TEAM 4

TECHNOLOGY STERIL
A S1 PHARMACY 2018

FORMULATION OF
KETOKONAZOL OPTHALMIC
OINTMENT USING COW
GHEE AS A BASE AND
PENETRATION ENHANCER
I MADE HARIADI WIJAYA (821418036)
JIHAD ALFARUQ LAMADI(821418025)
ASRIN MAHMUD (821418022)
KARMILA H. TOI (821418004)
MIMI FAUZIAH TAHIR (821416026)
TRI BELA A. SUWANDI (821418011)
SRI NURAIN IBRAHIM (821418009)
 INTRODUCTION

According to World Health Organization, corneal diseases arethe major cause of vision loss and
blindness. Fungal keratitis is the major cause of blindness in Asia and Candida albicans is aspecies
which is responsible for fungal keratitis

Ketoconazole is a known antifungal agent which is use for their superficial action as well as to treat
the infection of the internal eye. It is a potent inhibitor of ergosterol biosynthesis in Candida
albicans both in vitro and in vivo. Ergosterol is themajor sterol found in most yeasts and fungi and
by interferingwith this major template for mycotic biosynthesis
 INTRODUCTION
The ability of the compound to The cow’s gheecontains
penetrate the eye is several fatty acids with
dependingupon molecular varying
mass, route of administration, physiochemicalproperties.
duration ofcontact time. But the The lipoid nature of this
ketoconazole have a high substance aids passage
molecular massexceeding 500 ofmany drugs through many
Dalton, resulting in their poor physiological barriers because
penetration even ifit is lipophilic thenature of barrier is also
in nature. lipoidal
.

So it is necessary to enhance the

penetration of the drug
throughtranscorneal barrier to give
its 100% action. By
usingpenetration enhancers which
possible to penetrate the
drugthrough the corneal barrier.
MATERIAL AND METHOD

Ketoconazole was gift sample from Alkem

Pharmaceuticals,Mumbai, India. Cow ghee was
purchased from Madhuban dairyproducts, Nagpur (MS)
India. Dichloromethane R) andPotassium dihyrogen
phosphate (Merks Pvt.Ltd), Disodiumhydrogen
phosphate and Sodium chloride (Fisher ScientificIndia
Pvt. Ltd) and all other chemical were analytical grade.
 METHOD
3. Interaction study of Ketoconazole
1. Fractination of Cow and cow ghee (≥40oC)
Ghee
The fraction of cow ghee 2. Evaluation of Cow  UV/Visible spectroscopyDifferent
≥400C, were carried out Ghee ratios of ketoconazole : cow ghee
in B.O.Dincubator (≥40oC) (1:9, 2:8,3:7, 4:6, 7:3, 8:2,
( Thermotech TH-102) by Saponification 9:1) were prepared and each
maintaining the value=28.05(b-a)/w mixture wasdiluted in DCM to make
respectivetemperature up Acid value= concentration 100μg/ml and
to 24hr. fraction were 5.61n/w screenedspectrophotometrically in
collected and Evaluation the range of 200- 400nm
filteredthrough of cow ghee (≥400C) wavelength.
Whatmann filter paper
(no. 41)  Thermal Analysis (DSC) for cow
ghee (≥400C)A differential scanning
calorimeter model DSC Shimadzu
60with trend line software
(Shimadzu Co., Kyoto, Japan)
wasused
FORMULATION OF OPHTALMIC
OINTMENT
1. Formulation of FCA (using
cow ghee as base)

Required amount of ketoconazole and small amount of

moltenbase (Cow ghee ≥40oC) was triturated in sterilized mortar
andpestle.

Then remaining amount of base, benzalkonium chloride(0.01%w/v), butylated

hyroxytoluene B.P (0.02%) were transferto this, triturated thoroughly to room
temperature.

The ointmentwas stored in the glass vials for further study.All operation has
been carried out in a laminar flow formaintaining the aseptic condition
FORMULATION OF OPHTALMIC
OINTMENT
2. Formulation of FCB (using
Petrolatum base)

The Ointment was formulated using procedure same as given

inWith petrolatum base, instead of Cow ghee ≥40oC
EVALUATION OF OPHTHALMIC
PREPARATION

1. PH
2. Freeze Thaw Cycle
3. Isotonicity study
4. Drug Content
5. In vitro antifungal activity
6. In vitro drug ketoconazole, FCA and
FCB
7. In vivo eye irritancy test
8. Stability Study
 RESULT AND DISCUSSION
1. Evaluation of cow ghee (≥400C) : The result of acid and saponification value include in the normal value
2. UV/Visible spectroscopy : Result showing that cow’s ghee and ketoconazole is compatible with each other
3. Thermal analysis : The melting point, onset temp, end set temp, and enthalpy of fusion doesn’t show any significant
changes as per as the endothermic peaks of ketoconazole and cow ghee.
4. Physical parameters : both FCA and FCB were yellow in colour consistently smooth in appearance and found to be
stable on centrifugation at 1000 rpm for 1 hour.
5. PH : Both formulation show Ph result near to lacrimal fluid (7,4)
6. Freeze thaw cycle : The result showing that both formulation is termodinamically stable
7. Isotonicity studies : Both formulation are isotonic
8. Assay (Drug content) : FCA and FCB shows good agreement of result as per the % label claim is concern.
9. In vitro Antifungal activity: The MIZ of ketoconazole solution was greater than FCA and FCB. In comparison of FCB,
FCA shows most promising results.
10. In vitro drug release studies: FCA has significantly greater penetration than FCB and ketoconazole solution
11. In - vivo eye irritancy test (Draize test in rabbit): formulation shows no irritation or damage on cornea
12. Accelerated Stability study : PH, appearance and drug content stable up to 1 month
THANKS FOR ATTENTION
