Hot Melt Extrusion-Triggered Amorphization As a Continuous Process for Inducing Extended Supersaturable Drug Immediate-Release from SaSMSDs Systems

Overview

Journal Pharmaceutics

Publisher MDPI

Date 2022 Apr 23

PMID 35456600

Authors

Huan Yu

Yanfei Zhang

Yinghui Ma

Huifeng Zhang

Chengyi Hao

Yong Zhang

Zhengqiang Li

Xianrong Qi

Nianqiu Shi

Affiliations

Soon will be listed here.

Abstract

Hot melt extrusion (HME), a continuous manufacturing process for generating supersaturating amorphous self-micellizing solid dispersion systems (saSMSDs), holds promise for achieving amorphization of many pharmaceutical formulations. For saSMSDs generation, HME-triggered continuous processes offer advantages over traditional non-continuous processes such as fusion/quench cooling (FQC) and co-precipitation (CP). Here we employed HME, FQC, and CP to generate saSMSDs containing the water-insoluble BCS II drug nitrendipine (NIT) and self-micellizing polymer Soluplus. Scanning electron microscopy, powder X-ray diffraction, and differential scanning calorimetry results revealed that saSMSDs formed when NIT-Soluplus mixtures were subjected to the abovementioned amorphization methods. All saSMSDs outperformed crystalline NIT preparations and physical mixtures in achieving extended supersaturable immediate release states with superior solubility, "spring-parachute" process characteristics, and dissolution behaviors. Notably, Fourier transform-infrared spectroscopic results obtained for saSMSDs detected hydrogen bonding interactions between the drug and the carrier. Ultimately, our results revealed the advantages of HME-triggered amorphization as a continuous process for significantly improving drug dissolution, increasing solubility, and maintaining supersaturation as compared to traditional amorphization-based techniques.

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