Enhancing the Poor Flow and Tableting Problems of High Drug-Loading Formulation of Canagliflozin Using Continuous Green Granulation Process and Design-of-Experiment Approach

Maximization of drug-loading can significantly reduce the size of dosage form and consequently decrease the cost of manufacture. In this research, two challenges were addressed: poor flow and tableting problems of high-drug loading (>70%) formulation of canagliflozin (CNG), by adopting the moisture-activated dry granulation (MADG) process. In this method, heating and drying steps were omitted so, called green granulation process. A 32 full-factorial design was performed for optimization of key process variables, namely the granulation fluid level (X1) and the wet massing time (X2). Granulation of CNG was carried out in the presence of polyvinylpyrrolidone, and the prepared granules were compressed into tablets. Regression analysis demonstrated the significant (p ≤ 0.05) effect of X1 and X2 on properties of granules and corresponding tablets, with pronounced impact of X1. Additionally, marked improvement of granules’ properties and tableting of CNG were observed. Furthermore, the optimized process conditions that produced good flow properties of granules and acceptable tablets were high level of granulation fluid (3.41% w/w) and short wet massing time (1.0 min). Finally, the MADG process gives the opportunity to ameliorate the poor flow and tableting problems of CNG with lower amounts of excipients, which are important for successful development of uniform dosage unit.

Characterization and Evaluation of Carboxymethyl Starch of Cajanus Cajan Seeds as Tablet Binder

The aim of this study was to characterize carboxymethyl cajanus cajan starch (CMCCS) and evaluate its capacity as binder, using metronidazole as model drug. Wet granulation method was adopted in preparation of metronidazole tablets containing CMCCS. Native cajanus cajan starch (NCCS) was carboxymethylated using monochloroacetic acid (MCA) and sodium hydroxide. Also the effect of CMCCS concentration and wet massing time on the physical properties of metronidazole (200 mg) tablet formulations was tested in a 22 full factorial design. The degree of substitution, amylose content, moisture content, pH and moisture uptake of CMCCS were found to be 0.252, 20.92%, 8.86 %, 6.9 and 48.5 respectively. Also CMCCS dissolved in cold water forming viscous solution. Similarly amylose content, moisture content, pH and moisture uptake of NCCS were 32.9%, 9.6 %, 6.12 and 17.34% respectively. in terms of bulk density, NCCS gave higher values compared to CMCCS. The values of Hausner ratio were 1.42 and 1.46 for NCCS and CMCCS respectively. The results of angle of repose revealed that the CMCCS had good flow characteristics, while the NCCS had passable flow characteristics. FT-IR analysis of the CMCCS sample showed peak shifting compared to the NCCS sample indicating carboxymethylation. CMCCS with degree of substitution (DS) of 0.252 was synthesized and it was further evaluated as tablet excipient in metronidazole based tablets. The results of quality control tests which performed for metronidazole formulations that prepared by CMCCS as binder, showed that the increase of CMCCS concentration from 12.5 % to 17.5 % led to increase in hardness and decrease in % friability values significantly, but no significant effect on DT was observed when wet massing time was kept at 6 min but when wet massing time was increased to 12 min, DT was significantly increased. Also the increase of wet massing time from 6 to 12 min led to slight increase in tablets hardness. The % friability was decreased due to increasing in wet massing time only in formulations containing CMCCS at 17.5%. Also all the batches showed more 90 % drug release within 15 min. Generally, the physicochemical and functional properties of CMCCS and NCCS showing that both NCCS and CMCCS can be used as tablet excipient in pharmaceutical industries. With CMCCS having superior properties compared to unmodified cajanus cajan starch.