DESIGN AND EVALUATION OF TRANSDERMAL PATCHES OF MELOXICAM

M.PHARM DISSERTATION PROTOCOL

SUBMITTED TO THE

RAJIV GANDHI UNIVERSITY OF HEALTHSCIENCES,

BANGALORE, KARNATAKA.

By

LADHANE GANESH M.

Under the guidance of

S.B.SHIRSAND

M.Pharm. (Ph.D)

DEPARTMENT OF PHARMACEUTICAL TECHNOLOGY

H.K.E.S’s COLLEGE OF PHARMACY

GULBARGA-585105

2010-11

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) / LADHANE GANESH MOHANRAO
Permanent address / LADHANE GANESH MOHANRAO
GURUKUL NIVAS,
NEAR PETROLPUMP, BUASAHEB NAGAR.
AT/PO TAL:-KARJAT-414402
DIST: AHMEDNAGAR, STATE: MAHARASHTRA
2. / Name of the institution / H.K.E.SOCIETY’S COLLEGE OF PHARMACY
SEDAM ROAD,
GULBARGA-585105.
3. / Course of study and subjects / M.PHARM
(PHARMACEUTICAL TECHNOLOGY)
4. / Date of admission to the course / 14-07-2010
5. / Title of the topic / DESIGN AND EVALUATION OF TRANSDERMAL PATCHES OF MELOXICAM
6. / Briefs resume of the intended work
6.1 / Need for the study:
A transdermal patch is a medicated adhesive patch placed on skin to deliver a time released dose of medication through the skin for treating topical or systematic illness. Since early 1990, this dosage form of transdermal therapeutic system has been available in the pharmaceutical market.1 A recent approach to drug delivery is to 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 dose.2 Such a system offers variety of significant clinical benefits over other systems, such as tablet and injections. For example, it provides controlled release of the drug and produces a steady blood- level profile leading to reduced systemic side effects and, sometimes, improved efficacy over other dosage form. In addition transdermal dosage form is user-friendly, convenient, painless, and offers multi-day dosing, it generally leads to improved patient compliance.3
It offers many important advantages over oral drug delivery, e.g., gastrointestinal and hepatic first pass metabolism, reduces variation in delivery rates, avoids interference due to presence of food, controls absorption rate, suitable for unconscious patients, and enables fast termination of drug delivery, if needed.4
Meloxicam oral administration can result into G.I. toxicity & bleeding. It has been reported that meloxicam shows similar efficacy for reducing pain and inflammatory symptoms but lower toxicity than other NSAIDs. Additionally meloxicam is a drug having a low probability of inducing allergic reactions relating to the NSAID intolerance. Thus meloxicam is good alternative for patients who are intolerant to other NSAID drugs. Meloxicam was reported as a drug that can be applied to skin and mucosa because meloxicam has lower tissue toxicity than piroxicam, ketoprofen, indomethacin, diclofenac and ibuprofen.5
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, Thampi PP. 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 plasticiser and alupoly foil used as a backing membrane. A comparison of various polymers and plasticisers were also made. In vitro release studies through mouse skin have shown that sodium carboxymethyl guar as a suitable polymer.6
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 plasticizer.7
Padula C. et al have studied the in vitroin vivo behaviour of a skin bioadhesive film containing lidocaine. The film charactrization included drug transport studies through skin in vitroin vivo tape sripping 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 value.8
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 charactristics of the patches were evaluated by the standard techniques. In vitro studies 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. study.9
