Hajime Matsuda

Cyclodextrins in transdermal and rectal delivery.

Transdermal and rectal routes of drugs are very important as a useful supplement of oral routes and the direct exposing method of drugs when the systemic and local effects are required. The widespread use of parent cyclodextrins (CDs) and chemically modified CD derivatives (CD derivatives) for in-vitro and in-vivo dermal and rectal drug delivery have been evaluated. In addition, the application of hydrophilic CD derivatives to cosmetics have been progressing. In this article, the current status of parent CDs and CD derivatives in the transdermal and rectal delivery of conventional low molecular weight agents are reviewed.

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

A potential use of 2‐hydroxypropyl‐β‐cyclodextrin (HP‐β‐CyD) to solubilize methyl paraben and to suppress its percutaneous absorption was examined, and compared with nonionic surfactant HCO‐60.

Effect of 2-Hydroxypropyl-Cyclodextrins on Percutaneous Absorption of p-Hydroxybenzoic Acid

A potential use of 2-hydroxypropyl-cyclodextrins (HP-CDs) to solubilize p-hydroxybenzoic acid methyl ester (methyl paraben) and to suppress its percutaneous absorption was examined, and compared with nonionic sufactant HCO-60 (Hydrogenated castor oil 6OEO). HP-CDs significantly increased the solubility of methyl paraben in water, where the apparent 1:1 stability constant of the methyl paraben: HP- β -CD complex was determined to be 2150M−1. The in-vitro cutaneous permeability of methyl paraben through an isolated skin of hairless mouse was suppressed by HP-CDs, thus promoting the bioconversion of methyl paraben to the less toxic metabolite, p-hydroxybenzoic acid (p-HBA), in the epidermis. These effects of HP-CDs were greater than those of HCO-60. HP- β -CD (2% w/v) reduced the in-vivo percutaneous absorption of methyl paraben by 66% 24h after the topical application of a solution containing [14C] methyl paraben to hairless mouse skin. In addition, the percutaneous absorption of [14C] HP- β -CD was confirmed to be extremely low. These results suggest that HP- β -CD is useful in liquid preparations of methyl paraben for topical application.