International Journal of Innovative Pharmaceutical Sciences and Research

Transcription

1 International Journal of Innovative Pharmaceutical Sciences and Research FORMULATION AND EVALUATION OF DARIFENACIN IMMEDIATE RELEASE TABLETS BY USING DIFFERENT TECHNIQUES 1 D.Anand kumar*, 2 Dr.N.Srinvas Malla reddy institute of pharmaceutical sciences, Maisammaguda, Dhulapally, (Post Via Hakimpet, secunderabad , Telangana, INDIA Abstract The main objective of this research programme is to design and formulate different batches of Orodispersible tablets of Darifenacin by using liquisolid compaction technique, evaluate them and select the best formulation. The preformulation studies like melting point, flow properties, UV analysis of Darifenacin were compiled with IP standards. The FTIR spectra revealed that, there was no interaction between polymer and drug. Polymers used were compatible with Darifenacin. In vitro drug release of Darifenacin compacts showed increase in dissolution rate of Darifenacin. So PEG 400, PG, Tween 80 could be economic substitute as dissolution enhancing agent. Stability studies showed that there were no significant changes in physical and chemical properties of formulation F8 after 2 months Tween 80 in 1:1 ratio (F8) was showing best release. F8 was compared with marketed and prepared conventional formulation and result shows better dissolution profile. Keywords: Darifenacin, Oro-dispersible tablet, liquisolid compaction technique. Corresponding Author: D.Anand Kumar Deparment of Pharmaceutics Malla reddy institute of pharmaceutical sciences Secunderabad , Telangana, INDIA nandusri2143@gmail.com Mobile: Available online: October Issue 2386

2 INTRODUCTION Oral administration is the most popular route for systemic effects due to its ease of ingestion, pain, avoidance, versatility and most importantly, patient compliance. Also solid oral delivery systems do not require sterile conditions and are therefore, less expensive to manufacture. Patient compliance, highprecision dosing, and manufacturing efficiency make tablets the solid dosage form of choice. Excipients and equipments choices will be significantly affected should solid dosage form technologies change in response to the unprecedented shifts in the drug discovery such as genomics. Injections generally are not favoured for use by patients unless facilitated by sophisticated auto injectors. Inhalation is one good alternative system to deliver these drugs, but the increased research into biopharmaceuticals so far has generate predominantly chemical entities with low molecular weights. The development of enhanced oral protein delivery technology by immediate release tablets which may release the drugs at an enhanced rate are very Promising for the delivery of poorly soluble drugs high molecular weight protein and peptide. The oral route remains the perfect route for the administration of therapeutic agents because the low cost of therapy, manufacturing and ease of administration lead to high levels of patient compliance [1-8]. Many patients require quick onset of action in particular therapeutic condition and consequently immediate release of medicament is required. It is estimated that50% of the population is affected by this problem, which results in a high incidence of ineffective therapy [9-10]. The term immediate release pharmaceutical formulation includes any formulation in which the rate of release of drug from the formulation and/or the absorption of drug, is neither appreciably, nor intentionally, retarded by galenic manipulations. In the present case, immediate release may be provided for by way of an appropriate pharmaceutically acceptable diluent or carrier, which diluent or carrier does not prolong, to an appreciable extent, the rate of drug release and/or absorption. Thus, the term excludes formulations which are adapted to provide for modified, controlled, sustained, prolonged, extended or delayed release of drug [11-13]. Fig.1: Immediate release druf delivery system Available online: October Issue 2387

