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Dissolution testing of hardly soluble materials by surface sensitive techniques: clotrimazole from an insoluble matrix.

Ehmann HM, Winter S, Griesser T, Keimel R, Schrank S, Zimmer A, Werzer O - Pharm. Res. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Universititätsplatz 1, 8010, Graz, Austria.

ABSTRACT

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.

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Related in: MedlinePlus

Sauerbrey mass loss (Δm) as function of the water rinsing time of various films (a). Corresponding time derivatives over the rinsing time of same signals (b). Both graphs are plotted on the same x-axis for comparability.
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Fig3: Sauerbrey mass loss (Δm) as function of the water rinsing time of various films (a). Corresponding time derivatives over the rinsing time of same signals (b). Both graphs are plotted on the same x-axis for comparability.

Mentions: Within a QCM-D experiment the change in resonance frequency with mass load change is determined allowing the desorption from the surface being followed. In Fig. 3a the relative Sauerbrey mass losses of three different thin film samples are shown as function of MilliQ-water rinsing times. The pure PS thin film shows a constant frequency over time which means that this film is not affected by the continuous rinsing. However, the pure clotrimazole film reveals a different behavior and shows a typical trajectory (nearly exponential decay) for a controlled desorption from a solid surface with a steady change of mass load with rinsing time. After a time of 73 min. the corresponding mass loss is 3.9 μg cm−2. Similarly, the immersion of the PS-Clot composite film reveals a steady mass loss, but the trajectory of the dissolution profile (now a Boltzmann function like decay) and the maximum mass loss is significantly different; after 73 min only 0.9 μg cm−2 is lost.Fig. 3


Dissolution testing of hardly soluble materials by surface sensitive techniques: clotrimazole from an insoluble matrix.

Ehmann HM, Winter S, Griesser T, Keimel R, Schrank S, Zimmer A, Werzer O - Pharm. Res. (2014)

Sauerbrey mass loss (Δm) as function of the water rinsing time of various films (a). Corresponding time derivatives over the rinsing time of same signals (b). Both graphs are plotted on the same x-axis for comparability.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4197366&req=5

Fig3: Sauerbrey mass loss (Δm) as function of the water rinsing time of various films (a). Corresponding time derivatives over the rinsing time of same signals (b). Both graphs are plotted on the same x-axis for comparability.
Mentions: Within a QCM-D experiment the change in resonance frequency with mass load change is determined allowing the desorption from the surface being followed. In Fig. 3a the relative Sauerbrey mass losses of three different thin film samples are shown as function of MilliQ-water rinsing times. The pure PS thin film shows a constant frequency over time which means that this film is not affected by the continuous rinsing. However, the pure clotrimazole film reveals a different behavior and shows a typical trajectory (nearly exponential decay) for a controlled desorption from a solid surface with a steady change of mass load with rinsing time. After a time of 73 min. the corresponding mass loss is 3.9 μg cm−2. Similarly, the immersion of the PS-Clot composite film reveals a steady mass loss, but the trajectory of the dissolution profile (now a Boltzmann function like decay) and the maximum mass loss is significantly different; after 73 min only 0.9 μg cm−2 is lost.Fig. 3

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology, University of Graz, Universititätsplatz 1, 8010, Graz, Austria.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus