Influence of Oleic Acid on the In Vitro Penetration of Diclofenac Sodium Gel Repository - UNAIR REPOSITORY
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ISBN: 978-602-60569-3-1
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PROCEEDING
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st lnternational Conference
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on lVledicine and Health Sciences
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nal Collaboration to Achieve
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Hosted by:
Faculty of Pharmacy I Faculty of Dentistry |
Faculty of Medicine I
Faculty of Public Health I School of Nursing
University of Jember, lndonesia
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Insan$arytasi
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 Committee
Event Division
Drs. Moh. Hasan., Ph.D (Rector of
Diana 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.
University of Jember)
Drs. Zulfikar, Ph.D (Vice Rector for
Academic 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.
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.
Organizing Committee
Chairmain
Lestyo Wulandari, S.Si., M.Farm., Apt.
Secretary
Endah Puspitasari, S.Farm., M.Sc., Apt.
Treasurer
Yuni Retnaningtyas, S.Si., M.Si., Apt.
Nia Kristiningrum, M.Farm., Apt.
Secretariat, Publication, and
SponsorshipDivision
Logistic Division
Eka Deddy lrawan, S.Si., M.Sc., Apt.
Dwi Nurahmanto, S.Farm., 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.
111
CONTENT
PREFACE
..,.........t
EDrTORS........
.
CONFERENCE COMMITTEE
iii
coNTENT..........
iv
PHARMACY.............
................... 1
COMMUNITY PHARMACISTS' COUNSELLING SKILLS
M
EDTCATTONS
ON
OVER.THE-COUNTER (OTC)
....................2
FORMULATION AND OPTIMIZATION OF CAFFEINE NANOEMULSION USING FACTORIAL
DESTGN STUDY..
.................. 6
EFFECI
OF
7% : 2%
COMBINATION SODIUM ALGINATE-GELATN
CONTENT tN
CHARACIERISTIC AND ANTI M ICROBIAL ACTIVITY OF PROBIOTIC MICROSPHERES Lactobacillus
acidophilus.......
................ 10
ANTIDIABETIC ACTIVIW OF POWDER AND ETHANOLTC EXTRACT OF ANTLTON (Myrmeleon
sp.) ON WISTAR STRAIN WHITE MALE RATS WITH GLUCOSE PRELoAD
74
ANTIBACTERIAL AND ANTIBIOFILM POTENTIAL OF ETHANOLIC EXTRACT FROM BINTARO
FLOWER (Cerbera odollam) AGAINST Staphylococcus aureus ATCC 6538.............................. 17
STRUCTURE MODtFtCAT|ON
AND
MOLECULAR MODELTNG
OF
1_(BENZOYLOXY)UREA
DERIVATIVES AS ANTICANCER DRUG CANDIDATES..
................ 20
CHARACTERIZATION AND THE RELEASE TEST OF ANTI-AGING TRETINOIN IN NANOEMULSION
USING OLIVE OIL.......
EFFECT OF PARTICLE SIZE
AND SURFACE CHARGE ON THE UPTAKE AND IMMUNE RESPONSE
OF OVALBUMIN.ALGINATE MICROSPHERES
ANTIHYPE RCHOLESTE ROLEM
lC
EFFECT
OF
Arcangelisia
flava STEM
HYPERLIPIDEMIC RATS........
EXTRACT tN
.......'..'.... 31
GREEN TEA EXTRACT EFFECT ON BLOOD GLUCOSE LEVEL AND LIVER HISTOPATHOLOGY IN
D|ABETTC MtCE ...........
............ 35
TH REE-WAVELENGTH SPECTROPHOTOM ETRIC M ETHOD VALI DATION FOR DETERM INATION
OF PREDNISONE TABLET CONTAINING COLORING DYES ....
39
TNFLUENCE OF OLETC ACtD ON THE tN VTTRO PENETRATTON OF DTCLOFENAC SODTUM GEL
[3
ANTIOXIDANT ACTIVITY OF METHANOL EXTRACTS FROM THE STEM BARK OF MANGROVE
PLANT 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 AND
lsoPRoPYL MYRTSTATE)......
....................... 55
EFFECTIVENESS
OF BINTARO (Cerberra odollam Gaertn.) LEAF ETHANOLTC EXTRACT
AGAINST Staphylococcus aureus I N-VITRO BtOFILM FORMATION
lY
59
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29 " " """""" "
'toNVHrr rv3-t llllol vlt8vuv ro NollvNl€t^of All^llf,v lNVClxoll-NV lo ACnrs
t45
CORRELATION OF CD4 WITH TOTAL LYMPHOCYTE COUNTS IN HIV PATIENTS
...
DENTISTRY...........
... 148
Determinants of HIV/AIDS Awareness and Knowledge in Tanah Papua, lndonesia
""""""
149
THE ABILITY OF ANTI-INFLAMMATORY JATROPHA CURCAS LEAF EXTRACT AT COX'2
1-54
EXPRESSION ON MONOCYTES WERE EXPOSED LPS
........................ 158
NOVEL METHOD THYROID HORMONE MEASUREMENT ...."....
ROBUSTA COFFEE BEANS INCREASE LEVELS OF TNF-
o
AS
A
RESPONSE
mutans
TO Streptococcus
762
THE LEVE6 OF TNF-A lN GINGIVAL CREVICULAR FLUID (GCF) OF OSING TRIBE WOMEN WITH
................ 165
OCCLUSAL DISHARMONY...,...,......
Robusta Coffee Bean Extract (Coffea robusta) on the Viability
Exposed by Porphyromonas gingivalis.........'
Effects
of
of Neutrophils
...... 169
ROBUSTA COFFEE BEANS DECREASE OF INFLAMMATION IN DENTAL CARIES""......".......'' 173
................ L77
The Progressive Low Chronic lnflammation on OralTissues ln Elderly
DENTAL CARIES
IN
PREGNANT WOMEN WHO VISITED POSYANDU OF SEVERAL PUBLIC
782
HEALTH CENTERS IN JEMBER
Role of Che moattractant Chemokine (SDF-1/CXCR4) ln Bone Marrow
Niche "
" " " " " ' 185
Establishment of a Rat Model of Temporomandibular Joint Osteoarthritis using lntraarticular
..... 190
lnjection of Complete Freund's Adjuvant.......
.....794
PUBLIC HEALTH
RECIPROCAL DETERMINISM "DAKOCAN" CHALLENGE EFFORTS
CASES IN JEMBER DISTRICT.......
