Polymeric Amorphous Solid Dispersions: A Review of Amorphization, Crystallization, Stabilization, Solid-State Characterization, and Aqueous Solubilization of Biopharmaceutical Classification System Class II Drugs

Abstract

Poor water solubility of many drugs has emerged as one of the major challenges in the pharmaceutical world. Polymer-based amorphous solid dispersions have been considered as the major advancement in overcoming limited aqueous solubility and oral absorption issues. The principle drawback of this approach is that they can lack necessary stability and revert to the crystalline form on storage. Significant upfront development is, therefore, required to generate stable amorphous formulations. A thorough understanding of the processes occurring at a molecular level is imperative for the rational design of amorphous solid dispersion products. This review attempts to address the critical molecular and thermodynamic aspects governing the physicochemical properties of such systems. A brief introduction to Biopharmaceutical Classification System, solid dispersions, glass transition, and solubility advantage of amorphous drugs is provided. The objective of this review is to weigh the current understanding of solid dispersion chemistry and to critically review the theoretical, technical, and molecular aspects of solid dispersions (amorphization and crystallization) and potential advantage of polymers (stabilization and solubilization) as inert, hydrophilic, pharmaceutical carrier matrices. In addition, different preformulation tools for the rational selection of polymers, state-of-the-art techniques for preparation and characterization of polymeric amorphous solid dispersions, and drug supersaturation in gastric media are also discussed.

Dissolution behavior of co-amorphous amino acid-indomethacin mixtures: The ability of amino acids to stabilize the supersaturated state of indomethacin

“…Amorphous solid dispersions with polymers have been extensively studied and shown to stabilize both the drug supersaturation in solution and the amorphous form in the solid state [16,17]. In a solution, an amorphous form of a drug can be described as a spring that triggers the high initial concentration whereas the polymer acts as a parachute to prevent the recrystallization and precipitation of the drug [18].…”

Fibrous polymeric buccal film formulation, engineering and bio-interface assessment

“…Raman and FTIR spectroscopy were used to study structure and molecular conformation of fibrous films by probing band vibrations [52]. due to hydrogen bonding with the active and other co-polymers [53].…”

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“…[20,21] However, the major disadvantage of this approach is that solid dispersionslack physical stability and revert back to the crystalline state on storage. [22,23] Inclusion complexes can be easily developed as a viable and fruitful alternative for solid dispersions and other techniques for the development of solid state forms to improve the pharmaceutical characteristics.…”