title: Development and evaluation of accelerated drug release testing methods for a matrix-type intravaginal ring.
abstract: Accelerated drug release testing is a valuable quality control tool for long-acting non-oral extended release formulations. Currently, several intravaginal ring candidates designed for the long-term delivery of steroids or anti-infective drugs are being in the developing pipeline. The present article addresses the demand for accelerated drug release methods for these formulations. We describe the development and evaluation of accelerated release methods for a steroid releasing matrix-type intravaginal ring. The drug release properties of the formulation were evaluated under real-time and accelerated test conditions. Under real-time test conditions drug release from the intravaginal ring was strongly affected by the steroid solubility in the release medium. Under sufficient sink conditions that were provided in release media containing surfactants drug release was Fickian diffusion driven. Both temperature and hydro-organic dissolution media were successfully employed to accelerate drug release from the formulation. Drug release could be further increased by combining the temperature effect with the application of a hydro-organic release medium. The formulation continued to exhibit a diffusion controlled release kinetic under the investigated accelerated conditions. Moreover, the accelerated methods were able to differentiate between different prototypes of the intravaginal ring that exhibited different release profiles under real-time test conditions. Overall, the results of the present study indicate that both temperature and hydro-organic release media are valid parameters for accelerating drug release from the intravaginal ring. Variation of either a single or both parameters yielded release profiles that correlated well with real-time release.
authors: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17487 Greifswald, Germany.
authors: Anna
authors: A
authors: Externbrink
authors: Research Center Pharmaceutical Engineering GmbH, 8010 Graz, Austria.
authors: Karin
authors: K
authors: Eggenreich
authors: Research Center Pharmaceutical Engineering GmbH, 8010 Graz, Austria.
authors: Simone
authors: S
authors: Eder
authors: Research Center Pharmaceutical Engineering GmbH, 8010 Graz, Austria.
authors: Stefan
authors: S
authors: Mohr
authors: Evestra GmbH, 12439 Berlin, Germany.
authors: Klaus
authors: K
authors: Nickisch
authors: Department of Pharmacy, Biopharmaceutics and Pharmaceutical Technology, University of Greifswald, 17487 Greifswald, Germany. Electronic address: sandra.klein@uni-greifswald.de.
authors: Sandra
authors: S
authors: Klein
mesh_terms: D000282:Administration, Intravaginal; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D003274:Contraceptive Devices, Female; D003470:Culture Media / Q000737:chemistry; D003692:Delayed-Action Preparations; D004058:Diffusion; D016503:Drug Delivery Systems; D015195:Drug Design; D065546:Drug Liberation; D004867:Equipment Design; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D016014:Linear Models; D009930:Organic Chemicals; D011108:Polymers / Q000737:chemistry; D011786:Quality Control; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013256:Steroids / Q000008:administration & dosage / Q000737:chemistry; D013696:Temperature; D013997:Time Factors
chemical_list: D003470:Culture Media; D003692:Delayed-Action Preparations; D009930:Organic Chemicals; D011108:Polymers; D012997:Solvents; D013256:Steroids
keywords: Accelerated drug release methods; Diffusion controlled drug release; Drug release kinetics; Hydro-organic dissolution media; Temperature-controlled drug release; Vaginal drug delivery