3 MATERIALS Darifenac (API), Micro crystalline cellulose, Lactose monohydrate, Lactose anhydrous, Crospovidone, Croscarmellose sodium, Pregelatinized starch, Magnesium stearate, Opadry II blue (Y ) are obtained from Star TechLab Pvt. Ltd. Hyderbad, India. METHOD Methods used in the formulation of Darifenac immediate release tablets: 1. Direct compression method & 2. Wet granulation method Procedure for F-1(direct compression): All the ingredients were weighed except Magnesium stearate and the mix was passed through #40 mesh, and then mixed for 5 min in s blender. The above mixture was then lubricated with Magnesium stearate which was initially passed through sieve no 12 in blender for 2 mins. Then the lubricated blend was compressed using 16.5 x 8mm size punches. Procedure for F-2 to F-8(wet granulation): API, MCC ph 101, Lactose monohydrate, Crospovidone were weighed and passed through #40 meshes. The above mixture was mixed in a poly bag for 10 minutes. PG starch was added to sufficient quantity of purified water by stirring. The binder solution was added to the dry mixture within 2 minutes with impeller speed fast (600rpm). The wet mass was mixed for 1min with impeller and chopper fast (600rpm). The obtained wet mass was passed through #12 mesh. The sieved mixture was dried using FBD and the temperature was maintained at 60 C. until the moisture content in the blend comes to 1.0 to 2.0 % The dried blend was passed through #18 mesh and then pre lubricated using MCC ph 102, crospovidone for 5 minutes and then lubricated with Magnesium stearate in bender for 2mins. Physical characteristics of the lubricated blend were carried out. Available online: October Issue 2388

4 Then finally the lubricated blend was compressed using 16.5x8mm size, oval shape punches. The obtained tablets were coated using opadry II blue coating solution Methods of Preparation Darifenac immediate release tablets by Solid Dispersion technique Solvent method is physical mixture of the drug and carrier is dissolved in a common solvent, which is evaporated until a clear, solvent free film is left. The film is further dried to constant weight. Table 1: Formulation table of immediate release tablets Materials F1(mg) F2 F3 F4 F5 F6 F7 F8 Darifenacin Microcrystalline cellulose Lactose anhydrous Lactose monohydrate Crospovidone(intragranular) Croscarmellose sodium(intragranular) Pregelatinized starch Water - Q.S Q.S Q.S Q.S Q.S Q.S Q.S Microcrystalline cellulose(ph ) Crospovidone(extragranular) Croscarmellose sodium(extragranular) Magnesium stearate Core tablet weight Opadry blue II coat (2.3%) RESULT AND DISCUSSION Preparation of Standard Calibration Curve Standard curve of Darifenacin can be obtained by using 0.1 N HCL acid as a solvent to qunatiy the sample. All the solutions were prepared in fresh before use. Preparation of 0.1 N HCL acids: 8.5 ml of hydrochloric acid was taken in 1000ml of volumetric flask and volume made upto 1000ml with distilled water. Available online: October Issue 2389

5 Preparation of standard solution of Darifenacin in 0.1N HCL with water Preparation of stock I solution: 100 mg of Darifenacin was weighed accurately, transferred into 100ml volumetric flask. The volume was made to 100ml with 0.1 N HCL acid to give 1000mcg/ml solution. Preparation of stock II solution: 10 ml of stock I solution was pipetted out into a 100 ml volumetric flask and the volume was made up to 100 ml with 0.1 N HCL acid to get 100 mcg/ml solution. Preparation of stock III solution: 10 ml of stock II solution was pipetted out into a 100 ml volumetric flask and the volume was made up to 100 ml with 0.1 N HCL acid to get 10 mcg/ml solution. Stock solution: The resultant solution filtered with Whattman filter paper subsequently diluted with 0.1 N HCL to get concentration of 2,4,6,8,10,12 mcg/ml. The absorbance of above said concentration solution was measured at 260 nm using 0.1 N HCL as blank. The concentration of Darifenacin solution and corresponding absorbance. Table 2: Standard calibration data of DARIFENACIN in 0.1 HCL Concentration (mcg/ml) Absorbance (260 nm) Drug & Excipient compatibility Fig. 2: Standard Graph of DARIFENACIN in 0.1 HCL Fig. 3: FTIR of API(DARIFENACIN) Available online: October Issue 2390

