“FORMULATION AND EVALUATION OF EMULGELS FOR TOPICAL DELIVERY OF AN NSAID”
DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BANGALORE, KARNATAKA.
BY
NITHILA GEORGE
M.PHARM, PART-I
UNDER THE GUIDANCE OF
Dr. SANDHYA KV,
DEPARTMENT OF PHARMACEUTICS,
T.JOHN COLLEGE OF PHARMACY,
BANNERGATTA ROAD,GOTTIGERE
BANGALORE-83.
Under the Co-guidance of
.
Mrs. Sumati, K
ASST. PROFESSOR,
DEPT. OF PHARMACEUTICS.
DEPARTMENT OF PHARMACEUTICS
T.JOHN COLLEGE OF PHARMACY
BANNERGATTA ROAD , GOTTIGERE.
BANGALORE-8
ANNEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1. / NAME OF THE CANDIDATEAND ADDRESS (IN BLOCK LETTERS) / NITHILA GEORGE
T.JOHN COLLEGE OF PHARMACY, BANNERGHATTA ROAD, GOTTIGERE,
BANGALORE-83,
KARNATAKA.
2. /
NAME OF THE INSTITUTION
/ T.JOHN COLLEGE OF PHARMACY, BANNERGHATTA ROAD GOTTIGERE,BANGALORE-83,
KARNATAKA.
3. /
COURSE OF STUDY AND SUBJECT
/ MASTER OF PHARMACY IN PHARMACEUTICS4. / DATE OF ADMISSION OF COURSE / 09-07-2013
5. /
TITLE OF TOPIC
/ “FORMULATION AND EVALUATION OF EMULGELS FOR TOPICAL DELIVERYOF AN NSAID”6. / SIGNATURE OF THE CANDIDATE / (Nithila George)
7. / REMARKS OF THE GUIDE / RECOMMENDED FOR THE DISSERTATION WORK
8. / NAME AND DESIGNATION (in block letters)
8.1 GUIDE
8.2 SIGNATURE / SANDHYA KV, M. Pharm, Ph.D.
DEPARTMENT OF PHARMACEUTICS
T.JOHN COLLEGE OF PHARMACY.
(Sandhya KV, M. Pharm, Ph.D.)
8.3 NAME OF CO-GUIDE
8.4 SIGNATURE / MRS. SUMATI, K
ASST. PROFESSOR,
DEPT. OF PHARMACEUTICS.
T.JOHN COLLEGE OF PHARMACY.
(MRS. SUMATI, K)
8.5 HEAD OF THE DEPARTMENT
8.6 SIGNATURE / SANDHYA KV, M. Pharm, Ph.D.
DEPARTMENT OF PHARMACEUTICS
T.JOHN COLLEGE OF PHARMACY.
(Sandhya KV M, Pharm, Ph.D.)
9. / 9.1 REMARKS OF PRINCIPAL
9.2 SIGNATURE / FORWARDED AND RECOMMENDED FOR FAVOURABLE CONSIDERATION.
( Dr.Vineeth Chandy)
10
11
12 / BRIEF RESUME OF THE INTENDED WORK:
10.1 NEED FOR THE STUDY:
Topical drug administration is a localized drug delivery system anywhere in the body through ophthalmic, rectal, vaginal and skin as topical routes. Skin is one of the most readily accessible organs on human body for topical administration and is main route of topical drug delivery system. One side the topical applications of the drug offer the potential advantages of delivering the drug directly to the site of action and delivering the drug for extended period of time at the effected site that mainly acts at the related regions.