TO REDUCE HIV AND AIDS
. 195
IRON TABLETS DISTRIBUTION OF PREGNANT WOMAN IN THE DISTRICT AND CITY OF EAST
200
JAVA PROVINCE.....
RISK MANAGEMENT OF DUE TO EXPOSURE TO PESTICIDE POISONING FOR TOBACCO
............204
FARMERS IN THE JEMBER DISTRICT..
AN
OVERVIEW
OF MOTHER KNOWLEDGE AFTER GIVING BIRTH ABOUT
........ 208
BREASTFEEDING ......
D|SASTER PREPAREDNESS
EXCLUSIVE
AT PUBLIC HEALTH CENTER (PHC) BY SCORING ANALYSIS OF
GENERAL ASPECTS, HEALTH CARE, SURVEILLANCE, ENVIRONMENTAL SANITATION AND
...........272
LOGISTICS
INDEPENDENT FAMILY PLANNING IN RURALAND URBAN AREAS GRESIK DISTRICT .....,."...71.5
UNMET NEED FOR FAMILY PLANNING ON ELIGIBLE COUPLE IN INDONESIA: 2OO7 IDHS DATA
........219
ANALYSIS
shells That Have been Polluted by lead around Youtefa Bay in Jayapura City That Have
........................ 223
Potential Risk Of Non Carcinogenik.'...'. ........
IMPLEMENTATION DIARRHEAL SURVEILANCE REPORT INFORMATION SYSTEM
227
WITH WATERFALL METHOD IN HEALTH DEVELOPMENT OF JEMBER......"...
DESIGN
AND
\t
LOCAL WISDOM OF JEMBER COMMUNITY
IN REDUCING CYANOGENIC
LEVELS
URINE THIOCYANATE LEVELS
TO LOWER
229
UNDERWEIGHT AND MORBIDITY STATUS AMONG UNDER FIVE YEARS CHILDREN IN
) ?4.
suRABAYA..............
CONDOM USE AMONG EXIT CLIENTS OF FEMALE SEXUAL WORKERS FOR PREVENTION
237
HIV/AIDS IN MAKASSAR
THE SOCIAL SUPPORT AND PREVALENCE EMESIS GRAVIDARIUM ON PREGNANT MOTHER IN
TRIMESTER I AT PUSKESMAS KEMBARAN I BANYUMAS REGENCY...............,..,..,..,..,............247
245
NURSING..
We need a bigger bomb: a community attempt on fighting dengue fever in a suburban
Su ra
,.,.....,.......'.,'.,..,246
baya, lndonesia
APPLICATION OF STANDART NURSING LANGUAGE (NANDA, NOC. NIC) USING SOCIAL MEDIA:
INSTAGRAM@
TO
INCREASE INFORMATION SEEKING BEHAVIOUR
AND MOTIVATION
OF
.......250
NURSING STUDENT.....
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
spLtNTtNG SKTLL (PREHOSPTTAL
SETTING)....
STUDENTS
......................261
THE CORRELATION BETWEEN NURSE PERFORMANCE & THE LEVEL OF JAMKESMAS PATIENT
........266
SATISFACTION IN DAHLIA II WARD, NGUDI WALUYO WLINGI HOSPITAL
How To Maintain High Quality Cardiopulmonary Resuscitation ln Adults: Literature Review
270
SMOKING BEHAVIOUR AMONG MIDDLE AND LATE ADOLESCENTS IN A SUB DISTRICI OF
275
MALANG DISTRICT, EAST JAVA, IN DONESI4............
THE DIFFERENCES DECLINE BREAST ENGORGEMENT CONDUCTED CONVENTIONAL METHODS
(BREAST MASSAGE) WITH HERB YEAST-KATU..
v11
282
Jjah
INFLUENCE OF OLEIC ACID ON THE IN VITRO PENETRATION
D.D.
and
OF DICLOFENAC SODIUM GEL
sion
of
1't Lidya Ameliana, Faculty of Pharmacy, Jember University
7).
,c.
Kalimantan 1st street No 2, Jember, lndonesia,60121, lidyaa meliana @ya hoo.co.id
2nd
Esti Hendradi, 3'd Mochammad Yuwono, Faculty of Pharmacy,
Airlangga University, Su rabaya, lndonesia
ties
:red
l&
90R.
of
in
rnol
-65,
v]. E.
6th
]TRODUCTION
flclofenac sodium (DS) is a nonsteroidal
,tiinflammatory drugs (NSAlDs), that inhibits
Gldooxygenase-2 enzyme (COx-2). lt has first pass
rEtabolism hy 4O-5O%, because of its short
tiological halflife, the drug has to be given
l€quently (Ganiswara, 2005). Dose of
F
eetman, 2007). ln peroral use,
189
tory
GEntral nervous (Katzung, 2002, Chuasuwan,
tary
)AC
tion
-tion after transdermal application (Mohammed,
A)01; Ozguney, et a1.,2006). DS partition coefficient
h n-ostanol-buffer aqua (log P) was 1.1 (Chuasuwan,
2(D8). Lipophilic nature of the stratum corneum and
res:
ised
the hydrophilic nature of the underlying tissues
ilowed that the drug will penetrate the skin should
have an optimal balance between the lipophilic and
nof
lrydrophilic properties. ln general, the skin is more
pnrmeable to the material which has a partition
/sis.
ond
tzki,
lical
lical
,itio
Preparation of Topical Formulation
Gel was prepared with Carbopol
by stirring manually. Oleic acid was added to mixture
by stirring manually. The resulting gel stored at room
Constituents
coefficient (P) in octanol-water between 1.0-1000
(Michniac-Kohn et al., 2005).
Oleic acid enhances the penetration of drugs into
the skin by increasing the fluidity of the stratum
corneum lipids through
the
DS
Carbopol 940
Triethanolamine
Concentration (%)
FO
F1
t
1
0.6
F2
1
0.6
qs
30
30
30
35
L
100 100 100
s
0.6
qs
establishment of
Propylene glycol
drannels (water channels) (Fang, et al ,2003)
Oleic acid
This study aimed to know the influence of Oleic
Distilled water to
Acid {OA) in several concentrations O%, 3% and
temperature for 24 h study prior to use.
