Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica

Designing a robust direct compression (DC) formulation for an active pharmaceutical ingredient (API) with poor flow and compaction properties at a high API load is challenging. This study tackled two challenges: the unfavorable flow characteristics and tableting problems associated with a high-drug-loading canagliflozin (CNG), facilitating high-speed DC tableting. This was accomplished through a single-step dry coating process using hydrophilic nano-sized colloidal silica. A 3² full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X₁) and mixing time (X₂). Flow, bulk density, and compaction properties of CNG–silica blends were investigated, and the optimized blend was subsequently compressed into tablets using the DC technique. A regression analysis exhibited a significant (p ≤ 0.05) influence of both X₁ and X₂ on the characteristics of CNG with a predominant effect of X₁.

Additionally, robust tablets were produced from the processed powders in comparison with those from the control batch. Furthermore, the produced tablets showed significantly lower tablet ejection forces than those from the control batch, highlighting the lubrication impact of the silica nanoparticles. Interestingly, these tablets displayed improved disintegration time and dissolution rates. In conclusion, a dry coating process using silica nanoparticles presents a chance to address the poor flow and tableting problems of CNG, while minimizing the need for excessive excipients, which is crucial for the effective development of a small-sized tablet and the achievement of a cost-effective manufacturing process.

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Materials

Canagliflozin and nano-sized hydrophilic fumed silica “Aerosil 200^®” were supplied by JPI Ltd. Co. (Al-kharj, Saudi Arabia). Polyvinylpyrrolidone (Kollidon^® 25) was procured from BASF Co. (Ludwigshafen, Germany). Croscarmellose sodium (Vivasol^®) was purchased from JRS pharma (Rosenberg, Germany). All the other chemicals were of analytical grade.

Alrobaian, M.; Alalaiwe, A.; Almalki, Z.S.; Fayed, M.H. Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica. Pharmaceutics 2023, 15, 2552. https://doi.org/10.3390/pharmaceutics15112552

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