Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System

Research output: Contribution to journalArticlepeer-review

30 Citations (Scopus)

Abstract

The formulation of oral amorphous solid dispersions (ASD) includes the use of excipients to improve physical stability and enhance bioavailability. Combinations of excipients (polymers and surfactants) are often employed in pharmaceutical products to improve the delivery of poorly water-soluble drugs. However, additive interactions in multicomponent ASD systems have not been extensively studied and may promote crystallization in an unpredictable manner, which in turn may affect the physical stability and dissolution profile of the product. The main aim of this study was to understand the effect of different surfactant and polymer combinations on the solid-state properties and dissolution behavior of ternary spray-dried solid dispersions of dipyridamole and cinnarizine. The surfactants chosen for this study were sodium dodecyl sulfate and poloxamer 188, and the model polymers used were polyvinylpyrrolidone K30 and hydroxypropyl methylcellulose K100. The spray-dried ternary dispersions maintained higher supersaturation compared to either the crystalline drug equilibrium solubility or their respective physical mixtures. However, rapid and variable dissolution behavior was observed for different formulations. The maximum supersaturation level was observed with drug-polymer-polymer ternary dispersions. On the other hand, incorporating the surfactant into binary (drug-polymer) and ternary (drug-polymer-polymer) ASDs adversely affected the physical stability and dissolution by promoting crystallization. On the basis of these observations, a thorough investigation into the impact of combinations of additives on amorphous drug crystallization during dissolution and stability studies is recommended in order to develop optimized formulations of supersaturating dosage forms.

Original languageEnglish
Pages (from-to)3796-3812
Number of pages17
JournalMolecular Pharmaceutics
Volume15
Issue number9
DOIs
Publication statusPublished - 04 Sep 2018

Keywords

  • amorphous solid dispersion
  • crystallization
  • dissolution
  • drug-polymer interaction
  • nuclear magnetic resonance
  • spray drying
  • supersaturation
  • surfactant
  • synergism

Fingerprint

Dive into the research topics of 'Investigation into the Solid-State Properties and Dissolution Profile of Spray-Dried Ternary Amorphous Solid Dispersions: A Rational Step toward the Design and Development of a Multicomponent Amorphous System'. Together they form a unique fingerprint.

Cite this