Dissolution Testing of Hardly Soluble Materials by Surface Sensitive Techniques: Clotrimazole from an Insoluble Matrix

作者：Ehmann Heike M A; Winter Sascha; Griesser Thomas; Keimel Roman; Schrank Simone; Zimmer Andreas; Werzer Oliver^*

来源：Pharmaceutical Research, 2014, 31(10): 2708-2715.

DOI：10.1007/s11095-014-1368-5

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

Purpose The 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.
Methods In 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.
Results The 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.
Conclusion It 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.

• 出版日期2014-10