Dissolution Testing of Hardly Soluble Materials by Surface Sensitive Techniques: Clotrimazole from an Insoluble MatrixReport as inadecuate

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Pharmaceutical Research

, Volume 31, Issue 10, pp 2708–2715

First Online: 22 April 2014Received: 18 December 2013Accepted: 21 March 2014 ABSTRACT

PurposeThe low aqueous solubility of many drugs impedes detailed investigation as the detection limit of standard testing routines is limited. This is further complicated within application relevant thin films typical used in patches or stripes for buccal or topical routes.

MethodsIn this work a model system is developed based on spin – casting technique allowing defined clotrimazole and clotrimazole – polystyrene composite films preparation at a solid surface. Various highly sensitive techniques including quarz crystal microbalance QCM, X-ray reflevtivity XRR and X-ray photon spectroscopy XPS are used to investigate the drug release over time into an aqueous media.

ResultsThe results reveal a steady drug release for both samples over the course of the experiments but with the release from the composite being significantly slower. In addition the dissolution rate of the clotrimazole sample initially increases up to 30 min after which a decrease is noted. XRR shows that this is a result of surface roughening together with film thickness reduction. The results for the composite show that the release in the composite film is a result of drug diffusion within the matrix and collapsing PS film thickness whereby XPS shows that the amount of clotrimazole at the surface after 800 min immersion is still high.

ConclusionIt can be stated that the applied techniques allow following low mass drug release in detail which may also be applied to other systems like pellets or surface loaded nano-carriers providing information for processing and application relevant parameters.

KEY WORDSclotrimazole composite contact angle differential scanning calorimetry dissolution drug release polystyrene quartz crystal microbalance with dissipation thin film X-ray photoelectron spectroscopy X-ray reflectivity ABBREVIATIONSCAContact angle


DLSDynamic light scattering

DSCDifferential scanning calorimetry



QCM-DQuartz crystal micro balance with dissipation

XPSX-ray photoelectron spectroscopy

XRRX-ray reflectivity

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Author: Heike M. A. Ehmann - Sascha Winter - Thomas Griesser - Roman Keimel - Simone Schrank - Andreas Zimmer - Oliver Werzer

Source: https://link.springer.com/

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