5%) as penetration enhancer on the in vitro
Table 1. Composition (% w/w)of DSgels
penetration of topical DS gel. Furthermore, the
of the topical preparation
(organoleptic, pH and viscosity), and DS penetration
percutaneously through rat skin Then observed
that in spite of DS assay and penetrate through the
rat skin at certain intervals and observed by means
of HPLC.
physical properties
MATERIALS AND METHODS
Materials
a gift sample
from PT. Kimia Farma, Carbopol 940, Propylene
glycol, Triethanolamine, Potassium Chloride,
Diclofenac sodium was obtained as
940,
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 the
addition of triethanolamine. Mixture ll was obtained
by 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
the effective concentration at the site of
'sity
lisis
pH meter Denver, Viscometer Rion W-04E, filter
holder, Millipore Membrane Filters 0,45[m,
DS does not penetrate well through skin and cannot
rEach
p.a,
HPLC
et al.,
2m8).
Acid
lnstruments
UV Visible Spectrophotometer Hitachi UV1800, HPLC
Shimadzu, Dissolution Tester Pharmeq, diffusion cell,
cause the
risk of gastrointestinal bleeding, cardiovascular,
hypersensitivity reactions and disorders of the
Phosphate
Dibasic, Sodium Chloride, Glacial Acetic
Methanol p.a, distilled water, distilled water pro
DS in gel is 1%
it may
Potasium Phosphate Dibasic, Sodium
F3
7
0.6
qs
30
100
Evaluation of Gels
Visuol oppeo.once
The prepared gels were visually inspected for
consistency, color, and transparency.
pH of the gels
The pH of gel was determined after diluting and
dispersing it in distilled water (10% w/v). All the
measurements were made in triplicate and mean
calculated.
43
T
Table 2, visual appearances of sD Gels
Viscosity Determination
Gel viscosity measurements were evaluated using a
viscosimeter Rion VT-04. All viscosity measurements
were performed in triplicate and mean calculated
visual appearances
For-
0
Gel
White
Yes
1
Emulgel
Yellowish white
No
2
Emulgel
Yellowish white
No
3
Emulgel
Yellowish white
No
A series of working standard solution containing
(0.4-15.3 ffi/ml )of Ds were prepared. A 20 pl a
liquot of the solution was injected on to the column
duplicate and
the
chromatograms were
recorded
Exactly 0.25 g gel was completely dispersed in
distilled water to make final volume 25 mL by
subjecting it to stirring for 5 min. The dispersion was
than filtered to remove the undissolved residue.
Exactly 1 mL of the filtrate was diluted to 10 mL. An
unloaded gel was also subjected to a simllar
determination to observe the effect of excipients on
the absorbance. Using the standard curve of DS in
distilled water, the drug content in gel was finally
estimated by HPLC.
ln Vitro penetration studies
The abdominal hair of male Wistar rats, weighing
130-140 g was removed carefully, without damaging
the underlying skin, using clippers Full-thickness skin
was excised from the abdomen under
Trans-
consistency
Drug Content Uniformity
in a
color
mula
pare
pH Determinotion
The transport of DS across the abdominal rat skin
was investigated from a DS gel dosage form. The pH
value of the vehicle, the drug solubility in the vehicle
and the viscosity of the gel are three important
factors to consider in the evaluation of drug
penetration from a gel dosage form across the skin
(Ho et al., 1994). Therefore, carbopol gels were
adjusted to pH 7 to minimize any pH effect Oleic
acid is acidic and has a pH of 4.4 ( Rowe , 2006) . On
the addition of oleic acid at a concentration of 5 %
pH value becomes smaller than the other formulas
V i s cosity Dete rm i n
ot i o n
ether
The viscosity of the gel matrix may play an important
anesthesia.(Hadgraft and Ridout, 1987; Miller et al.,
1993). Adhering subcutaneous fat phases were
disposed from the dermal surface. The samples were
then allowed to diffusion cell, with the stratum
corneum facing the donor separate into two phases
and the concentration of DS in compartment.DS
penetration rates through rat skin were measured
using a system of Dissolution Tester-diffusion cells.
with an available diffusion area of 1.77 cmr. ln this
role in controlling the release of the drug into the
study, 500 ml of phosphate buffer saline (PBS)
solution (pH 7.4) was used as the receptor medium
and 2 g of the test gel was placed on the donor side.
The receptor medium was kept at 37 oC and stirred
at 50 rpm. At predetermined time intervals, 5-ml
samples were taken from the receptor
compartment, for an 8-h period, and replaced by the
same volume of fresh PBS to maintain a constant
volume. DS was determined by HPLC. DS steady-
receptor compartment when
the drug
diffusion
through the gel matrix is a rate determining step.
However, formulations as they are contents OA
caused a decrease in the viscosity. The viscosity of
the gel without OA (F0) was the highest, whereas
that of the gel containing 5% OA was the lowest,
because the amount of water used to swell Carbopol
decrease with the addition of OA, so it become less
swelling. The pH and viscosity readings are reported
in Table 3.
Drug Content Uniformity
Calibration curves were constructed in the range of
concentrations of 0.4 - 15.3 prg/ml for DS. The linear
regression equation obtained was y = 42971.L3x +
481.72, with a correlation coefficient (r) = 0.9998.
The calibration curve are presented in Fig 1.
state flux, J, was estimated from the slope of the
straight line portion of the cumulative amount of
drug absorbed against time profiles.
Analytical procedure
The amount of DS in permeation samples was
determined using HPLc apparatus (Shimadzu).
Elution was carried out at room temperature with a
mobile phase consisting of methanol-water (9:l,v/v)
adjusted to pH 2.2 with glacial acetic acid; the flowrate was 1 ml /min. Detection was at 276 nm.
Table 3. pH and Viscosity of DS gels
Viscosity (dPaslt 5D
Formula pH i SD
FO
F1,
F2
F3
RESULTS AND DISCUSSIONS
Evaluations of Gels
Visuol oppeoronce
The prepared gels consistency, color, smell, and
transparency are reported in Table 2
14
7,1010,03
7,!0 ! o,o1
723,33
!
706,27
,02 !O,08
6,69 10,04
97,33
78,33
r 2,49
! 2,52
! 2,89
7
2,89
Figure 2. Penetration profiles showing the effect
different grades of Oleic acid on the penetration
@
of
of
diclofenac sodium
@
T,**
@
parencY
200
18tD
Yes
E
No
-----il-
1000
Ds
co.cardir
15.00
l!!Jml-)
!
E!
No
fture
1. Calibration curve of diclofenac sodium by HPLc
analysis
kin
pH
cle
rnt
The drug content uniformity of all formula are
rtported in Table 4.
