamad

Zainuddin

... 21 PERIPLASMIC EXPRESSION OF GENE ENCODING ANTI-EGFRvIIISINGLE-CHAIN VARIABLE FRAGMENT ANTIBODY USING PelB LEADER SEQUENCE lN ESCHER/CHIA COLI

lGrtika Sari Dewi, Debbie Sofie Retnoningrum, Catur Riani, Asrul Muhamad Fuad ...24

IN VIVO ANTIMALARIAL ACTIVIry OF ETHANOL EXTRACT AND ETHYL ACETATE FRACTION OF

Alectryon serrotus LEAVES ON Plasmodium bergheilNFECTED MICE

Aty Widyawaruyanti, Uswatun Khasanah, Lidya Tumewu, Hilkatul llmi, Achmad Fuad Hafid, Indah S Tantular

...

... 30

PROFILE OF COMMUNIry PHARMACISTS KNOWLEDGE IN PATIENT ASSESSMENT WITH INFLUENZA SYMPTOMS AND ITS PRODUCTS

MoDlFlcArtoNPRocEssoFNATURALCASSAVAsTARcH:THESTUDYoFCHARACIERISTICSAND

PHYSICAL

PROPERTIES

r---.:

a

A D a<rilti- N-W.N Yulianingsih, I

M'A'(''

Prasetia, Jemmy n,

il'S'

Arisanti' N'P'P'A' Dewi'

G'A'R' As'tuti' N'W'N Yulianingsih' I M'A'C

Wirasuta

""

133

DRUGUSEPRoFTLEoFDIABETICPATIENTSINEASTSURABAYAPRIMARYHEALTHCARE I Nyoman wiiaya,

o-."-i"i"ir"hmah,

o""

Y;;;;f"rriha,

Tesa Geovani santoso' Dina Kartika'

Hikmah Prasasti n,

wi"iiiwido

Agustin

"""""""

135

,-'*

urra,*,

MAX DETAM lt vARtEw As _'REVENTI'E AND cuRATlvE

.RGAN DAMAGE DUE To

'#"";ii[:I$*'*?[oP]"

Ressandv' Gusti Avu Putu

Puspika"ll1]llll1ilj;:'l:::::""'

Dffi

Ayu Kusuma Dewi

"""""'

"""""""""'L42

ANACTIVITYTESToFMAToALEAVESE}ffRAcTASHEARTRATEFREQUENCYREDUSTIoNWITH

ADRENALTNE

lNDucrloN

r--

r-r^

Ei,tri.nnv

"""t4

lka Purwidyaning'Jt' irin Yulinah Sukandar' lrda

Fidrianny

EFFoRTToREDUCEcoMPRESSIBILITYoFRAMIPRILTHRoUGHCRYSTALENGINEERING

lndra,Sundani N Soewandhi

"""""""

""""""""""

147

INVITRoALPHA-GLUCoSIDASEINHIBIToRYACTIVITYoFETHANoLICLEAFEXTRACTANDFRAcnoIG oF Rauvolfia serpentina (L') Benth' ex

Kurz

...'-...- 150

Julie Anne D' Bolafros' lvan L' Lawag

PERIPLASMIC EXPRESSION OF GENE ENCODING ANTI-EGFRVItI

STNGLE'CHAIN VARIABLE FRAGMEilT

i$'fgJ;$:*:ii:,1*r"':r:',r:"?rH:*#','i?#j'n

,u, Muhamad Fuad...-

153

CHARACTERIZATIoNANDLD5oVALUEDETERMINATIoNoF

1,5-bis(3'-etht-;:;;;;pienvl)-r'a-pentadiene-3-one

(EH P)

Lestari Rahayu, Septian' Esti Mumpuni

""""'-"""'

""""""""""

159

DEVELOPMENT OF MELOXICAM TRANS-DERMAL MATRIX

TYPE PATCH USING

PoLwINYLPYRRoLIDoNE,

,,0*O*,0*Oi,i-,U'iTHY'.''ruLOSE,

AND ETHYL CELLULOSE

t coMgtNRttott

.

- .. A:_

...- 162

Lidya Ameliana, Monica lwud' Selly Rio

"""""""

ANT|HEPATIT|ScVlRUsAcTlVlTYSCREENlNGoNHarputliaorboreaEXTRACTSANDiSoLAIED

:fl

["X'*iu,EvhvApryani'Y:'.*i":11::]:-ll-Ylii1''lli::fi:H1il:1ili"'

Myrna Adianti,

-aii"

oir.i

Aty widyawliuyanti,lctrmad Fuad Hafid' Maria lnge Lusida'

Soetjipto, Hak

Hotta""

"""""""""""'

166

HPLCMETHoDPRECISIoNToASSAYoFA-MANGoSTINlNMangosteen(Garciniamangostonaq FRulr RIND

tti*oii

to*MuLATED lN oRAL

soLUTloN

..."""""""'

