Solid Nanocrystalline Dispersions
For drugs with low solubility or bioavailability, Capsugel Dosage Form Solutions offers a wide range of formulation options and technologies that maximize the opportunity for development and commercial success of drug candidates.
Our solid nanocrystalline dispersions (SNCD) technology offers another formulation tool to enhance the bioavailability of low-solubility compounds.
SNCDs, which consist of drug crystals embedded in a polymer-rich matrix, are created by purposeful formation of submicron, high-energy crystals from amorphous dispersions. They can be formed through crystallization of the drug in a spray-dried dispersion (SDD) under controlled conditions (i.e., temperature and humidity) that favor high nucleation rates over crystal growth.
SNCDs have two important advantages:
- the high-energy nature of the drug nanocrystals enhances dissolution performance
- the crystalline nature stabilizes the drug form and allows higher drug-loadings
Thus, it is possible to attain both good performance and good stability with SNCDs.
SNCD PROCESS OVERVIEW:
TRANSMISSION ELECTRON MICROSCOPY (TEM) ANALYSIS OF AN SNCD
SNCDs are best used in cases where any of the following apply:
- improved stability is needed (relative to amorphous drug forms) because a high drug-loading is required or because the amorphous drug has a low glass-transition-temperature (Tg);
- improved chemical stability (relative to an amorphous drug form) is needed; or
- small crystals with rapid dissolution rates are sufficient to meet pharmacokinetic (PK) targets.
Through our SNCD work, we have demonstrated the following:
- successful formulation based on neutral and anionic polymers;
- manufacture at kilogram scales under Good Manufacturing Practice (GMP) protocols;
- improved performance over crystals and, in some cases, performance equal to that of spray-dried dispersions (SDDs);
- excellent chemical and physical stability; and
- flexible use in dosage forms for human and animal studies. Dosage forms have included osmotic tablets, matrix tablets, granulated formulations and layered on multiparticulate beads.