Development of orally disintegrating tablets comprising controlled-release multiparticulate beads

Abstract

Melperone is an atypical antipsychotic agent that has shown a wide spectrum of neuroleptic properties, particularly effective in the treatment of senile dementia and Parkinson’s-associated psychosis, and is marketed in Europe as an immediate-release (IR) tablet and syrup. An orally disintegrating tablet (ODT) dosage form would be advantageous for patients who experience difficulty in swallowing large tablets or capsules or those who experience dysphagia. Controlled-release (CR) capsule and ODT formulations containing melperone HCl were developed with target in vitro release profiles suitable for a once-daily dosing regimen. Both dosage forms allow for the convenient production of dose-proportional multiple strengths. Two ODT formulations exhibiting fast and medium release profiles and one medium release profile capsule formulation (each 50 mg) were tested in vivo using IR syrup as the reference. The two medium release formulations were shown to be bioequivalent to each other and are suitable for once-daily dosing. Based on the analytical and organoleptic test results, as well as the blend uniformity and in-process compression data at various compression forces using coated beads produced at one-tenth (1/10) commercial scale, both formulations in the form of CR capsules and CR ODTs have shown suitability for progression into further clinical development.

Keywords::

• Once-daily multi-particulate dosage forms
• AdvaTab^®
• Diffucaps^®
• melperone
• pharmacokinetic modeling
• process optimization design

The authors would like express their heartfelt thanks to Craig Kramer, Julius King, Oscar Batista, Bennie Young, Jeffrey Overfield, Ken Easter, Jennifer Fielder, Mark Dahlin, Dan Hensley, Jennifer Neuforth, for their technical and analytical support.

Declaration of interest

The product was co-developed in partnership with a pharmaceutical company which was responsible for designing and performing multiple clinical studies using the clinical trial materials (CTMs) manufactured by Aptalis Pharma. However, the partner does not want to be publicly acknowledged.