title: Determination of the mechanical properties of solid and cellular polymeric dosage forms by diametral compression.
abstract: At present, the immediate-release solid dosage forms, such as the oral tablets and capsules, are granular solids. They release drug rapidly and have adequate mechanical properties, but their manufacture is fraught with difficulties inherent in processing particulate matter. Such difficulties, however, could be overcome by liquid-based processing. Therefore, we have recently introduced polymeric cellular (i.e., highly porous) dosage forms prepared from a melt process. Experiments have shown that upon immersion in a dissolution medium, the cellular dosage forms with polyethylene glycol (PEG) as excipient and with predominantly open-cell topology disintegrate by exfoliation, thus enabling rapid drug release. If the volume fraction of voids of the open-cell structures is too large, however, their mechanical strength is adversely affected. At present, the common method for determining the tensile strength of brittle, solid dosage forms (such as select granular forms) is the diametral compression test. In this study, the theory of diametral compression is first refined to demonstrate that the relevant mechanical properties of ductile and cellular solids (i.e., the elastic modulus and the yield strength) can also be extracted from this test. Diametral compression experiments are then conducted on PEG-based solid and cellular dosage forms. It is found that the elastic modulus and yield strength of the open-cell structures are about an order of magnitude smaller than those of the non-porous solids, but still are substantially greater than the stiffness and strength requirements for handling the dosage forms manually. This work thus demonstrates that melt-processed polymeric cellular dosage forms that release drug rapidly can be designed and manufactured to have adequate mechanical properties.
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: D002214:Capsules / Q000737:chemistry; D004304:Dosage Forms; D065546:Drug Liberation; D055119:Elastic Modulus; D005079:Excipients / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D011108:Polymers / Q000737:chemistry*; D016062:Porosity; D012995:Solubility; D013607:Tablets / Q000737:chemistry; D013678:Technology, Pharmaceutical / Q000379:methods; D013718:Tensile Strength
chemical_list: D002214:Capsules; D004304:Dosage Forms; D005079:Excipients; D011108:Polymers; D013607:Tablets; D011092:Polyethylene Glycols
keywords: Cellular dosage forms; Cellular materials; Diametral compression test; Drug manufacture; Mechanical characterization of cellular solids; Mechanical properties of pharmaceutical tablets