Open AccessFormulation optimization of hot‐melt extruded abuse deterrent pellet dosage form utilizing design of experiments
Author(s) -
Maddineni Sindhuri,
Battu Sunil Kumar,
Morott Joe,
Soumyajit Majumdar,
Repka Michael A.
Publication year - 2014
Publication title -
journal of pharmacy and pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.745
H-Index - 118
eISSN - 2042-7158
pISSN - 0022-3573
DOI - 10.1111/jphp.12129
Subject(s) - box–behnken design , extrusion , pellets , response surface methodology , materials science , particle size , pellet , dosage form , chromatography , chemical engineering , chemistry , composite material , engineering
Abstract Objective The objective of this study was to develop techniques for an abuse‐deterrent ( AD ) platform utilizing the hot‐melt extrusion ( HME ) process. Methods Formulation optimization was accomplished by utilizing B ox– B ehnken design of experiments to determine the effect of the three formulation factors: PolyOx WSR 301, B enecel K15M and C arbopol 71 G ; each of which was studied at three levels on tamper‐resistant ( TR ) attributes of the produced melt extruded pellets. A response surface methodology was utilized to identify the optimized formulation. Lidocaine hydrochloride was used as a model drug, and suitable formulation ingredients were employed as carrier matrices and processing aids. Key findings All of the formulations were evaluated for the TR attributes, such as particle size post‐milling, gelling and percentage of drug extraction in water and alcohol. All of the design of experiments formulations demonstrated sufficient hardness and elasticity, and could not be reduced into fine particles (<150 μm), which is a desirable feature to prevent snorting. In addition, all of the formulations exhibited good gelling tendency in water with minimal extraction of drug in the aqueous medium. Moreover, B enecel K15M , in combination with PolyOx WSR 301, could be utilized to produce pellets with TR potential. Conclusion HME has been demonstrated to be a viable technique with a potential to develop novel AD formulations.