Development of a Video-Microscopic Tool To Evaluate the Precipitation Kinetics of Poorly Water Soluble Drugs: A Case Study with Tadalafil and HPMC

Research output: Contribution to journalJournal article – Annual report year: 2017Researchpeer-review

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  • Author: Christfort, Juliane Fjelrad

    University of Copenhagen, Denmark

  • Author: Plum, Jakob

    University of Copenhagen, Denmark

  • Author: Madsen, Cecilie Maria

    University of Copenhagen, Denmark

  • Author: Nielsen, Line Hagner

    Nanoprobes, Department of Micro- and Nanotechnology, Technical University of Denmark, Ørsteds Plads, 2800, Kgs. Lyngby, Denmark

  • Author: Sandau, Martin

    Philips Biocell A/S, Denmark

  • Author: Andersen, Klaus

    Philips Biocell A/S, Denmark

  • Author: Müllertz, Anette

    University of Copenhagen, Denmark

  • Author: Rades, Thomas

    University of Copenhagen, Denmark

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Many drug candidates today have a low aqueous solubility and, hence, may show a low oral bioavailability, presenting a major formulation and drug delivery challenge. One way to increase the bioavailability of these drugs is to use a supersaturating drug delivery strategy. The aim of this study was to develop a video-microscopic method, to evaluate the effect of a precipitation inhibitor on supersaturated solutions of the poorly soluble drug tadalafil, using a novel video-microscopic small scale setup. Based on preliminary studies, a degree of supersaturation of 29 was chosen for the supersaturation studies with tadalafil in FaSSIF. Different amounts of hydroxypropyl methyl cellulose (HPMC) were predissolved in FaSSIF to give four different concentrations, and the supersaturated system was then created using a solvent shift method. Precipitation of tadalafil from the supersaturated solutions was monitored by video-microscopy as a function of time. Single-particle analysis was possible using commercially available software; however, to investigate the entire population of precipitating particles (i.e., their number and area covered in the field of view), an image analysis algorithm was developed (multiparticle analysis). The induction time for precipitation of tadalafil in FaSSIF was significantly prolonged by adding 0.01% (w/v) HPMC to FaSSIF, and the maximum inhibition was reached at 0.1% (w/v) HPMC, after which additional HPMC did not further increase the induction time. The single-particle and multiparticle analyses yielded the same ranking of the HPMC concentrations, regarding the inhibitory effect on precipitation. The developed small scale method to assess the effect of precipitation inhibitors can speed up the process of choosing the right precipitation inhibitor and the concentration to be used.
Original languageEnglish
JournalMolecular Pharmaceutics
Volume14
Issue number12
Pages (from-to)4154–4160
ISSN1543-8384
DOIs
Publication statusPublished - 2017
CitationsWeb of Science® Times Cited: No match on DOI

    Research areas

  • Crystalline, Oral drug delivery, Precipitation, Supersaturation

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