title: Enhanced release of poorly water-soluble drugs from synergy between mesoporous magnesium carbonate and polymers.
abstract: The need to combat poor water solubility has increased interest in supersaturating drug delivery systems. In this study, amorphous mesoporous magnesium carbonate (MMC) was used as a drug carrier to achieve supersaturation of tolfenamic acid and rimonabant, two drug compounds with low aqueous solubility. The potential synergy between MMC and hydroxypropyl methylcellulose (HPMC), a polymer commonly included as a precipitation inhibitor in drug delivery systems, was explored with the aim of extending the time that high supersaturation levels were maintained. Release was studied under physiological conditions using USP-2 dissolution baths. A new small-scale method was developed to enable measurement of the initial drug release occurring when the MMC is immersed in the water phase. It was shown that MMC and HPMC together resulted in significant supersaturation and that the polymer enabled both the achievement of a higher API concentration and extension of the supersaturation period. The new small-scale release method showed that the release was linearly increasing with the dose and that similar release rates were observed for the two model compounds. It was hence concluded that the MMC release was diffusion limited for the compounds explored.
authors.affiliation: Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-75121, Sweden.
authors.forename: Jiaojiao
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, P.O. Box 580, Uppsala SE-751 23, Sweden.
authors.forename: Caroline
authors.initials: C
authors.lastname: Alvebratt
authors.affiliation: Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-75121, Sweden.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-75121, Sweden.
authors.forename: Teresa
authors.initials: T
authors.lastname: Zardán Gómez de la Torre
authors.affiliation: Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-75121, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Strømme
authors.affiliation: Department of Pharmacy, Uppsala Biomedical Center, Uppsala University, P.O. Box 580, Uppsala SE-751 23, Sweden. Electronic address: christel.bergstrom@farmaci.uu.se.
authors.forename: Christel A S
authors.initials: CAS
authors.lastname: Bergström
authors.affiliation: Division of Nanotechnology and Functional Materials, Department of Engineering Sciences, Uppsala University, Uppsala SE-75121, Sweden. Electronic address: ken.welch@angstrom.uu.se.
authors.forename: Ken
authors.initials: K
authors.lastname: Welch
mesh_terms: D065546:Drug Liberation; D065347:Hypromellose Derivatives / Q000737:chemistry*; D008274:Magnesium / Q000737:chemistry*; D011108:Polymers; D012995:Solubility; D014867:Water
chemical_list: D011108:Polymers; D014867:Water; C005479:magnesium carbonate; D065347:Hypromellose Derivatives; D008274:Magnesium
keywords: Hydroxypropyl methylcellulose; Magnesium carbonate; Mesoporous; Rimonabant; Supersaturation; Tolfenamic acid