161

@

rcPffi2oL4

Proceeding

n

.l"nt"rnational

Gorfiercn

on Pharmaceutics & Pharmaceutical

Sciersi

DEVELOPMENT

OF

MELOXICAM

TRANSDERMAL MATRIX

TYPE

PATC}I

USING

POLYVINYLPYRROLIDONE,

HYDROXYPROPYL

METHYLCELLI,'-LOSE,

AND

ETHYL

CELLULOSE

COMBINATION

t*lout

oPharmaceo

Lidva Ameliana. Faculty of Pharmacy, Jember University, lidyaameliana@yahoo.co.id, O33t 324736; lwud. Faculty of Pharmacy, Jember University, miiwudh@gmail.com, 0331324736;8llLB!g, Faculty of Pt'

Jember University, rio.selly@yahoo.co.id, 033L-324736

AND

rlation rrnal I

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'€f'c l"s c INTRODUCTION

Transdermal drug delivery system is an ad-ministration

of a

therapeutic agent

in

the

form

of

patches

or

semisolids

that

deliver drugs through intact skin for systemic effect1.

The advantages

of

transdermal

drug

deliv-ery systems are

to

avoid

of

hepatic first pass

metabolism, ability

to

discontinue

adminis-tration by removal of the system,

to

controll drug delivery for a longer time than the usual gastrointestinal transit

of

oral dosage form3,

to

prevent irritation

of

the

digestive tract8,

improves patient compliance3. Transdermal

drug

delivery systems may prevent the drug

from enzymatic reactions in the

gastrointesti-nal tract wall5

Meloxicam is a nonsteroidal anti-inflammato-ry drug (NSAID) class enolate acid derivative oxicam6. Meloxicam inhibit

the

synthesis of cyclooxygenase-2 (COX-2) a nd prostaglandi n2.

Meloxicam has

a

partition coefficient octa-nol

/

water (log P octanol

/

water)

3.43 and a molecular weight 351.4 Dalton4. The dose of Meloxicam

is

7.5-15 mg/daV7. Meloxicam was reported as a drug that can be applied to skin and mucosa because meloxicam has

low-er tissue toxicity than piroxicam, ketoprofen, indomethacin, diclofenac and ibuprofen6 The important component in the preparation

of

the

patch is a polymer. The polymer used

in

this

patch are hydrophilic and

hydropho-bic polymer. This research would be develop Meloxicam transdermal patch

with

some of hydrophilic and hydrophobic polymers,

eth-ylcellulose (EC) -polivinilpirolidon (PVP),

hy-droxypropylmethylcellulose (HPMC) - EC, then compared the physical _{properties and the}

re-lease of Meloxicam between the formulas.

MATERIALS AND METHODS Meloxicam was obtained as a gift

PT. Dexa Medica, HPMC, PVP K-30, Erhd

lose N-22, Propylene glycol,

col, Potassium Chloride, Potasium

F

Dibasic, Sodium Phosphate Dibasic Chloride, Backing, Aquadest

Formulation of transdermal patches Matrix type transdermal patches Meloxicam were prepared by solvert

technique. HPMC or PVP K30 and EC

lution was prepared using ethanol as

Polymeric solutions

were

mixed with the help

of

magnetic stirrer

fo:

15

utes. Meloxicam was added to col and polyethyleneglycol and stirrec minutes and then were poured into

dried at room temperature for 24 composition of transdermal patches s

in Table 1.

Materiai Formula {mg}

&

p3

ffi

I

It t)

uetoxrcim

l5--tT

i5:-15

-,

PVP 57.75 38.5 19.25

HP[4C 57.75 i: ;

EC 13415 154 17325 13475 'rd

Propy{ene 150 150 150 150 'rI

qtlcol

Plasticizer 150 150 '150 150 'i:

I orl' 500

-

5OO ro0 SOO =

Table 1. The Composition of Meloxicam -iffidl Patches

Evaluation Test

The prepared formulation were evar

different physiochemical

characteris:'-as color, odor, consistency, weight r.,r-n

thickness, moisture content,

drug :

and in vitro release study.

1..{ , .";), ' ij::t: I

7g.l11i 11i,11111-.\:

,;:!! r,,r,:r::::: i:::jj::;; ..

t

hrr

tScfurr-PATC}I

ETII}

rp[e f,-mm

hr/f Cdhn-/lerp gtF lrceennn

,Sodfim

i ofnbrfriltE

It

ca$lll;

l-N22

sr.

s sohmnt-tqu.,qilllh r 15 :rrn-

deresfu-edtulD

nokbilil

q.rs- mG 6

hoceeding

lhl*

kremafiond

Gonfiurence

qr Pharmaceutics & Pharmaceutical Sciences

ESULTS AND DISCUSSION

Formulation

and

Evaluation

of

Meloxicam BansdermalPatch

kansdermal drug delivery system containing

Meloxicam was prepared

by

using different

polymeric ratios of HPMC, PVP and hydropho-.bic'polymer of EC in combination. The

meloxi-'tam _patchs

can be seen in Fig.1. They alt

yel-hn,

odorless, and dry. The results of various physico-chemical parameters

were

listed in

bbles 2 The weight of the patches varied from 535.53

*

0.67 to 574.53

r

0.40 mg. The

thick-+os

of the patches varied from 0.224t0.001

b0.22910.001mm

Ieloxicam

in

methanol was scanned

in

the

llV

wavelength region

of

200-400

nm

for reximum absorption

(l

max). The

I

max was frund to be at 364 nm. Linear relationship was dserved between the concentration and

ab-srbance

value. _{{Slope=0.045, r=0.998).} This :Bression equation was used to calculate the

*ug

content of meloxicam patch.

drug content of meloxicarn patches were

in Table 3. They varied frorn 96.833 10.673 98.200

t

0.610 %. There were in accordance the requirement of that the drug content

range 85% -

tt\%

and _{the coefficient}

vari-is less than 6 %.

