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Journal of Drug Delivery & Therapeutics; 2012, 2(5), 20-23

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RESEARCH ARTICLE FORMULATION AND EVALUATION OF FEXOFENADINE HYDROCHLORIDE TRANSDERMAL PATCH

Department of Pharmaceutics, Rayat Institute of Pharmacy, Railmajra, Punjab-144533, India Department of Pharmacology, Rayat Institute of Pharmacy, Railmajra, Punjab-144533, India *Corresponding Authors Email: heena.daksh87@gmail.com, Mobile: +919780136963

Received 22 July 2012; Review Completed 03 Aug 2012; Accepted 14 Aug 2012, Available online 15 Sep 2012 ABSTRACT To treat allergic disorders on long term therapy needs plasma concentration of drug in better manner. This was achieved by formulating the drug in controlled release pattern. Fexofenadine hydrochloride is almost completely absorbed from the gastrointestinal tract following oral administration,but bioavailability is reported to be only about 45% due to hepatic first-pass metabolism. The present study aims to prepare Transdermal patch of Fexofenadine hydrochloride. Preparation of transdermal patches of Fexofenadine hydrochloride using polymers: Hydroxypropyl methyl cellulose, Ethyl cellulose plasticized with Glycerol. The patches were evaluated for various parameters like Thickness, Water-Vapor Permeability, Tensile Strength, Drug Content,Diffusion and Dissolution studies. Prepared patches exhibited Zero Order Kinetics and the permeation profile was matrix diffusion type.In-vitrorelease study of Fexofenadine hydrochloride transdermal patch shown release of drug 79 % at 24 h and also follows zero order kinetics release pattern. Keywords: Fexofenadine Hydrochloride, Ethyl cellulose, Hydroxypropyl methyl cellulose, In-vitro.

INTRODUCTION Transdermal drug delivery system is a therapeutic system carboxylic acid metabolite of terfenadine, and is a nondesigned to transfer drugs through intact skin for systemic sedating selective histamine H1 receptor antagonist. treatment. It offers controlled drug release pattern by a Unlike its precursor, fexofenadine lacks the cardiotoxic simple application to the skin's surface, eliminating the potential, since it does not block the potassium channel vagaries influencing the gastrointestinal absorption involved in repolarization of cardiac cells. Fexofenadine is associated with oral administration and providing for more effective in the management of allergic rhinitis and chronic efficient drug utilization.It offers various advantages such idiopathic urticaria for which it is a suitable option for as:avoidance the risk and inconvenience of intravenous first-line therapy. It is taken by mouth twice a daily with therapy (noninvasive), avoidance of first pass hepatic food. The pharmacokinetics of Fexofenadine metabolism (avoiding the deactivation by digestive and hydrochloride has been studied. It is completely absorbed liver enzymes) thus increasing bioavailability and efficacy from the gastro-intestinal tract following oral of drugs, no gastrointestinal degradation (pH, enzymatic administration, but bioavailability is reported to be only activity, drug interaction with food, drink and other orally about 45% due to hepatic first pass metabolism. Most of administered drugs) andsubstitute for oral administration the drug is eliminated in liver as metabolites and only 1% of medication when that route is unsuitable as with of the intact drug is excreted from the kidney. Therefore, vomiting and diarrohea1-3. A list of current FDA-approved Fexofenadine hydrochloride might be designed as a transdermal drug delivery systems is given in Table 14-7. suitable delivery system with long term effect and bypass Extended therapy avoiding frequent dose the liver, such as transdermal delivery system, the delivery administration.Fexofenadine,, - Dimethyl 4 - [1system may have constant drug delivery rate to the hydroxy 4 - [4 - (hydroxydiphenyl-methyl) 1 circulation system and convenient use for children8-11. piperidinyl]butyl]- benzene acetic acid is the active Table 1: Currently Approved TDDS Year 1979 1984 1986 1990 1991 1993 1995 1998 1999 2001 2003 2003 Generic (Brand) Names Scopolamine (Transderm Scop) Clonidine (Catapres TTS) Estradiol (Estraderm) Fentanyl (Duragesic) Nicotine (Nicoderm, Habitrol, Prostep) Testosterone (Androderm) Lidocaine/epinephrine (Iontocaine) Estradiol/norethindrone (Combipatch) Lidocaine (Lidoderm) Ethinyl estradiol/norelgestromin (OrthoEvra) Estradiol/levonorgestrel (Climara Pro) Oxybutynin (Oxytrol)
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Indication Motion Sickness Hypertension Menopausal Symptoms Chronic Pain Smoking Cessation Testosterone Deficiency Local Dermal analgesia Menopausal Symptoms Post-herpetic neuralgia pain Contraception Menopause Overactive bladder
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Heena et al 2004 2005 2006 2006 2007 2008 2009 2010

