P.D. Jogani’s research while affiliated with USV Limited and other places

Direct compression is the preferred method for the preparation of tablets. The present review outlines the importance of the functionality of the directly compressible adjuvants in the formulation of tablets. The co-processing is the most widely explored method for the preparation of directly compressible adjuvants because it is cost effective and can be prepared in-house based on the functionality required. Hence, the present review focuses on the properties of the co-processed directly compressible adjuvants available in the market.

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 degrees) 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).

The objective of the present investigation was to prepare and evaluate lactose and microcrystalline cellulose based, directly compressible adjuvant using melt granulation technique. The percentage of polymer blend (PVP K 30 and PEG 4000; 5, 10, or 15%) and the polymer blend ratio (9:1, 1:1, or 1:9) were selected as independent variables in a 3(2) full factorial design. The lactose and microcrystalline cellulose blend (3:1) was mixed with the meltable binder on a water bath at 90 degrees C. The agglomerates were cooled to 35 degrees C and subsequently passed through 30 mesh. A batch containing 12.5% of the polymer blend containing 1:9 ratio of PVP:PEG was used for further studies. In an another 3(2) full factorial design, disintegrant (crospovidone, croscarmellose sodium, or sodium starch glycolate) and mode of addition of disintegrant (intragranular, extragranular, or combination of intragranular and extragranular) were used as independent variables. The agglomerates were evaluated for percentage fines and Carr's index. Tablets were prepared on a single-punch tablet machine, and they were evaluated for tensile strength, friability, and disintegration time. Regression analysis was carried out to evolve full and refined models. Contour plots are presented for graphical expression of the results. The use of composite index is demonstrated for the selection of an appropriate batch. The disintegration time of tablets reduced from 18 min to 6 min when 6% crospovidone was included in the product. The optimized adjuvant was characterized for particle size distribution, granular friability, Kawakita's and Kuno's equation, and dilution potential study. Turmeric, glycyrrhiza, acetaminophen, and metformin HCl were used as model drugs for the preparation of tablets. The present study underlines the fact that melt granulation technique may be adopted for the development of multifunctional directly compressible adjuvant for use in pharmaceuticals. The advantages of melt granulation technique over the classical wet granulation and spray-drying are presented.

Present investigation was aimed to prepare economical lactose based directly compressible adjuvant with improved flowability and compressibility. A 32 full factorial design was employed to study the effect of lactose/starch ratio (X1; 50:50, 65:35 or 80:20) and the % starch paste (X2; 6, 10, or 14 %). Starch paste was prepared by heating the aqueous dispersion of starch at 80° for 15 min. The paste was used to prepare granules. Tablets were prepared on a single stroke tablet machine. The % fines, Carr's index, granular friability, crushing strength and % friability were selected as the dependent variables. Diltiazem HCI and acetaminophen were used as model drugs for evaluating the characteristics of the optimized batch. Medium to high level of both the variables favoured the formation of excellent directly compressible adjuvant. The lactose/starch ratio (X1) exhibited greatest effect on the crushing strength, Carr's index and tablet friability. As the lactose/starch ratio was increased, Carr's index and crushing strength of the tablets increased and friability of the tablets decreased. The friability of the tablets was inversely related with % of starch paste. A check-point batch was prepared to validate evolved refined models. Good agreement was observed between actual and predicated values of the dependent variables, indicating predictive power of the derived equations. Starch paste prepared by the conventional method yielded weak tablets. Kawakita's and Kuno's parameters suggest that the granules of the check-point batch undergo packing at faster rate than the physical blend of lactose and starch. Up to 30% of acetaminophen could be successfully incorporated into tablets. The crushing strength, friability and disintegration time of diltiazem HCI tablets were found 5.5 kg, 0.5% and 4 min, respectively. Nearly complete release of diltiazem HCI was observed in 15 min in water. The preparative conditions of starch paste determine the product quality. The present study demonstrates the use of experimental design for the preparation of an economical directly compressible adjuvant. The results of multiple regression analysis can be used to predict the effect of independent variables on the dependent variables, A product consisting of (lactose/starch ratio-71:29) exhibited excellent functionality and good tableting characteristics. The developed product can be explored as an economical alternative to the other lactose based directly compressible adjuvants available in the market.

The authors prepared and evaluated a directly compressible multifunctional adjuvant containing lactose, polyvinyl-pyrrolidone, and croscarmellose sodium. They showed that the flowability and compressibility of the prepared agglomerates were significantly superior to those of lactose monohydrate.

The authors prepared and evaluated directly compressible diluents containing lactose and microcrystalline cellulose (MCC) to determine their tableting characteristics. The ratio of lactose to MCC and percentage of starch in the binder solution were investigated as independent variables in a 32 full batches assessed bulk density, Carr's index, fines, friability, tensile strength, and Carr's index were the developed models. Actual and predicted values of the important dependent variables were in good agreement. Formulated tablets containing either possessed satisfactory crushing strength, friability, immediate-release characteristics during an in vitro dissolution test.