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

This work aims at investigating different types and levels of hydrophilic matrix agents, including Hydroxy Propyl Methyl Cellulose K15M (HPMC K15M), Hydroxy Propyl Methyl Cellulose K4M (HPMC K4M) and Carbopol 974P, in an attempt to formulate controlled release matrix tablets containing 200 mg of levodopa (LD) and 50 mg of carbidopa (CD). The tablets were prepared by direct compression. Majority of the matrix tablets that contained less than 7.5% of the polymer disintegrated prematurely. Polymers, HPMC K15M and Carbopol 974P produced the desired drug release at 10% concentration whereas HPMC K4M at 20% concentration of the tablet weight. The prepared matrix tablets were evaluated for weight variation, hardness, friability, drug content and in vitro drug release studies. From the in vitro release studies of the prepared formulations, one formula was optimized from each polymer. HPMC K15M and Carbopol 974P based tablet formulations showed high release retarding efficiency. Matrix tablets produced with Carbopol 974P showed sticking and weight variation problems. All the formulations showed linear release profiles (r²=0.96) and sustained the release of levodopa and carbidopa over 8– 12 h. The release profiles of levodopa and carbidopa from the selected formulations are close to zero order and follow diffusion dependent release. The prepared matrix tablets produced from the optimized formulations were compared with standard commercial tablets (SYNDOPA). The similarity factor (f2 value) was calculated for all these formulations and found to be above 50. Irrespective of the polymer type and its concentration, the prepared hydrophilic matrix tablets showed non-Fickian (anomalous) release, coupled diffusion and polymer matrix relaxation as the values of release exponent (n) are in between 0.5 and 0.89. Finally it was clear that it is possible to design a formulation with any of the above three polymers giving the desired drug release profile suggesting that HPMC K15M and HPMC K4M are good candidates for preparing controlled release matrix tablets of levodopa and carbidopa.