DESIGN AND EVALUATION OF TRANSDERMAL PATCHES OF olmesaRtan medoxomil

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCES,

BANGALORE, KARNATAKA.

By

HARSHA

Under the guidance of

Dr. S.S. BUSHETTI

M.Pharm.,Ph.D

DEPARTMENT OF INDUSRIAL PHARAMACY

H.K.E.S’s MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARAMCEUTICAL SCIENCES SEDAM ROAD

GULBARGA-585105

2011-12

RAJIV GANDHI UNIVERSITY OF HEALTH SCIENCE, KARNATAKA

BANGALORE

ANNEXURE-II

PROFORMA FOR REGISTRATION OF SUBJECTS FOR DISSERTATION

1. / Name of the candidate
(In block letters) / HARSHA
Permanent address / HARSHA
C/O SANGAM MEDICAL HALL,
M.S.K. MILL ROAD, GULBARGA
2. / Name of the institution / H.K.E.SOCIETY’S MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARMACEUTICAL SCIENCES
SEDAM ROAD,GULBARGA-585105.
3. / Course of study and subjects / M.PHARM
(INDUSTRIAL PHARMACY)
4. / Date of admission to the course / 12-07-2011
5. / Title of the topic / DESIGN AND EVALUATION OF TRANSDERMAL PATCHES OF olmesaRtan MEDOXoMIL
6. / Brief resume of the intended work
6.1 / Need for the study:
Olmesartanmedoxomilis anangiotension II receptor antagonistused to treathigh blood pressure.Presently it is available in the form of a oral tablet, after its oral administration it under goes pre-systemic metabolism, resulting into an inactive metabolites which shows a poor bioavailability of 26%1. The bioavailability of the drug can be improved by delivering through a non-per-oral routes which includes transdermal,buccal,ophthalmic,nasal and rectal etc2. In the proposed research work an attempt will be made to prepare transdermal patches of olmesartanmedoxomilto improve the bioavailability by by-passing the pre-systemic metabolism.
The preparation of transdermal patch is a recent approach to drug delivery which deliver the drug into systemic circulation at predetermined rate using skin as a site of application. A transdermal drug delivery is a formulation or device that maintains the blood concentration of the drug within therapeutic window ensuring that drug levels neither fall below the minimum effective concentration nor exceed minimum toxic dose3.
Transdermal drug delivery system offers variety of significant clinical benefits over other systems which provides controlled release of the drug and produces a steady blood- level profile leading to reduced systemic side effects and increased bioavailability thereby improved efficacy. In addition transdermal drug delivery system is user-friendly, convenient, painless, suitable for unconscious patients, and enables fast termination of drug delivery if neededand overall it improves the patient compliance4.
6.2 / Review of Literature
The literature survey was carried out by referring various scientific journals and with the facility of internet. Some of the published reports of similar work for various medicinal agents are:
Paranjothy KLK, et al. Have developed of transdermal patches of verapamil hydrochloride using sodium carboxy methyl guar as a monolithic polymer matrix and their in- vitro release studies. Propylene glycol used as a plasticizer and alupoly foil used as a backing membrane. A comparison of various polymers and plasticisers were also made. In- vitrorelease studies through mouse skin have shown that sodium carboxymethyl guar as a suitable polymer4.
Sankar V. et al have prepared transdermal drug delivery system of nifedipine, prepared drug free polymeric film of ethyl cellulose [EC], to explore their suitability for transdermal application as the rate controlling membrane. Castor oil, glycerol was incorporated at a concentration of 30 % w/w , 40% w/w of dry polymer, as plasticizer5.
Padula C. et al have studied the in-vitroin-vivo behaviour of a skin bioadhesive film containing lidocaine. The film characterization included drug transport studies through skin in- vitroin vivo tape stripping with & without iontophoresis. They studied the effect of drug loading in order to identify the release mechanism. Finally, release rate was compared with a lidocaine commercial gel, to assess the therapeutic value6.
Lewis S, Pandey S, Udupa N. have prepared and evaluated matrix type & membrane controlled transdermal delivery system of nicotine suitable for use in smoking cessation. In this study, two types of patches, monolayered and bilayered, were prepared. The monolayer patch bore a rate-controlling membrane, whereas the bilayered served as a matrix type. The physical characteristics of the patches were evaluated by the standard techniques. In- vitrostudies of the transdermal patches showed a biphasic release pattern, with diffusion as a dominating mechanism of drug release for matrix type, while the membrane controlled released nicotine, gradually over the 24 hr. study7.
Wahid A, Sridhar BK, Shivakumar S. have prepared & evaluated transdermal drug delivery system of etorcoxib using modified chitosan. In this investigation, chitosan has been chemically modified by treating with two different aldehydes like acetaldehyde & propionaldehyde to form Schiff’s base. Drug free polymeric films of chitosan, chemically modified chitosanhydroxypropylmethylcellulose blend were prepared and evaluated for various physicochemical characters8.
Kavita.k et al. developed transdermal patches of nicardipine hydrochloride using different ratios of hydrophilic and hydrophobic polymeric combinations. By solvent evaporation technique. Polymers are hpmc, ethylcellulose etc. the relese Rate of drug through patches increased when the concentration of hydrophilic polymer was incresed9.
Nirav.s.seth et al have made formulation and evaluation of transdermal patches and to study permeation enhancement effect of eugenol. Using different polymer such as polyvinylpyrrolidone, hpmc and ethylcellulose. Propylene glycol using as a plasticizer. The cumulative drugrelese is depend upon the concentration of pvp,hpmc,ec if concentration of polymer increases there would be decrese in the relese of drug10.
Shailesh.t.prajapati, et al they have done formulation and evaluation of transdermal patches of repaglinide was prepared to sustaine release and improve bioavailability of drug using different polymeric grade of hpmc and pvpk30 by solvent casting method. It was concluded that hpmc,pvpk30 of moderate level useful for preparation of sustained released matrix transdermal patch formulation11.
Gulamirfaniet al have made design and evaluation of transdermal drug delivary system of valsartan using glycerine as plasticizer. Used polymers such as pvpk30,hpmc,eudragit rs100 (10%,20%,30%)in different concentrations by solvent casting method. In this stydy the result indicates , as in the concentration of glycerin, incerse the diffusion rate of valsartan patch among polymers, the combination of eudragit RS 100 with hpmchad increased diffusion rate12.
6.3 / Objectives of the study:
In the proposed research work, olmesartanmedoxomiltransdermal patches will be prepared with the following objectives.
  • Olmesartanmedoxomiltransdermal patches will be prepared usingvarious polymers like, Hydroxy propyl cellulose, Methyl cellulose, Eudragit, Carbopol, HPMC 15cps, etc, in varying concentration by solvent casting technique.
  • The prepared transdermal patches will be evaluated for various parameters like… weight variation, thickness, folding endurance, tensile strength, drug content, percentage of moisture content, in-vitro release study etc.
  • To improve the bioavailability by by-passing pre-systemic metabolism of the drug.
  • Drug level can be maintained in the systemic circulation,within the therapeutic window.
  • Improved patient compliances and acceptability of the drug therapy.
  • Drug input can be terminated simply by removal of olmesartan medoxomil patch.
  • To improve the therapeutic efficacy of the drug.

