title: Polymer excipients enable sustained drug release in low pH from mechanically strong inorganic geopolymers.
abstract: Improving acid resistance, while maintaining the excellent mechanical stability is crucial in the development of a sustained and safe oral geopolymer dosage form for highly potent opioids. In the present work, commercially available Methacrylic acid-ethyl acrylate copolymer, Polyethylene-glycol (PEG) and Alginate polymer excipients were included in dissolved or powder form in geopolymer pellets to improve the release properties of Zolpidem, herein acting as a model drug for the highly potent opioid Fentanyl. Scanning electron microscopy, compression strength tests and drug release experiments, in gastric pH 1 and intestinal pH 6.8 conditions, were performed. The polymer excipients, with an exception for PEG, reduced the drug release rate in pH 1 due to their ability to keep the pellets in shape, in combination with the introduction of an insoluble excipient, and thereby maintain a barrier towards drug diffusion and release. Neither geopolymer compression strength nor the release in pH 6.8 was considerably impaired by the incorporation of the polymer excipients. The geopolymer/polymer composites combine high mechanical strength and good release properties under both gastric and intestinal pH conditions, and are therefore promising oral dosage forms for sustained release of highly potent opioids.
authors.affiliation: Division for Nanotechnology and Functional Materials, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Jämstorp
authors.affiliation: Division for Nanotechnology and Functional Materials, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden.
authors.forename: Tejaswi
authors.initials: T
authors.lastname: Yarra
authors.affiliation: Division for Applied Materials Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden.
authors.forename: Bing
authors.initials: B
authors.lastname: Cai
authors.affiliation: Division for Applied Materials Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden.
authors.forename: Håkan
authors.initials: H
authors.lastname: Engqvist
authors.affiliation: Division for Applied Materials Science, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden ; Orexo AB, P.O. Box 303, SE-751 05 Uppsala, Sweden.
authors.forename: Susanne
authors.initials: S
authors.lastname: Bredenberg
authors.affiliation: Division for Nanotechnology and Functional Materials, Department of Engineering Sciences, The Ångström Laboratory, Uppsala University, Box 534, SE-751 21 Uppsala, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Strømme
keywords: Acidic conditions; Controlled release; Geopolymers; Opioids; Oral administration; Polymers