MBP Technology: Composition and Design Considerations

Abstract

An increasing number of poorly soluble drugs emerging from discovery organizations is a major challenge for drug development. Formulation approaches such as particle size reduction, use of solubilizers, and complexing agents, in addition to lipid formulations, have been conventionally used but with limited success. When such approaches fail to provide desired bioavailability, amorphous formulations can be used as an alternate approach. However, amorphous formulations face significant challenges owing to their inherent physical and chemical instability. One way to achieve amorphous stability is by developing an amorphous solid dispersion (ASD) with a stabilizing polymer. In the ASD preparation, polymer and active pharmaceutical ingredient (API) are coprocessed by either spray drying, melt extrusion, or fluid-bed layering techniques. Although these techniques provided adequate solution for many APIs, some compounds commonly referred to as “brickdust” were not readily amenable to these techniques either due to their high melting points and thermal instability or due to insufficient solubility in volatile organic solvents. An innovative technology, known as microprecipitated bulk powder (MBP) technology, was developed utilizing the exceptional solubility power of super solvents such as dimethylacetamide (DMA) and the concept of solvent-controlled coprecipitation to produce an ASD. The details of MBP technology covering the development of product from intermediate to final dosage form including theoretical aspects of coprecipitation, relevant properties of API and polymer, manufacturing process, and in-process controls are presented in this chapter.