Purdon, Carryn Hamilton (2001) In vitro passage of ibuprofen through synthetic and biological membranes. Masters thesis, Rhodes University.
Ibuprofen is a non-steroidal anti-inflammatory drug with three major types of effect: anti-inflammatory, analgesic and antipyretic. Ibuprofen may be administered in a number of different forms via the oral as well as the topical route. Published evidence suggests that topical, unlike oral, non-steroidal anti-inflammatory drugs are associated with few systemic side effects as plasma concentrations are low compared to oral therapy. In some countries it is particularly difficult to obtain human skin for in vitro experimentation and it is therefore important to have alternate biological or synthetic membranes which mimic human skin for diffusion experiments. Synthetic membranes serve as predictive models for topical drug release and in South Africa, shed snake skin is easily obtainable from the many snake parks present in the country. The FDA guidelines were considered when choosing the apparatus to be used in the comparative diffusion study on proprietary ibuprofen-containing topical preparations from three countries and the verification of the usefulness, or otherwise, of shed snake skin as a biological membrane for the assessment of the permeation of ibuprofen. Two diffusion techniques were considered appropriate for the measurement of the amount of ibuprofen released from a topical formulation during in vitro testing. One was the Franz diffusion cell, as modified by Keshary and Chien (88,169) and the other was the European Pharmacopoeia diffusion cell (187). High performance liquid chromatography was used as the analytical technique for the analysis of ibuprofen in aqueous solution using ultraviolet detection at 222 nm. The validated method was applied to the determination of the diffusion of ibuprofen from topical ibuprofen-containing formulations (gels, creams and mousse) through synthetic silicone membrane and shed snake skin biological membrane from four different species. In a study of fifteen topical ibuprofen-containing formulations (gels, creams and mousse) from three countries (South Africa, United Kingdom and France) it was found that there was a trend of products from two countries consistently exhibiting superior diffusion characteristics as well as products from the same two countries consistently exhibiting the lowest diffusion of ibuprofen. Interpretation of the results of these studies demonstrated the importance of employing a combination of statistical analyses and peak integration values when drawing conclusions regarding comparative diffusion characteristics. Shed snake skin has been described as a 'model' membrane, i.e. a membrane which shows similar permeability to human stratum corneum. The results reported here show clearly that, for ibuprofen, the four species of snake produce shed skin with completely different diffusion characteristics when all other conditions are identical. It may well be that there is one particular species of snake which produces shed skin of identical permeability to human stratum corneum, but to describe shed snake skin in general as a model membrane seems incorrect. It is therefore important that if shed snake skin is used as a membrane, the species, skin site and orientation should be reported. The European Pharmacopoeia diffusion apparatus was judged to be the better of the two diffusion techniques assessed for the measurement of the amount of ibuprofen released from a topical formulation during in vitro testing using silicone membranes and for the measurement of the amount of ibuprofen diffusing across the ventral outside orientation of shed skin during in vitro testing, whereas the Franz diffusion apparatus was judged to be better for the measurement of the amount of ibuprofen diffusing across the dorsal outside orientation of shed skin during in vitro testing. However, the choice of this diffusion apparatus must be weighed against the relatively poor reproducibility as compared with the European Pharmacopoeia diffusion apparatus.
|Item Type:||Thesis (Masters)|
|Uncontrolled Keywords:||Ibuprofen, Diffusion processes|
|Subjects:||Q Science > QD Chemistry > QD241 Organic chemistry|
|Divisions:||Faculty > Faculty of Pharmacy|
|Deposited By:||Ms Chantel Clack|
|Deposited On:||21 Jun 2012 09:09|
|Last Modified:||21 Jun 2012 09:09|
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