{rr}

f5}

4

Frg.l The Meloxicarn Palch of Varjous Fonnulaticn

Ftg-1 The Meloxicam Patch olvarious Formulation

wffizal,r.

Forrnula Appeirrnce Weigh.t flrbfnes-s

-lnitormity (mm) rSD

__"_{gt9_iJD

-

FZ

"--

t-ess-smootfr,

\i:Sry;E

-lfi,,.

0226iooo2

-tess itexible uufjj t 0.2?7 I o.oo1 Less smoolh,

less tlex,ble 563_80 _0.60I 9.224*.A,pAz

F4

smoolh, *exible

ttjff *

0.227 r o.oo?

F5

6nnooth. flexibre

u.j.;t-

a.i;;aso,

-T;t6* _{t :} -Filys6ocienffif-Froperrlles

of

Melo:;ieam palehe$

The

moisture

content

in the

formulations ranged from 3.52810.024

to

7.53010.023 %.

The highest percentage

of

moisture content was found in F1 7.530

I

0.023 % respectively which may be due to the hygroscopicity of na-ture

of

PVP. The highest perc€ntage

of

mois-ture

content

of

HPMC patchs was found in

F4 because

it

was

the

highest concentration

of HPMC in patch. The results of patch,s drug

content and moisture content were listed in Table 3.

The ln vitro drug release studies were carried

out

using cellophane membrane.

The

cel-lophane was mounted

on the

diffusion cell which acted as a donor compartment. 500 ml of phosphate buffer saline pH 7.4 as a diffusion

medium was taken in the dissolution chamber

which acted as the receptor _{compartment to} maintain the sink condition. The donor

com-partment was kept in contact

with

receptor compartment and receptor compartrnent was stirred with paddle during the study. Sample 5 rnl was withdrawn and replaced with 5 ml of PBS pH 7.4 at different time intervals. The samples were analyzed using UV

spectropho-tometer at 364 nm to estimate Meloxicam.

Meloxicam

in

PBS was scanned

in the

UV

wavelength

at

354 nm.

Linear relationship was _{observed between the concentration and} absorbance value. _{{Slope=0.0293,} r=0.9933}.

meloxicam patch. Flux

of

Meloxicam release study from patches can be seen in Fig.2.

Table 3. Drug Content and Moisture Content Properties of Meloxicam patches

I

Fig 2. Flux

of

Meloxicam release study from patches

The flux ranged _{from 354,865 to} 677,851 pgl

txr).setonSl)).1he

h\ghes\ l\ux was lound

ln

fo rm u I ation t 3"67 7,853, pg/c m 2. seco n d3. _f 2, r

e-spectively which may be due to the nature of

PVP (Fig.2).

coNctusroN

Meloxicam patch in PVP-EC had moisture con-tent and Meloxicam flux release higher than

Meloxicam patch

in

HPMC-EC polymers. The highest flux and moisture content was on the

highest PVP in Meloxicam patch formula.

Proceeding

fipl*htenrndmd

on Pharmaceutics & Pharmaceutical

REFERTNCES

Aulton. M.E.{2002). Pharmaceuiils The science of Dosage form Design,

Churchill Livingstone, Elsevier. 499-s33

Jayaprakash S., Ramkanth 5., Anitha

P., Alagusundaram M., Saleem M., Chetty M.C. {2011). Design and emh,r

ation of monolithic drug in adhesiue tra nsdermal patches _of

meloxicarn-Malaysian Journal Of PharmaceutitC

Sciences. Vol.8 (2): 25-43.

Modamio, P., Lastra, C. F. and Marmr E. L. {2000} A comparative in vitro

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Ranade, V. V., and Hollinger, M.

A

{2004). Drug Delivery Systems. 5ec

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Stei, P., Kruss, B., Wiegleb, J. &

V. {1.996}. LocalTissue Tol

Meloxicam, a New NSAID:

for Parental, Dermal and ministration, British Journal

cf

ma\ology, 35(Supp\. 1i: 44-5C.

Sweetman, S. C., Paul, S. B- &/

ison, 8., Julie, M. M., Gail, C

lL

dan Anne, V. P. (2009)Mar

tindale: The Complete Dng Reference, Thir

sixth edition. London:

Press.

Zadeh, B. S. M., and

Harsarn-2010. The Effect of Chem-s'

Physical Enhancers on licylate Permeation througf

Trop J Pharm Res. _{Vol.9 {6:}

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