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dc.contributor.authorOjaranta, Rami
dc.contributor.authorHeikkinen, Aki T.
dc.contributor.authorSievänen, Elina
dc.contributor.authorLaitinen, Riikka
dc.date.accessioned2016-12-14T09:58:40Z
dc.date.available2017-11-22T22:45:10Z
dc.date.issued2017
dc.identifier.citationOjaranta, R., Heikkinen, A. T., Sievänen, E., & Laitinen, R. (2017). Dissolution behavior of co-amorphous amino acid-indomethacin mixtures : The ability of amino acids to stabilize the supersaturated state of indomethacin. <i>European Journal of Pharmaceutics and Biopharmaceutics</i>, <i>112</i>, 85-95. <a href="https://doi.org/10.1016/j.ejpb.2016.11.023" target="_blank">https://doi.org/10.1016/j.ejpb.2016.11.023</a>
dc.identifier.otherCONVID_26327381
dc.identifier.otherTUTKAID_71785
dc.identifier.urihttps://jyx.jyu.fi/handle/123456789/52340
dc.description.abstractArginine, phenylalanine, and tryptophan have been previously shown to improve the solid-state stability of amorphous indomethacin. The present study investigates the ability of these amino acids to prolong the supersaturation of indomethacin in both aqueous and biorelevant conditions either when freely in solution or when formulated as co-amorphous mixtures. The co-amorphous amino acid-indomethacin mixtures (molar ratio 1:1) and amorphous indomethacin were prepared by cryomilling. Dissolution and precipitation tests were performed in buffer solutions (pH 5 and 6.5) and in Fed and Fasted State Simulated Intestinal Fluids (FeSSIF and FaSSIF, respectively). Precipitation tests were conducted with the solvent shift method. The supersaturation stability of indomethacin and the precipitation inhibitory effect of amino acids were evaluated by calculating the supersaturation factor and the excipient gain factor, respectively. Biorelevant media exerted a significant effect on indomethacin solubility but had little effect on the supersaturation stability. Arginine had the most significant impact on the dissolution properties of indomethacin, but also phenylalanine and tryptophan stabilized supersaturation in some media when formulated as co-amorphous mixtures with indomethacin. Only arginine stabilized supersaturation without co-amorphization, an effect only observed in media of pH 6.5. The unique behavior of the arginine-indomethacin mixture was further demonstrated by the abrupt formation of a precipitate, when an excess physical mixture of arginine and indomethacin was added to FeSSIF (pH 6.5). The solid-state investigation of this precipitate indicated that it probably consisted of crystalline arginine-indomethacin salt with possibly some residual crystalline starting materials.
dc.language.isoeng
dc.publisherElsevier BV; Arbeitsgemeinschaft fuer Pharmazeutische Verfahrenstechnik e.V.
dc.relation.ispartofseriesEuropean Journal of Pharmaceutics and Biopharmaceutics
dc.subject.otherco-amorphous
dc.subject.otheramino acid
dc.subject.othersupersaturation
dc.subject.otherprecipitation
dc.subject.otherbiorelevant
dc.titleDissolution behavior of co-amorphous amino acid-indomethacin mixtures : The ability of amino acids to stabilize the supersaturated state of indomethacin
dc.typearticle
dc.identifier.urnURN:NBN:fi:jyu-201612024902
dc.contributor.laitosKemian laitosfi
dc.contributor.laitosDepartment of Chemistryen
dc.contributor.oppiaineOrgaaninen kemiafi
dc.contributor.oppiaineOrganic Chemistryen
dc.type.urihttp://purl.org/eprint/type/JournalArticle
dc.date.updated2016-12-02T04:23:53Z
dc.type.coarjournal article
dc.description.reviewstatuspeerReviewed
dc.format.pagerange85-95
dc.relation.issn0939-6411
dc.relation.numberinseries0
dc.relation.volume112
dc.type.versionacceptedVersion
dc.rights.copyright© 2016 Elsevier B.V. This is a final draft version of an article whose final and definitive form has been published by Elsevier. Published in this repository with the kind permission of the publisher.
dc.rights.accesslevelopenAccessfi
dc.relation.doi10.1016/j.ejpb.2016.11.023


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