MICROEMULSION BASED TRANSDERMAL DRUG DELIVERY
FOR ANTI-FUNGAL DRUG
M.PHARM DISSERTATION PROTOCOL
SUBMITTED TO
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
KARNATAKA
BY
RAMARAJU ABHINAV
I M.PHARM
UNDER THE GUIDANCE
MRS.BENY BABY
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
BANGALORE-560064
(2011-2012)
RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES
BENGALURU, KARNATAKA
ANEXURE-II
PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION
1 / Name of the Candidate and Address / RAMARAJU ABHINAVKarnataka College of Pharmacy
#33/2, Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560 064
PERMANENT ADDRESS
#B-51,Patigadda Colony
Rasoolpura ‘x’ roads
Secunderabad
Andhra Pradesh-500003
2 / Name of the Institute / Karnataka College of Pharmacy
#33/2, Thirumenahalli
Hegde Nagar Main Road
Bengaluru-560064
3 / Course of the Study & Subject / Master of Pharmacy (Pharmaceutics)
4 / Date of the Admission to the Course / July 15th 2011
5 / Title of Topic
MICROEMULSION BASED TRANSDERMAL DRUG DELIVERY
FOR ANTI-FUNGAL DRUG
6 / BRIEF RESUME OF THE INTENDED WORK
6.1
6.2 / Need of Study
Micro emulsions are isotropic, thermodynamically stable transparent or translucent systems of oil, water and surfactant, frequently in combination with a co- surfactant .Their size generally range from 10-200nm. They can be classified as oil-in-water (o/w), water-in-oil (w/o) or bicontinuous systems depending on their structure and are characterized by ultra low interfacial tension between oil and water phases.
Micro emulsions avoid first pass metabolism, and their ease of administration with good control over rate of drug delivery. In topical formulations they have been proved to increase the cutaneous absorption of both lipophilic and hydrophilic API’s. In this type of applications the micro emulsions attribute to the performance to generally a higher solubility of the API’S of micro emulsions, generating increased concentration gradient towards skin.
In Transdermal drug delivery because of their high drug loading capacity they can provide higher concentration gradient, thus increasing driving force across the skin. Microemulsions has low inter facial tension and will allow excellent contact with skin surface, with the vehicle filling even wrinkles and microscopic gaps. This enhances the vehicle skin drug transfer. They have been used to improve the bioavailability of various poorly soluble drugs including anti fungal drugs1.
Anti fungal agents belonging to the class polyenes act by interacting with the microtubules and interfering with the process of mitosis where as the agents belonging to the class of azoles act upon by interfering with the amino acid transport in to the fungus by their action on the cell membrane.
The current research is to develop an antifungal micro emulsion adaptable transdermal delivery systems which may provide protection against oxidation, improves drug dissolution, enzymatic hydrolysis,fastabsorption, improves the solubilisation of lipophilic drugs, balance bioavailability, prolonged release and enables reduction in dose.
Review of Literature
Gives review on microemulsions, which are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a co surfactant. These systems are currently of interest to the pharmaceutical scientist because of their considerable potential to act as drug delivery vehicles by incorporating a wide range of drug molecules. The use of micro emulsions and closely related micro emulsions-based systems as drug delivery vehicles is reviewed, with particular emphasis being placed on recent developments and future directions.2
Investigation on photo degradation of some tretinoin cream formulations was evaluated. Several oils were selected to prepare the cream formulations: olive oil, maize oil, castor oil, isopropyl myristate and miglyol 812. The photo stability of tretinoin in oils is comparable with the photo stability of a tretinoin lotion (ethanol/propylene glycol 50/50), castor oil and olive oil giving slightly better results than the other oils. Tretinoin is far more stable in the cream formulations than in the respective oils; however it is not clear whether this is due to the formulation or due to a different irradiation technique.3
Glipizide based micro emulsion was developed and its usefulness as topical drug carrier system for the non-insulin dependent diabetes mellitus (NIDDM) was investigated. The results indicated that the developed micro emulsion systems may be promising vehicles for the transdermal delivery of glipizide. Micro emulsion system provides viscous consistency for the topical application, which delivered the drug in sustained or controlled manner and prolonged delivery as compared to conventional dosage form.4
