Mechanisms of increased bioavailability through amorphous solid dispersions: a review

Abstract

Amorphous solid dispersions (ASDs) can increase the oral bioavailability of poorly soluble drugs. However, their use in drug development is comparably rare due to a lack of basic understanding of mechanisms governing drug liberation and absorption in vivo. Furthermore, the lack of a unified nomenclature hampers the interpretation and classification of research data. In this review, we therefore summarize and conceptualize mechanisms covering the dissolution of ASDs, formation of supersaturated ASD solutions, factors responsible for solution stabilization, drug uptake from ASD solutions, and drug distribution within these complex systems as well as effects of excipients. Furthermore, we discuss the importance of these findings on the development of ASDs. This improved overall understanding of these mechanisms will facilitate a rational ASD formulation development and will serve as a basis for further mechanistic research on drug delivery by ASDs.

Molecular Dynamics Simulations Reveal Membrane Interactions for Poorly Water-Soluble Drugs: Impact of Bile Solubilization and Drug Aggregation

“…Indeed, this may be one reason why amorphous solid formulation achieve better permeability through the intestinal membrane than crystalline formulations. 61,62…”

Hyperbranched poly(glycerol esteramide): A biocompatible drug carrier from glycerol feedstock and dicarboxylic acid

“…As a consequent, the crystalline drug was converted into an amorphous SD with lower lattice forces. 68 Formulations in amorphous form with lower T A B L E 5 Dissolution and solubility performances of solid dispersion (SD) prepared with hyperbranched poly(glycerol esteramide) (HPGEA) and commercial polymers, pure drug (LOV) and marketed product Figure 5).…”

Self-assembled hydrophobic Ala-Aib peptide encapsulating curcumin: a convenient system for water insoluble drugs

“…1,2 Various techniques are used to increase their solubility, which include physical and chemical modications of the drug, particle size reduction, salt formation, solid dispersion, use of surfactant, complexation, and so forth. 3,4 In recent years, the exploitation of self-assembled systems to improve the solubility of drugs has gained increasing attention as they have demonstrated many advantages including biocompatibility, biodegradability, high efficiency for drug loading, reducing drug toxicity, controlling drug release rate and protection against biochemical degradation. [5][6][7] Several types of self-assembled structures have been studied to develop new drug carriers involving micelles, hydrogels, vesicles, polymers, microcapsules, lipoproteins, liposomes, cubosomes, colloidosomes, etc.…”