title: An active film-coating approach to enhance chemical stability of a potent drug molecule.
abstract: Peliglitazar, a PPAR α/γ agonist, was found to undergo acid as well as base catalyzed degradation. The acid catalyzed degradation led to the formation of benzylic alcohol and glycine carbamate and the base catalyzed degradation led to formation of p-hydroxyanisole and an amine degradant. In capsule formulations, the capsules with the lowest drug-loading exhibited maximum instability even at 25 °C/60% RH storage condition. Incorporation of pH-modifiers to maintain 'micro-environmental pH' acidic did not prevent the formation of the base-catalyzed degradants. Traditional dry granulated tablet formulation which is qualitatively similar to the capsule formulations showed the presence of acid-catalyzed degradants even without the presence of an acidifying agent. On the other hand, traditional wet granulated tablet formulation showed mainly base-catalyzed degradants. Stability problems of the tablet formulation were aggravated because the potent molecule required low tablet strengths which resulted in low drug to excipient ratio. To stabilize the molecule, an active film-coating approach was explored. In this approach, the drug was sprayed with the coating material onto non-active containing tablet cores. This approach of trapping the drug particles into the coating material provided tablets with satisfactory chemical stability. The stability enhancement observed in the active coating approach is attributed to the higher drug to excipient ratio in the film coat of non-reactive coating material compared to that in the traditional dry or wet granulated formulations.
authors.affiliation: Research and Development, Bristol-Myers Squibb Company, New Brunswick, New Jersey 08903-0191, USA. divyakant.desai@bms.com
authors.forename: Divyakant
authors.initials: D
authors.lastname: Desai
authors.forename: Venkatramana
authors.initials: V
authors.lastname: Rao
authors.forename: Hang
authors.initials: H
authors.lastname: Guo
authors.forename: Danping
authors.initials: D
authors.lastname: Li
authors.forename: Daniel
authors.initials: D
authors.lastname: Stein
authors.forename: Frank Y
authors.initials: FY
authors.lastname: Hu
authors.forename: Chris
authors.initials: C
authors.lastname: Kiesnowski
mesh_terms: D002214:Capsules; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005998:Glycine / Q000031:analogs & derivatives* / Q000737:chemistry; D010080:Oxazoles / Q000737:chemistry*; D047493:PPAR alpha / Q000819:agonists*; D047495:PPAR gamma / Q000819:agonists*; D011108:Polymers / Q000737:chemistry; D013607:Tablets
chemical_list: D002214:Capsules; D005079:Excipients; D010080:Oxazoles; D047493:PPAR alpha; D047495:PPAR gamma; D011108:Polymers; D013607:Tablets; C557782:peliglitazar; D005998:Glycine