Hydroxymethyl and acyloxymethyl prodrugs of theophylline: enhanced delivery of polar drugs through skin
1982; Elsevier BV; Volume: 12; Issue: 4 Linguagem: Inglês
10.1016/0378-5173(82)90101-6
ISSN1873-3476
AutoresKenneth B. Sloan, Nicholas Bodor,
Tópico(s)Surfactants and Colloidal Systems
ResumoA series of 7-acyloxymethyl prodrugs of theophylline has been prepared by the acylation of 7-(hydroxymethyl)theophylline and by the alkylation of theophylline with an acyloxymethyl halide. The lipid solubilities of all the prodrugs were markedly improved over that of theophylline but, in addition, the succinamate and the glycinate derivatives exhibited increased water solubilities. As a result, prodrugs which exhibited partition coefficients between 0.03 and 16.7 were obtained. Selected acyloxymethyl prodrugs as well as 7-(hydroxymethyl)theophylline were effective in increasing the delivery of theophylline through hairless mouse skin by 3.5–5 times that of theophylline. Several of the prodrugs, when applied topically to normal and hairless mice, inhibited DNA synthesis in the skins of the mice after they had undergone UV irradiation.
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