Development of Agglomerated Directly Compressible Diluent Consisting of Brittle and Ductile Materials

Abstract

The objective of this investigation was to develop a novel multifunctional coprocessed adjuvant consisting of three known diluents that show different consolidation mechanisms. The method of wet granulation was adopted for the preparation of coprocessed product. Microcrystalline cellulose (MCC) and colloidal silicon dioxide (X1), lactose monohydrate (X2), and dibasic calcium phosphate dihydrate (X3, DCP) were used as independent variables in a simplex lattice design. Croscarmellose sodium was used at 4% level intragranularly in all the batches. The granules (44/120 #) were characterized for angle of repose, bulk density, tapped density, and Carr's index. The tablets of coprocessed adjuvants were characterized for crushing strength, friability, and disintegration time. Multiple linear regression was adopted for evolving refined mathematical models. A checkpoint batch was prepared and evaluated for particle size distribution, moisture uptake, and dilution potential by using nimesulide as a model drug. Microcrystalline cellulose shows poor flowability due to irregular shape and interlocking. Moreover, it loses a part of its compactibility on wet granulation. To attend these problems, a physical blend of 97% microcrystalline cellulose and 3% colloidal silicon dioxide M5 was prepared and used. The blend of MCC and colloidal silicon dioxide showed better flow than that of the original MCC. Hence, it may be easier to mix with lactose and dibasic calcium phosphate. The loss in compactibility of microcrystalline cellulose on wet granulation was also reduced due to presence of colloidal silicon dioxide. As expected, all the batches exhibited acceptable angle of repose (<35°) and quick disintegration (<1 min). Full and refined models for Carr's index and crushing strength were evaluated. Based on the results of grid analysis, a checkpoint (50% MCC, 40% lactose, and 10% DCP) that satisfies both the conditions of Carr's index and crushing strength was selected. The adjuvants absorb very little moisture in the moisture uptake study. The results of dilution potential study reveal that up to 30% nimesulide, a poorly compressible drug, can be incorporated in the coprocessed product. In vitro drug dissolution from capsules containing pure drug powder and compressed tablets was comparable (f2=79). The results reveal that the desired product characters can be obtained by varying the quantity of MCC (a ductile material that undergoes plastic deformation), lactose (brittle material with low-fragmentation propensity), and DCP (brittle material with high-fragmentation propensity).