DESIGN AND DEVELOPMENT OF DANTROLENE SPHERICAL AGGLOMERATES FOR IMPROVEMENT IN BIOAVAILABILITY

The purpose of this research was to obtain directly compressible agglomerates of Dantrolene using spherical agglomerates. Spherical agglomeration technique enables simultaneous crystallization and agglomeration. Sodium hydroxide acted as a good solvent, aqueous solution of PEG 6000 in hydrochloric acid served as bad solvent and isopropyl acetate was used as bridging liquid. The optimization of formula was carried out by using 2³ factorial design, where the factors were speed of rotation, polymer: drug ratio and amount of bridging liquid. The responses evaluated were % drug release, MYP and Carr’s Index. The optimized agglomerates and Dantrolene was evaluated by powder X-ray diffractometry (PXRD) and scanning electron microscopy (SEM). PXRD showed reduction in crystalline nature of Dantrolene and SEM demonstrated spherical and smooth surface. The agglomeration improved the micromeritic properties of Dantrolene (Carr’s index16 and hausner ratio between 1.2 and mean yield pressure 3.58 tons). In-vitro dissolution increased by 10 fold. The AUC (35.19%), C_max (23%) and t_max (reduced by 1 h) also recorded improvement. From the results, the conclusion is that spherical agglomerates is a suitable alternative method to the granulation process and can be used for design of immediate release formulation.