The role of the carrier in the formulation of pharmaceutical solid dispersions. Part II: amorphous carriers

Abstract

Amorphous solid dispersions are considered as one of the most powerful strategies to formulate poorly soluble drugs. They are made up of an active pharmaceutical ingredient (API) dispersed at the molecular level in an amorphous polymeric carrier. As the latter component constitutes the largest part of the formulation, its characteristics will contribute to a large extent to the properties and behavior of the solid dispersion. Areas covered: Amorphous polymers are most often used in modern solid dispersion formulations. This review discusses carrier properties like molecular weight, conformation, hygroscopicity, their stabilization effects, issues related to solid dispersion manufacturing technology, response to downstream processing, and potential to generate supersaturation, next to criteria to select a carrier to formulate stable amorphous solid dispersions. Expert opinion: Different amorphous carriers lead to solid dispersions with various properties in terms of physical stability, phase behavior and drug release rate and extent. Despite more than 50 years of intensive research in this field it remains difficult to predict what carrier is best suited for a given API, pointing to the complex nature of this formulation strategy. Sustained efforts to understand the link and complex interplay between material properties, processing parameters, physical stability and dissolution behavior are required from pharmaceutical scientists with a strong physicochemical background to shift the development from trial and error to science driven.

Spectroscopic Investigation of the Formation and Disruption of Hydrogen Bonds in Pharmaceutical Semicrystalline Dispersions

“…In fact, as the carrier normally constitutes the largest part of the formulation, its characteristics will greatly contribute to the properties and behavior of solid dispersions. 4,5 However, studies on solid dispersions have mainly focused on how carriers affect properties of APIs. There have been only few studies dealing with the influence of APIs and preparation processes on the properties of carriers as well as the behavior of the carriers in the system.…”

“…For amorphous carriers, although the amorphous state of the carriers remain unchanged in either the absence or presence of APIs, the modifications in their conformation under the influence of solvent quality, 6 pH, 7,8 ionic strength 9 or mechanical stress 10 might result in significant differences in drug-carrier interactions, the drug stabilization and supersaturation maintenance effect of the carriers. 5 The story becomes even more complicated with semi-crystalline carriers like polyethylene glycol. On the one hand, the presence of PEG either accelerated, slowed down or had no influence on the crystallization process of APIs; on the other hand, APIs have been found to affect the crystallization of the polymer 11,12 that in turn might influence the microstructure and hence the physicochemical properties and the pharmaceutical performance of the system.…”

Processing of Polyvinyl Acetate Phthalate in Hot-Melt Extrusion—Preparation of Amorphous Solid Dispersions

“…Several polymers have been established as carriers for ASDs [14,15] and pH-dependent soluble polymers have also been shown to be particularly well suited [16][17][18][19]. These polymers are capable of protecting an acid-labile drug from the gastric juice [20], or from varying gastric pH-conditions [21].…”

Applications of Dynamic Mechanical Analysis in the Engineering of Amorphous Solid Dispersions

“…The formation of amorphous solid dispersions (ASDs) of a poorly soluble drug in suitable polymer carriers is an innovative and enabling technique for enhancing the dissolution and oral delivery of many poorly water-soluble active pharmaceutical ingredients (APIs). 1 The approach has become increasingly important due to the growing number of poorly water-soluble APIs identified in the drug discovery process. 2,3 These ASD systems can achieve a transiently higher solubility and a faster dissolution rate due to the inherently more energetic amorphous form of a poorly soluble API as compared with that of the pure crystalline drug, thereby increasing the diffusional driving force to enable enhanced drug absorption with improved bioavailability.…”