Journal of Drug Delivery & Therapeutics; 2012, 2(5), 20-23 Table 1 Continue.. Lidocaine/ultrasound (SonoPrep) Local Dermal anaesthesia Lidocaine/tetracaine (Synera) Local Dermal Analgesia Fentanyl/iontophoresis (Ionsys) Acute Postoperative pain Methylphenidate (Daytrana) ADHD Rivastigmine (Exelon) Parkinsons Disease Granisetron (Sancuso) Chemo- induced emesis Oxybutynin (Gelnique) Overactive bladder Buprenorphine (Butrans) Chronic pain individually in 5 ml of ethanol. The drug was then dispersed in the polymeric solution and then plasticizer of glycerol was added. The solution was stirred to attain semisolid like consistency and casted on a glass substrate containing o ring, the rate of evaporation of solvent from polymeric solution was controlled by placed an inverted funnel at room temperature for a day. The formed films were separated. Formulation of Fexofenadine hydrochloride patches was given in Table: 2.

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MATERIALS AND METHODS Fexofenadine hydrochloride was obtained as gift sample from Ranbaxy Pvt Limited, Toansa. HPMC K-100M, HPMC K-4M, ETHYL CELLULOSE was purchased fromColorcon Asia Pvt Ltd, Goa, India. All other chemicals used were of analytical grade. Preparation of matrix patches

Polymers of ethyl cellulose and hydroxyl propyl methyl cellulose were accurately weighed and dissolved Table 2: Composition of Transdermal Patches Sr.No 1 2 3 4 5 6 Formulation HPMCK100M HPMCK100M HPMCK4M HPMCK4M ETHYL CELLULOSE ETHYL CELLULOSE Code A B C D E F Composition (drug: polymer) 1:1.4 1:2 1:1.4 1:2 1:1.4 1:2

Plasticizer (Glycerol) 0.1-0.5 ml 0.1-0.5 ml 0.1-0.5 ml 0.1-0.5 ml 0.1-0.5 ml 0.1-0.5 ml

Casting solvent Ethanol: Dichloromethane Ethanol: Dichloromethane Ethanol: Dichloromethane Ethanol: Dichloromethane Ethanol: Dichloromethane Ethanol: Dichloromethane

Preparation of rate controllingmembrane The transdermal patches of compositionlisted in Table 1 were prepared by solvent casting method. The polymer (HPMC K100M), (HPMC K4M) and (EC) were dissolved in Ethanol at room temperature. Glycerol was used as a plasticizer, with continuous mixing at lower rpm initially and later at a higher speed. The drug was incorporated with continuing agitation and the volume was made up. The films were cast onto a suitably designed and fabricated glass mould and then dried in oven at 40oC for six hours in an oven. The films were removed by using sharp blade by inserting along the edges of the film12. The dried films were wrapped in butter paper and stored in a closed container away from light and in cool place.

Patch thickness was measured by a dial caliper. The average of the five observations was calculated12. Result was shown in Table 2. Weight Uniformity: The dried patches were weighed on digital balance. The average of five observations ofeach formulation was calculated13. Result was shown in Table 2. Folding endurance:

The folding endurance is expressed as the number of folds (no. of times the film is folded at the same place) either to break the specimen or to develop visible cracks. This test is important to check the ability of sample to withstand folding. This also gives an indication of brittleness; less Physical Appearance: folding endurance indicates more brittleness. Folding endurance of the film was determined by repeatedly All the transdermal patches were visually inspected for folding a small strip of film (2cm x 2cm) at the same place color, clarity, flexibility and smoothness. till it broke. The number of times, the film could be folded at the same place, without breaking gave the valve of Measurement of Thickness: folding endurance14. Result was shown in Table 3. Table 3: Thickness, weight and folding endurance of the patches Patch A B C D E F
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Mean Thickness (mm) n=5 0.413 0.015 0.366 0.011 0.383 0.015 0.393 0.015 0.380 0.030 0.416 0.015

