A rapid method for creating drug implants: translating laboratory-based methods into a scalable manufacturing process.
Low compliance with medication is the major cause of poor outcome in schizophrenia treatment. While surgically implantable solvent-cast pellets were produced to improve outcome by increased compliance with medication, this process is laborious and time-consuming, inhibiting its broader application (Siegel et al., Eur J Pharm Biopharm 2006;64:287-293). In this study, the previous fabrication process was translated to a continuous and scalable extrusion method. Extrusion processes were modified based on in vitro release studies, drug load consistency examination, and surface morphology analysis using scanning electron microscopy. Afterward, optimized haloperidol implants were implanted into rats for preliminary analysis of biocompatibility. Barrel temperature, screw speed and resulting processing pressure influenced surface morphology and drug release. Data suggest that fewer surface pores shift the mechanism from bulk to surface PLGA degradation and longer lag period. Results demonstrate that extrusion is a viable process for manufacturing antipsychotic implants.
Stanley Center for Experimental Therapeutics, Department of Psychiatry, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Cheng-Kuo
CK
Wang
Wan-Yi
WY
Wang
Robert F
RF
Meyer
Yuling
Y
Liang
Karen I
KI
Winey
Steven J
SJ
Siegel
D000818:Animals; D014150:Antipsychotic Agents / Q000493:pharmacokinetics* / Q000494:pharmacology; D004343:Drug Implants / Q000493:pharmacokinetics* / Q000494:pharmacology; D006220:Haloperidol / Q000493:pharmacokinetics* / Q000494:pharmacology; D051381:Rats; D012559:Schizophrenia / Q000188:drug therapy*
D014150:Antipsychotic Agents; D004343:Drug Implants; D006220:Haloperidol