Mechanistic studies of the effect of hydroxypropyl-β-cyclodextrin on in vitro transdermal permeation of corticosterone through hairless mouse skin

• Published in: International journal of pharmaceutics 2003-03, Vol.253 (1), p.1-11
• Main Authors: Shaker, D.S, Ghanem, A.-H, Li, S.K, Warner, K.S, Hashem, F.M, Higuchi, W.I
• Format: Article
• Language: English
• Subjects: 2-Hydroxypropyl-beta-cyclodextrin; Adjuvants, Pharmaceutic - chemistry; Adjuvants, Pharmaceutic - pharmacology; Administration, Cutaneous; Animals; beta-Cyclodextrins; Biological and medical sciences; Biological Transport; Cellulose - analogs & derivatives; Cellulose - chemistry; Corticosterone - chemistry; Corticosterone - pharmacokinetics; Cyclodextrins - chemistry; Cyclodextrins - pharmacology; Drug Stability; Enhancer; Female; General pharmacology; Hairless mouse; Hormones. Endocrine system; Hot Temperature; Hydroxypropyl-β-cyclodextrin; In Vitro Techniques; Medical sciences; Membranes, Artificial; Mice; Mice, Hairless; Permeability; Permeability coefficient; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Povidone - chemistry; Povidone - pharmacology; Skin; Skin Absorption - drug effects; Solubility; Supersaturation
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00625-7

Literature reports reveal that the issue of whether cyclodextrins may act as skin permeation enhancers has not been resolved. Accordingly, in vitro skin transport studies were conducted to address this question. Corticosterone ( 3 H -CS and/or non-radiolabeled CS) was chosen as the model permeant for transport experiments with hairless mouse skin (HMS) and with a synthetic cellulose membrane of 500 molecular weight cut off (MWCO), the latter to help establish baseline behavior. Hydroxypropyl-β-cyclodextrin (HPβCD) was selected as the representative cyclodextrin. The CS/HPβCD complexation constant was determined both from solubility data (saturation conditions) in phosphate buffered saline (PBS), pH 7.4 and with data obtained from PBS/silicone polymer partitioning experiments, the latter experiments permitting the determination of the complexation constant at low CS concentrations. These results were used in the calculations of the free CS concentrations in the donor chamber of the transport experiments. The CS transport experiments were conducted at CS solubility saturation and under supersaturation (resulting from autoclaving at 121 °C) conditions as well at very low (tracer level) concentrations. The effect of polyvinylpyrrolidone as a solution additive was also evaluated. The following were the key outcomes of this study. Contrary to literature reports, there was no evidence that HPβCD is an enhancer for CS transport through HMS. The CS permeability coefficient values obtained with HMS in all of the experiments were found to be the same within experimental error when calculated on the basis of the free CS concentration as the driving force for permeation. The constancy of the permeability coefficient in the presence and absence of HPβCD is interpreted to mean that, in these experiments, HPβCD did not alter the barrier properties of HMS stratum corneum to any significant extent nor did it enhance CS transport in any other manner such as by a carrier mechanism involving the aqueous boundary layer or by a carrier mechanism within the stratum corneum.