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

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.

Solvent Vapor Annealing of Amorphous Carbamazepine Films for Fast Polymorph Screening and Dissolution Alteration

“…Depending on the processing conditions the films might be crystalline or amorphous. Employing faster processing like present in spin coating, amorphous phases frequently remain after solvent removal as found in samples of acetometaphene, clotrimazole, − or phenytoin. ,, Having such an amorphous film, crystallization routes distinct from standard bulk solution processes can be tested. For instance, mechanical stressing using atomic force microscopy might be employed for understanding crystallization in more detail.…”

Polymer Encapsulation of an Amorphous Pharmaceutical by initiated Chemical Vapor Deposition for Enhanced Stability

“…This results in a solid state solution, exhibiting a strongly retarded drug release. 27 In general, amorphous clotrimazole films persist for several days on storage under ambient conditions. Enhanced crystallization rates result, for instance, from heat treatment or solvent vapor annealing, which lead to a variation in the crystallite morphology but leave the polymorphic form unaffected; extended spherultic type growth, dendritic growth, or extended bar shape crystallites were observed.…”

“…Additionally, the usage of solution processes in the film preparation allows also for coprocessing clotrimazole with polymeric materials like polystyrene. This results in a solid state solution, exhibiting a strongly retarded drug release . In general, amorphous clotrimazole films persist for several days on storage under ambient conditions.…”

Wrinkle formation in a polymeric drug coating deposited via initiated chemical vapor deposition

“…The results shown here demonstrate also the advantage of using such deposition technique when compared, for instance, with a solution cast technique. 4 In such solution cast films, the matrix material and the clotrimazole layers formed a solid state solution but the XPS results revealed that a significant amount was hosted at the sample surface. While this may be interesting for a ready drug delivery, the drug molecules are not as well-protected against the environment as in the case of the iCVD encapsulation.…”

“…This is generally achieved by biocompatible polymer/drug composite layers or by dispersing the drug itself within a soluble or insoluble polymer matrix, thus forming a solid-state dispersion or solution. 3 , 4 …”