Comparison of the in vitro release rate of diclofenac sodium from micro emulsion vehicles containing soybean oil, non-ionic surfactants, and different alcohols as co surfactant. The optimum surfactant: co-surfactant weight ratios and micro emulsion areas were detected by the aid of phase diagrams. Three micro emulsion formulations were selected, and their physicochemical properties were examined for the pH, viscosity, and conductivity. Moreover, viscosity measurements were examined as a function of shear rate, and newtonian fluid characterization was observed for each micro emulsion system.5
Metaprolol tartarate as a transdermal drug delivery system for controlledrelease of drug for extended period of time was studied. Eudragit RL and hydroxy propyl methylcellulose were used for fabrication of the formulation. These systems were characterized for their thickness, tensile strength and drug content. Then it was evaluated in vitro release kinetics and skin permeation studies and compared its drug plasma profile with metaprolol tartarate.6
The potential application of highly biocompatible o/w micro emulsions as topical drug carrier systems for the percutaneous delivery of anti-inflammatory drugswas investigated. Microemulsions were made up of triglycerides as oil phase, a mixture of lecithin and n-butanol as a surfactant/co-surfactant system and an aqueous solution as the external phase. No significant percutaneous enhancer effect was observed for ketoprofen-loaded oleic acid–lecithin micro emulsion. The human skin tolerability of various micro emulsion formulations was evaluated on human volunteers. Microemulsions showed good human skin tolerability.7
For topical administration of Meloxicam, micro emulsion gels and lipogels containing either ethyl oleate or oleic acid as an oil phase were prepared. In addition, hydro gel and hydro alcoholic gels containing carbopol 940 as a gelling agent were also prepared. The permeation properties of ME from ethyl oleate micro emulsion which is the best formula achieved was studied in comparison to the commercially available piroxicam gel. Meloxicam gel showed good protection against inflammation as compared to feldene gel in rats.8
Methoxsalenhas been used for the treatment of psoriasis. Alternative formulations for the topical administration of methoxsalen, chitosan coated micro emulsion were evaluated as delivery vehicle. Microemulsions were prepared using water, soya bean oil. The ability of the system to deliver into the skin was evaluated using dialysis membrane and human cadaver skin. These in vitro studies clearly show that methoxsalen loaded chitosan-coated micro emulsion provides control release of methoxsalen with retention on the skin.9
Alternative formulations for the topical administration of 8-MOP, micro emulsions were evaluated as delivery vehicles. Six micro emulsion formulations were prepared using water, isopropyl myristate (IPM) and tween80: span80: 1, 2-octanediol (3:1, 1:2 w/w). The in vitro permeation data showed that the novel micro emulsions increased the 8-MOP total penetration through the skin by order of 1.9–4.5, as compared with IPM. These results suggest that the studied micro emulsion systems may be appropriate vehicles for the topical delivery of 8-MOP.10
Topical micro emulsions of nimesulide, a poorly water-soluble non steroidal anti-inflammatory drug, using olive oil as oil phase and tween 80/iso-octanol as surfactant/co-surfactant were designed.In vitro permeation study of the gel was carried out through excised hairless rat skin and compared with a marketed preparation. The drug release after 24 h from the prepared micro emulsion gel and marketed formulation was found to be 72% and 81% respectively. Micro emulsion-based gel of poorly water-soluble nimesulide was successfully developed with in vitro release rates comparable to that of the marketed gel formulation.11
6.3 / Objective of the study
The objective of the study is as follows:
- To develop and formulate Microemulsions using a suitable method as drug carrier system
- To formulate a suitable method for microemulsions
- Characterization of formulated microemulsions
- Evaluation of formulated micro emulsions
- Stability studies for the selected formulations
7 / Material & Methods
7.1 / Source of Data
- The data will be obtained from the literature survey and internet source.
- The data will be obtained from the experimental work, which includes formulation of self micro emulsion, evaluation and stability studies.
7.2 / Method of Collection of Data
- Data on drug and excipients are collected from the drug information centre, patents, reference books, text books, catalogs, journals etc.
- Data will be collected from the prepared formulations, in-vitro dissolution studies and stability studies.
7.3 / Materials
Drug
The anti-fungal drug will be procured or obtained from suitable pharma grade manufacturer.
Excipients
The natural, synthetic, biodegradable polymers, oils, surfactant, co-surfactant will be procured from pharma grade manufacturer.All other chemicals will be used of analytical grade.
