Calculation of drug-polymer mixing enthalpy as a new screening method of precipitation inhibitors for supersaturating pharmaceutical formulations

dc.accessRightsAnonymous*
dc.audienceScienceen_US
dc.contributor.authorKuentz, Martin
dc.date.accessioned2020-02-06T10:57:34Z
dc.date.available2020-02-06T10:57:34Z
dc.date.issued2019-03-12
dc.description.abstractSupersaturating formulations are widely used to improve the oral bioavailability of poorly soluble drugs. However, supersaturated solutions are thermodynamically unstable and such formulations often must include a precipitation inhibitor (PI) to sustain the increased concentrations to ensure that sufficient absorption will take place from the gastrointestinal tract. Recent advances in understanding the importance of drug-polymer interaction for successful precipitation inhibition have been encouraging. However, there still exists a gap in how this newfound understanding can be applied to improve the efficiency of PI screening and selection, which is still largely carried out with trial and error-based approaches. The aim of this study was to demonstrate how drug-polymer mixing enthalpy, calculated with the Conductor like Screening Model for Real Solvents (COSMO-RS), can be used as a parameter to select the most efficient precipitation inhibitors, and thus realize the most successful supersaturating formulations. This approach was tested for three different Biopharmaceutical Classification System (BCS) II compounds: dipyridamole, fenofibrate and glibenclamide, formulated with the supersaturating formulation, mesoporous silica. For all three compounds, precipitation was evident in mesoporous silica formulations without a precipitation inhibitor. Of the nine precipitation inhibitors studied, there was a strong positive correlation between the drug-polymer mixing enthalpy and the overall formulation performance, as measured by the area under the concentration-time curve in in vitro dissolution experiments. The data suggest that a rank-order based approach using calculated drug-polymer mixing enthalpy can be reliably used to select precipitation inhibitors for a more focused screening. Such an approach improves efficiency of precipitation inhibitor selection, whilst also improving the likelihood that the most optimal formulation will be realized.en_US
dc.description.urihttps://www.ncbi.nlm.nih.gov/pubmed/30877067en_US
dc.identifier.doi10.1016/j.ejps.2019.03.006
dc.identifier.issn0928-0987
dc.identifier.issn1879-0720
dc.identifier.urihttps://irf.fhnw.ch/handle/11654/30425
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofEuropean Journal of Pharmaceutical Sciencesen_US
dc.subjectBioenabling formulationsen_US
dc.subjectEnthalpyen_US
dc.subjectPrecipitation inhibitionen_US
dc.subjectScreeningen_US
dc.subjectSupersaturationen_US
dc.subjectin silico toolsen_US
dc.titleCalculation of drug-polymer mixing enthalpy as a new screening method of precipitation inhibitors for supersaturating pharmaceutical formulationsen_US
dc.type01A - Beitrag in wissenschaftlicher Zeitschrift
dc.volume132en_US
dspace.entity.typePublication
fhnw.InventedHereYesen_US
fhnw.IsStudentsWorknoen_US
fhnw.PublishedSwitzerlandYesen_US
fhnw.ReviewTypeAnonymous ex ante peer review of a complete publicationen_US
fhnw.affiliation.hochschuleHochschule für Life Sciencesde_CH
fhnw.affiliation.institutInstitut für Pharma Technologyde_CH
fhnw.pagination142-156en_US
fhnw.publicationOnlineJaen_US
fhnw.publicationStatePublisheden_US
relation.isAuthorOfPublication68819448-8611-488b-87bc-1b1cf9a6a1b4
relation.isAuthorOfPublication.latestForDiscovery68819448-8611-488b-87bc-1b1cf9a6a1b4
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