Preparation and Characterization of Spray-Dried Hybrid Nanocrystal–Amorphous Solid Dispersions (HyNASDs) for Supersaturation Enhancement of a Slowly Crystallizing Drug

Mahbubur Rahman, Keanu Radgman, James Tarabokija, Stephanie Ahmad, Ecevit Bilgili

Research output: Contribution to journalArticlepeer-review

Abstract

We prepared hybrid nanocrystal–amorphous solid dispersions (HyNASDs) to examine their supersaturation capability in the release of a poorly soluble drug, itraconazole (ITZ), a slow crystallizer during dissolution. The HyNASD formulations included a polymer (HPC: hydroxypropyl cellulose, Sol: Soluplus, or VA64: Kollidon-VA64) and a surfactant (SDS: sodium dodecyl sulfate). Additionally, the dissolution performance of the HyNASDs and ASDs was compared. To this end, wet-milled aqueous nanosuspensions containing a 1:5 ITZ:polymer mass ratio with/without SDS as well as solutions of the same ratio without SDS in dichloromethane were spray-dried. XRPD–DSC confirmed that ASDs were formed upon spray drying the solution-based feeds, whereas HyNASDs (~5–30% amorphous) were formed with the nanosuspension-based feeds. SDS aided to stabilize the ITZ nanosuspensions and increase the amorphous content in the spray-dried powders. During dissolution, up to 850% and 790% relative supersaturation values were attained by HyNASDs with and without SDS, respectively. Due to the stronger molecular interaction between ITZ–Sol than ITZ–HPC/VA64 and micellar solubilization by Sol, Sol-based HyNASDs outperformed HPC/VA64-based HyNASDs. While the ASD formulations generated greater supersaturation values (≤1670%) than HyNASDs (≤790%), this extent of supersaturation from a largely nanocrystalline formulation (HyNASD) has not been achieved before. Overall, HyNASDs could boost drug release from nanoparticle-based formulations and may render them competitive to ASDs.

Original languageEnglish (US)
Article number2419
JournalNanomaterials
Volume13
Issue number17
DOIs
StatePublished - Sep 2023

All Science Journal Classification (ASJC) codes

  • General Chemical Engineering
  • General Materials Science

Keywords

  • amorphous solid dispersions
  • drug nanoparticles
  • nanocomposites
  • poorly soluble drugs
  • slow crystallizer
  • spray drying
  • supersaturation
  • wet media milling

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