Formulation optimization of hot-melt extruded abuse deterrent pellet dosage form utilizing design of experiments

Abstract

The objective of this study was to develop techniques for an abuse-deterrent (AD) platform utilizing the hot-melt extrusion (HME) process. Formulation optimization was accomplished by utilizing Box-Behnken design of experiments to determine the effect of the three formulation factors: PolyOx WSR301, Benecel K15M and Carbopol 71G; 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. 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, Benecel K15M, in combination with PolyOx WSR301, could be utilized to produce pellets with TR potential. HME has been demonstrated to be a viable technique with a potential to develop novel AD formulations.