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dc.contributor.authorOjarinta Rami
dc.contributor.authorHeikkinen Aki T
dc.contributor.authorSievänen Elina
dc.contributor.authorLaitinen Riikka
dc.date.accessioned2017-03-30T07:23:25Z
dc.date.available2017-03-30T07:23:25Z
dc.date.issued2016
dc.identifier10.1016/j.ejpb.2016.11.023
dc.identifier.issn0939-6411
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/1185
dc.descriptionArticle
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
dc.relation.ispartofseriesEUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
dc.relation.urihttp://dx.doi.org/10.1016/j.ejpb.2016.11.023
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.rights.urihttp://dx.doi.org/10.1016/j.ejpb.2016.11.023
dc.subjectCo-amorphous
dc.subjectAmino acid
dc.subjectSupersaturation
dc.subjectPrecipitation
dc.subjectBiorelevant
dc.titleDissolution behavior of co-amorphous amino acid-indomethacin mixtures: The ability of amino acids to stabilize the supersaturated state of indomethacin
dc.typehttp://purl.org/eprint/type/JournalArticle
dc.rights.licenseCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.description.versionfinal draft
dc.contributor.departmentSchool of Pharmacy, Activities
uef.solecris.id43827931
eprint.statushttp://purl.org/eprint/status/PeerReviewed
dc.type.publicationinfo:eu-repo/semantics/article
dc.rights.accessrights© Elsevier BV
uef.citationinfo.issueVolume 112, March 2017
uef.citationinfo.pages85-95
dc.relation.doi10.1016/j.ejpb.2016.11.023
dc.description.reviewstatushttp://purl.org/eprint/status/PeerReviewed
dc.format.pagerange85-95
dc.relation.issn0939-6411
dc.relation.volume112


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