Flgure 3. Mean maximum fluxes obtained from the
penetration of diclofenac sodium from abdomen rat skin
Table 4, Drug Content Uniformity
Drug Content (%)
ln the formula l 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 stratum
corneum lipids through the water channels (Fang, et
al ,2003), so that the DS permeation was more
easier to penetrate the stratum corneum ln the
formula 3 conta!ns OA 5% caused skin more
lipophilic, 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
(n=3)
'ug
kin
i SD
Formula
-:re
eic
FO
95.2910.91
On
F7
94.48 !O.32
rnt
F2
97 .1,6
!O,71,
F3
96.36
r 0.94
RSD (%)
0.95
0.33
0.73
0.98
:he
ft was observed that the drug content of all formulas
yas fulfilled the requirement, between 80-110% and
on
nSD less than 6%
ep.
OA
of
tas
rst,
col
-5SS
:ed
of
-"4
r
(+
98.
h
Yrtro penetration studies
ffth
respect to drug permeation through the skin
from vehicles, a drug should first diffuse out from
the vehicle to the skin. Thus, the influence of OA on
tie penetration of DS from the carbopol gels
through abdomen rat skin was examined. The
p€netration profiles of DS from these gels through
the abdomen rat skin are presented in Fig. 2. The
p€netration profiles of F1(OA 1%) was almost similar
to that from the gel F2 (OA 3%), but F2 has the
higher penetration flux of DS. F3(OA 5%) has more
bwer penetration flux of DS than F1 and F2. F0 (OA
096) has the lowest fluxes. The mean maximum
fluxes obtained from the penetration
of
DS from
abdomen rat skin are presented in Fig. 3.
containing propylene glycol. lmproved solubility of
the active ingredient in the gel matrix was usually
followed by a decrease in partition coefficient, so,
the ability of DS to penetrate the stratum corneum
was also decrease (Arellano et al , L998)
.
coNcrusroN
The results presented in this article showed, the
penetration enhancer action
of
of OA in
the
rat skin from
carbopol gels was increasing the fluidity of the
penetration
DS across abdomen
stratum corneum Iipids through the water channels.
Carbopol gels contained OA 1% and 3% provide the
similar penetration flux and more hlgher than OA 0%
and 5%.
affi
t
SD
tt^
;;l
REFERENCES
1.
Arellano, A., Santoyo, S., Martin, C., Ygartua, P.,
Influence of Propylene Glycol and lsopropyl
Myristate
i
on The In Vitro
Percutaneous
Penetration of Diclofenac sodium from carbopol
t,.
Gels. Europeon Joumol
2.
of
Phormoceutical
Science, No.7, p. 129-135 (1998)
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 lmmediate
Release Solid Oral Dosage Forms: Diclofenac
45
Sodium and Diclofenac Potassium. Journol of
3.
Pho rmoceuticol
Sciences.p.l-13.(2008)
vitro and in
yiyo evaluations of the efficacy and safety of
Fang, J.Y., Hwang, T.1., Fang, C.L. ln
skin permeation enhancers using flurbiprofen as
a
4.
5.
6.
model. lnterndtionol Journol of
Phormoceutics.255(1-2): 153-166 (2003)
Ganiswara, S.G. Formokologi don Teropi, Edisi 4,
Bagian Farmakologi FKUI, Jakarta, hal. 218
(200s)
Hadgraft, J., Ridout, G., Development of model
the percutaneous
membranes for
measurements. l. lsopropyl myristate. /rt J.
Phorn., L49-756(l9a7l
Ho, H.-O., Huang, F.-C., Sokoloski, T.D., Sheu,
M.T., The influence of cosolvents on the in vitro
percutaneous penetration of diclofenac sodium
from a gel system. J. Pharm. Pharmacol.636642.l.7994].
7.
8.
Katzung. B.G. .Bosic ond ClinicalPhormocology.
Pathways.
Handbook
/n;
Rosen, M.R., Delivery System
Personol core ond Cosmetic
Products-Technology, Applicotions, dnd
Formulotions. New York: William Andrew,
for
lnc.p.95(2005)
9. Mohammed, F.A. Topical
Permeation
from Na
Diclofenac
Sodium
Characteristics
in
Comparison
with
Conventlonal
Gel
CMC Gels
Formulations. Drug Development ond lndustriol
of
Phormocy,Vol2T, No.11, p. 1083-1097 (2001)
10. Ozguney, 1.S., Karasulu, H.Y., Kantarci G.,
S.,
Sozer,
Guneri, T., Erthan, G.Transdermal Delivery of
Diclofenac Sodium Through Rat Skin From
Various Formulation. AAPS Phormoceuticol
scie nces
ond Technology, No.7, v ol.4(2006l
11. Rowe, CR., Sheskey, J.P., Owen, s.c. Hdndbook
of Phormoceutical Excipient, Fifth edition,
London : American Pharmaceutical Association,
p. 777-1L4, 624- 626 (2006l
12. Sweetman
10th ed, New York:Mc Graw Hill Companies
SC lEdl. Mdrtindole 35: The Complete
Drug Reference. London: Pharmaceutical Press.
(Electronic version) (2007)
(Electronic version) (2007)
Michniac-Kohn, 8,8., Wertz, P.W., Al-Khalili, M.,
Meidan, V.M.Skin: Physiology and Penetration
46
1
ISBN: 978-602-60569-3-1
l
{
PROCEEDING
1" ICMHS
st lnternational Conference
1
on lVledicine and Health Sciences
a
I
lnter pro
I
susta !
nal Collaboration to Achieve
le Development Goals (SDGs)
I
I
t
,,
M^';ft'"",:ki:l:
-"Ilndonesia
I
I
i
I
Hosted by:
Faculty of Pharmacy I Faculty of Dentistry |
Faculty of Medicine I
Faculty of Public Health I School of Nursing
University of Jember, lndonesia
'"Wh#
gvlcnSangun
$rlenxju
$ercrasi
Insan$arytasi
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 Committee
Event Division
Drs. Moh. Hasan., Ph.D (Rector of
Diana 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.
University of Jember)
Drs. Zulfikar, Ph.D (Vice Rector for
Academic 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.
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.
Organizing Committee
Chairmain
Lestyo Wulandari, S.Si., M.Farm., Apt.
Secretary
Endah Puspitasari, S.Farm., M.Sc., Apt.
Treasurer
Yuni Retnaningtyas, S.Si., M.Si., Apt.
