Direct Drug Loading into Preformed Porous Solid Dosage Units by the Controlled Particle Deposition (CPD), a New Concept for Improved Dissolution Using SCF-Technology

Abstract

The controlled particle deposition (CPD), a supercritical fluid precipitation process, is used to load porous tablets with ibuprofen to improve drug dissolution. Porous tablets (porosity 44.3 +/- 5.5%), consisting of microcrystalline cellulose pellets and hydroxyethylcellulose, or sugar cubes (porosity 37.2 +/- 0.5%), are used as carrier material. Loading experiments are conducted at 313 K and 25 MPa, drug concentrations between 6.25 and 33.3 mg ibuprofen/mL supercritical carbon dioxide and contact times of 15.5 h or 5 min. The resulting products have drug contents of 3-5 g ibuprofen/mL void volume in the carrier. Comparison of a predicted value, calculated from pore volume and loading concentration to the actual drug concentrations yielded by the loading process demonstrates the efficiency and controllability of the process. The mean particle size d(50) of deposited ibuprofen is around 25 microm, half the size of the starting material. Drug dissolution from loaded carriers is significantly increased by a rise in the dissolution coefficient from 0.07 min(-1) for the starting material to 0.13 or 0.14 min(-1) for the CPD products. The CPD method therefore is presented as a feasible and controllable process to load porous solid dosage forms with drug particles in order to improve dissolution.