Superiority of Mesoporous Silica-Based Amorphous Formulations over Spray-Dried Solid Dispersions.

Hongwei Zhang,Minglu Li,Anjali Agrawal,Demin Liu,Ho-Wah Hui,Jianmin Li

doi:10.3390/pharmaceutics14020428

Hongwei Zhang, Minglu Li + Show 4 more

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https://doi.org/10.3390/pharmaceutics14020428

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Journal: Pharmaceutics	Publication Date: Feb 16, 2022
Citations: 3	License type: CC BY 4.0

Affiliation: Bristol-Myers Squibb (United States)

Abstract

The aim of this study was to compare the performance of two amorphous formulation strategies: mesoporous silica via solvent impregnation, and solid dispersions by spray drying. Poorly soluble fenofibrate was chosen as the model drug compound. A total of 30% Fenofibrate-loaded mesoporous silica and spray-dried solid dispersions (SDD) were prepared for head-to-head comparisons, including accelerated stability, manufacturability, and in vitro biorelevant dissolution. In the accelerated stability study under 40 °C/75% RH in open dish, mesoporous silica was able to maintain amorphous fenofibrate for up to 3 months based on solid-state characterizations by PXRD and DSC. This result was superior compared to SDD, as recrystallization was observed within 2 weeks. Under the same drug load, fenofibrate-loaded mesoporous silica showed much better flowability than fenofibrate-loaded SDD, which is beneficial for powder handling of the intermediate product during the downstream process. The in vitro 2-stage dissolution results indicated a well-controlled release of fenofibrate from mesoporous silica in the biorelevant media, rather than a burst release followed by fast precipitation due to the recrystallization in the early simulated gastric phase for SDD. The present study demonstrates that mesoporous silica is a promising formulation platform alternative to prevailing spray-dried solid dispersions for oral drug product development.

Highlights

Academic Editor: Anne Marie HealyPoor aqueous solubility is a common challenge for most of the biopharmaceutics classification system’s (BCS) class II or IV drug candidates in the oral route development pipelines
The objective of the current study is to explore the advantages of a mesoporous silica-based amorphous formulation platform over conventional spray-dried amorphous dispersions
A head-to-head comparison of stability, manufacturability, and release in 2-stage biorelevant media was performed between the two-formulation platform

Summary

Introduction

Academic Editor: Anne Marie HealyPoor aqueous solubility is a common challenge for most of the biopharmaceutics classification system’s (BCS) class II or IV drug candidates in the oral route development pipelines. In the recent decades, loading drug molecules into the mesoporous silica (MS) has been considered as a novel promising alternative to the traditional methods of amorphous formulation development [6]. Credited to their unique characteristics of nanoscale mesopores with high pore volumes and high surface areas, MS materials can effectively entrap drug molecules in the mesopores and suppress the recrystallization by virtue of finite-size effects [7]. Amorphous drugs entrapped in the mesopores can enhance dissolution rate and generate drug supersaturation in aqueous media, leading to a superior bioavailability over the crystalline form [8].

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