7.4 / Methods
1) Preformulation Studies
a) Thermal analysis
b) Incompatibility studies
2) Formulation Studies
a)Micro emulsion method
b)Self-emulsification
c) Particle sizing
d) Droplet method
3) Characterisation of Microemulsions
a)Surface morphology
b) Particle size analysis
4) Evaluation of Microemulsions
a)PH
b)Viscosity
c)Transmission test
d)Droplet size measurement
e)Particle size determination
f)Zeta potential measurement
g)Content uniformity
h)Drug loading efficacy
i)Assay
5) Stability Studies as per ICH guidelines
7.5 / Does the study require any investigations or interventions to be conducted
On patients or other human or animals? If so please describe briefly
NOT APPLICABLE
7.6 / Has the Ethical Clearance been obtained from your Institution in case of 7.5?
NOT APPLICABLE
8 / LIST OF REFERENCES
1 Monzer F.Micro Emulsion, Properties and Applications Transdermal Drug
Delivery.CRC Press Taylor and Francis Group. Surfactant Science Series
Vol 144.274-76
2 Lawrence MJ, Gareth D. Micro Emulsion Based Novel Drug Delivery Systems.
Advs Drug Delivery 2000;45:89-121
3 Brisaert M, Plaizier JA,Vercammen. Investigation on the photo stability of
tretinoin in creams.Int J Pharm 2007;334: 56-61.
4 Suman R, Manish K, Vikas C, Vandana G. Formulation Development and
characterization of Micro Emulsion For Topical Delivery Of Glipizide. Der
Pharmacia Lettre 2010;2:33-42.
5 Sevgi A, Gulten K, Ozguney I, Yesim K. Comparison of Different Water/Oil
Micro Emulsions Containing Diclofenac Sodium Preparation,Characterization,
Release Rate, And Skin Irritation Studies. AAPS Pharm SciTech 2007; 8:
91.
6Sedigeh D, Behzad S, Makhmal Z, Rahim F. Preparation and evaluation of the self emulsifying drug delivery system containing loratadine.Int J Adv Pharm Sci2010;239-48.
7Donentella P, Cinzia AV, Steven N, Giovanni P, Massimo F. Lecithin micro emulsions for the topical administration of ketoprofen; percutaneous adsorption through human skin and in vivo human skin tolerability. Int J Pharm 2002; 44:21–31.
8El-Nahas, Nagia AE, Hanan M, Gehan FB. Formulation and Evaluation of Meloxicam Gels for Topical Administration.Faculty of pharmacy. University of Zagazig. Egypt. ME Paper Revised 2555 cited Faculty.ksu.Edu.sa/hisham/documents/hisham_misc/5/ME/Paper Revised 2555
9Jitendra B, Raj K.K, Arvind Y.Methoxsalen loaded chitosan coated micro emulsion for effective treatment of psoriasis. Int J Drug Del 2010;2:159-67.
10Bianca BM, Arturo LQ, Begona M, Delgado C,Anna M. F, Jose BM. Micro emulsions for topical delivery of 8-methoxsalen. J Contr Release 2000;69: 209–18.
11Derle DV, Sagar BSH, Pimpale S. Micro emulsion as a vehicle for transdermal permeation of nimesulide. Ind J Pharm Sci 2006;68:622-5.
9. / Signature of the Candidate / (RAMARAJU ABHINAV)
10 / Remarks of the Guide
The topicSelected for dissertation is satisfactory. Adequate equipment & chemicals are available to carry out the project work.
11 / Name & Designation
11.1 / Guide / MRS. BENY BABY.
ASSISTANT PROFESSOR
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2 THIRUMENAHALLI
HEGDENAGAR MAIN ROAD
BENGALURU-64.
11.2 / Signature of Guide / s. OHI ( MRS. BENY BABY)
11.3 / Co-Guide / NOT APPLICABLE
11.4 / Signature of Co-Guide / NOT APPLICABLE
11.5 / Head of the Department / DR. K. RAMESH
PROFESSOR AND HOD OF PHARMACEUTICS
DEPARTMENT OF PHARMACEUTICS
#33/2 THIRUMENAHALLI
HEGDENAGAR MAIN ROAD
BENGALURU-64
11.6 / Signature of HOD / (DR. K.RAMESH )
12
12.1 / Remark of the Principal
All the required facilities will be provided to carry out dissertation work under the supervision of the guide.
12.2 / Principal / DR.K.RAMESH.
PRINCIPAL
DEPARTMENT OF PHARMACEUTICS
KARNATAKA COLLEGE OF PHARMACY
#33/2 THIRUMENAHALLI
HEGDENAGAR MAIN ROAD
BENGALURU-560064
12.2 / Signature of the Principal / (DR. K.RAMESH )