Nia Kristiningrum, M.Farm., Apt.
Secretariat, Publication, and
SponsorshipDivision
Logistic Division
Eka Deddy lrawan, S.Si., M.Sc., Apt.
Dwi Nurahmanto, S.Farm., 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.
111
CONTENT
PREFACE
..,.........t
EDrTORS........
.
CONFERENCE COMMITTEE
iii
coNTENT..........
iv
PHARMACY.............
................... 1
COMMUNITY PHARMACISTS' COUNSELLING SKILLS
M
EDTCATTONS
ON
OVER.THE-COUNTER (OTC)
....................2
FORMULATION AND OPTIMIZATION OF CAFFEINE NANOEMULSION USING FACTORIAL
DESTGN STUDY..
.................. 6
EFFECI
OF
7% : 2%
COMBINATION SODIUM ALGINATE-GELATN
CONTENT tN
CHARACIERISTIC AND ANTI M ICROBIAL ACTIVITY OF PROBIOTIC MICROSPHERES Lactobacillus
acidophilus.......
................ 10
ANTIDIABETIC ACTIVIW OF POWDER AND ETHANOLTC EXTRACT OF ANTLTON (Myrmeleon
sp.) ON WISTAR STRAIN WHITE MALE RATS WITH GLUCOSE PRELoAD
74
ANTIBACTERIAL AND ANTIBIOFILM POTENTIAL OF ETHANOLIC EXTRACT FROM BINTARO
FLOWER (Cerbera odollam) AGAINST Staphylococcus aureus ATCC 6538.............................. 17
STRUCTURE MODtFtCAT|ON
AND
MOLECULAR MODELTNG
OF
1_(BENZOYLOXY)UREA
DERIVATIVES AS ANTICANCER DRUG CANDIDATES..
................ 20
CHARACTERIZATION AND THE RELEASE TEST OF ANTI-AGING TRETINOIN IN NANOEMULSION
USING OLIVE OIL.......
EFFECT OF PARTICLE SIZE
AND SURFACE CHARGE ON THE UPTAKE AND IMMUNE RESPONSE
OF OVALBUMIN.ALGINATE MICROSPHERES
ANTIHYPE RCHOLESTE ROLEM
lC
EFFECT
OF
Arcangelisia
flava STEM
HYPERLIPIDEMIC RATS........
EXTRACT tN
.......'..'.... 31
GREEN TEA EXTRACT EFFECT ON BLOOD GLUCOSE LEVEL AND LIVER HISTOPATHOLOGY IN
D|ABETTC MtCE ...........
............ 35
TH REE-WAVELENGTH SPECTROPHOTOM ETRIC M ETHOD VALI DATION FOR DETERM INATION
OF PREDNISONE TABLET CONTAINING COLORING DYES ....
39
TNFLUENCE OF OLETC ACtD ON THE tN VTTRO PENETRATTON OF DTCLOFENAC SODTUM GEL
[3
ANTIOXIDANT ACTIVITY OF METHANOL EXTRACTS FROM THE STEM BARK OF MANGROVE
PLANT 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 AND
lsoPRoPYL MYRTSTATE)......
....................... 55
EFFECTIVENESS
OF BINTARO (Cerberra odollam Gaertn.) LEAF ETHANOLTC EXTRACT
AGAINST Staphylococcus aureus I N-VITRO BtOFILM FORMATION
lY
59
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ztr """"" ltl^trfv
Nt
vt^Hlsv lo IIU:l^ls oNV
tl^l'l
Nnuls l9l NllMrlg Nolrvllossv
6-dhrrA NorlrsrHNr He nouHl ulf NVI l-svlu8 Jo slsvrsvllt l sll€lHNl
NDI8nUOXOO ONV elldas snlrl 'ezrqJoqtuex eurnrrnl lO NOtjVNtgtAOl flISlgUlNAS
ttr """ "'
'Al-lv^o]
l-tr]vno rfl^Urs luvfHl'lvlH lo srf,rdsv rH1 lo slsAlvNv NV
" " " Af,Nl9rU Urs^rr]Vl-rdSOH IONV€IOS Nl A8V8 NUO8 A IN iO
0tr
vtxlHdsv lHt_ or vtsd^\flf,rrud rur^ls'rvNurrvt^ clr\n3u lvHr suol-fvl lo sls^lvNv
""" " "'sfNltlvd ltul_vtcld
9Zr
NI Vr rHj_SV lO Al-tUlAlS lHl 0NV NOrrVZrlrSNrS Nl9UlllVOUlV NlsMrls NOll-Vl3oSSV
IN:iltvd OI Norl\flru
Nr
'ullNlf,
TZT
Hr'lv:tH
lINnNNol Nol9lu ulSt llf
Nt suolrvi )stu lt8vHtcot^ H9nouHl Hf,vouddv rNltAl9vNVtA NolsNlluld^H
(dtem (r) elelnrrn8un eu8rl) yy99111'11 SNVIV)
9II
't
CNV ( laa/v\S snleunl snloaseqd) )OIVU) OUO) iO ll-l'lvnD CNV A-tlSNlO NllIOUd
cvotrud rsolnrS Hr_rM srvu srvt^ uvlstM lo ll^r] rsofnr9 00018
ZIT
lsvlulSc 01 ulcMod sclls I elerlrnur euouuv lo If,vuIxl lt'loNvHll lo lf,llll
80I"" " """" " NlglINV VS83V srsolnrraqnl unuapeqocA6l Jo N6ltll6lud ld6ltdl1"gl-E
" " " "stlvu1xl
,OT
('l srsuaurs etglau4) VII S1O1UVA JO llt1tlfv AUOt_tgtHNt lsv6ts6lntg-lc OUI-1A Nt
"tZ6SZlf,lV
r00T""" " """ "
snaJne snrrorol!qdels SCUVMO1
(lCAHlClVUVlntD Ul)Nt'l-SSOUI HItM l.l-ItVdVAXOUCAH
V Nl NIIVXO]jOUdll rO AVSSV 'lvl80u3ltA '
"sSAVlt rrriol vf rsvuv cNV vISnSou lo lrvuur ll'loNvHl-lt l
96
Nt Al-tAU_3V INVOtXOt-LNV CNV t-NtrNOf ll'lONlHd '1V101 lo NollvNllAUlflo
rNrAoS- NVSOTHf) rN\fldrAr rNOs
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
OOOJ'IVNI]IO]W SV NIVIN\Nd CNV VNVNV8
LA
ca
NON VIA
SlNll
llll
" " " " """ "'lvMHlVd ltlot-dodv
UllNVf, SlSSlUddnS DVUIXI ll'lONVHll SlAVll e^elJ etstla8ue:rv
T8
slNlttvd NvrsrNocNr
Nl
lll'l
U]3NVf, IVf,IAU]] HII/VI
Jo ll-llvnD No ldvurrotArHf lsv€ Nll\fldsll
" " " ""ooHrltA ftdH 9Nlsn
6L""
lo lfvdt/\ll
sdlHf, o1v10d
Nt sts^'tvNv st-t oNV ooHlltA Slufxor 9Nlsn sllllflxor lclN\fllufv Jo lonls ofl'lls Nl
cllv f tNotvn - Wnt3tvl Nrlvlsv^Uolv lo'lvrs^Uf,ol
sL""
......
