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Dissolution and precipitation behavior of ternary solid dispersions of ezetimibe in biorelevant media
Umeå universitet, Medicinska fakulteten, Institutionen för farmakologi och klinisk neurovetenskap, Farmakologi.
2017 (engelsk)Inngår i: Drug Development and Industrial Pharmacy, ISSN 0363-9045, E-ISSN 1520-5762, Vol. 43, nr 1, s. 79-88Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The effects of different formulations and processes on inducing and maintaining the supersaturation of ternary solid dispersions of ezetimibe (EZ) in two biorelevant media fasted-state simulated intestinal fluid (FaSSIF) and fasted-state simulated gastric fluid (FaSSGF) at different temperatures (25 °C and 37 °C) were investigated in this work.

Ternary solid dispersions of EZ were prepared by adding polymer PVP-K30 and surfactant poloxamer 188 using melt-quenching and spray-drying methods. The resulting solid dispersions were characterized using scanning electron microscopy, differential scanning calorimetry (DSC), modulated DSC, powder X-ray diffraction and Fourier transformation infrared spectroscopy. The dissolution of all the ternary solid dispersions was tested in vitro under non-sink conditions.

All the prepared solid dispersions were amorphous in nature. In FaSSIF at 25 °C, the melt-quenched (MQ) solid dispersions of EZ were more soluble than the spray-dried (SD) solid dispersions and supersaturation was maintained. However, at 37 °C, rapid and variable precipitation behavior was observed for all the MQ and SD formulations. In FaSSGF, the melting method resulted in better solubility than the spray-drying method at both temperatures.

Ternary solid dispersions show potential for improving solubility and supersaturation. However, powder dissolution experiments of these solid dispersions of EZ at 25 °C may not predict the supersaturation behavior at physiologically relevant temperatures.

sted, utgiver, år, opplag, sider
2017. Vol. 43, nr 1, s. 79-88
Emneord [en]
Poorly soluble drugs, ternary solid dispersions, supersaturation, biorelevant media, dissolution
HSV kategori
Identifikatorer
URN: urn:nbn:se:umu:diva-133258DOI: 10.1080/03639045.2016.1220566ISI: 000394022300009PubMedID: 27487184OAI: oai:DiVA.org:umu-133258DiVA, id: diva2:1088140
Tilgjengelig fra: 2017-04-11 Laget: 2017-04-11 Sist oppdatert: 2018-06-09bibliografisk kontrollert

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