When gels and emulsions are used in combined form the dosage forms are referred as emulgels. Emulgels are emulsions, either of the oil-in-water or water in-oil type, which are gelled by mixing with a gelling agent. The main advantage of the emulgel is that lipophilic drugs can be easily formulated into gels. Due to solubility problems, most of lipophilic drugs cannot be formulated directly as hydrogel. For this reason, emulgel provides better stability and release of the lipophilic drug in comparison with simple hydrogel base. Other advantages for emulgel include; better stability, high loading efficiency, more production, economical with low cost. The main constituents in emulgel preparation include water, oils mainly mineral oils as paraffin oil either used alone or mixed with vaseline or wax emulsifiers, gelling agent, and permeation enhancers.They have a high patient acceptability since they possess theadvantages of both emulsions and gels. Therefore, they have been recently used as vehicles to deliver various drugs to the skin. They are also called as creamed gel, quassi emulsion, gelled
emulsion.1
Non-steroidal anti inflammatory drugs (NSAIDs) are widely used for the treatment of fever, acute and chronic arthritic conditions. They act by inhibiting cyclooxygenase (COX) thereby reducing the release of prostaglandins (PGs), well known inflammatory and nociceptive mediators. PGs are gastro protective in that they enhance the bicarbonate secretion and reduce the gastric acid secretion. However, their systemic use is often limited because of severe upper gastrointestinal ulcers and other side effects. Thus, pharmaceutical dosage forms that deliver drugs to the inflammation site at a sustained, concentrated level over an extended period of time without altering pharmacodynamic activities have the advantages of avoiding the systemic side effects.2
10.2 REVIEW OF LITERATURE
Extensive literature review was made by referring various National and International Journals, various databases and other web resources along with general books for pharmaceutical scientists.
1.Kaushal R. Sabuet al,.(2013) worked on to develop an emulgel formulation of Terbinafine hydrochloride using carbopol 934 as a gelling agent for topical delivery with the aim to avoid hepatic first-pass metabolism, improve stability of emulsion, reduce dosage regimen and enhance residence time in the treatment of fungal infection. The effect of concentration of the oil phase and emulsifying agent on the drug release was investigated using a 22 factorial design. The developed emulgels were evaluated for their physicochemical properties like colour, homogeneity, consistency, spreadability, pH value, rheological behaviour, drug content, drug release and stability.3
2. Piyusha Deved et al (2010),prepared gellified emulsion for sustained delivery of itraconazole. The prepared formulations were evaluated on the basis of pH, spreadability, viscosity, drug content, in vitro drug release and stability studies. The microbial assay and skin irritation studies on rabbit was also performed. It was concluded that emulsion based system was more effective and safe system for sustained delivery of itraconazole4
3.Joshi Baibhav et al, (2012)work onformulating Clarithromycin Emulgel using high molecular weight water soluble polymer of Hydroxypropyl methylcellulose (HPMC K4M), Carbopol 940,Carbopol 934. Oleic acid is used as permeation enhancer. All the prepared Emulgel showed acceptable physical properties, homogeneity, consistency, spreadability, viscosity and pH value. The Emulgel were found to be stable with respect to physical appearance, pH, rheological properties and drug content at all temperature and conditions for three month.5
4. Magdy I. Mohamed (2004) developed an emulgel formulation of chlorphenesin emulgel using 2 types of gelling agents. Hydroxy propyl methyl cellulose and Carbopol 934 was developed. The prepared emulgels were evaluated for their physical appearance, rheological behavior, drug release, antifungal activity, and stability. It was found that the emulsifying agent concentration had the most pronounced effect on the drug release from the emulgels. Rheological studies revealed that the emulgels exhibited a shear-thinning behavior with thixotropy. Stability studies showed that the physical appearance, rheological properties, drug release, and antifungal activity in all the prepared emulgels remained unchanged upon storage for 3 months.6
