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A comparative study of an in situ adapted diffusion cell and an in vitro Franz diffusion cell method for transdermal absorption of doxylamine.
Eur J Pharm Sci 2001; 13(2):169-77EJ

Abstract

In order to determine whether a drug shows the potential for percutaneous absorption, both in situ and in vitro studies are used. In vitro studies are good indicators of transdermal drug delivery, but the possibility exists that anatomical changes in excised skin can influence drug delivery. The aim of this study was to compare the in vitro Franz diffusion cell method with an in situ adapted diffusion cell method. A saturated aqueous solution of doxylamine succinate was used as model drug and the receptor phase was an isotonic Sörensen buffered solution. The in vitro permeation studies were conducted using vertical Franz diffusion cells with nude mice skin. For in situ studies, a diffusion cell was implanted under the dorsal skin of a nude mouse, simulating the in vitro method. Both in situ and in vitro experiments were conducted over a period of 12 h during which samples were collected every 90 min. The mean steady-state flux from Franz diffusion cells was 0.164+/-0.045 microg/cm2/h and flux determined by the in situ method was 0.113+/-0.034 microg/cm2/h. A statistical significant difference existed between the permeation results of the in vitro and in situ experimental methods. A subjective, semi-quantitative assessment of histological changes to excised nude mouse skin was done using light microscopy. This showed that excised skin undergoes sub-lethal injury (necrosis) during in vitro experiments, which may lead to increased permeability of the drug. It was noticed that in vitro and in situ permeation results showed very close correlation until approximately 4.5 h after commencement of experiments, after which, the permeation through excised skin increased. It was assumed that cell necrosis occurred to such an extent after approximately 4.5 h, that the barrier function of the stratum corneum decreased and permeation of the drug increased.

Authors+Show Affiliations

Department of Pharmaceutics, School of Pharmacy, Potchefstroom University for Christian Higher Education, Private Bag X6001, 2520, Potchefstroom, South Africa.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

11297901

Citation

Venter, J P., et al. "A Comparative Study of an in Situ Adapted Diffusion Cell and an in Vitro Franz Diffusion Cell Method for Transdermal Absorption of Doxylamine." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 13, no. 2, 2001, pp. 169-77.
Venter JP, Müller DG, du Plessis J, et al. A comparative study of an in situ adapted diffusion cell and an in vitro Franz diffusion cell method for transdermal absorption of doxylamine. Eur J Pharm Sci. 2001;13(2):169-77.
Venter, J. P., Müller, D. G., du Plessis, J., & Goosen, C. (2001). A comparative study of an in situ adapted diffusion cell and an in vitro Franz diffusion cell method for transdermal absorption of doxylamine. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 13(2), pp. 169-77.
Venter JP, et al. A Comparative Study of an in Situ Adapted Diffusion Cell and an in Vitro Franz Diffusion Cell Method for Transdermal Absorption of Doxylamine. Eur J Pharm Sci. 2001;13(2):169-77. PubMed PMID: 11297901.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A comparative study of an in situ adapted diffusion cell and an in vitro Franz diffusion cell method for transdermal absorption of doxylamine. AU - Venter,J P, AU - Müller,D G, AU - du Plessis,J, AU - Goosen,C, PY - 2001/4/12/pubmed PY - 2001/7/6/medline PY - 2001/4/12/entrez SP - 169 EP - 77 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 13 IS - 2 N2 - In order to determine whether a drug shows the potential for percutaneous absorption, both in situ and in vitro studies are used. In vitro studies are good indicators of transdermal drug delivery, but the possibility exists that anatomical changes in excised skin can influence drug delivery. The aim of this study was to compare the in vitro Franz diffusion cell method with an in situ adapted diffusion cell method. A saturated aqueous solution of doxylamine succinate was used as model drug and the receptor phase was an isotonic Sörensen buffered solution. The in vitro permeation studies were conducted using vertical Franz diffusion cells with nude mice skin. For in situ studies, a diffusion cell was implanted under the dorsal skin of a nude mouse, simulating the in vitro method. Both in situ and in vitro experiments were conducted over a period of 12 h during which samples were collected every 90 min. The mean steady-state flux from Franz diffusion cells was 0.164+/-0.045 microg/cm2/h and flux determined by the in situ method was 0.113+/-0.034 microg/cm2/h. A statistical significant difference existed between the permeation results of the in vitro and in situ experimental methods. A subjective, semi-quantitative assessment of histological changes to excised nude mouse skin was done using light microscopy. This showed that excised skin undergoes sub-lethal injury (necrosis) during in vitro experiments, which may lead to increased permeability of the drug. It was noticed that in vitro and in situ permeation results showed very close correlation until approximately 4.5 h after commencement of experiments, after which, the permeation through excised skin increased. It was assumed that cell necrosis occurred to such an extent after approximately 4.5 h, that the barrier function of the stratum corneum decreased and permeation of the drug increased. SN - 0928-0987 UR - https://www.unboundmedicine.com/medline/citation/11297901/A_comparative_study_of_an_in_situ_adapted_diffusion_cell_and_an_in_vitro_Franz_diffusion_cell_method_for_transdermal_absorption_of_doxylamine_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928098701001105 DB - PRIME DP - Unbound Medicine ER -