Incorporation Of Floating Drug Delivery System In Formulation And Evaluation Of Meloxicam Floating Capsules

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1 Incorporation Of Floating Drug Delivery System In Formulation And Evaluation Of Meloxicam Floating Capsules Prabhat Dessai* and Neha Mesta Dnyanprassarak Mandal s College And Research Centre, Assagao, Bardez- Goa desaiprabhat@yahoo.com Abstract: Oral drug deliveries have recently been of great interest in pharmaceutical field to achieve improved therapeutic efficacy. The idea of floating principles of drug delivery system would have the advantage of low-density systems having sufficient buoyancy to float over the gastric contents. The objective of present investigation was to formulate and evaluate a floating drug delivery system of Meloxicam. Meloxicam floating capsules were prepared using various excipients. In vitro dissolution was carried out in phosphate buffer 7.4 at 37 C ± 0.5 C using USP apparatus II at 100 rpm. Developed formulations were evaluated for their physical characteristics, drug content, In-vitro drug release profile, floating lag time, floating time, buoyancy, Drug-excipient compatibility studies using FTIR. Drug release of various formulations at 15hrs, (%) ranges from 60% - 99%. Keywords: Meloxicam, drug delivery, floating capsules INTRODUCTION Meloxicam (an oxicam derivative), (4-hydroxy-2-methyl-N-{5-methyl-2-thiazolyl}-H-1,2 benzothiazine-3-caboxamide 1,1- dioxide), is a member of enolic acid group of non-steroidal anti-inflammatory drugs. It is generally used in the treatment of rheumatoid arthritis, osteoarthritis and other joint pains. It is a relatively new cyclo-oxygenase inhibitor and this enzyme is responsible for converting arachidonic acid into prostaglandin H2 which is the first step in the synthesis of prostaglandins, the mediators of inflammation. It is well known that there are two COX isoforms, COX-1 & COX-2, and that the extent of NSAID-associated relative inhibition of COX-1 & COX-2 activities varies among the drugs. Commonly administered NSAID s such as flunixin, phenylbutazone and ketoprofen, are relatively non-selective and inhibit both COX-1 andcox-2 to various degrees. Because COX-1-derived prostaglandins play a role in protecting the gastrointestinal mucosa, NSAIDs that inhibit COX-1 have been associated with adverse events such as gastric and intestinal ulcers, gastrointestinal bleeding, and renal injury. This has led to development of newer NSAIDs such as meloxicam with COX-2 selectivity on the order of 5 to 12 times and firocoxib which are more selective for the inhibition of the COX-2 isoenzyme. Meloxicam has most commonly been used for the alleviation of inflammation and relief of pain in both acute and chronic musculo-skeletal disorders or for the relief of pain associated with equine colic. Meloxicam is available for oral administration or IV daily administration and can be administered once daily for periods up to 14 days. MATERIALS AND METHODS SR.NO CHEMICALS USED MANUFACTURER 1 Meloxicam Unichem laboratories 2 HPMC (K4M) SD fine chem lite 3 Sodium CMC Vikashpharma 4 Ethyl cellulose Loba chemicals 5 Stearic acid Research lab fine chemicals 6 Magnesium stearate Burgoyne Burbides& Co. Table No.1 Various chemicals used in the formulation of meloxicam floating capsules 247

