Transdermal Delivery of Cimetidine Across Microneedle-Treated Skin: Effect of Extent of Drug Ionization on the Permeation.
The objective of this work was to optimize a gel formulation of cimetidine to maximize its transdermal delivery across microporated skin. Specifically, the effect of extent of ionization in formulation on permeation of cimetidine across microporated skin was studied. Cimetidine was formulated into a gel using propylene glycol, water, and carbopol 980NF. Three strengths of gels (0.1% w/w, 0.5% w/w, and 0.8% w/w) were made and Tris base was used to adjust the pH of formulations to pH 5, pH 6.8, and pH 7.5. In vitro permeation testing was performed on vertical Franz cells with dermatomed porcine ear skin. Permeation studies suggested that pH 5 gels showed highest permeation through microchannels. This trend was more prominent with an increase in drug loading. The total amount of cimetidine delivered from 0.8% w/w gel at pH 5 at 24 h was 28.20 ± 4.63 μg, which was significantly higher than that from pH 6.8 (16.89 ± 3.56 μg) and pH 7.5 (12.03 ± 1.66 μg) gels. Cimetidine permeation across microporated skin was found to be pH dependent, with lower pH/highest ionization resulting in greatest permeation. The effect of ionization contributing to faster release was more pronounced when drug concentration was increased.
Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341.
Yang
Y
Song
Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341.
Anushree
A
Herwadkar
Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341.
Meera G
MG
Patel
Department of Pharmaceutical Sciences, Mercer University, Atlanta, Georgia 30341. Electronic address: banga_ak@mercer.edu.
Ajay K
AK
Banga
D000279:Administration, Cutaneous; D000818:Animals; D000897:Anti-Ulcer Agents / Q000008:administration & dosage / Q000378:metabolism; D002927:Cimetidine / Q000008:administration & dosage* / Q000378:metabolism*; D016503:Drug Delivery Systems / Q000379:methods*; D008845:Microinjections / Q000379:methods*; D009924:Organ Culture Techniques; D010539:Permeability / Q000187:drug effects; D012869:Skin Absorption / Q000187:drug effects / Q000502:physiology*; D013552:Swine
D000897:Anti-Ulcer Agents; D002927:Cimetidine
carbopol gel; drug ionization; hydrophilic; skin irritation; skin microchannels; transdermal delivery