Effect of 2-Hydroxypropyl-β-cyclodextrin on Percutaneous Absorption of Methyl Paraben

Abstract

A potential use of 2-hydroxypropyl-beta-cyclodextrin (HP-beta-CyD) to solubilize methyl paraben and to suppress its percutaneous absorption was examined, and compared with nonionic surfactant HCO-60. HP-beta-CyD significantly increased the solubility of methyl paraben in water, where the apparent 1:1 stability constant of the soluble complex was determined to be 2150 M-1. The in-vitro cutaneous permeability of methyl paraben through an isolated skin of hairless mouse was suppressed by HP-beta-CyD, thus promoting the bioconversion of methyl paraben to the less toxic metabolite, p-hydroxybenzoic acid (p-HBA) in the epidermis. These effects of HP-beta-CyD were greater than those of HCO-60. HP-beta-CyD (2% w/v) reduced the in-vivo percutaneous absorption of methyl paraben by 66% 24 h after the topical application of a solution containing [14C]methyl paraben to hairless mouse skin. Additionally, the percutaneous absorption of [14C]HP-beta-CyD was confirmed to be extremely low. These results suggest that HP-beta-CyD is useful in liquid preparations of methyl paraben for topical application.

Pharmaceutical Applications of Cyclodextrins. III. Toxicological Issues and Safety Evaluation

“…73 This limited availability is also the case in most other membranes. 75 In contrast, when CDs are applied under the occlusivedressing conditions and/or with vehicles containing absorption-promoting agents, they are able to permeate the skin and exert some effects. 74 Similarly, when HP--CD in an aqueous solution was applied to the skin of hairless mice, its percutaneous absorption was extremely low at ∼0.02% of the amount applied 24 h after topical application.…”

Behavior of α-, β-, and γ-Cyclodextrins and Their Derivatives on an in Vitro Model of Blood-Brain Barrier

“…It is worth mentioning that a similar conclusion was made on other membrane types. Indeed, ␤-CD and its methylated derivatives pass slowly through the intestinal wall by passive diffusion (Takakura and Hashida, 1996), or HP-␤-CD is poorly absorbed transdermally (Tanaka et al, 1995).…”

Effects of Cyclodextrins on Drug Delivery Through Biological Membranes

“…The chemical structure of CDs is associated with a large number of hydrogen bond donors and acceptors, a high molecular weight (from 972 to over 2000 Da) and a low octanol/water partition coefficient (Log P o/w from less than −3 to almost 0) predicting that they do not readily penetrate biological membranes 7. In fact, experimental evidence has shown that only negligible amounts of hydrophilic CDs (Log P o/w <−3) penetrate lipophilic biological membranes such as skin and the gastrointestinal mucosa 8–12. Only the free drug is able to permeate lipophilic membranes13–15 and excess CD, more than is needed to solubilize the drug in the aqueous exterior, in fact reduces drug penetration through membranes (Table 2).…”