5. Dignesh M. Khunt et al,(2012)worked on to develop emulgel of piroxicam which would increase skin penetrationof drug in comparison with the present marketed preparations of the drug. Based on solubility studies oleic acid asoil, Tween-80 and Span-80 as emulsifiers and propylene glycol and cetostearyl alcohol as co-surfactant wereselected for preparation of emulgel. The emulgels were prepared using different combinations of oil,emulsifiers, co-surfactant and carbomer (Carbompol 940 and Carbopol 934). They were optimized using 32 fullfactorial designs to study the effect of independent variables.The prepared emulgels were evaluated interms of appearance, average globule size, drug content and in-vitro drug release.7
6.Ranga Priya et al,(2012) work on to develop & characterize an emulgelformulation of ciprofloxacin. Ciprofloxacin gellified emulsion formulations were prepared by using Carbopol 934. Evaluation of the ciprofloxacin emulgel was carried out for physical appearance, pH values, spreadability, rheological study, drug content determination, In vitro release study, skin irritation test, accelerated stability studies and fitting ofresults into different kinetic equations was also carried out. It was observed that all the formulationswere liquefied and diluted at the end of the experiments, indicating water diffusion through themembrane. In general, it was observed that the better release of the drug was seen from allformulations.8
7.Rachit Khullar et al(2012)studied on to prepare emulgel of mefenamic acid, a NSAID, using Carbapol 940 as a gelling agent. Mentha oil and clove oil were used as penetration enhancer.The emulsion was prepared and it was incorporated in gel base.It was concluded that topical emulgel of mefenamic acid posses an effective anti-inflammatory and analgesic activity.9
8.Sushil Raut et al (2012) made acomparative evaluation of Zidovudine loaded hydrogels and emulgels .Zidovudine (AZT) on the widely used anti-retroviral drug, associated with serious gastric side effects upon oral delivery also having short half life and poor partition coefficient. Upon oral administration it also undergoes first pass metabolism. The present study we developed hydrogels as well as emugels loaded with AZT and investigated the ability of hydrogels as well as emulgels to deliver the AZT via transdermal route. All the gels were evaluated for their physical properties, drug content, viscosity, pH, spreadability and invitrodrug release. Among all the formulations emulgels were found to be effective vehicles for delivery AZT because of the effective partition in both oil and aqueous phases10
9. Ankur Jain et al (2010)work was to investigate the potential of emulgel in enhancing the topicaldelivery of ketoconazole. Emulgel formulations of Ketoconazole were prepared using 2 types of gellingagents: Carbopol 934 and Carbopol 940. The influence of the type of the gelling agent and theconcentration of both the oil phase and emulsifying agent on the drug release from the prepared emulgelwas investigated using a 23 factorial design. The prepared emulgel were evaluated for their physicalappearance, viscosity, drug release, globule size, skin irritation test, antifungal activity, transmissionelectron microscopy and stability. The antifungal activity and drug release
were found to behigher for optimized formulation as compared to the marketed ketoconazole cream. In general conclusion, it was suggested that the emulgelformulation succeed the drug release for sust1ained drug delivery in a controlled manner in comparisonwith cream.11
10.3 OBJECTIVES OF THE STUDY:
The present study is planned with the following objectives:
Formulation of emulgel using various emulsifying and gelling agents in different combinations and ratios by suitable methods.
Evaluation of the emulgel formulations for its physico-chemical properties like visual appearance, viscosity, pH, spredability, uniformity, drug content etc.
In vitrodrug release permeation studies through the suitable membrane models using Franz-Diffusion cell.
To predict the shelf life of the formulation by conducting stability studies as per the ICH guidelines.
MATERIALS AND METHODS:
Materials: Aqueous Material, Oils, Gelling agents, emulsifiers
Drug: NSAIDS like
Method:
STEP 1: OIL/WATER EMULSION
Drug can be incorporated either in oil or aqueous phase depending upon its solubility
STEP 2: FORMATION OF GEL BASE
STEP 3: INCORPORATION OF EMULSION IN GEL BASE
12.1. SOURCE OF DATA
1) Review of literature from:
a. Journals: such as
- International Journal of Pharmacy and Pharmaceutical Sciences
- International Journal of drug development and research
- International Journal of PharmTech Research
-Pharmaceutical Research.
- AsianJournal of Pharmaceutical Sciences
-International Journal of Pharmacy and Biological Sciences
b. Internet browsing.
c.Helinet consortium (www. rguhs.ac.in)
2) e-Library: T.John College of Pharmacy.
