Development and evaluation of nano-formulations for immediate release oral dosage forms of poorly soluble drugs / Zun Huang

Solubility and dissolution rate are essential for the oral absorption and thus bioavailability of poorly soluble drugs. Currently, there are various formulation approaches available to overcome issues in solubility and dissolution rate. However, single formulation approach always has its drawback. The purpose of this work was to explore the nano-cocrystal formulation by combining cocrystal and nanocrystal formulation technologies and to optimize the formulation by investigating its dissolution mechanism. A downstream process investigation was also explored to transform the nano-cocrystal formulation into a final oral solid dosage form. Preparation and optimization of nanocrystal formulations with different lab-scale wet milling methods Different laboratory-scale nanocrystal preparation methods were compared as milling efficiency and process attributes. Dual centrifugation milling was considered the most promising method with higher milling efficiency, formulation screening efficiency, and broader controllable process attributes. Applying the dual centrifugation milling method to efficiently screen stabilizers and adjust process parameters, optimized itraconazole nanocrystal stabilized by poloxamer 407 was produced with a mean particle size of 200 nm and PDI 0.2. The nanosuspension was physically stable at 4, 25 and 40 °C for one month. The optimized nanocrystal formulation exhibited a faster dissolution rate than the physical mixture and raw drug under sink or non-sink conditions in in vitro dissolution study. While compared with commercial product Sporanox®, nanocrystal formulation exhibited faster drug release under sink conditions but lower and limited solubility increment under non-sink conditions. Itraconazole nanocrystal formulation might not exhibit advantageous in vivo behavior compared to the commercial product. A selection of a suitable in vitro dissolution test to evaluate nanocrystal formulation was crucial. In addition, nanocrystalline formulation significantly improved the dissolution rate of ....

Medienart:	E-Book

Erscheinungsjahr:	2022
Erschienen:	Berlin: Freie Universität Berlin ; 2022

Sprache:	Englisch

Weiterer Titel:	Entwicklung und Bewertung von Nano Formulierungen für orale Darreichungsformen von schwerlöslichen Arzneimitteln mit sofortiger Freisetzung

Beteiligte Personen:	Huang, Zun [VerfasserIn]
Hochschulschrift:	Dissertation, Berlin, Freie Universität Berlin, 2021

Links:	refubium.fu-berlin.de [kostenfrei]

BKL:	58.28 / Pharmazeutische Technologie
Themen:	Hochschulschrift

Umfang:	1 Online-Ressource

doi:	10.17169/refubium-32963
Weitere IDs:	urn:nbn:de:kobv:188-refubium-33242-4

funding:
Förderinstitution / Projekttitel:

PPN (Katalog-ID):	1788384911