Extemporaneous Preparation Strategy for Early Phase Clinical Studies

Publication date: Available online 25 July 2018Source: International Journal of PharmaceuticsAuthor(s): Rampurna P. Gullapalli, Carolyn L. Mazzitelli, Christina M. Charriez, David J. Carpenter, Rebecca D. Crean, Bobbie Carter, Phil PereraAbstractExtemporaneous preparations (EPs) of investigational drugs, which are compounded at the clinical study site by a pharmacist, are being increasingly used in early phase clinical studies to accelerate the development of new medicines. The successful application of EP strategies in clinical studies requires ‘fit-for-purpose’ formulation design and preparation processes, as well as administration procedures that are safe, flexible, cost-effective, and simple to adapt by a compounding pharmacist at the clinical site. DNS-7801 is a weakly basic investigational compound that exhibits a higher aqueous solubility at lower pH with its solubility dropping off precipitously with increase in pH. This phenomenon is known to result in potential risk of variable and decreased exposure in vivo. Combination of citrate buffer at pH 3.0 and hydroxypropylbetadex enabled formulation of DNS-7801 solutions that were stable as formulated and up on manipulation for oral administration. The solutions were compatible with apple juice, used to mask (blind) the potential taste differences between the placebo and DNS-7801 solutions when dosing study subjects. The oral administration of the solutions resulted in dose proportional Cmax, AUC0-24, and AUC0-∞ of D...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research