Development of Directly Compressible Co-processed Excipient for Dispersible Tablets Using 3 Full Factorial Design

The purpose of the present research was to prepare and evaluate mannitol and cellulose based, directly compressible excipient using freeze-thawing technique. The mannitol to cellulose ratio (50:50, 60:40, and 70:30) and the rotation speed of propeller stirrer (200, 600, and 1000 rpm) were selected as independent variables in a 3 full factorial design. Water acted as a good medium for mannitol as well as a bridging liquid for agglomeration of mannitol with cellulose. The agglomerates were evaluated for percentage fines and carr’s index. Tablets were prepared on a rotary tablet press, and they were evaluated for friability, tensile strength, water absorption ratio, and disintegration time. Multiple linear regression analysis was carried out to evolve full and reduce models. The use of composite index was demonstrated for the selection of an appropriate batch. The optimized batch was characterized by different scanning calorimetry (DSC), scanning electron microscopy, Fourier Transform Infrared (FTIR) Spectral Study, granular friability, Kawakita’s equation, Kuno’s equation and Heckle equation. The results of dilution potential study reveal that up to 30% nimesulide, a poorly compressible drug and 50% metformin, a hygroscopic drug, can be incorporated in the co-crystallized product. The product was less sensitive to lubricant in lubricant sensitivity test. In conclusion, the properties of agglomerated product, such as flowability, compactibility, and dissolution rate were improved profoundly using the developed technique resulting in successful direct tableting without need to additional process of physical blending of agglomerates.