Advances in the development of amorphous solid dispersions: The role of polymeric carriers

Abstract

Amorphous solid dispersion (ASD) is one of the most effective approaches for delivering poorly soluble drugs. In ASDs, polymeric materials serve as the carriers in which the drugs are dispersed at the molecular level. To prepare the solid dispersions, there are many polymers with various physicochemical and thermochemical characteristics available for use in ASD formulations. Polymer selection is of great importance because it influences the stability, solubility and dissolution rates, manufacturing process, and bioavailability of the ASD. This review article provides a comprehensive overview of ASDs from the perspectives of physicochemical characteristics of polymers, formulation designs and preparation methods. Furthermore, considerations of safety and regulatory requirements along with the studies recommended for characterizing and evaluating polymeric carriers are briefly discussed.

Keywords: Amorphous solid dispersions; Bioavailbility; Dissolution; Molecular interactions; Polymeric carriers; Stability.

Graphical abstract

Fig. 1

Classification of polymeric carriers based on their chemical structures.

Fig. 2

The hydrogen bonding interactions in rafoxanide-PVP ASDs. Adapted from with the permission.

Fig. 3

Two hydrogen-bonded patterns formed between POSA and HPMCAS . Adapted from with the permission.

Fig. 4

¹³C SSNMR spectra of Eudragit E (EGE), Naproxen (NAP)−EGE with different ratio ASDs, and crystalline NAP. Adapted from with the permission.

Fig. 5

Schematic illustration of the polymer characteristics needed for ASD formation.

Fig. 6

A typical temperature-composition phase diagram for an ASD.

Fig. 7

A schematic model for the ionic interactions between clofazimine and PAA. Adapted from [114]with the permission.

Fig. 8

The α-relaxation and β-relaxation times for different systems vs temperature (a). Crystallization for different systems vs time at 82 °C (b). Adapted from with the permission.

Fig. 9

The impacts of different polymers on the nucleation rate (J) and growth rate (u) of fluconazole Form II. Adapted from with the permission.

Fig. 10

Graphical illustration of the spring and parachute effect. Adapted from with the permission.

Fig. 11

Schematic representation of the impacts of polymers on balancing solid-state stabilities and dissolution rates of lumefantrine ASDs . Adapted from with the permission.

Fig. 12

Percentages of RTV and PVPVA release from ASDs with different drug loadings . Adapted from with the permission.

Fig. 13

The contact angles of water on IMC, IMC-ASD tablets. Adapted from with the permission.

Fig. 14

Gel layers formation and dry cores within tablets after exposure to a dissolution medium for approximately 10 min; (A) 40% neat PVPVA; (B) 40% PVPVA-drug 80:20; (C) 40% neat HPMC and (D) 40% HPMC-drug 80:20 . Adapted from with the permission.

Fig. 15

Schematic for the relationships between drug-polymer interactions and the LoCs for ASDs . Adapted from [201]with the permission.

Fig. 16

Schematic for the dissolution and crystallization for bicalutamide/PVPVA ASDs (a) without residual crystallinity and (b) with residual crystallinity. Adapted from [209]with the permission.

Fig. 17

Schematic illustration of the interactions between ketoconazole and PAA, which were confirmed by two-dimensional ¹H NOESY and the dissolution of KTZ ASDs formulated with PAA and PVP. Adapted from with the permission.

Fig. 18

AFM images for HPMCAS adsorbed to felodipine (a) at pH 3, (b) pH 6.8, and (c) no HPMCAS adsorbed. (d) desupersaturation in the absence of HPMCAS (◆) and in the presence of HPMCAS at pH 3 (■) and pH 6.8 (▲) . Adapted from with the permission.

Fig. 19

Schematic illustration of IBP-rich nanodroplets stabilized by HPMC in supersaturated solution. Adapted from with the permission.

Fig. 20

Schematic illustration of the impacts of SLS on dissolution and bioavailability of PSZ/HPMCAS ASDs. Adapted from with the permission.

Fig. 21

Detailed considerations for ASD formulation development.