2 FORMULATION OF GASTRO-RETENTIVE CAPSULE FORMULATION The physical mixture of the polymers was prepared by gentle and smooth mixing of the hydrocolloids using mortar and pestle. The powdered blend was filled in hard gelatin capsules manually. Each 113 mg of the blend per capsule contains 10 mg of Meloxicam. Sr no. Ingredients in mg F1 F2 F3 F4 1 Meloxicam HPMC Ethyl cellulose Carboxymethylcellulose sodium salt Stearic acid Magnesium stearate Table No. 2 Composition of meloxicam floating capsules EVALUATION OF FORMULATIONS Preparation of calibration curve 100mg of Meloxicam was accurately weighed and dissolved in 40ml of methanol in a 100ml volumetric flask and the volume was made upto the mark with 100ml with Phosphate buffer ph 7.4 to get a concentration of 1000µg/ml. from this solution an aliquot of 10ml was withdrawn and it was diluted to 100ml with Phosphate buffer ph 7.4 to get a concentration of 100 µg/ml. various dilutions were prepared to obtain different concentrations upto 20µg/ml. the absorbance of the solutions were determined using UV/VIS spectrophotometer at 363nm. Duration of buoyancy Duration of buoyancy was observed simultaneouslywhen the dissolution was carried out. The time takenfor the capsule to sink to the bottom was noted, thisgives the buoyancy of the capsule. Drug content estimation Accurately weighed quantity (113 mg) of formulation (equivalent to 10 mg of meloxicam) was taken into a beaker and 100ml of phosphate buffer ph 7.4 was added, and stirred for 2 hrs. The solution was filtered through whatman filter paper No. 40, into a 100ml volumetric flask. The volume was made up with a phosphate buffer ph 7.4. From the above solution 10ml was pipetted into a separate 100ml volumetric flask and volume was made up with phosphate buffer ph 7.4. The absorbance was measured at 363 nm. The drug content was calculated by using the following equation. In vitro release profile USP dissolution test apparatus (type I) was used.the capsules were placed in the dissolution vesselsfitted with baskets. 900 ml of phosphate buffer (ph 7.4) was taken into the vessels asdissolution medium and temperature was maintainedat 37 C. The paddle was rotated at 100 rpm. 5ml ofthe dissolution medium was withdrawn at pre-determined intervals and fresh dissolution mediumwas replaced. The samples withdrawn wereanalyzed by UV method at 363nm against reagentblank (phosphate buffer (ph 7.4). Drug-Excipient compatibility studies using FTIR The FTIR spectra of drug, polymer and optimized formulation. Sample about 5 mg was mixed thoroughly with 100 mg potassium bromide IR powder. The resultant disc was mounted in a suitable holder in SHIMADZU IR spectrophotometer and the IR spectrum was recorded from 4000cm -1 to 600cm -1 in a scan time of 5minutes. 248

3 RESULTS AND DISCUSSION The floating capsules is known for its zero density nature. The purpose of these formulations was to study the effect of various concentrations of hydrocolloids as well as the nature of floating tendency. To study the impact of release retardant ethyl cellulose and stearic acid used, ethyl cellulose concentration was varied to study the effect on the release from formulation. Calibration Curve The linearity and range was studied using various concentrations and plotting against absorbance. The solutions were found to obey the Beer-Lambert s law with R2 values of in the range of 2-20µg/ml. Vol. of stock solution in 50ml Concentration Absorbance Table no. 3 Calibration curve Fig 1: Graph pf Concentration v/s Absorbance for Calibration curve In vitro buoyancy studies The time taken by the formulation to emerge on the medium surface (floating lag time) and the time for which the formulation continuously floated (duration of floating) are shown in table no. All the formulations showed floating lag time 0secs and the duration of floating were seen to be of above 8 hrs. 249

4 Formulations Floating lag time Duration of Buoyancy F1 0 sec 8 hrs F2 0 sec 8 hrs F3 0 sec 8 hrs F4 0 sec 8 hrs Table no. 4 Buoyancy studies Determination of Drug Content This is an important requirement for any type of dosage form. The amount of drug present in the formulation should not deviate beyond certain specified limits from the labeled amount. It was found that drug content was obtained in the range of 97-98%. Formulations % drug content F1 98 F2 98 F3 97 F4 98 Table no. 5 Drug Content In vitro Dissolution studies Release from these formulations was as presented graphically in figure. Formulation F1 is considered the optimum formulation, with a release of upto 15hrs, longer than any other formulation. Time % Drug Dissolved F1 F2 F3 F Table no. 6 In vitro Dissolution studies 250

