Rajiv Gandhi University of Health Science, Karnataka, Bengalore

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE, KARNATAKA, BENGALORE.

M.PHARM.SYNOPSIS

YEAR OF ADMISSION AUGUST-2013

TITLE OF THE SYNOPSIS

“FORMULATION AND EVALUATION OF MICROEMULSION FOR NON-STEROIDAL ANTI-INFLAMMANTORY DRUG”

BY

MR.DARSHAN.B.PATIL,

M.Pharm. Part-1

Department of Pharmaceutics.

UNDER THE GUIDANCE OF

MR. SIDHARTH.M.PATIL, M.Pharm, ASSISTANT PROFFESOR DEPARTMENT OF PHARMACEUTICS.

K.L.ES’s COLLEGE OF PHARMACY,

AKKOL ROAD, NIPANI-591237, KARNATAKA.

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES

KARNATAKA, BENGALORE.

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECT FOR DISSERTATION

1. / NAME OF THE CANDIDATE AND ADDRESS / MR.DARSHAN.B.PATIL
A/P-Borgaon-591261 Tal - Chikkodi Dist ; Belgum
KARNATAKA.
2. / NAME OF THE INSTITUTE / KLES’s COLLEGE OF PHARMACY
Akkol road Nipani-591237
Tal; chikkodi Dist;Belgum
KARNATAKA.
3. / COURSE OF STUDY AND SUBJET / Master of Pharmacy in Pharmaceutics.
4. / DATE OF ADMISSION / August – 2013.
5. TITLE OF THE TOPIC :-
“FORMULATION AND EVALUATION OF MICROEMULSION FOR NON-STEROIDAL ANTI-INFLAMMATORY DRUG”.
6.0
/ BRIEF REVIEW OF THE INTENDED WORK:-
6.1-Need for the Study
The concept of microemulsion was first introduced by Hoar and Schulman in 1943. They
prepared the first microemulsions by dispersing oil in an aqueous surfactant solution and adding
alcohol as a co-surfactant, leading to a transparent, stable formulation. This lead to a faster absorption allowing a more rapid onset of drug action. But microemulsions also overcome food effect and reduce subject to subject variability by levelling the differences indigestive capabilities.1
Microemulsions are clear, stable, isotropic mixtures of oil, water and surfactant, frequently in combination with a co-surfactant.. The two types of microemulsions are direct (oil dispersed in water, o/w) and reversed (water dispersed in oil, w/o). Their size range beetween 10-200nm. In contrast to ordinary emulsions. microemulsions form upon simple mixing of the components and do not require the high shear conditions generally used in the formation of ordinary emulsions. The current research is to develop an NSAID microemulsion based transdermal drug delivery systems which may exhibit protection against oxidation, improved drug dissolution, enzymatic hydrolysis, fast absorption, improved the solubilisation of lipophilic drugs, prolonged release and enhance bioavailability.2
In topical formulations microemulsions increase the cutaneous absorption of both lipophilic and hydrophilic active medicament. In this type of applications the microemulsions attribute to the performance to generally a higher solubility of the medicament of microemulsions, One major advantage of microemulsion as topical formulation is to avoid first pass metabolism, and their easy administration with good control over rate of drug delivery generating increased concentration gradient towards skin.3
Topical preparations pertain to medicaments applied to the surface of a part of the body and are a term used to describe formulations that have effects only in a specific area of the body and are formulated in such a manner that the systemic absorption of the medicament is minimal. The methods involved in conventional topical drug delivery basically involve either assisting or manipulating the barrier function of the skin (topical antibiotics, antibacterials, emollients, sun screen agents) or breaching the horny layer at the molecular scale so as to direct drugs to the viable epidermal and dermal tissues without using oral, systemic or other therapies.4
6.2-Review of Literature:-
1.  Schwarz J.C. Klang V. Hoppel M. - Microemulsions are thermodynamically stable, colloidal drug delivery systems. This study presents the first substantiated comparison of natural, skin-compatible and biodegradable surfactants in terms of their suitability to form isotropic microemulsions and their skin interaction. Pseudoternery phase diagrams were constructed for lecithin, sucrose laurate and alkylpolyglycoside as single surfactants. the lecithin-based microemulsions showed the highest permeation rates followed by the alkylpolyglycoside–lecithin microemulsions.5
2.  Hu L. Yang J. Liu W. Li L. - Improved the solubility of ibuprofen, a poorly water-soluble drug, in a microemulsion system that is suitable for oral administration. The optimal formulation consists of 17% labrafil M 1944CS, 28% cremophor RH40/transcutol P (3:1, w/w) and 55% water, with a maximum solubility of ibuprofen up to 60.3 mg/ml. The mean droplet size of microemulsion was 57 nm. The pharmacokinetic study of microemulsion was performed in rats and compared with granule formulation. The microemulsion has significantly increased the Cmax and area under the curve (AUC) compared to that of the granule (p < 0.05).6
