Limits...
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.

Show MeSH

Related in: MedlinePlus

DSC measurements of clotrimazole, polystyrene (PS) and the PS-Clot composite on increasing heat. For the sake of clarity curves are shifted by means of their y-axis.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4197366&req=5

Fig1: DSC measurements of clotrimazole, polystyrene (PS) and the PS-Clot composite on increasing heat. For the sake of clarity curves are shifted by means of their y-axis.

Mentions: Polystyrene, clotrimazole and a composite with a 1:1 ratio of clotrimazole and PS were drop casted and dried. The drop casted films contrarily to the spin coated films crystallize very fast (in the first 30 min), while the spin coated films are amorphous over several weeks (23). Anyway, for the identification of PS – clotrimazole interactions this kind of sample provides some insight even thought the other films are amorphous. The first heating run at a heating rate of 10°C/min is shown in Fig. 1. The drug free PS sample shows a glass transition (Tg) at 98°C. The polymer free clotrimazole sample has a melting peak at 143°C. The polystyrene –clotrimazole composite reveals that Tg and the melting point of the one-component systems have changed. Tg shifted towards lower temperatures to 77°C. The melting point present in the clotrimazole sample has shifted by 17°C down to 126°C. This shows that both, i.e. clotrimazole and PS, are affected by the intermixing.Fig. 1


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)

DSC measurements of clotrimazole, polystyrene (PS) and the PS-Clot composite on increasing heat. For the sake of clarity curves are shifted by means of their y-axis.
© Copyright Policy - OpenAccess
Related In: Results  -  Collection

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

Fig1: DSC measurements of clotrimazole, polystyrene (PS) and the PS-Clot composite on increasing heat. For the sake of clarity curves are shifted by means of their y-axis.
Mentions: Polystyrene, clotrimazole and a composite with a 1:1 ratio of clotrimazole and PS were drop casted and dried. The drop casted films contrarily to the spin coated films crystallize very fast (in the first 30 min), while the spin coated films are amorphous over several weeks (23). Anyway, for the identification of PS – clotrimazole interactions this kind of sample provides some insight even thought the other films are amorphous. The first heating run at a heating rate of 10°C/min is shown in Fig. 1. The drug free PS sample shows a glass transition (Tg) at 98°C. The polymer free clotrimazole sample has a melting peak at 143°C. The polystyrene –clotrimazole composite reveals that Tg and the melting point of the one-component systems have changed. Tg shifted towards lower temperatures to 77°C. The melting point present in the clotrimazole sample has shifted by 17°C down to 126°C. This shows that both, i.e. clotrimazole and PS, are affected by the intermixing.Fig. 1

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