]UVf, ''IVf, IlN]]VIAUVHd NI UOIAVH]8 S,.LSI]VIAUVHd
'lvf,lln3f,vt^UvHd Jo lf,NlnlJNl lHr
NO S9nUC NolldlU3SlUd Nl llOOtA S,lf,lAU,ls luvf
oL""
NOtlVtrNlUlll lc
99"
0NV NO|IVUSlltOUd Sll_llodlcvlud lvu No slAV3l lLue'l erloluln eurn2en9 lo
llvulxr f,r'roNVHll lo sNollJVUr u\nod-rnrs cNV u\nod-NoN lo llllll AUollSlHNl
" " I1vu1x1 ullvM]vlld ul^ oll l.l'llsou oNV rlvul-xl
29 " " """""" "
'toNVHrr rv3-t llllol vlt8vuv ro NollvNl€t^of All^llf,v lNVClxoll-NV lo ACnrs
t45
CORRELATION OF CD4 WITH TOTAL LYMPHOCYTE COUNTS IN HIV PATIENTS
...
DENTISTRY...........
... 148
Determinants of HIV/AIDS Awareness and Knowledge in Tanah Papua, lndonesia
""""""
149
THE ABILITY OF ANTI-INFLAMMATORY JATROPHA CURCAS LEAF EXTRACT AT COX'2
1-54
EXPRESSION ON MONOCYTES WERE EXPOSED LPS
........................ 158
NOVEL METHOD THYROID HORMONE MEASUREMENT ...."....
ROBUSTA COFFEE BEANS INCREASE LEVELS OF TNF-
o
AS
A
RESPONSE
mutans
TO Streptococcus
762
THE LEVE6 OF TNF-A lN GINGIVAL CREVICULAR FLUID (GCF) OF OSING TRIBE WOMEN WITH
................ 165
OCCLUSAL DISHARMONY...,...,......
Robusta Coffee Bean Extract (Coffea robusta) on the Viability
Exposed by Porphyromonas gingivalis.........'
Effects
of
of Neutrophils
...... 169
ROBUSTA COFFEE BEANS DECREASE OF INFLAMMATION IN DENTAL CARIES""......".......'' 173
................ L77
The Progressive Low Chronic lnflammation on OralTissues ln Elderly
DENTAL CARIES
IN
PREGNANT WOMEN WHO VISITED POSYANDU OF SEVERAL PUBLIC
782
HEALTH CENTERS IN JEMBER
Role of Che moattractant Chemokine (SDF-1/CXCR4) ln Bone Marrow
Niche "
" " " " " ' 185
Establishment of a Rat Model of Temporomandibular Joint Osteoarthritis using lntraarticular
..... 190
lnjection of Complete Freund's Adjuvant.......
.....794
PUBLIC HEALTH
RECIPROCAL DETERMINISM "DAKOCAN" CHALLENGE EFFORTS
CASES IN JEMBER DISTRICT.......
TO REDUCE HIV AND AIDS
. 195
IRON TABLETS DISTRIBUTION OF PREGNANT WOMAN IN THE DISTRICT AND CITY OF EAST
200
JAVA PROVINCE.....
RISK MANAGEMENT OF DUE TO EXPOSURE TO PESTICIDE POISONING FOR TOBACCO
............204
FARMERS IN THE JEMBER DISTRICT..
AN
OVERVIEW
OF MOTHER KNOWLEDGE AFTER GIVING BIRTH ABOUT
........ 208
BREASTFEEDING ......
D|SASTER PREPAREDNESS
EXCLUSIVE
AT PUBLIC HEALTH CENTER (PHC) BY SCORING ANALYSIS OF
GENERAL ASPECTS, HEALTH CARE, SURVEILLANCE, ENVIRONMENTAL SANITATION AND
...........272
LOGISTICS
INDEPENDENT FAMILY PLANNING IN RURALAND URBAN AREAS GRESIK DISTRICT .....,."...71.5
UNMET NEED FOR FAMILY PLANNING ON ELIGIBLE COUPLE IN INDONESIA: 2OO7 IDHS DATA
........219
ANALYSIS
shells That Have been Polluted by lead around Youtefa Bay in Jayapura City That Have
........................ 223
Potential Risk Of Non Carcinogenik.'...'. ........
IMPLEMENTATION DIARRHEAL SURVEILANCE REPORT INFORMATION SYSTEM
227
WITH WATERFALL METHOD IN HEALTH DEVELOPMENT OF JEMBER......"...
DESIGN
AND
\t
LOCAL WISDOM OF JEMBER COMMUNITY
IN REDUCING CYANOGENIC
LEVELS
URINE THIOCYANATE LEVELS
TO LOWER
229
UNDERWEIGHT AND MORBIDITY STATUS AMONG UNDER FIVE YEARS CHILDREN IN
) ?4.
suRABAYA..............
CONDOM USE AMONG EXIT CLIENTS OF FEMALE SEXUAL WORKERS FOR PREVENTION
237
HIV/AIDS IN MAKASSAR
THE SOCIAL SUPPORT AND PREVALENCE EMESIS GRAVIDARIUM ON PREGNANT MOTHER IN
TRIMESTER I AT PUSKESMAS KEMBARAN I BANYUMAS REGENCY...............,..,..,..,..,............247
245
NURSING..
We need a bigger bomb: a community attempt on fighting dengue fever in a suburban
Su ra
,.,.....,.......'.,'.,..,246
baya, lndonesia
APPLICATION OF STANDART NURSING LANGUAGE (NANDA, NOC. NIC) USING SOCIAL MEDIA:
INSTAGRAM@
TO
INCREASE INFORMATION SEEKING BEHAVIOUR
AND MOTIVATION
OF
.......250
NURSING STUDENT.....
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
spLtNTtNG SKTLL (PREHOSPTTAL
SETTING)....
STUDENTS
......................261
THE CORRELATION BETWEEN NURSE PERFORMANCE & THE LEVEL OF JAMKESMAS PATIENT
........266
SATISFACTION IN DAHLIA II WARD, NGUDI WALUYO WLINGI HOSPITAL
How To Maintain High Quality Cardiopulmonary Resuscitation ln Adults: Literature Review
270
SMOKING BEHAVIOUR AMONG MIDDLE AND LATE ADOLESCENTS IN A SUB DISTRICI OF
275
MALANG DISTRICT, EAST JAVA, IN DONESI4............
THE DIFFERENCES DECLINE BREAST ENGORGEMENT CONDUCTED CONVENTIONAL METHODS
(BREAST MASSAGE) WITH HERB YEAST-KATU..
v11
282
Jjah
INFLUENCE OF OLEIC ACID ON THE IN VITRO PENETRATION
D.D.
and
OF DICLOFENAC SODIUM GEL
sion
of
1't Lidya Ameliana, Faculty of Pharmacy, Jember University
7).
,c.
Kalimantan 1st street No 2, Jember, lndonesia,60121, lidyaa meliana @ya hoo.co.id
2nd
Esti Hendradi, 3'd Mochammad Yuwono, Faculty of Pharmacy,
Airlangga University, Su rabaya, lndonesia
ties
:red
l&
90R.
of
in
rnol
-65,
v]. E.
6th
]TRODUCTION
flclofenac sodium (DS) is a nonsteroidal
,tiinflammatory drugs (NSAlDs), that inhibits
Gldooxygenase-2 enzyme (COx-2). lt has first pass
rEtabolism hy 4O-5O%, because of its short
tiological halflife, the drug has to be given
l€quently (Ganiswara, 2005). Dose of
F
eetman, 2007). ln peroral use,
189
tory
GEntral nervous (Katzung, 2002, Chuasuwan,
tary
)AC
tion
-tion after transdermal application (Mohammed,
A)01; Ozguney, et a1.,2006). DS partition coefficient
h n-ostanol-buffer aqua (log P) was 1.1 (Chuasuwan,
2(D8). Lipophilic nature of the stratum corneum and
res:
ised
the hydrophilic nature of the underlying tissues
ilowed that the drug will penetrate the skin should
have an optimal balance between the lipophilic and
nof
lrydrophilic properties. ln general, the skin is more
pnrmeable to the material which has a partition
/sis.
ond
tzki,
lical
lical
,itio
Preparation of Topical Formulation
Gel was prepared with Carbopol
by stirring manually. Oleic acid was added to mixture
by stirring manually. The resulting gel stored at room
Constituents
coefficient (P) in octanol-water between 1.0-1000
(Michniac-Kohn et al., 2005).
Oleic acid enhances the penetration of drugs into
the skin by increasing the fluidity of the stratum
corneum lipids through
the
DS
Carbopol 940
Triethanolamine
Concentration (%)
FO
F1
t
1
0.6
F2
1
0.6
qs
30
30
30
35
L
100 100 100
s
0.6
qs
establishment of
Propylene glycol
drannels (water channels) (Fang, et al ,2003)
Oleic acid
This study aimed to know the influence of Oleic
Distilled water to
Acid {OA) in several concentrations O%, 3% and
temperature for 24 h study prior to use.
5%) as penetration enhancer on the in vitro
Table 1. Composition (% w/w)of DSgels
penetration of topical DS gel. Furthermore, the
of the topical preparation
(organoleptic, pH and viscosity), and DS penetration
percutaneously through rat skin Then observed
that in spite of DS assay and penetrate through the
rat skin at certain intervals and observed by means
of HPLC.
physical properties
MATERIALS AND METHODS
Materials
a gift sample
from PT. Kimia Farma, Carbopol 940, Propylene
glycol, Triethanolamine, Potassium Chloride,
Diclofenac sodium was obtained as
940,
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 the
addition of triethanolamine. Mixture ll was obtained
by 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
the effective concentration at the site of
'sity
lisis
pH meter Denver, Viscometer Rion W-04E, filter
holder, Millipore Membrane Filters 0,45[m,
DS does not penetrate well through skin and cannot
rEach
p.a,
HPLC
et al.,
2m8).
Acid
lnstruments
UV Visible Spectrophotometer Hitachi UV1800, HPLC
Shimadzu, Dissolution Tester Pharmeq, diffusion cell,
cause the
risk of gastrointestinal bleeding, cardiovascular,
hypersensitivity reactions and disorders of the
Phosphate
Dibasic, Sodium Chloride, Glacial Acetic
Methanol p.a, distilled water, distilled water pro
DS in gel is 1%
it may
Potasium Phosphate Dibasic, Sodium
F3
7
0.6
qs
30
100
Evaluation of Gels
Visuol oppeo.once
The prepared gels were visually inspected for
consistency, color, and transparency.
pH of the gels
The pH of gel was determined after diluting and
dispersing it in distilled water (10% w/v). All the
measurements were made in triplicate and mean
calculated.
43
T
Table 2, visual appearances of sD Gels
Viscosity Determination
Gel viscosity measurements were evaluated using a
viscosimeter Rion VT-04. All viscosity measurements
were performed in triplicate and mean calculated
visual appearances
For-
0
Gel
White
Yes
1
Emulgel
Yellowish white
No
2
Emulgel
Yellowish white
No
3
Emulgel
Yellowish white
No
A series of working standard solution containing
(0.4-15.3 ffi/ml )of Ds were prepared. A 20 pl a
liquot of the solution was injected on to the column
duplicate and
the
chromatograms were
recorded
Exactly 0.25 g gel was completely dispersed in
distilled water to make final volume 25 mL by
subjecting it to stirring for 5 min. The dispersion was
than filtered to remove the undissolved residue.