3.  Yun S. R., et al. - A transdermal preparation containing ketoprofen was developed using o/w microemulsion system. Oleic acid was chosen as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. The optimum formulation of the microemulsion consisted of 3% ketoprofen, 6% oleic acid, 30% labrasol/cremophor RH 40 (1:1) and water. Terpenes were added to the microemulsion at the level of 5% and their effect on the skin permeation of ketoprofen from the microemulsion was evaluated. Of the four terpenes used, only limonene resulted in a powerful enhancing activity.7
4.  Tian Q. Ren F. Xu Z. Xie Y. Zhang S. To improve the skin permeation of naproxen with larger dosage, microemulsion with high content of naproxen was investigated for transdermal delivery and its solubilization mechanism was studied. Naproxen micoremulsions composed of 4% isopropyl myristate, 18% Tween 80, 18% ethanol and water were prepared and phase inversion temperature (PIT) method was used to increase drug content. The using of PIT method resulted in the maximum content of naproxen in microemulsion increased
from 1.98 ± 0.13% to 4.12 ± 0.07%, accordingly the permeation rate of naproxen from microemulsion through excised mice skin increased from 135.13 ± 5.50 to 214.46 ± 7.53 μg cm(-2)h(-1). The analyses of Natural Bond Orbital and interaction energy using the B3LYP and MP2 (fc) methods suggested that the solubilization mechanism of microemulsion for naproxen mainly might be the formation of complex between the hydrogen atom of hydroxyl in Tween 80 and the oxygen atom of carbonyl group in naproxen, as is in accordance with the result from (1)H NMR experiments. The change of thermodynamic function with temperature confirmed that, because the complex was easy to be formed in high temperature and that formed at PIT became more stable when the temperature decreased to below PIT, the solubilization ability of microemulsion for naproxen could be improved by the PIT method. The powerful permeation enhancing ability of microemulsion induced by the solubilization of PIT method makes it a promising vehicle for the transdermal delivery of naproxen.8
5.  Yuan X. Capomacchia A. C. - The thermodynamic, eutectic, and crystalline
properties of ibuprofen and ketoprofen binary mixtures were investigated using
differential scanning calorimetry (DSC) and X-ray powder diffractometry
(XRPD). Due to the melting-poin depression and enhanced skin lipid solubility,
the steady state flux of ibuprofen and ketoprofen from preparations of the binary
eutectic increased as compared to pure NSAIDs using shed snakeskin as a model
membrane. The proposed flux ratio equations correctly predicted flux increase.9
6.  Yang J.H., Kim Y.I., Kim K.M. - To develop novel transdermal formulation for aceclofenac, microemulsion was prepared for increasing its skin permeability. Based on solubility and phase studies, oil and surfactant was selected and composition was determined. Microemulsion was spontaneously prepared by mixing ingredients and the physicochemical properties such was investigated. The mean diameters of microemulsion were approximately 90 nm and the system was physically stable at room temperature at least for 3 months. In addition, the in vitro and in vivo performance of microemulsion formulation was evaluated. Aceclofenac was released from microemulsion in acidic aqueous medium, and dissolved amounts of aceclofenac was approximately 30% after 240 min. Skin permeation of aceclofenac from microemulsion formulation was higher than that of cream.10
6.3 Objectives of the study:-
The objectives of the study are as follows :-
·  To develop micro emulsion by any suitable method.
·  To characterize the formulated microemulsion.
·  Evaluation of formulated microemulsion.
·  To carry out stability studies as per as ICH guidelines.
7.0 MATERIALS AND METHODS:-
Materials-:
Drug : NSAID.
Polymers : HPMC. Sodium CMC. Carbopol 934. etc.
Surfactant : Polysorbate (Teen 80&20). Decyl polyglucoside. etc.
Co-surfactant : Sorbitan monooleate. Propylene glycol. etc.
Oils : Olive oil. Mineral oil. etc.
Method :
·  Formulation and Evaluation of microemulsion by any suitable method or any developed method.
7.1-Source of Data:
A) Journals such as,
1) Indian Journals of Pharmaceuticals Sciences.
2) International Journal of Pharmaceutics.
3) European Journal of Pharmaceutical Sciences.
4) Drug development & Industrial Pharmacy.
5) Journal of Controlled Release.
B) Review articles.
C) Science direct, Pub med.
D) J-gate@Helinet.
E) World wide web.
F) Library: KLE’s College of Pharmacy.
G) E-library: KLE’s College of Pharmacy.
7.2- Method of collection of data:-
1)Preformulation Studies for possible drug or other excipient.
2) Peparation of microemulsion of NSAID for transdermal drug delivery system based
method or any suitable/developed method.
3) Evaluation of Microemulsions:
a)  pH.
b)  Viscosity.
c)  Transmission electrone microscopy. (SEM)
d)  Particle size analysis.(XRD)
4) Carry out stability studies as per ICH guideline.
7.3- Does the study require any investigations or interventions to be conducted
On patients or other human or animals? If so please describe briefly

