A compaction process to enhance dissolution of poorly water-soluble drugs using hydroxypropyl methylcellulose.
The purpose of this study was to develop a technique to enhance the dissolution rate of poorly water-soluble drugs with hydroxypropyl methylcellulose (HPMC) without the use of solvent or heat addition. Three poorly water-soluble drugs, naproxen, nifedipine, and carbamazepine, were studied with low-viscosity HPMC USP Type 2208 (K3LV), HPMC USP Type 2910 (E3LV and E5LV), and methylcellulose. Polymer and drug were dry-blended, compressed into slugs on a tablet press or into ribbons on a roller compactor, and then milled into a granular powder. Dissolution testing of the milled powder was performed on USP Apparatus II, 100 rpm, 900 ml deionized water, 37 degrees C. Drug distribution vs. particle size was also studied. The compaction processes enhanced drug dissolution relative to drug alone and also relative to corresponding loosely mixed physical mixtures. The roller compaction and slugging methods produced comparable dissolution enhancement. The mechanism for dissolution enhancement is believed to be a microenvironment HPMC surfactant effect facilitated by keeping the HPMC and drug particles in close proximity during drug dissolution. The compaction methods in this study may provide a lower cost, quicker, readily scalable alternative for formulating poorly water-soluble drugs.
Mitchell
Shawn A
SA
Water Soluble Polymers, The Dow Chemical Company, Midland, MI 48674, USA. samitchell@dow.com
Reynolds
Thomas D
TD
Dasbach
Tina P
TP
D002220:Carbamazepine / Q000008:administration & dosage / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000008:administration & dosage* / Q000031:analogs & derivatives*; D009288:Naproxen / Q000008:administration & dosage / Q000737:chemistry; D009543:Nifedipine / Q000008:administration & dosage / Q000737:chemistry; D012995:Solubility; D013678:Technology, Pharmaceutical
D002220:Carbamazepine; D065347:Hypromellose Derivatives; D009288:Naproxen; D008747:Methylcellulose; D009543:Nifedipine