Evaluation and enhancement of physical stability of amorphous solid dispersions
type: CreativeWork
description: A major concern during formulation development has been to enhance the dissolution rate and bioavailability of poorly water-soluble drugs.[1],[2] The amorphous forms of APIs have attracted considerable attention as the amorphous forms tend to exhibit significantly higher levels of supersaturation in aqueous media when compared to the crystalline forms.[3],[4] For drugs which bioavailability is limited by aqueous solubility (biopharmaceutical classification system (BCS) class II drugs), which is a significant number of recently discovered drug candidates, the improved solubility may lead to enhanced bioavailability.[5-7] Oral absorption of APIs depends on two broad, but crucial, events, namely drug solubilization and gastrointestinal permeation.[8] Amorphous solid dispersions have been widely investigated to increase the gastrointestinal permeability, and the roles played by polymers and other excipients were also studied.[9],[10] However, even after 40 years of active research there have not been many commercial products that have reached the market based on amorphous solid dispersion technology. [11, 12] The primary reason for this is a combination of the stability and scale up issues associated with this approach, which has been reported by several authors.[13-15] Hot-melt extrusion currently stands as the most promising approach for solving the scale up issues associated with amorphous solid dispersion systems.[16] Unfortunately, amorphous solid dispersion systems still face the issue that the amorphous form is, in general, thermodynamically unstable relative to its crystalline counterpart(s), [17], [18] and therefore may ultimately result in unacceptable changes in the API’s physical properties. [19] The most comapproach of preserving the solubility/bioavailability enhancement imparted by the high-energy amorphous form is to kinetically stabilize the drug substance in the amorphous state for the duration of the anticipated shelf life. Amorphous solid dispersions…
abstract: A major concern during formulation development has been to enhance the dissolution rate and bioavailability of poorly water-soluble drugs.[1],[2] The amorphous forms of APIs have attracted considerable attention as the amorphous forms tend to exhibit significantly higher levels of supersaturation in aqueous media when compared to the crystalline forms.[3],[4] For drugs which bioavailability is limited by aqueous solubility (biopharmaceutical classification system (BCS) class II drugs), which is a significant number of recently discovered drug candidates, the improved solubility may lead to enhanced bioavailability.[5-7] Oral absorption of APIs depends on two broad, but crucial, events, namely drug solubilization and gastrointestinal permeation.[8] Amorphous solid dispersions have been widely investigated to increase the gastrointestinal permeability, and the roles played by polymers and other excipients were also studied.[9],[10] However, even after 40 years of active research there have not been many commercial products that have reached the market based on amorphous solid dispersion technology. [11, 12] The primary reason for this is a combination of the stability and scale up issues associated with this approach, which has been reported by several authors.[13-15] Hot-melt extrusion currently stands as the most promising approach for solving the scale up issues associated with amorphous solid dispersion systems.[16] Unfortunately, amorphous solid dispersion systems still face the issue that the amorphous form is, in general, thermodynamically unstable relative to its crystalline counterpart(s), [17], [18] and therefore may ultimately result in unacceptable changes in the API’s physical properties. [19] The most comapproach of preserving the solubility/bioavailability enhancement imparted by the high-energy amorphous form is to kinetically stabilize the drug substance in the amorphous state for the duration of the anticipated shelf life. Amorphous solid dispersions…
author: Feng, Xin
keywords: amrphous, hot melt extrusion, polymer, recrystallization, solid dispersion, Pharmacy and Pharmaceutical Sciences
date published: 2016-01-01T08:00:00Z
date modified: 2026-07-24T03:06:53Z
provider: University of Mississippi
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Mississippi