An improved manufacturing approach expands possibilities for poorly soluble drugs
Increasing the solubility and bioavailability of poorly water-soluble drug candidates is critical to successful drug development and translation. While 90% of drug candidates in development and 40% of all marketed drugs exhibit poor solubility, this remains a major obstacle for the pharmaceutical industry.1,2 Hot melt extrusion (HME) is a well-known process in plastic industry that has recently been adopted by the pharmaceutical industry to produce amorphous solid dispersion (ASD) to enhance bioavailability of poorly soluble APIs.3 While HME has produced several commercially and clinically successful drug formulations, the conditions of HME limit applicability to many heat- or shear-sensitive APIs. Widening the processing window to allow for gentler HME processing conditions would unlock further applications for production of poorly soluble drugs.
In collaboration with Eli Lilly and Merck, researchers at The University of Texas at Austin have developed a novel method that extends the possible applications of HME by using drug solvates to prepare ASDs. Using the solvate form of a crystalline drug as the starting material permits gentler extrusion conditions compared to using the non-solvate drug form. In particular, this method allowed a reduction in the operating temperature from 140°C to 60°C. This approach substantially extends the processing window of HME, making this technique compatible with a range of APIs for pharmaceutical manufacturing of poorly water-soluble drugs previously incompatible with thermal processing. As an example, the researchers used this method to enable production of ASDs from carbamazepine dihydrate with no sacrifice to the stability and solubility of the final drug product.4 Offering more favorable operational conditions, this versatile pharmaceutical manufacturing platform has the potential to drastically advance drug development pipelines.
1. Jermain, S.V.; et al., Amorphous solid dispersions and nanocrystal technologies for poorly water-soluble drug delivery—an update. Int. J. Pharm. 535 (1-2), 379-392 (2018). https://doi.org/10.1016/j.ijpharm.2017.10.051
2. Kawabata, Y.; et al. Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: Basic approaches and practical applications. Int. J. Pharm. 420 (1), 1-10 (2011) https://doi.org/10.1016/j.ijpharm.2011.08.032
3. Agrawal, A., et al., Hot Melt Extrusion: Development of an Amorphous Solid Dispersion for an Insoluble Drug from Mini-scale to Clinical Scale. AAPS PharmSciTech. 2016 Feb; 17(1): 133-147. https://doi.org/10.1208/s12249-015-0425-7
4. Ma X., et al., Influence of Carbamazepine Dihydrate on the Preparation of Amorphous Solid Dispersions by Hot Melt Extrusion. Pharmaceutics. 12(4):379 (2020). https://doi.org/10.3390/pharmaceutics12040379