2 0 0 0 OA 経皮吸収に適する薬物および構造活性相関による皮膚透過の予測
- 著者
- 小木曽 太郎
- 出版者
- 公益社団法人 日本薬剤学会
- 雑誌
- 薬剤学 (ISSN:03727629)
- 巻号頁・発行日
- vol.61, no.3, pp.119-127, 2001 (Released:2019-05-18)
- 参考文献数
- 35
- 被引用文献数
- 1
Delivery of drugs via the skin has many attractions, including avoidance of gastro-intestinal disturbance and first-path metabolism, long-term maintenance of therapeutic plasma concentration and increased patient acceptability. This paper discusses the factors influencing the percutaneous absorption of drugs: lipophilicity, molecular size, melting point, cutaneous metabolism and skin binding of drugs. Additionally, quantitative structure-permeability relationships (QSPR) for skin penetration were discussed based on the octanol-water partition coefficient, molecular weight and electronic charge of drugs. Nonirritant enhancement methods, such as use of nonirritant penetration enhancers and formation of a complex or an ion pair, for drug penetration through skin were also described. As a result, the suitability of a drug for transdermal drug delivery was proposed.
1 0 0 0 OA 薬物の経毛嚢送達:ヒト頭皮薬物吸収の特性と利点
- 著者
- 小木曽 太郎
- 出版者
- 公益社団法人 日本薬剤学会
- 雑誌
- 薬剤学 (ISSN:03727629)
- 巻号頁・発行日
- vol.63, no.1, pp.34-45, 2003 (Released:2019-05-12)
- 参考文献数
- 31
Recent studies have focused on the hair follicle as a potential pathway for both localized and systemic drug delivery. When drug penetration through human scalp skin was investigated using liquid formulations containing lipophilic and hydrophilic drugs in vitro, lipophilic melatonin (MT) and ketoprofen (KP) showed high permeabilities through scalp skin. Absorption enhancers, N-methyl-2-pyrrolidone and isopropylmyristate, only slightly increased the fluxes. Hydrophilic fluorouracil (5FU) and acyclovir (ACV) also penetrated across the skin with relatively large fluxes. However, there was large variability in the fluxes of drugs across scalp skins. There was a correlation between the flux and hair follicle density (r=0.651 for MT and r=0.666 for ACV). Fluorescent probes, nile red and sodium fluorescein, permeated into the junction of the internal and external root sheath of follicles and diffused into the dermis via the outer root sheath at the initial times. The penetration of MT and 5FU through scalp skin was much higher (37 and 48 times, respectively) than that via human abdominal skin. It has been demonstrated that topically-applied liposomes and microspheres are efficient in specifically targeting the delivery of a wide variety of compounds into the hair follicles. Additionally, hair follicles were a significant pathway for electroosmotic solution flow during iontophoresis. This review indicates a basis that drug delivery through human scalp skin will offer an available delivery means for many lipophilic and hydrophilic drugs.