“NO”

7.4- Has the Ethical Clearance been obtained from your Institution in case of 7.3?
“NOT APPLICABLE”
/ 8.0: LIST OF REFERENCES:-
1.  www.vetcontact.com/presentations/midler1/abstracts/midler.pdf.
2.  Sushama T., Adnan A., Farhan J.A., Roop K.K., Shadab A.P., Zeenat I.K. “Micro emulsions: A novel approach to enhanced drug delivery”. Bentham Science Publishers Limited. 2008; 2:238-57.
3.  Grampurohit N., Mallya R., Ravikumar P. “Microemulsions for topical use – A review”. Indian Journal of Pharmaceutical Education and Research. 2011; 45(1):100-101.
4.  Katiyar B.S., Katiyar S.S., Mishra P.S., Sailaja D.L. “Microemulsion: A Novel drug carrier System”. International Journal of Pharmaceutical Science. 2013; 20(2):138-48.
5.  Schwarz J.C., Klang V., Hoppel M. “Natural microemulsions: formulation design and skin interaction”. European Journal of Pharmaceutics & Biopharmaceutics. 2012; 81:557–62.
6.  Hu L.,Yang J.,Liu W.,Li L. “Preparation and evaluation of ibuprofen-loaded microemulsion for improvement of oral bioavailability”. Drug Delivery. 2011; 18(1):90-95.
7.  Rhees Y-S., Choi J-G., Park E-S., Chi S-C. “Transdermal delivery of ketoprofen using microemulsions”. International Journal of Pharmaceutics. 2001; 228(1-2):161-70.
8.  Tian Q., Ren F., Xu Z., Xie Y, Zhang S. “Preparation of high solubilizable microemulsion of naproxen and its solubilization mechanism”. International Journal of Pharmaceutical Science.20121; 426:202-10.
9.  Yuan X.,Capomacchia A.C. “Physicochemical studies of binary eutectic of ibuprofen and ketoprofen for enhanced transdermal drug delivery”. Drug Development & Industrial Pharmacy.2010; 36(10):1168-176.
10.  Yang J.H.,Kim Y.I.,Kim K.M. “Preparation and evaluation of aceclofenac topical microemulsion”. Archives of pharmacal research.2002; 25(4):534-40.
9. / Signature of the Candidate
10. / Remarks of the Guide / Recommended
11. / Name & Designation of
11.1 Guide / Mr.Sidharth. M. Patil
M.Pharm
Asst.Professor of pharmaceutics
11.2 Signature of Guide / s. OHI
11.3 Co-Guide
11.4 Signature
11.5 Head of the Department / PROF.( DR).J.K.SABOJI.M.Pharm.Ph.D
PROFESSOR AND HEAD
DEPARTMENT OF PHARMACEUTICS
11.6 Signature
12. / 12.1 Remark of the
Principal / Forwarded to the university for approval
12.2 Signature / Principal
Prof.(Dr).J.K.SABOJI. M.pharm. Ph.D
KLES’s College of Pharmacy Akkol Road. NIPANI-591237

`

1