8 / 7 / Materials and Methods
7.1 / Source of Data:
Internet.
Helinet facility of our affiliating university RGUHS Bangalore.
International pharmaceutical journals.
National pharmaceutical journals.
7.2 / Drug: Olmesartanmedoxomil
Polymers: Hydroxypropylmethylcellulose (HPMC), Hydroxypropylcellulose (HPC) Methylcellulose (MC), Hydroxyethylcellulose (HEC), Eudragits, Carbapol, Chitosan etc.
Plasticizers: Glycerin, Dibutyl phthalate, Propylene glycol etc.
.
Equipments:
  • UV-visible spectrophotometer (Shimadzu 1700).
  • PH-meter (Elico LI 122).
  • Ultrasonicator (Flexit Laboratories Pvt.Ltd).
  • Screw guage
  • Magnetic stirrer (Remi Equipment, Mumbai).
  • Single Pan electronic balance.
  • Digital Controlled Speed Stirrer (Remi motors RQ 121/D).
  • Tensile strength apparatus etc.
Preparation of OLMESARTAN MEDOXOMIL Transdermal Patch:
The transdermal patch of OLMESARTAN MEDOXOMIL will be prepared using above listed materials by solvent casting techniques11.The solvent-casting technique was used to formulate the patches containing different grades of polymer. The drug polymer solution was transferred into a glass Petridish containing mercury. The Petridish was then kept in an air circulation drier and maintained at a temperature of 45-500 C for 6 hours. Poly vinyl acetate (PVA) membrane was used as the backing membrane. One surface of the drug reservoir matrix was slightly moistened with water and placed against the PVA membrane and allowed to dry at 45-500 C for 2 hours. This served as a matrix-type transdermal delivery system.
Evaluation of OLMESARTANMEDOXOMILTransdermal Patch for Transdermal Drug Delivery: 11
  • The prepared transdermal patches will be evaluated for….
  • Physical appearance: All the transdermal patches were visually inspected for color, flexibility, homogenicity and smoothness11.
  • Weight variation :A set of three patches from each batch having a diameter of 1cm2 were weighed on a digital balance and the mean values were calculated. The tests were performed on the films which were dried at 60oC for 4 hours prior to testing11.
  • Thickness: Patch thickness was measured using screw gauge at three different places and the mean value was calculated11.
  • Folding endurance: A strip of 4 cm2 was subjected to folding endurance by folding the patch at same place repeatedly several times until a visible crack was observed and the values were reported11.
  • Tensile strength: Determined by using tensile strength apparatus, weight was gradually increased so as to increase pulling force till the patch broke, and the tensile strength was calculated11.
  • Flatness: Three longitudinal strips were cut from each film: 1 from centre, 1 from left side, 1 from right side. The length of each strip was measured and variation in the length because of non-uniformity in flatness was measured by determining percent constriction, with 0% constriction equivalent to 100% flatness11.
  • Percentage of moisture content: The film was weighed & kept in dessicator containing calcium chloride at 400 C and dried at least for 24 hours. The film was weighed until it showed constant weight. The moisture content was the difference between the constant weight taken and the initial weight. It was reported in terms of percentage (by weight) moisture content11.
  • In- vitrorelease study:

7.3 / Does the study require any investigation or invervention to be conducted on patients or other humans or animals? If so please describe briefly
…………………. Not under the plan of work…………………..
7.4 / Has ethical clearance have been obtained from your institution in case of 8.4?
………………….. Not applicable…………………….
8. / LIST OF REFRENCES:
  1. Sweetman SC. The editor Martindale: The complete drug reference. Martindale. 35 edn. London: Pharmaceutical press. p. 1224-1225.
  1. D.M.Brahmankar and Sunil B Jaiswal. Biopharmaceutics and pharmacokinetics. Vallabh Prakashan2nd edition. P.66-67.
  1. Shah SS, Joshi R, Prabhakar P. Formulation and evaluation of transdermal patches of papaverine hydrochloride. Asian J Pharm. 2010;4(1):79-86.
  1. Ren C et-al. Design and in vivo evaluation of an indapamidetransdermal patch. Int J Pharm. 2009;370:129-135.
  1. Paranjothy KLK, Thampi PP. Development of transdermal patches of verapamil hydrochloride using sodium carboxy methyl guar as a monolithic polymer matrix and their in- vitrorelease studies. Indian J Pharm Sci. 1997,59(2):49-54.
  1. Sankar V et al. Design ane evaluation of nifedipine transdermal patches. Indian J Pharm Sci. 2003;65(5):510-15.
  1. Padula C et al. Bioadhesive film for transdermal delivery of lidocaine. J Control Release. 2003;88:277-85.
  1. Lewis S, Pandey S, Udupa N. Design and evaluation of matrix type & membrane controlled transdermal delivery system of nicotine suitable for use in smoking cessation. Indian J Pharma Sci. 2006;68(2):179-84.
  1. Wahid A, Sridhar BK, Shivakumar S. Preparation & evaluation of transdermal drug delivery system of etoricoxib using modified chitosan. Indian J Pharma Sci. 2008;70(4):455-60.
  1. Kavitha.k andp.dipenkumar. Development of transdermal patches of nicardipinehydrochloride:an attempt to improve bioavailability.Int J Res Pharm and Bio 2011; 2(1): 285-293.
  1. Nirav s seth, Rajab b mystry. Formulation and evaluation of transdermal patches and to study permeation enhancement of eugenol. J App Pharm Sci. 2011; 01(03): 96-101.
  1. Shailesh.t.prajati, charmi.g.patel, chhagan.n.patel. Formulation and evaluation of transdermal patch of repaglinide. IntSch Res Net.2011: 01-09.
  1. Gulamirfani, raga sunil raj, Amittondare, noolashivanand. Design and evaluation of transdermal drug delivary system of valsartan using glycerine as a plasticizer. Int J Pharm. 2011; 3: 185-192.

9. / Signatures of candidate / [Mr.HARSHA]
10. / Remarks of Guide / The work proposed is novel one.We can deliver the drug more efficiently and effectively. The proposed work is neither published nor reported any where, so recommended for registration.
11. / Name and designation of
(in block letters)
11.1 Guide / Dr. S.S. BUSHETTI
M. Pharm.,Ph.D PROFESSOR
DEPT.OF INDUSTRIAL PHARMACY H.K.E.SOCIETY’S MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARMACEUTICAL SCIENCES
SEDAM ROAD,GULBARGA-585105.
11.2 Signature
11.3Head of the Department / Dr. S.S. BUSHETTI
M. Pharm.,Ph.D
PROFESSOR AND HOD
DEPT.OFINDUSTRIAL PHARMACY
H.K.E.SOCIETY’S MATOSHREE TARADEVI RAMPURE INSTITUTE OF PHARMACEUTICAL SCIENCES
SEDAM ROAD,GULBARGA-585105.
11.4 Signature
12 / 12.1 Remarks of chairman and Principal
12.2 Signature

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