Approximately 65% of all prescription drugs are manufactured as solid dosage forms, which includes tablets and capsules. For very potent drugs, the amount of Active Pharmaceutical Ingredient (API) in the solid dosage form can be as low as 0.1% by weight. This very low API loading poses one of the biggest challenges in pharmaceutical product development: the control of dose uniformity. Low API content variability in the blend are highly desired and strictly enforced by the U.S. Food and Drug Administration. Another challenge in product development is that about 40% of newly discovered drug compounds have poor solubility which subsequently affects their bioavailability. An important aspect of pharmaceutical process development is the final product cost. As pharmaceutical companies strive to develop more affordable drugs, any possible elimination of lengthy and expensive unit operations becomes commercially advantageous. One group of such unit operations is associated with the control of API attributes (size, size distribution, shape, bulk density, etc.). These unit operations can include crystallization and various milling steps. The need for control of API attributes is solely dictated by the drug product development and usually is associated with desired improvements in blend uniformity or release profile. Having a formulation process that can make these and other steps unnecessary can provide a large advantage to pharmaceutical companies. In this talk, we will discuss a manufacturing method for solid dosage forms using fluidized bed impregnation of APIs onto porous excipients (inactive filler powders) that can potentially address all of the above challenges in drug substance and product development.
Fluidized bed impregnation can be summarized as the combination of three distinct processes taking place simultaneously. These include fluidization of the porous carrier, spraying API solution within the bed, which penetrates the excipient due to capillary forces, and drying of the porous particles causing the API to be deposited within. In this talk, we will present results showing that this process can deliver powder with high blend uniformity and tablets/capsules with high content uniformity. In addition, we show that the final API loading is not limited by its solubility in the organic solvent. Our results also show that fluidized bed impregnation does not depend on the nature of the API but rather on the nature of the excipient used. The product is an excipient impregnated with API that has flow properties that depend on the excipient and not on the physical properties of the API. In addition, we show that the product that is produced can significantly increase the dissolution kinetics of poorly soluble APIs. Implementing fluidized bed impregnation in drug manufacturing could allow for significant cost savings due to elimination of several unit operations.