A rapid method for creating drug implants: Translating laboratory-based methods into a scalable manufacturing process

• Published in: Journal of biomedical materials research. Part B, Applied biomaterials Vol. 93B; no. 2; pp. 562 - 572
• Main Authors: Wang, Cheng-Kuo, Wang, Wan-Yi, Meyer, Robert F., Liang, Yuling, Winey, Karen I., Siegel, Steven J.
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2010; Wiley-Blackwell
• Subjects: Animals; Antipsychotic Agents - pharmacokinetics; Antipsychotic Agents - pharmacology; Biological and medical sciences; controlled drug release; Drug Implants - pharmacokinetics; Drug Implants - pharmacology; extrusion; formulation; General pharmacology; Haloperidol - pharmacokinetics; Haloperidol - pharmacology; implant; Medical sciences; Neuropharmacology; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; polylactic-co-glycolic acid (PLGA); Psycholeptics: tranquillizer, neuroleptic; Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; scanning electron microscopy (SEM); Schizophrenia - drug therapy; Rat; controlled drug release; Neuroleptic; Psychotropic; Lactic acid copolymer; Drug carrier; Haloperidol; Formulation; Antagonist; Manufacturing; scanning electron microscopy (SEM); Biomedical engineering; Glycolic acid copolymer; Delivery system; Scanning electron microscopy; Lactone copolymer; Pharmaceutical technology; Implant; Controlled release form; Control release polymer; Dopamine antagonist; Rodentia; Butyrophenone derivatives; polylactic-co-glycolic acid (PLGA); Vertebrata; Mammalia; D2 Dopamine receptor; Animal; Extrusion
• ISSN: 1552-4973; 1552-4981; 1552-4981
• DOI: 10.1002/jbm.b.31617

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. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2010.