Pelletization of a β-Cyclodextrin-Acetaminophen Interaction Compound in a Rotary Fluid Bed Granulator : an Optimization Study

Drug/cyclodextrin (CD) interaction compounds are widely used in the design of solid dosage forms for their ability to improve drug bioavailability, especially where poorly soluble active ingredients are concerned. Because of high CD molecular weights and fixed drug/CD interaction ratios (generally ≤ 1 mol/mol), major issues may have to be faced when formulating high-dose drug products. In the present work, high-density pellets prepared by rotary processing in fluid bed equipment are proposed for the oral administration of drug/CD interaction compounds. The manufacturing process of pellets containing approximately 75% of an acetaminophen/ß-CD kneaded product was developed based on a sequential statistical optimization study. In particular, the effect of the quantity of water, air-flow rate and plate rotational speed on the process yield and physical-technological characteristics of pellets was studied. The optimization study performed was helpful in providing an overall understanding of the process and a predictive model for its further development.