Biopharmacy Day location:Leuven, Belgium date:31 May 2008
Purpose. To develop suspendable powders for reconstitution of a next-generation non-nucleoside reverse transcriptase inhibitor (NNRTI; denoted as X) with low water solubility by using a spray-dry technology. Their flexible dosing ability provides patients with another option to taking tablets. The selection of formulation excipients was based on their potential to create and maintain supersaturation solubility of the active compound in 0.01 M HCl.
Materials and methods. Suitable water-soluble carriers for X were selected by a supersaturation screening and formulated into powders for reconstitution by spray-drying. The selected powders for reconstitution were then compared to a developed tablet formulation of X, in vitro using dissolution and stability testing, and in vivo through administration to beagle dogs, fed immediately after dosing.
Results. The spray-dried powders for reconstitution made up of X/PVP-VA 64 1:9 (w/w) and X/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w) showed ease of suspendability, nearly complete dissolution of the drug substance and acceptable stability after one month storage at 25°C and 40°C. In dogs, X was more slowly absorbed from tablets than from the suspended powders for reconstitution. Compared to the tablet, the relative biovailability obtained with the powders ranged from 69 to 89% for X/PVP-VA 64 1:9 (w/w) and from 85 to 157% for X/PVP-VA 64/Cremophor EL 1:8.5:0.5 (w/w/w).
Conclusions. The absence of in vivo and in vitro differences between the powders made an eventual choice very difficult. Their advantageous in vivo behaviour and alternate dosing possibility may provide a starting point for pediatric formulations.