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

Authors :
Bjad K. Almutairy
El-Sayed Khafagy
Ahmed Alalaiwe
Mohammed F. Aldawsari
Saad M. Alshahrani
Bader B. Alsulays
Abdullah S. Alshetaili
Sultan M. Alshehri
Mohamed H. Fayed
Source :
Pharmaceuticals, Vol 13, Iss 12, p 473 (2020)
Publication Year :
2020
Publisher :
MDPI AG, 2020.

Abstract

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.

Details

Language :
English
ISSN :
14248247
Volume :
13
Issue :
12
Database :
Directory of Open Access Journals
Journal :
Pharmaceuticals
Publication Type :
Academic Journal
Accession number :
edsdoj.5e190f96a9ba47b98955ca155fd6cdfa
Document Type :
article
Full Text :
https://doi.org/10.3390/ph13120473