Formulation of Ketoconazole Nanocrystal-Based Cryopellets

Area of Science:

• Pharmaceutical Technology
• Materials Science
• Nanotechnology

Background:

• Commercial nanosuspension development for oral delivery requires stable, rapidly releasing nanocrystal products.
• Drying techniques are crucial for processing nanosuspensions into final dosage forms like capsules.
• Cryopelletisation offers a freeze-drying approach to produce flowable, lyophilized micrometric spheres.

Purpose of the Study:

• To investigate the formulation of redispersible ketoconazole nanocrystal-based cryopellets.
• To assess the mechanical stability and handling properties of these cryopellets.
• To evaluate the impact of formulation components on nanocrystal recovery and dissolution.

Main Methods:

• Ketoconazole nanosuspensions were formulated and droplets were freeze-dried using liquid nitrogen and sublimation.
• Cryopellets were stabilized using hydroxypropyl cellulose SSL grade and vitamin E TPGS.
• The effect of micronized crospovidone on dissolution was studied.

Main Results:

• Low-friability (<1%) cryopellets were produced by embedding nanocrystals in a hydroxypropyl cellulose SSL grade matrix.
• A specific ratio of hydroxypropyl cellulose SSL grade and vitamin E TPGS was found essential for nanocrystal recovery during storage.
• Micronized crospovidone addition enhanced the dissolution performance of the cryopellets.

Conclusions:

• Cryopelletisation can yield mechanically robust, redispersible nanocrystal formulations.
• The combination of hydroxypropyl cellulose SSL grade and vitamin E TPGS is critical for nanocrystal stability.
• This technique offers potential advantages over other drying methods for oral nanocrystal drug delivery.