PhD ceremony: Ms. P. Srinarong, 13.15 uur, Academiegebouw, Broerstraat 5, Groningen
Title: Improved dissolution behavior of lipophilic drugs by solid dispersions: a matter of composition
Promotor(s): prof. H.W. Frijlink
Faculty: Mathematics and Natural Sciences
Solid dispersions can be used to improve the dissolution behavior of poorly water-soluble drugs and thereby their bioavailability after oral administration. Solid dispersions are generally composed of drugs incorporated in hydrophilic carriers. Parinda Srinarong has investigated the effects of the type and molecular weight of the hydrophilic carrier, the drug load and the presence of additives on the dissolution behavior and stability of tablets prepared from solid dispersions were.
It was found by her that when the drug load was high and/or when the carrier dissolved fast, the dissolution rate of the drug was slow. This phenomenon was attributed to uncontrolled crystallization of the drug in the near vicinity of the dissolving tablet due to a high supersaturation. Higher drug loads could be applied without the occurrence of recrystallization of the drug when carriers were used that interacted with the drugs. This could Srinarong ascribe to an increased solubility of the drug in the near vicinity of the dissolving tablet due to a high local concentration of the carrier. Furthermore, it was found by her that the incorporation of a superdisintegrant in the solid dispersion tablets can also prevent recrystallization of the drug. In this case, the tablet disintegrated so fast that supersaturation of the drug in the near vicinity of the dissolving tablet was prevented. To demonstrate the potential of this platform technology, it was applied to a range of different drugs such as diazepam, fenofibrate, ritonavir, efavirenz and tacrolimus.
Finally, a number of the solid dispersion tablets that showed excellent dissolution behavior also showed an excellent storage stability.
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