Exactly 1 mL of the filtrate was diluted to 10 mL. An
unloaded gel was also subjected to a simllar
determination to observe the effect of excipients on
the absorbance. Using the standard curve of DS in
distilled water, the drug content in gel was finally
estimated by HPLC.
ln Vitro penetration studies
The abdominal hair of male Wistar rats, weighing
130-140 g was removed carefully, without damaging
the underlying skin, using clippers Full-thickness skin
was excised from the abdomen under
Trans-
consistency
Drug Content Uniformity
in a
color
mula
pare
pH Determinotion
The transport of DS across the abdominal rat skin
was investigated from a DS gel dosage form. The pH
value of the vehicle, the drug solubility in the vehicle
and the viscosity of the gel are three important
factors to consider in the evaluation of drug
penetration from a gel dosage form across the skin
(Ho et al., 1994). Therefore, carbopol gels were
adjusted to pH 7 to minimize any pH effect Oleic
acid is acidic and has a pH of 4.4 ( Rowe , 2006) . On
the addition of oleic acid at a concentration of 5 %
pH value becomes smaller than the other formulas
V i s cosity Dete rm i n
ot i o n
ether
The viscosity of the gel matrix may play an important
anesthesia.(Hadgraft and Ridout, 1987; Miller et al.,
1993). Adhering subcutaneous fat phases were
disposed from the dermal surface. The samples were
then allowed to diffusion cell, with the stratum
corneum facing the donor separate into two phases
and the concentration of DS in compartment.DS
penetration rates through rat skin were measured
using a system of Dissolution Tester-diffusion cells.
with an available diffusion area of 1.77 cmr. ln this
role in controlling the release of the drug into the
study, 500 ml of phosphate buffer saline (PBS)
solution (pH 7.4) was used as the receptor medium
and 2 g of the test gel was placed on the donor side.
The receptor medium was kept at 37 oC and stirred
at 50 rpm. At predetermined time intervals, 5-ml
samples were taken from the receptor
compartment, for an 8-h period, and replaced by the
same volume of fresh PBS to maintain a constant
volume. DS was determined by HPLC. DS steady-
receptor compartment when
the drug
diffusion
through the gel matrix is a rate determining step.
However, formulations as they are contents OA
caused a decrease in the viscosity. The viscosity of
the gel without OA (F0) was the highest, whereas
that of the gel containing 5% OA was the lowest,
because the amount of water used to swell Carbopol
decrease with the addition of OA, so it become less
swelling. The pH and viscosity readings are reported
in Table 3.
Drug Content Uniformity
Calibration curves were constructed in the range of
concentrations of 0.4 - 15.3 prg/ml for DS. The linear
regression equation obtained was y = 42971.L3x +
481.72, with a correlation coefficient (r) = 0.9998.
The calibration curve are presented in Fig 1.
state flux, J, was estimated from the slope of the
straight line portion of the cumulative amount of
drug absorbed against time profiles.
Analytical procedure
The amount of DS in permeation samples was
determined using HPLc apparatus (Shimadzu).
Elution was carried out at room temperature with a
mobile phase consisting of methanol-water (9:l,v/v)
adjusted to pH 2.2 with glacial acetic acid; the flowrate was 1 ml /min. Detection was at 276 nm.
Table 3. pH and Viscosity of DS gels
Viscosity (dPaslt 5D
Formula pH i SD
FO
F1,
F2
F3
RESULTS AND DISCUSSIONS
Evaluations of Gels
Visuol oppeoronce
The prepared gels consistency, color, smell, and
transparency are reported in Table 2
14
7,1010,03
7,!0 ! o,o1
723,33
!
706,27
,02 !O,08
6,69 10,04
97,33
78,33
r 2,49
! 2,52
! 2,89
7
2,89
Figure 2. Penetration profiles showing the effect
different grades of Oleic acid on the penetration
@
of
of
diclofenac sodium
@
T,**
@
parencY
200
18tD
Yes
E
No
-----il-
1000
Ds
co.cardir
15.00
l!!Jml-)
!
E!
No
fture
1. Calibration curve of diclofenac sodium by HPLc
analysis
kin
pH
cle
rnt
The drug content uniformity of all formula are
rtported in Table 4.
Flgure 3. Mean maximum fluxes obtained from the
penetration of diclofenac sodium from abdomen rat skin
Table 4, Drug Content Uniformity
Drug Content (%)
ln the formula l 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 stratum
corneum lipids through the water channels (Fang, et
al ,2003), so that the DS permeation was more
easier to penetrate the stratum corneum ln the
formula 3 conta!ns OA 5% caused skin more
lipophilic, 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
(n=3)
'ug
kin
i SD
Formula
-:re
eic
FO
95.2910.91
On
F7
94.48 !O.32
rnt
F2
97 .1,6
!O,71,
F3
96.36
r 0.94
RSD (%)
0.95
0.33
0.73
0.98
:he
ft was observed that the drug content of all formulas
yas fulfilled the requirement, between 80-110% and
on
nSD less than 6%
ep.
OA
of
tas
rst,
col
-5SS
:ed
of
-"4
r
(+
98.
h
Yrtro penetration studies
ffth
respect to drug permeation through the skin
from vehicles, a drug should first diffuse out from
the vehicle to the skin. Thus, the influence of OA on
tie penetration of DS from the carbopol gels
through abdomen rat skin was examined. The
p€netration profiles of DS from these gels through
the abdomen rat skin are presented in Fig. 2. The
p€netration profiles of F1(OA 1%) was almost similar
to that from the gel F2 (OA 3%), but F2 has the
higher penetration flux of DS. F3(OA 5%) has more
bwer penetration flux of DS than F1 and F2. F0 (OA
096) has the lowest fluxes. The mean maximum
fluxes obtained from the penetration
of
DS from
abdomen rat skin are presented in Fig. 3.
containing propylene glycol. lmproved solubility of
the active ingredient in the gel matrix was usually
followed by a decrease in partition coefficient, so,
the ability of DS to penetrate the stratum corneum
was also decrease (Arellano et al , L998)
.
coNcrusroN
The results presented in this article showed, the
penetration enhancer action
of
of OA in
the
rat skin from
carbopol gels was increasing the fluidity of the
penetration
DS across abdomen
stratum corneum Iipids through the water channels.
Carbopol gels contained OA 1% and 3% provide the
similar penetration flux and more hlgher than OA 0%
and 5%.
affi
t
SD
tt^
;;l
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Influence of Propylene Glycol and lsopropyl
Myristate
i
on The In Vitro
Percutaneous
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t,.
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2.
of
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a
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5.
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Diclofenac
Sodium
Characteristics
in
Comparison
with
Conventlonal
Gel
CMC Gels
Formulations. Drug Development ond lndustriol
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ond Technology, No.7, v ol.4(2006l
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46