PFI:AIR - TT: Manufacturing of Pharmaceuticals by Fluidized Bed Impregnation of Active Pharmaceutical Ingredients onto Porous Carriers

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This PFI: Accelerating Innovation Research (AIR) Technology Translation (TT) project focuses on translating fluidized bed impregnation technology to improve manufacturing of pharmaceuticals. This technology is important because pharmaceutical tablets and capsules are manufactured primarily by an inefficient process, which involves blending drug crystals called the API (Active Pharmaceutical Ingredient) with inactive filler powders (called excipients). The resulting mixture of powders is then further processed and fed into capsules or compressed to make tablets. During blending, it is difficult to make sure that the correct amount of the API is distributed throughout the excipient powders. During subsequent processing of the powder mixture it is challenging to keep the mixture mixed and prevent the excipients from segregating or flowing to different regions from the API. This is a particular challenge for low dose pharmaceuticals. If there is segregation or inadequate blending, it can lead to tablets or capsules with too much or too little drug substance. The resulting out-of-spec tablets and capsules must then be discarded. This project will result in a prototype of fluidized bed impregnation technology for manufacturing of pharmaceuticals. This technology has the following unique features: the impregnation of porous excipients with a solution containing the API and subsequent drying to produce excipients uniformly impregnated with the API. The excipients impregnated with the API can then be fed into capsules or compressed into tablets without concern for de-mixing or segregation of the API and excipients since the API is now present in the pores of the excipients. These features provide advantages of improved product quality and reductions in out-of-spec product when compared to the usual method of blending API crystals with excipients for making pharmaceuticals. This project addresses the following technology gaps as it translates from research discovery toward commercial application: 1) For very potent drugs, the amount of API in the solid dosage form can vary from 1% to 0.1% by weight. These very low API loadings pose one of the biggest challenges in pharmaceutical product development: the control of dose uniformity. Low API content variability is highly desired and strictly enforced by the U.S. Food and Drug Administration. 2) Another challenge in product development is that a large fraction of newly discovered drug compounds have poor solubility which subsequently affects their bioavailability. 3) Another 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. Fluidized bed impregnation of APIs onto porous excipients can potentially address all of the above challenges in drug substance and product development by improving dose uniformity, enhancing bioavailability and reducing the number of manufacturing steps. In addition, personnel involved in this project, graduate and undergraduate students, will receive innovation and technology translation experiences through specific training that will address these topics and by being involved with the commercialization of the technology.