6 Fig 4: IR of API +Excipients Pre-Formulation Parameters [14, 15, 16] Precompression parameters such as bulk density, tapped density, angle of repose, Carr s index and Hausner ratio which are evaluated for prepared tablets are given in following table: Evaluation of tablet: [17, 18] Weight variation: Twenty tablets were randomly selected from each batch individually weigh, the average weight and standard deviation of 20 tablet calculated. Thickness: The thickness of the tablet was measured by using digital venire caliper, twenty tablets from each batch were randomly selected and thickness was measured (The British Pharmacopoeia, 2005). Hardness: Hardness was measured using Pfizer hardness tester, for each batch three tablets were tested (The United State of Pharmacopoeia, 1995). (Table no-6) Friability: Twenty tablets were weight and placed in the Roche friabilator and apparatus was rotated at 25 rpm for 4 min. After revolution the tablets were dusted and weighed. (Chaudhari PD, 2005). In-vitro disintegration test: The test was carried out on 6 tablets using Tablet disintegration tester. Distilled water at 37 C± 2 C was used as a disintegration media and the time in seconds taken for complete disintegration of the tablet with no palable mass remaining in the apparatus was measured. Available online: October Issue 2391

7 Table 3: Post-compression parameters for F-1to F-8 Formula Average weight(mg) Thickness (mm) Hardness (Kg/cm 2 ) Friability (%) Disintegration Time F min 10sec F min 16sec F min 13sec F min 18sec F min 29sec F min 30sec F min 39sec F min 55sec Table 4: Dissolution profile of formulations (F-1 to F-8) Time (min) F-1 F-2 F-3 F-4 F-5 F-6 F-7 F CONCLUSION Fig.5: INVITRO Dissolution profile of All Fotmulation Based on the results of the above mentioned tests F8 was selected as the best formulation as it showed drug release profile matching with the Innovator product. Stability studies were performed for this batch under accelerated testing conditions. The product was evaluated for assay Available online: October Issue 2392

8 and dissolution and the results obtained were found to be within the specified limits indicating the product is stable. REFERENCES 1. Leon Lachmann, Herbert A, Liberman, Joseph L.Kaing, The theory and practice of Industrial Pharmacy: Ansel`s Pharmaceutical dosage forms & drug delivery systems, eighth edition, Aulton`s Pharmaceutics, The design & manufacture of medicines,biopharmaceutics and pharmacokinetics, A Treatise, second edition, Valabh Prakashan, Debjit Bhowmik, Chiranjib.B, Krishnakanth, Pankaj, R.Margret Chandira,. 5. Fast Dissolving Tablet: An Overview, Journal of Chemical and Pharmaceutical Research, 2009, 1(1): Dali Shukla, Subhashis Chakraborty, Sanjay Singh, Brahmeshwar Mishra, Mouth Dissolving Tablets II:An Overview of Evaluation Techniques, 7. Susijit Sahoo, B. Mishra, P.IK. Biswal, Omprakash Panda, Satosh Kumar Mahapatra, Goutam Kumar Jana, FastDisslving Tablet: As A Potential Drug Delivery System, Drug Invention Today 2010,(2), A Gupta, AK Mishra, V Gupta, P Bansal, R Singh, AK Singh, Review Article, Recent Trends of Fast Dissolving Tablet An Overview of Formulation Technology, International Journal of Pharmaceutical & Biological Archives2010; 1(1): A Review On New Generation Orodispersible Tablets And Its Future Prospective, Tanmoy Ghosh, Amitava. Ghosh And Devi Prasad, International Journal of Pharmacy and Pharmaceutical Sciences, 2011;3(1): Reddy.L.H et al., Fast dissolving drug delivery systems: A review of the literature, IJPS., July 2002: Jon Gabrielsson, Nils-Olof Lindberg and Torbjorn Lundstedt, Multivariate Methods in Pharmaceutical Applications, J.Chemom 2002; 16: Dedhiya et al, Lercanidipine immediate release compositions United States Patent Application Eriksson et al, New oral immediate release dosage form United States Patent Application Available online: October Issue 2393

9 14. Subramanyam CVS. Textbook of Physical Pharmaceutics, Vallabh Prakashan, 2nd ed; Mehta RM. Pharmaceutics-I, Vallabh Prakashan, 2nd ed; The United States Pharmacopoeia-National Formulary ed, Rockville: The United States Pharmacopoeial Convention; Vol-I, Gwen MJ and Joseph RR and Rhodes CT. Modern Pharmaceutics, Marcel Dekker, Inc., New York, 72(3), 1996, Goldstein J L, Femilial hypercholesterolemia, in the metabolic and molecular bases of coronary heart disease, Basic research cardiol, 98 (2001) Available online: October Issue 2394