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Krishnaiah, Y.S. et al.

Krishnaiah, Satyanarayana, Karthikeyan,

Effect of the solvent system on the in vitro permeability of nicardipine hydrochloride through excised rat epidermis.

PURPOSE: The present investigation was carried out to study the effect of the solvent system on the permeation of nicardipine hydrochloride across excised rat epidermis in order to select a suitable solvent system for use in the development of a transdermal therapeutic system. METHODS: The solubility of nicardipine hydrochloride in pure and mixed solvent systems was determined. The solvents used were water, propylene glycol, ethanol or various proportions of ethanol and water. The effect of these pure or mixed solvent systems on the skin permeation of nicardipine hydrochloride was also studied using in vitro permeation studies through excised rat epidermis mounted in modified Keshary-Chien diffusion cells. Fourier Transform Infrared Spectroscopy (FT-IR) and Differential Scanning Calorimetry (DSC) studies were carried out to study the effect of these solvents on the biophysical properties of rat' stratum corneum. RESULTS: Although the solubility of nicardipine hydrochloride in propylene glycol (51.23 mg/mL) was higher than that in water (7.90 mg/mL) and ethanol (20.01 mg/mL), the flux of the drug from propylene glycol was as low (7.25+/-0.13 microg/cm(2)/h) as that from water (7.05+/-0.15 microg/cm(2)/h) and lower than that from ethanol (21.51+/-0.81 microg/cm(2)/h). The solubility of nicardipine hydrochloride in binary ethanol-water solvent systems in various proportions was higher than in pure solvents. The highest permeability was observed from an ethanol-water (70:30 v/v) solvent system (56.10+/-1.23 micro g/cm(2)/h) which showed the highest solubility (224.21 mg/mL). The DSC and FT-IR data indicated that the binary solvent system containing ethanol-water in the ratio of 70:30 v/v increased the drug permeability through the skin by disrupting the highly ordered intercellular lipid structure of the stratum corneum in comparison with the untreated stratum corneum. CONCLUSIONS: The results of the study indicate that the use of a binary solvent system, ethanol and water in the ratio of 70:30 v/v, is an effective vehicle for the development of a transdermal therapeutic system for nicardipine hydrochloride.[1]

References

Effect of the solvent system on the in vitro permeability of nicardipine hydrochloride through excised rat epidermis. Krishnaiah, Y.S., Satyanarayana, V., Karthikeyan, R.S. Journal of pharmacy & pharmaceutical sciences [electronic resource] : a publication of the Canadian Society for Pharmaceutical Sciences, Société canadienne des sciences pharmaceutiques. (2002) [Pubmed]

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