5 120 Concentartion vs Absorbance 100 Absorba % Drug Dissolved F1 % Drug Dissolved F2 % Drug Dissolved F3 % Drug Dissolved F concentration (µg/ml) Fig 2: Graph pf Concentration v/s Absorbance of In vitro Dissolution studies Drug-Excipient compatibility studies using FTIR 100 %T API Melox Fig 3: IR Spectra of Active Pharmaceutical Ingredient /cm 80 %T drug Mel + excipients Fig 4: IR Spectra of Drug with excipients /cm 251

6 CONCLUSION Floating formulations of meloxicam in the form of hydrodynamically balanced systems was formulated and evaluated. The formulation was capable of sustaining the release of the drug upto 15 hours. Capsule formulation have the advantage of unit dosage form, hence these formulations have promising market potential but still further studies are warranted for clinical and patient compliance. ACKNOWLEDGEMENT The authors are grateful to the Principal and Management of Dnyanprassarak Mandal s College Research Centre for their encouragement and support in carrying out the work. REFERENCES Teelavath Mangilal*, K. S. K. RaoPatnaik, KiranThadkala, University College of Technology, Osmania University, Hyderabad , A.P - Formulation and Evaluation of Gastric Oral Floating Capsules Containing Captopril. International Journal of Pharmaceutical Research & Allied Sciences, Volume 3, issue 3 (2014)17-28 N. M. Moursy*, N. N. Afifi, D. M. Ghorab, Y. EL-Saharty, Department of Pharmaceutics1, Department of Analytical Chemistry2, Faculty of Pharmacy, Cairo University, Cairo, Egypt - Formulation and evaluation of sustained release floating capsules of Nicardipin Hydrochloride.Pharmazie 58: (2003) Abdul Hafeez*, ArunMaurya, Jagpal Singh, Ankit Mittal, LakhanRana,-An overview on floating microsphere: Gastro Retention Floating drug delivery system (FDDS). The Journal of Phytopharmacology 2013; 2(3): 1-12 S. B. Bhise * and N. H. Aloorkar - Formulation and in vitro Evaluation of Floating Capsules of Theophylline. Indian journal of Pharmaceutical science Mar-Apr; 70(2): Md. Ismail Mouzam a,*, M.H.G. Dehghan a, ShaikhAsif b, TruptiSahuji a, PoojaChudiwal a Preparation of a novel floating ring capsule-type dosage form for stomach specific delivery, Saudi Pharmaceutical Journal (2011) 19, Asha Patel, Subhabrata Ray, Ram Sharnagat Thakur, Krupanidhi College of Pharmacy, Bangalore, India- In vitro evaluation and optimization of controlled release floating drug delivery system of metformin hydrochloride, DARU Volume 14, No. 2, 2006 Manish Dubey 1, Prashant Kesharwani 2*, Amit Tiwari 2, Roshni Chandel 2,K. Raja 1 and T. Sivakumar 1, (1)Department of Pharmaceutics, Nandha College of Pharmacy,Tamil Nadu, India. (2) Department of Pharmaceutical Sciences, Dr. Hari Singh Gour Central University,Sagar, IndiaFormulation and Evaluation of Floating Microsphere Containing Anti Diabetic Drug. International journal of pharmaceutical and chemical sciences, issn: Vol. 1 V.Wamorkar*,A. Samar,A.R Reddy, ChAnusha, C.V. Saikrishna, and N.Santoshkumar, Dept of Pharmaceutics, Srikrupa Institute of Pharmaceutical sciences, Velkatta Rd, Siddipet, Medak(AP) , India- Development and evaluation of Novel floating drug delivery systems of Metoclopramide Hydrochloride. International Journal of Pharmaceutical Sciences and Nanotechnology, volume 4, issue 3, October-December