Formulation and Evaluation of Transdermal Patches of Curcumin

Transcription

1 Available online at ISSN: INTERNATIONAL JOURNAL OF NOVEL TRENDS IN PHARMACEUTICAL SCIENCES Formulation and Evaluation of Transdermal Patches of Curcumin RESEARCH ARTICLE L Karpagavalli *, A Mahaeswaran, P Praveena, S Sharmila, M Priya, B Meena Department of Pharmaceutics, Jaya college of pharmacy, Thiruninravur, Chennai, Tamil Nadu Abstract Transdermal patch of curcumin (curcuma longa) was prepared by using two different grades of hydroxy propyl methyl cellulose and other additives. Curcumin an ayurvedic herbal drug used as an anti arthritic agent. Dimethyl sulfoxides (DMSO), polyvinyl alcohol (PVA) were used as permeation enhancers and polyethylene glycol (400% w/v) was used as plasticizer. The prepared films exhibited satisfactory physiochemical characters such as percentage moisture absorption, percentage moisture loss, thickness & weight of drug content. In vitro drug release release. The present work showed that drug of ayurvedic origin can be utilized in a better form with was determined by semi permeable membrane using Franz diffusion cell ]. The films formed using HPMC were thin, flexible and smooth and these patch with permeation enhancer showed maximum enhanced efficacy for incorporation into modern dosage forms. The sustained release of curcumin from transdermal patches can minimize the frequent administration of conventional curcumin dosage forms. Keywords: Curcumin, Dimethyl sulfoxide, Hydroxy propyl methylcellulose, Polyethylene glycol (400%), Transdermal. INTRODUCTION TDDS are adhesives drug contains devices of defined surface area that delivers predetermined amount of drug to the intact skin at a preprogrammed rate [1]. The TDDS has gained importance in recent years. The major advantages for TDDS include avoidance of gastro intestinal in compatibility and variable absorption, avoidance of hepatic first pass metabolism and consequent degradation and reduce bioavailability reduced frequency of dosing with improved patient compliance and rapid termination of drug input by removal of system from the skin [2]. Curcumin a herbal drug is used in treatment of arthritis oral dosage forms undergoes hepatic first pass metabolism, its systemic bioavailability is 50%. Curcumin is unstable in the gastro intestinal tract and the traces that pass through the GI tract rapidly degrades or undergoes conjugation through glucuronidation. Hence it is co-supplemented with 20mg of piperine. In the present study transdermal films of curcumin were prepared and evaluated with a view to prevent its first pass metabolism and to achieve controlled drug release with improved bioavailability. MATERIALS AND METHODS Curcumin, Hydroxy propyl methyl cellulose (HPMC 6cps ), Hydroxy propyl methyl cellulose (HPMC 15cps), Dimethyl sulfoxide (DMSO), polyvinyl alcohol (PVA). All the ingredients used are of analytical standard. Preparation of Curcumin Transdermal patches The transdermal patches of Curcumin were prepared by a solvent prepared by a solvent casting techniques using different grades of HPMC (6cps, 15cps). Weighed quantity of poly vinyl alcohol and drug was added to 10ml of distilled water and occasionally stirred to get a clear solution. 10ml of the polymer solution was poured within the glass plate in the formulation of the backing membrane for films I, II, III and then allowed for drying at room temperature over night. For the fabrication of films II and III expect that third had an inclusion of a permeation enhancer dimethyl sulfoxide. The polymeric solution was poured on to a prepared To whom correspondence should be addressed: L.Karpgavalli karpagavalliev@gmail.com VOLUME 7 NUMBER 1 FEB

2 cavity and dried at room temperature for 24Hrs with an inverted funnel overhead to provide a uniform rate of evaporation [3-5]. Formulated patches were allowed to equilibrate in desiccators over aluminium chloride for another 3 days. The evaluation process is to ensure total hydration and to exclude air. The patches were evaluated within one week from the date of casting. In vitro Characterization of Curcumin Transdermal Patches Drug content For the drug determination the total content of transdermal patches was dissolved in an hydro alcoholic medium and made upto 50ml with same [4]. The solution was filtered and 1ml of resultant solution was diluted upto five concentration and the absorption maximum were measured spectrophotometrically at 420nm. Percentage moisture absorption A 2.00 sq.cm patches were cut and weighed accurately when the patches was placed in Desiccator containing 100ml of saturated solution of aluminium chloride keeping the humidity inside the desiccator as 79.5%RH. After three days the film were removed and reweighed. The moisture absorption capacity of the films were calculated in terms of percentage increase in the weight of film over the initial weight of the specimen [4,5]. The % moisture absorption is calculated by using. Percentage moisture absorption: PMA = (Final weight - Initial weight) / Initial weight x 100 Percentage moisture Loss The integrity of patches can be determined at dry conditions. A 2.00 sq.cm patches were cut and weighed accurately and placed in desiccator containing anhydrous calcium chloride. After three days of patches were removed and reweighed. The percentage moisture loss is calculated by using. Percentage moisture Loss: PML = (Final weight - Initial weight) / Initial weight x 100 Thickness Thickness of patches were measured at 3 different points using a screw guage. receptor compartment. The donor compartment was open at top end and exposed to atmosphere. The temperature was maintained at 37± 0.5 c and receptor compartment was providing with sampling port. The diffusion medium used in hydro alcoholic solution. The drug containing film was kept in donor compartment and separated from receptor compartment by semi permeable membrane. The donor and receptor compartments were held together using clamp. The receptor compartment with hydro alcoholic solution was maintained at 37±0.5 c and stirred with magnetic stirrer, to prevent the formation of concentrated drug solution below the semi permeable membrane. The samples of 1 ml were collected at pr determined time intervals and replaced with fresh solution of same. The concentration of drug was determined spectrophotometrically at 420 nm. RESULTS AND DISCUSSION Drug Contents The drug content was determined by dissolving patches each of 2.0cm in hydro alcoholic medium and absorbance values were found at 420nm and by using calibration curve. Results are tabulated. The drug content analysis of the prepared formulation has shown that the process employed to prepare the patches were capable of giving uniform drug content with minimum batch variability (Table 2). Folding endurance All the patches showed good folding enhance properties (Table 3). Moisture content Moisture content of various patches were determined as described in experiment section (Table 4 and Graph 1 & 2). THICKNESS Thickness of each film was determined individually and decrease in thickness of various TDDS were found to be of order F3>F1>F2. The result of in vitro drug studies from transdermal patches are depicted was increase in the following order. F3>F2>F1 (Table 5). In Vitro release studies RELEASE STUDIES In vitro release was carried out with semi permeable Various release profile of Curcumin from different membrane using Franz diffusion cell. The cell experimental patches composed of various ratio of consists of two chambers which act as donor and HPMC. The process of drug release in most VOLUME 7 NUMBER 1 FEB

3 controlled release device is governed by amount diffusion as the motion of a small molecules is restricted by three dimensional network of polymer chains. Release rate were increased when concentration of HPMC is increased in the formulations. This is because as the proportion of this polymer in the matrix increased, there was an increase in amount of water uptake and hydration of the polymeric matrix and thus more drug was released. Formulation F1 showed less drug release compared to formulation F3 because of high proportions of HPMC (Table 6). Table 1. Curcumin Loaded Transdermal Patches S. No Formulation Polmer (3% w/v) Solvent used Plasticizer (PEG 400% w/v) Permeation enhancer (DMS0% w/v) Drug (mg/ml) 1 HPMC-I (F1) HPMC- 6cps Acetone HPMC- II (F2) HPMC- 15cps Acetone HPMC-III (F3) HPMC- 6cps Acetone Table 2. Drug content analysis of patches S.NO FORMULATION FORMULATION(%W/V) AMOUNT(mg) 1 F1 HPMC F2 HPMC F3 HPMC Table 3. Folding endurance of patches FORMULATION PARAMETER (Folding endurance) F F F Table 4. Moisture Content of Transdermal Patches S.NO FORMULATION INITIAL Wt(mg) FINAL Wt(mg) Wt LOSS % of LOSS F F F Table 5.Thickness of Transdermal Patches FORMULATION PARAMETER (THICKNESS) mm F F F Table 6. Cumulative Percent Release Studies TIME F1 % CUMULATIVE TIME F2 % CUMULATIVE TIME F3 % CUMULATIVE VOLUME 7 NUMBER 1 FEB

4 Graph 1. Percentage moisture content of patches Percent Moisture uptake Graph 2.Percentage Moisture Content Percentage Moisture Content Moisture Uptake % Moisture Content % HPMCI HPMCII HPMCIII HPMCI HPMCII HPMCIII Graph 3. Comparison of in vitro release studies 90 COMPARISON OF IN VITRO RELEASE STUDIES Cumulative % Release PATCH 1 PATCH 2 PATCH TIME ( mins) VOLUME 7 NUMBER 1 FEB

5 CONCLUSION Ayurvedic systems of medicine has described specified methods and natural drugs. TDDS was ideally suited for drugs that undergoes hepatic first pass metabolism with a short elimination half life. Among the three formulations, transdermal patches with 6cps HPMC and 6%w/v DMSO as permeation enhancer showed maximum release. Through the present experimentation, it has been found that the drugs of ayurvedic origin can be utilized in a better form with enhanced efficacy for incorporation in REFERENCES 1. Sahila L, Pandey S, Udupa N. Design and evaluation of matrix type and membrane controlled transdermal delivery systems of nicotinic using HPMC. Indian J. pharma science, 2006, 68, Sharma RA, Gescher AJ. Studied regarding Curcumin. European journal of cancer, 2005, 41, Jamakandi VG, Mulla JS. Evaluated matrix type transdermal patches of antihypertensive drug. Asian j pharm, 2009, 3, modern dosage form. This work is one of the first few attempts to utilize ayurvedic drugs through TDDS. ACKNOWLEDGEMENT Nil. CONFLICT OF INTEREST No Conflict of Interest. 4. Kuntal MKM, Arunava G, Bishnu PS and Mukherjee PK et al., developed a novel formulation of Curcumin in combination with the phospholipids. 5. Nita Chainani Wu et al., Studied the safety and Anti-Inflammatory Activity of Curcumin: A Component of Turmeric (curcuma longa). The Journal of Alternative and Complimentary Medicine, 2003, 9(1), VOLUME 7 NUMBER 1 FEB