Wahid A, Sridhar BK, Shivakumar S. have prepared & evaluated transdermal drug delivery system of etoricoxib 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 chitosan & hydroxypropylmethylcellulose blend were prepared and evaluated for various physicochemical characters.10
Sadashivaiah R, Dinesh BM, Patil UA, Desai BG, Raghu KS. have designed and carried out in vitro evaluation of haloperidol lactate transdermal patches containing ethyl cellulose providone as film formers. Matrix type transdermal drug delivery of haloperidol lactate were prepared using different ratio of ethyl cellulose [EC] : polyvinyl pyrrolidone [PVP] (3:2, 2:3, 4:1, 1:2, 2:1, 1:4) by solvent evaporation technique.11
Shinde AJ, Garala KC, More HN. have developed & characterised transdermal therapeutic system of tramadol hydrochloride, using hydroxyl propyl methyl cellulose [HPMC], Eudragit RL-100 & Eudragit RS-100 with triethyl citrate as plasticizer & dimethyl sulfoxide [DMSO] as a penetration enhancer. Different batches developed using Eudragit RL 100 : HPMC and Eutragit RS 100 : HPMC in a ratio of 2:8, 4:6, 6:4, 8:2.12
Patel RP, Patel G, Baria A. have formulated & evaluated transdermal patches of aceclofenac. Aceclofenac with different ratios of hydrophilic [hydroxyl propyl cellulose] and hydrophobic [ethyl cellulose] polymeric systems by solvent evaporation technique by using 15% w/w of dibutyl phthalate to the polymer weight, incorporated as plasticizer.13
Ren C. et al have developed and evaluated a novel drug-in-adhesive transdermal patch system for indapamide. Initial in vitro experiments were conducted to optimize formulation parameters prior to transdermal delivery in rats. The effect of type of adhesion & content of permeation enhancer on idapamide transport across excised rat skin was evaluated14
Zhao L. et al have prepared transdermal delivery of tolterodine using O-acylmethanol derivatives as enhancers as well as to correlate their enhancing activity under in vitroin vivo conditions. The in vitro permeation studies of tolterodine were conducted in isopropyl myristate [IPM] solution or from patches in side-by-side diffusion cell. Tolterodine pharmacokinetic parameters were determined after intravenous administration & topical application of patches without enhancer or with l-methanol & (E)-2-isopropyl-5-methylcyclohexyl octadec-9-enoate as enhancers in rats.15
Xi H. et al have prepared transdermal patches for site specific delivery of anastrazole & carried out in vitro and local tissue disposition evaluation. Different adhesive matrixes, permeation enhancers and amout of anastrazole were investigated for promoting the passage of anastrazole through the skin of rats in vitro. For local tissue disposition studies, the anastrazole patch was applied to the mouse abdominal skin, and blood, skin, and muscle samples were taken at different times after removing the residual adhesive from the skin.16
6.3 / Objectives of the study:
In the proposed research work, we are planning to prepare transdermal patches of meloxicam with the following objective.
  • Meloxicam transdermal patches will be prepared using polymers in varying concentration by solvent casting technique.
  • The prepared transdermal patches will be evaluated for various parameters like… weight variation, thickness, flatness, folding endurance, tensile strength, drug content, percentage of moisture content, in-vitro release study etc.
  • To improve the therapeutic efficacy of the drug.
  • Avoidance of hepatic metabolism because the drug from the transdermal patch is directly entering in to the systemic circulation.
  • Avoidance of gastrointestinal disturbances.
  • These prepared transdermal patches may fulfill the need of present work.

