Hybrid nanocrystal–amorphous solid dispersions (HyNASDs) as alternative to ASDs for enhanced release of BCS Class II drugs

Mahbubur Rahman, Faustin Arevalo, Alexander Coelho, Ecevit Bilgili

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

A major shortcoming of drug nanocomposites as compared with amorphous solid dispersions (ASDs) is their limited supersaturation capability in dissolution media. Here, we prepared drug hybrid nanocrystal–amorphous solid dispersions (HyNASDs) and compare their performance to ASDs. A wet-milled griseofulvin (GF, BCS II drug) nanosuspension and a GF solution, both containing the same dissolved polymer–surfactant (SDS: sodium dodecyl sulfate) with 1:1 and 1:3 GF:polymer mass ratios, were spray-dried. Hydroxypropyl cellulose (HPC) and Soluplus (Sol) were used as matrix-forming polymers. XRPD, DSC, and Raman spectroscopy reveal that ASDs were formed upon spray-drying the solution-based feed, whereas nanocomposites and nanocomposites with >10% amorphous content, HyNASDs, were formed with the nanosuspension-based feed. Sol provided higher GF relative supersaturation, up to 180% and 360% for HyNASDs and ASDs, respectively, in the dissolution tests than HPC (up to 50% for both) owing to Sol's stronger intermolecular interactions and miscibility with GF and its recrystallization inhibition. Besides the higher kinetic solubility of GF in Sol, presence of GF nanoparticles vs. micron-sized particles in the nanocomposites enabled fast supersaturation. This study demonstrates successful preparation of fast supersaturating (190% within 20 min) HyNASDs, which renders nanoparticle formulations competitive to ASDs in bioavailability enhancement of poorly soluble drugs.

Original languageEnglish (US)
Pages (from-to)12-26
Number of pages15
JournalEuropean Journal of Pharmaceutics and Biopharmaceutics
Volume145
DOIs
StatePublished - Dec 2019

All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Pharmaceutical Science

Keywords

  • Amorphous solid dispersion
  • Dissolution
  • Nanocomposites
  • Nanoparticles
  • Spray drying
  • Wet stirred media milling

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