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

• Published in: Nanomaterials (Basel, Switzerland) Switzerland), 2023-08, Vol.13 (17), p.2419
• Main Authors: Rahman, Mahbubur, Radgman, Keanu, Tarabokija, James, Ahmad, Stephanie, Bilgili, Ecevit
• Format: Article
• Language: English
• Subjects: Analysis; Bioavailability; Cellulose; Dichloromethane; Dispersions; Dissolution; Drug dosages; drug nanoparticles; Hydroxypropyl cellulose; Identification and classification; Itraconazole; Molecular interactions; Nanocomposites; Nanocrystals; Nanoparticles; Particle size; Pharmaceutical industry; Polymers; poorly soluble drugs; Properties; slow crystallizer; Sodium dodecyl sulfate; Sodium lauryl sulfate; Solubilization; Spray drying; Supersaturation; Surfactants; wet media milling
• ISSN: 2079-4991; 2079-4991
• DOI: 10.3390/nano13172419

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.