Formulation Development and Optimization of Anti-Hypertensive Orally Disintegrating Tablets

Abstract

Antihypertensive potent drug is used in emergency condition like cardiac stroke and angina pectoris. In such emergencies, quick action of drug may be achieved by orally disintegrating formulation (ODF). The aim of the present investigation was to formulate and optimize the ODF of anti-hypertensive drug by industrially adoptable approaches. Several approaches and platform technologies have been explored for formulation of ODF like Direct compression, Phase transition technology, Melt granulation, Freeze drying and cotton candy process. Among all, direct compression and phase transition are the most preferred methods from the pharma industries point of view. Direct compression method involves the use of super-disintegrant(s), whereas phase transition approach is possible by use of sugar alcohols of different melting points. For direct compression approach; crospovidone, croscarmellose sodiumand sodium starch glycolate were explored as super disintegrants. Each excipient were used alone and in combinations at different concentrations to obtain the desired formulation characteristics like disintegration time below 30 sec along with acceptable tablet parameters like hardness, friability, etc. The 32 full factorial design was applied to study the relationship of effect of each super-disintegrants and diluents in different proportions, and the optimized formulation was developed from validated model using overlay contour plots. For Phase transition method, various sugar alcohols of different melting points were explored (i.e. Mannitol, Erythritol, Sorbitol and Xylitol). Effect of proportions of excipient and the effects of temperature and exposure time for heating in vaccum oven were studied by series of formulations, which were evaluated for hardness, friability and disintegration time. The optimized formulations developed by both the approaches were compared based on several parameters like formulation characteristics, stability study data, industrial adoptability and the cost of formulation. In conclusion, two approaches for formulation development of ODF were explored and optimized by appropriate Design of Experiment.