Cargando…

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-...

Descripción completa

Detalles Bibliográficos
Autores principales: Alrobaian, Majed, Alalaiwe, Ahmed, Almalki, Ziyad S., Fayed, Mohamed H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674408/
https://www.ncbi.nlm.nih.gov/pubmed/38004532
http://dx.doi.org/10.3390/pharmaceutics15112552
_version_ 1785140820896120832
author Alrobaian, Majed
Alalaiwe, Ahmed
Almalki, Ziyad S.
Fayed, Mohamed H.
author_facet Alrobaian, Majed
Alalaiwe, Ahmed
Almalki, Ziyad S.
Fayed, Mohamed H.
author_sort Alrobaian, Majed
collection PubMed
description 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 3(2) full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X(1)) and mixing time (X(2)). 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 X(1) and X(2) on the characteristics of CNG with a predominant effect of X(1). 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.
format Online
Article
Text
id pubmed-10674408
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-106744082023-10-29 Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica Alrobaian, Majed Alalaiwe, Ahmed Almalki, Ziyad S. Fayed, Mohamed H. Pharmaceutics Article 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 3(2) full-factorial experimental design was carried out to optimize the independent process variables, namely, the weight percent of silica nanoparticles (X(1)) and mixing time (X(2)). 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 X(1) and X(2) on the characteristics of CNG with a predominant effect of X(1). 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. MDPI 2023-10-29 /pmc/articles/PMC10674408/ /pubmed/38004532 http://dx.doi.org/10.3390/pharmaceutics15112552 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Alrobaian, Majed
Alalaiwe, Ahmed
Almalki, Ziyad S.
Fayed, Mohamed H.
Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
title Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
title_full Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
title_fullStr Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
title_full_unstemmed Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
title_short Application of Response Surface Methodology to Improve the Tableting Properties of Poorly Compactable and High-Drug-Loading Canagliflozin Using Nano-Sized Colloidal Silica
title_sort application of response surface methodology to improve the tableting properties of poorly compactable and high-drug-loading canagliflozin using nano-sized colloidal silica
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10674408/
https://www.ncbi.nlm.nih.gov/pubmed/38004532
http://dx.doi.org/10.3390/pharmaceutics15112552
work_keys_str_mv AT alrobaianmajed applicationofresponsesurfacemethodologytoimprovethetabletingpropertiesofpoorlycompactableandhighdrugloadingcanagliflozinusingnanosizedcolloidalsilica
AT alalaiweahmed applicationofresponsesurfacemethodologytoimprovethetabletingpropertiesofpoorlycompactableandhighdrugloadingcanagliflozinusingnanosizedcolloidalsilica
AT almalkiziyads applicationofresponsesurfacemethodologytoimprovethetabletingpropertiesofpoorlycompactableandhighdrugloadingcanagliflozinusingnanosizedcolloidalsilica
AT fayedmohamedh applicationofresponsesurfacemethodologytoimprovethetabletingpropertiesofpoorlycompactableandhighdrugloadingcanagliflozinusingnanosizedcolloidalsilica