title: Melt-processed polymeric cellular dosage forms for immediate drug release.
abstract: The present immediate-release solid dosage forms, such as the oral tablets and capsules, comprise granular matrices. While effective in releasing the drug rapidly, they are fraught with difficulties inherent in processing particulate matter. By contrast, liquid-based processes would be far more predictable; but the standard cast microstructures are unsuited for immediate-release because they resist fluid percolation and penetration. In this article, we introduce cellular dosage forms that can be readily prepared from polymeric melts by incorporating the nucleation, growth, and coalescence of microscopic gas bubbles in a molding process. We show that the cell topology and formulation of such cellular structures can be engineered to reduce the length-scale of the mass-transfer step, which determines the time of drug release, from as large as the dosage form itself to as small as the thickness of the cell wall. This allows the cellular dosage forms to achieve drug release rates over an order of magnitude faster compared with those of cast matrices, spanning the entire spectrum of immediate-release and beyond. The melt-processed polymeric cellular dosage forms enable predictive design of immediate-release solid dosage forms by tailoring microstructures, and could be manufactured efficiently in a single step.
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA. Electronic address: ablaesi@mit.edu.
authors.forename: Aron H
authors.initials: AH
authors.lastname: Blaesi
authors.affiliation: Department of Mechanical Engineering, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
authors.forename: Nannaji
authors.initials: N
authors.lastname: Saka
mesh_terms: D000082:Acetaminophen / Q000737:chemistry*; D004304:Dosage Forms; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D007700:Kinetics; D008956:Models, Chemical; D011092:Polyethylene Glycols / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013499:Surface Properties; D044366:Transition Temperature
chemical_list: D004304:Dosage Forms; D005079:Excipients; D000082:Acetaminophen; D011092:Polyethylene Glycols; C000595216:polyethylene glycol 8000
keywords: Cellular dosage forms; Cellular materials; Drug manufacture; Drug release