.
12.2. METHOD OF COLLECTION OF DATA
- Laboratory studies which include,
Formulation of stable gel using appropriate gelling agents.
Development of emulgel of selected NSAID for topical delivery.
Evaluation of the developed formulations:
- Visual appearance test: Colour, and appearance of the formulation.
- Physico-chemical test: pH of the formulation using pH meter.
- Apparent viscosity studies to determine the flow behavior of the formulation
- Spreadability test.
- Assay and uniformity content.
- In vitrodrug release permeation studies using Franz-diffusion cell.
- Stability studies: To conduct the studies for the optimized formulation as per ICH guideline and shelf life prediction.
-NO-
12.4. Has ethical clearance been obtained from your institution in case of 12.3?
- NOT APPLICABLE-
LIST OF REFERENCES:
1.Rachit Khullar, Saini S, Seth N, Rana AC.Emulgels: a surrogate approach for topically used hydrophobic drugs,International Journal of Pharmacy and Biological Sciences2011;1(3):117-128
- 2. S Padi, M Gupta, J Kehal, A Aggarwal, N Kumar, R Marwaha.Evaluation of Topical Gels Containing Non-Steroidal Anti-Inflammatory Drugs on Inflammation and Hyperalgesia in rats.The Internet Journal of Pharmacology2007;6(1)
4. Piyusha Deveda , Ankur jain, Naveen Vyas, Hemant Khambete, Sanjay Jain ,Gellified emulsion for sustain delivery of Itraconazole for topical fungal disease International Journal of Pharmacy and Pharmaceutical Sciences2010;2(1):104-112
5. Joshi Baibhav, Singh Gurpreet, Rana AC, Saini Seema.Development and Characterization of Clarithromycin Emulgel for topical delivery. International Journal of drug development and research,2012;4(3):310- 323
6. Magdy I. Mohamed.Optimization of Chlorphenesin EmulgelFormulation.The AAPS Journal 2004; 6(3):1-7
7. Dignesh M. Khunt, Ashish D. Mishra, Dinesh R. Shah. Formulation Design & Development of Piroxicam Emulgel. International Journal of PharmTech Research2012;4(3):1332-1334
8.Ranga Priya M, Sellakumar V, Natarajan R and Mohan Kumar Ks Formulation and In-Vitro Evaluation of Ciprofloxacin Loaded Topical Emulgel.International journals of pharmaceutical and chemical sciences2012;1(1):237-242
9.Rachit Khullar, Deepinder Kumar,Nimrata Seth, andSeema Saini,Formulation and evaluation of mefenamic acid emulgel for topical delivery.Saudi Pharmaceutical Journal2012;20(1):63-67
10. Sushil Raut,Vaibhav Uplanchiwar , Santosh Bhadoria, Avinash GahaneSunil Kumar JainShrishail Patil. Comparative evaluation of Zidovudine loaded hydrogels and emulgel
Research J. Pharm. and Tech2011;5(1):41-43
11. Ankur Jain, Gautam SP, Gupta, Jain S. Development and characterization of Ketoconazole emulgel for topicaldrug delivery. Der Pharmacia Sinica 2010;1(3):221-231
12.Kasliwal N, Derle D, Negi J, Gohil J. Effect of permeationenhancers on the release and permeation kinetics ofmeloxicam gel formulations through rat skin. AsianJournal of Pharmaceutical Sciences2008;3(5):193-199
13. A. S. Panwar, N. Upadhyay, M. Bairagi, S. Gujar, G. N. Darwhekar, D. K. Jain. Emulgel: a review.Asian Journal of Pharmacy and Life Science2011; 1(3):335-343
14.Vikas singla, seema saini1, baibhav joshi1 and a.c rana. Emulgel: a new platform for topical drug delivery. International Journal of Pharma and Bio Sciences2012 ;3(1):485-498
1