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A study of the transdermal drug diffusion properties of rooperol tetra-acetate

  • Authors: Pefile, Sibongile C.
  • Date: 1998 , 2013-08-29
  • Subjects: Transdermal medication , Skin absorption , Dermatologic agents
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:3838 , http://hdl.handle.net/10962/d1007649 , Transdermal medication , Skin absorption , Dermatologic agents
  • Description: The rapidly growing interest in the potential use of topical drug delivery formulations has resulted in increased use of the skin as a vital port for drug delivery. Extensive research has been conducted in designing vehicles capable of delivering a desired amount of drug to a specific site, to produce the desired pharmacological response. Rooperol tetra-acetate is a lipophilic, cytotoxic drug with the potential for use in the treatment of solar keratosis. For effective pharmacological action, delivery of the drug to the epidermal/dermal junction of the skin is required. A study of the topical penetration properties of rooperol tetra-acetate from different topical bases, each possessing different physico-chemical properties, was performed. The assessment involved a comparison of the diffusion properties under occlusive and non occlusive conditions when the drug was formulated into a gel, Cetomacrogol Cream B.P. (oil-inwater), Simple Ointment B.P. and an extemporaneously prepared water-in-oil topical cream. The in vitro experiments were conducted using polydimethylsiloxane and rat membrane mounted in a Franz diffusion cell. The topical permeation kinetics of rooperol tetra-acetate were determined by exploring the release characteristics of the active ingredient from the vehicles formulated and the permeability properties of the drug through the membranes employed. Further studies involved investigating the utilization of supersaturated systems intended to increase the thermodynamic activity of the drug when formulated into a propylene glycol/water vehicle (with and without polymer). To measure the release of rooperol tetra-acetate into the skin from a topical base it was necessary to, firstly, develop a suitable quantitative method for the analysis of the active drug in the aqueous receptor phase of in vitro diffusion cells. The second stage of product development was the design of an effective delivery system to facilitate the release of the diffusant from its base. A high performance liquid chromatographic method was utilized for the identification and quantification of the active drug. As validation is an important aspect in the development and subsequent utilization of an analytical procedure, the developed HPLC technique was validated by determining the precision, accuracy, range, limit of quantitation and sensitivity of the system. Lastly, the stability of rooperol tetra-acetate at elevated temperatures was assessed and a stability profile of the drug was generated for the three-month period of analysis. The results obtained following chromatographic analysis of the receptor phase sampled during the diffusion experiments indicate that the gel and oil-in-water formulations most effectively promoted the diffusion of rooperol tetra-acetate across polydimethylsiloxane membrane. The water-in-oil system exhibited lower flux rates and the ointment showed the least drug release. Occlusion of the topical vehicle increased the diffusitivity of the permeant from all formulations analysed. The permeation assessment results of the supersaturated systems showed enhanced diffusion of rooperol tetra-acetate across polydimethylsiloxane and rat membrane. The high thermodynamic activity existing in supersaturated systems most effectively increased the driving force for drug diffusion resulting in enhanced percutaneous penetration of rooperol tetra-acetate beyond the release and transport limitations of saturated solutions. These results provide the basis on which an effective topical drug delivery vehicle may be designed for this new drug entity.
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  • Date Issued: 1998

Tropical corticosteroid bioequivalence testing comparison of chromameter and visual data

  • Authors: Demana, Patrick Hulisani
  • Date: 1998
  • Subjects: Dermatopharmacology , Dermatologic agents , Skin absorption
  • Language: English
  • Type: Thesis , Masters , MSc
  • Identifier: vital:3755 , http://hdl.handle.net/10962/d1003233 , Dermatopharmacology , Dermatologic agents , Skin absorption
  • Description: The major criticism of the human skin blanching assay is the subjective nature of grading the response. Recently the American FDA released a Guidance document for topical corticosteroid bioequi valence testing. The guidelines require the use of a chromameter as a reliable method to estimate skin blanching. The purpose of this study was to evaluate the recommendations of this document for appropriateness by comparing visual and chromameter data. The visually-assessed blanching assay methodology routinely practised in our laboratories was modified to comply with the specifications of the Guidance. The preliminary trial indicated that the training period that is required for a novice to be classified as an experienced observer is not a major problem. The major trend that emerged from the pilot study was that visual assessment was better than the chromameter. Longer dose durations were found to be more discriminatory than shorter durations. The visual data were best described by the sigmoid Emax model and the chromameter data were best described by the simple Emax model. The pivotal results indicated that the D2/Dj criterion to determine sample size of "acceptable blanchers" produced only few subjects suggesting that the validity of this criterion requires extensive investigations. The estimates of the Locke's confidence interval method were simiJar to those for the general simple formula. However, due to undefined parameters of the Locke's method in the Guidance, the validity of the Locke's method requires evaluation. The chromameter b-scale parameter was the least sensitive in estimating skin blanching whereas the a- and L-scale parameters produced similar results. Poor correlation between visual and chromameter was noted indicating that the visual method is still the best method.
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  • Date Issued: 1998

The in vivo and quantitative assessment of topical corticosteroid formulations

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