Mean Weight (gm.) (10-3) n=5 0.200.020 0.203 0.011 0.200 0.017 0.196 0.025 0.153 0.115 0.2060.011
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Mean Folding Endurance n=5 >100 >100 >150 >100 >100 >100
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Heena et al Journal of Drug Delivery & Therapeutics; 2012, 2(5), 20-23 Tensile strength and % Elongation In-vitro drug release The films were taken in rectangular containers using proportionate quantity of the solution calculated on the basis of area. The films were cut into strips of 1cm width and 15cm length. The films were fixed onto the Tensile strength apparatus in such a way that the length of film between the jaws was initially 10 cm. The trials where the breakage occurred at the jaw were invalid and the result was repeated on another strip. The Tensile strength was calculated by the formula, Tensile strength = Break force [1 + change in length] / (width) (breadth) [initial length of the film].The percent elongation was determined by noting the length just before the break point and substituting the formula % Elongation = [Final length - Initial length] /Initial length * 10015-17. The prepared Fexofenadine hydrochloride patch was evaluated for release pattern using commercially available semi permeable membrane. The membrane and patch were fitted between donor & receptor compartment of selffabricated modified Franz diffusion cell. The donor compartment was empty & receptor compartment was containing 50 ml of phosphate buffer pH 7.4. The samples were collected at different time intervals for analyzing the drug content in the receptor compartment for release pattern of drug and replaced with equal volume of freshly prepared phosphate buffer pH 7.4. The drug content was analyzed at 259 nm using U.V double beam spectrophotometer (Table: 4). From the study best formulation was selected for further studies18-20.

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Table 4: In-vitro Release of Fexofenadine hydrochloride Transdermal patches Formulation code A B C D E F RESULTS AND DISCUSSION The prepared films were smooth, flexible and uniform. Total twenty four formulations were formulated using HPMCK100M, HPMCK4M and ETHYL CELLULOSE in different ratios. The composition of various formulations is shown in Table 1. Weight variation test was performed by weighing three patches and average value was taken as the weight of the film. All the formulations exhibited uniform weight with low standard deviation values indicating the uniformity of the films prepared by solvent casting method. The weight of the films varied between 0.200.020 to 0.2060.011 mg. Thickness of transdermal patches was measured by screw gauge. The thickness of the patches varies between 0.4130.015 to 0.4160.015 mm. Low standard deviation values in the film thickness measurements ensure uniformity of the patches prepared by solvent casting technique. The area of the patch was found to be 2.5 cm2. The folding endurance of transdermal patches was measured manually. The folding endurance of the patches is shown in Table 2. Folding endurance test results indicated that the patches would not break and would maintain their integrity with general skin folding when applied. The drug content uniformity was determined for all formulations by UV spectrophotometer method. The results of drug content vary between 18.040.047 to Cumulative percentage of release 78.2% 69.0% 61.2% 59.4% 70.2% 65.3% Time of release 24hr 24hr 24hr 24hr 24hr 24hr

20.880.07 mg as shown in Table 4.7. The results indicated that the process employed to prepare patches in this study was capable of producing patches with uniform drug content and minimal patch variability. The results of in vitro drug permeation from different formulations are depicted in Table 3. The corresponding value of cumulative percentage drug permeated from the formulations A, B, C, D, E and F after 24 hrs were 78.2%, 69%, 61.2%, 59.4%, 70.2% and 65.3% respectively. From the in vitro skin permeation study it was confirmed that release of formulations A and E after 24 hrs was found to be higher than other formulations (B, C, D and F). The kinetic studydata also proves that which follows zero order kinetics for controlled release ofdrug to maintain drug concentration in better manner CONCLUSION The drug selected of fexofenadinehydrochloride for transdermal therapeutic system of anti-histaminic study shown appropriate release in in-vitro studies. This confirms that the formulation A and F may control the allergic disorder in better manner by achieving drug concentration in steady manner for over a day. ACKNOWLEDGMENT I am thankful to Ranbaxy Pvt. Ltd, Toansa for providing gift sample of Fexofenadine hydrochloride. I also wish to thank to staffs of the laboratory of RayatInstitute of Pharmacy, Railmajra.

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Heena et al
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Journal of Drug Delivery & Therapeutics; 2012, 2(5), 20-23

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