Blinding controlled-release tablets for clinical trials.
The objective of the current study was to develop a method to blind commercially available Wellbutrin SR 150 mg sustained-release tablets for a clinical study. Overcoating was selected as the most appropriate blinding method. Hydroxypropyl methylcellulose (Opadry II) containing red iron oxide and titanium dioxide was applied to the Wellbutrin tablets at coating levels ranging from 0.5% to 4% weight gain. When compared against the uncoated product, no significant differences in drug release were noted over an 8-hr period. Matching placebo tablets, prepared using specially designed tablet tooling, were coated with the same cellulosic polymer that was used for the active. The coated active and placebo tablets were virtually indistinguishable. To test the applicability of this overcoating technique for blinding other controlled release products, the same procedure was used to coat Glucotrol XL 5 mg tablets and Theo-Dur 200 mg tablets. The debossing on the Theo-Dur tablets and the laser-drilled hole on the surface of the Glucotrol tablets prevented blinding. The Theo-Dur tablets were mechanically weak and not able to withstand the coating process. Dissolution testing revealed significantly higher amounts of drug were released from the blinded Glucotrol tablets compared to the unblinded product at the 12 hr time point. The findings from this study suggest that overcoating with pigmented hydroxypropyl methylcellulose may not be useful for blinding all controlled-release tablets.
Felton
Linda A
LA
College of Pharmacy, University of New Mexico, Albuquerque, New Mexico 87131, USA. lfelton@unm.edu
Wiley
Cody J
CJ
D000284:Administration, Oral; D016642:Bupropion / Q000008:administration & dosage / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D002986:Clinical Trials as Topic / Q000379:methods; D004311:Double-Blind Method; D004339:Drug Compounding / Q000295:instrumentation; D005913:Glipizide / Q000008:administration & dosage / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D010919:Placebos; D012995:Solubility; D013608:Tablets, Enteric-Coated; D013806:Theophylline / Q000008:administration & dosage / Q000737:chemistry; D013997:Time Factors
D010919:Placebos; D013608:Tablets, Enteric-Coated; D016642:Bupropion; D013806:Theophylline; D005913:Glipizide