Bharath Srinivasan

Solubility and Dissolution Enhancement of Candesartan Cilexetil by Liquisolid Compacts

Solubility and Dissolution Enhancement of Candesartan Cilexetil by Liquisolid Compacts Candesartan cilexetil belong to the class angiotensin-II receptor antagonist used in the treatment of hypertension. It is practically insoluble in water, belongs to a BCS class-II and its half life is 5.1 h with bioavailability of 15 - 40%. The aim of this study was to investigate the use of liquisolid technique in improving the dissolution profile of candesartan cilexetil. The liquisolid tablets were formulated using a non-volatile liquid vehicle PEG 400 at three drug concentrations of 40%, 50% and 60% w/w and at an excipient ratio of 10, 20 and 30 using methyl cellulose 4000 cps and dibasic calcium phosphate as carrier and coating material. The Angle of slide, Liquid load factor and Flowable liquid retention potential concepts were applied to calculate the amounts of carrier and coating material required to prepare candesartan cilexetil liquisolid tablets.

Improvement of bone microarchitecture in methylprednisolone induced rat model of osteoporosis by using thiolated chitosan-based risedronate mucoadhesive film

Abstract Objective: In this study, we investigated the potential of thiolated chitosan-based mucoadhesive film, loaded with risedronate sodium in the treatment of osteoporosis. Significance: Risedronate sodium is a bisphosphonate derivative having very low bioavailability when administered through the oral route. Moreover, the adverse effects associated with the drug when administered through GIT necessitate an alternative and feasible route which can improve its bioavailability and therapeutic efficacy. Methods: Thiolation of chitosan was interpreted by different analytical techniques. The mucoadhesive films were prepared by the solvent evaporation method and evaluated for drug content analysis, swelling degree, mucoadhesive parameters, and permeation characterization. For the screening of preclinical efficacy and pharmacodynamic parameters, a methylprednisolone induced osteoporotic rat model was used. The trabecular microarchitecture and biochemical markers were evaluated for determination of bone resorption. Results: The different analytical characterization of synthesized thiolated chitosan revealed that chitosan was successfully incorporated with thiol groups. The formulation containing 2:1 ratio of thiolated chitosan and HPMC-4KM was found to have the maximum swelling degree, mucoadhesive strength with a good force of adhesion and better in vitro permeability compared to the marketed formulation. With respect to trabecular microarchitecture, the drug-loaded film formulation showed superior and promising results. Furthermore, the film formulation also improved the serum level of biomarkers better than the marketed formulation. Conclusions: The results significantly suggest that risedronate loaded novel mucoadhesive film formulation could be a logical approach in the therapeutic intervention of osteoporosis.

Statistical optimization and in vitro evaluation of metformin hydrochloride asymmetric membrane capsules prepared by a novel semiautomatic manufacturing approach.

Asymmetric membrane capsules (AMCs) are one of the novel osmotic delivery devices which deliver a wide range of drugs in controlled manner. In the present work, we developed and validated a semiautomatic process by fabricating a hydraulic assisted bench top model for manufacturing AMCs. The capsule walls of AMCs were prepared by dip coating phase inversion process using cellulose acetate butyrate (CAB) as coating polymer and propylene glycol (PG) as plasticizer and pore former. The comparative examination of physical parameters confirmed the consistency, efficiency, and reproducibility of the semiautomatic process over the manual procedure. The SEM studies revealed a thin dense region supported on a thicker porous membrane of the capsule shells. Formulations of AMCs were prepared based on a 23 full factorial design using metformin hydrochloride as the model drug. The effect of formulation variables such as concentration of PG and levels of fructose and potassium chloride were studied on the in vitro drug release using Design-Expert 8.0.2 (USA) software. From the in vitro release studies, it was observed that the concentration of pore former and level of osmogents had a direct effect on the drug release. From the validation studies of the optimized formulation (OPT) with the predicted response, it was observed that the drug release was independent of pH and agitation intensity but dependent on osmotic pressure of the dissolution medium. The OPT followed controlled zero-order release kinetics over a period of 13 h.