FORMULATION AND EVALUATION OF MODIFIED RELEASE MATRIX TABLETS OF TOLTERODINE TARTRATE FOR TREATMENT OF OVERACTIVE BLADDER DISEASE

Many problems are associated with conventional multiple-dosing regimen of long-acting therapy, such as systemic accumulation of the drug leading to side effects or toxicities, flip-flop profile of the plasma drug level, and poor patient compliance. The objectives identified as the outputs for addressing the identified development problem and provide a means to assess performance of modified release formulation. In the present research, an attempt has been made to formulate modified release oral matrix tablets of Tolterodine tartrate to overcome the existing problems using Hydroxypropyl methyl cellulose (HPMC K4M), Sodium carboxy methyl cellulose (SCMC), Guar Gum and Xanthan Gum as rate controlling polymer for the treatment of overactive bladder. The tablets were prepared by wet granulation method and studied the effect of the matrix former such as Guar Gum and Xanthan Gum separately. Tablets were evaluated for uniformity of weight, drug content, friability, hardness, thickness, swelling study, in vitro drug release study and finally stability study. All the formulation had shown compliance with pharmacopoeial standard. As the time increases, the swelling index was increased, later on decreases gradually due to dissolution of outer most gel barrier of tablet into the dissolution medium. Comparison between Hydroxypropyl methyl cellulose (HPMC K4M), Sodium carboxy methyl cellulose (SCMC), it has been observed that swelling index of Hydroxypropyl methyl cellulose (HPMC K4M) was significantly more compared to Sodium carboxy methyl cellulose (SCMC). Similarly, comparison between xanthan gum and guar gum, it has been observed that swelling index of guar gum was significantly more compared to xanthan gum. The drug release study shows that an increase amount of polymer resulted in retarded drug release. The maximum drug release was found to be 95% over a period of 12 hours in guar gum based formulations (F9-F12) at a concentration ranging from 15 to 60mg per tablet. Similarly maximum drug release was found to be 92% over a period of 12 hours in Xanthan gum to gum based formulations (F13-F16) at a concentration ranging from 15 to 60mg per tablet. The drug release from optimized formulation (F12) fitted to various kinetic models and the drug release was found to follow zero-order kinetics and diffusion release mechanism. This modified release matrix tablet dosage form will be good for the treatment of over active bladder/urinary incontinence by improving patient compliance and reducing dosing frequency.