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

• Published in: Journal of pharmacy and pharmacology 2014-02, Vol.66 (2), p.309-322
• Main Authors: Maddineni, Sindhuri, Battu, Sunil Kumar, Morott, Joe, Soumyajit, Majumdar, Repka, Michael A.
• Format: Article
• Language: English
• Subjects: abuse-deterrent; Acrylates - chemistry; Administration, Inhalation; Cellulose - chemistry; Chemistry, Pharmaceutical - methods; design of experiment; Drug Carriers - chemistry; Drug Compounding - methods; Drug Stability; Elasticity; Excipients - chemistry; Freezing; Gels; Hardness; Hot Temperature; hot-melt extrusion; Humans; insufflation; Lidocaine - administration & dosage; Lidocaine - chemistry; optimization; Particle Size; Polyethylene Glycols - chemistry; Solubility; Substance-Related Disorders - prevention & control
• ISSN: 0022-3573; 2042-7158
• DOI: 10.1111/jphp.12129

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 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. 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 (