Formulation of Controlled Release Levodopa and Carbidopa Matrix Tablets: Influence of Some Hydrophilic Polymers on the Release Rate and InVitro Evaluation

Order of Publishing in Issue: 
Volume :3
Issue :2
April, 2009
Page No: 
Jagan Mohan. S1,2, Kishan V1, Madhusudan Rao Y1 and Chalapathi Rao N.V2
1University College of Pharmaceutical Sciences, Kakatiya University, Warangal, Andhra Pradesh
2 Danmed Pharma (Group of Medopharma), Phase III, Charlapally, Hyderabad, Andhra Pradesh

AbstractThis work aims at investigating differenttypes and levels of hydrophilic matrix agents,including Hydroxy Propyl Methyl CelluloseK15M (HPMC K15M), Hydroxy Propyl MethylCellulose K4M (HPMC K4M) andCarbopol 974P, in an attempt to formulate controlledrelease matrix tablets containing 200 mgof levodopa (LD) and 50 mg of carbidopa (CD).The tablets were prepared by direct compression.Majority of the matrix tablets that containedless than 7.5 % of the polymer disintegrated prematurely.Polymers, HPMC K15M andCarbopol 974P produced the desired drug releaseat 10 % concentration whereas HPMCK4M at 20 % concentration of the tablet weight.The prepared matrix tablets were evaluated forweight variation, hardness, friability, drug contentand in vitro drug release studies. From thein vitro release studies of the prepared formulations,one formula was optimized from eachpolymer. HPMC K15M and Carbopol 974Pbased tablet formulations showed high releaseretarding efficiency. Matrix tablets produced withCarbopol 974P showed sticking and weightvariation problems. All the formulations showedlinear release profiles (r2=0.96) and sustainedthe release of levodopa and carbidopa over 8–12 h. The release profiles of levodopa andcarbidopa from the selected formulations areclose to zero order and follow diffusion dependentrelease. The prepared matrix tablets producedfrom the optimized formulations werecompared with standard commercial tablets(SYNDOPA). The similarity factor (f2 value)was calculated for all these formulations andfound to be above 50. Irrespective of the polymertype and its concentration, the preparedhydrophilic matrix tablets showed non-Fickian(anomalous) release, coupled diffusion and polymermatrix relaxation as the values of releaseexponent (n) are in between 0.5 and 0.89. Finallyit was clear that it is possible to design aformulation with any of the above three polymersgiving the desired drug release profile suggestingthat HPMC K15M and HPMC K4Mare good candidates for preparing controlledrelease matrix tablets of levodopa andcarbidopa.

levodopa, carbidopa, HPMC K15M, HPMC K4M, Carbopol 974P, controlled release tablets
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