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: Meloxicam
Polymers: Hydroxypropylmethylcellulose (HPMC), Hydroxypropylcellulose (HPC) Methylcellulose (MC), Hydroxyethylcellulose (HEC), Eudragits, Carbapol, Chitosan etc.
Plasticizers: Glycerin or 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 Meloxicam transdermal patch:
The transdermal patch of meloxicam will be prepared using above listed materials by solvent casting techniques.The solvent-casting techniquewas 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 45-50o 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 45-50o C for 2 hours. This served as a matrix-type transdermal delivery system.
Evaluation of Meloxicam transdermal patch for Transdermal Drug Delivery:
The prepared transdermal patches will be evaluated for….
Physicalappearance: All the transdermal patches were visually inspected for color, flexibility, homogenicity and smoothness.2
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 600c for 4 hours prior to testing.2
Thickness: Patch thickness was measured using micrometer at three different places and the mean value plus standard deviation (SD) was calculated.1
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 reported.2
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 calculated.1
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% flatness.13
Percentage of moisture content: The film was weighed & kept in dessicator containing calcium chloride at 400C 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 content.1
In vitro release 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 references
  1. Iman IS, Nadia AS, Ebtsam MA. Formulation and stability study of chlorpheniramine maleate transdermal patch. Asian J Pharm. 2010;70(4):455-60
  2. Shah SS, Joshi R, Prabhakar P. Formulation and evaluation of transdermal patches of papaverine hydrochloride. Asian J Pharm. 2010;4(1):79:86
  3. Ren C et-al. Design and in vivo evaluation of an indapamide transdermal patch. Int J Pharm. 2009;370:129-135
  4. Shinde AJ, Shinde AL, More HN. Design and evaluation of transdermal drug delivery system of gliclazide. Asian J Pharm. 2010;4(2):121-9
  5. Sweetman SC. The editor Martindale: The complete drug reference. Martindale. 35 edn. London: Pharmaceutical press. p. 468-9.
  6. Paranjothy KLK, Thampi PP.Development of transdermal patches of verapamil hydrochloride using sodium carboxy methyl guar as a monolithic polymer matrix and their in vitro release studies. Indian J Pharm Sci. 1997,59(2):49-54
  7. Sankar V et al. Design ane evaluation of nifedipine transdermal patches. Indian J Pharm Sci. 2003;65(5):510-15
  8. Padula C et al. Bioadhesive film for transdermal delivery of lidocaine. J Control Release. 2003;88:277-85
  9. 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
  10. 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
  11. Sadashivaiah R, Dinesh BM, Patil UA, Desai BG, Raghu KS. Design and in vitro evaluation of haloperidol lactate transdermal patches containing ethyl cellulose-providone as film formers. Asian J Pharm. 2008;2(1):43-9
  1. Shinde AJ, Garala KC, More HN. Developement & characterization of transdermal therapeutic system of tramadol hydrochloride. Asian J Pharm. 2008;2(4):265-9
  2. Patel RP,Patel G,Baria A. Formulation & evaluation of transdermal patches of aceclofenac. Int J Drug Delivery. 2009;41-51
  3. Ren C. et al. Design and in vivo evaluation of an indapamide transdermal patch. Int J Pharm. 2009;370:129-35
  4. ZhaoL. et al. Transdermal delivery of tolterodine by O-acylmethanol : in vitro/ in vivocorrelation. Int J Pharm. 2009;374:73-81
  5. Xi H. et al. Transdermal patches for site specific delivery of anastrazole: in vitro and local tissue disposition evaluation. Int J Pharm. 2010;391:73

9. / Signatures of candidate / [MR. Ladhane Ganesh Mohanrao]
10. / Remarks of Guide / The proposed research work is novel one and with the development of transdermal patches. We can deliver meloxicam more efficiently and effectively. So recommended for registration.
11. / Name and designation of
(in block letters)
11.1 Guide / S.B SHIRSAND
M. Pharm. (Ph.D)
ASST. PROFESSOR
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S COLLEGE OF PHARMACY,
GULBARGA-585105.
11.2 Signature
11.3 Co-guide / Dr. S.S BUSHETTI
M. Pharm. Ph.D
PROFESSOR
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S COLLEGE OF PHARMACY, GULBARGA-585105.
11.4 Signature
11.5 Head of the Department / Dr. P.V SWAMY
M. Pharm. Ph.D
PROFESSOR
DEPT.OF PHARMACEUTICAL TECHNOLOGY
H.K.E.S COLLEGE OF PHARMACY,
GULBARGA-585105.
11.6 Signature
12 / 12.1 Remarks of chairman and Principal
12.2 Signature

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