Exploring the Role of Surfactants in Enhancing Drug Release from Amorphous Solid Dispersions at Higher Drug Loadings.

Sugandha Saboo,Lynne Taylor,Umesh Kestur,Pradnya Bapat,Dana Moseson

doi:10.3390/pharmaceutics13050735

Abstract

To reduce the dosage size of amorphous solid dispersion (ASD)-based formulations, it is of interest to devise formulation strategies that allow increased drug loading (DL) without compromising dissolution performance. The aim of this study was to explore how surfactant addition impacts drug release as a function of drug loading from a ternary ASD, using felodipine as a model poorly soluble compound. The addition of 5% TPGS (d-α-tocopheryl polyethylene glycol 1000 succinate, a surfactant) to felodipine-polyvinylpyrrolidone/vinyl acetate ASDs was found to facilitate rapid and congruent (i.e., simultaneous) release of drug and polymer at higher DLs relative to binary ASDs (drug and polymer only). For binary ASDs, good release was observed for DLs up to <20% DL; this increased to 35% DL with surfactant. Microstructure evolution in ASD films following exposure to 100% relative humidity was studied using atomic force microscopy coupled with nanoscale infrared imaging. The formation of discrete, spherical drug-rich domains in the presence of surfactant appeared to be linked to systems showing congruent and rapid release of drug and polymer. In contrast, a contiguous drug-rich phase was formed for systems without surfactant at higher DLs. This study supports the addition of surfactant to ASD formulations as a strategy to increase DL without compromising release. Furthermore, insights into the potential role of surfactant in altering ASD release mechanisms are provided.

Highlights

A minimal difference was found between critical micelle concentration (CMC) and CAC values, whereby this difference is insignificant in terms of the tocopheryl polyethylene glycol succinate (TPGS) concentrations used in this study, which are both above and below CMC values depending on the drug loading and % TPGS in the formulation (Table S2)
The addition of TPGS alleviated the low limit of congruency and the low drug loading limitation of binary felodipinePVPVA amorphous solid dispersion (ASD)
The limit of congruency scaled with the TPGS level in the ASDs, increasing from 15% drug loading with no surfactant to 45% drug loading with the addition of

Summary

Introduction

The dissolution advantage derived from polymer-controlled dissolution of amorphous solid dispersions (ASDs), where drug is molecularly dispersed in a hydrophilic polymer matrix, is gaining increased attention from drug product formulators and researchers [5,6]. The drug in excess of amorphous solubility phase separates to form in situ amorphous drug-rich nanoparticles that are dispersed in the bulk aqueous phase, which is a phenomenon referred to as liquid–liquid phase separation [9]. These nanoparticles, owing to their small size (

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