7-alkylcarbonyl and 7-alkyloxycarbonyl prodrugs of theophylline
Sloan, KB; Dellavecchia, SA; Estes, JV; Roberts, WJ
| HERO ID | 1617096 |
|---|---|
| In Press | No |
| Year | 2000 |
| Title | 7-alkylcarbonyl and 7-alkyloxycarbonyl prodrugs of theophylline |
| Authors | Sloan, KB; Dellavecchia, SA; Estes, JV; Roberts, WJ |
| Journal | International Journal of Pharmaceutics |
| Volume | 205 |
| Issue | 1-2 |
| Page Numbers | 53-63 |
| Abstract | Five members (6-10) of an homologous series of 7-alkyloxycarbonyltheophylline (7-AOC-Th) and four members (2-5) of a homologous series of 7-alkylcarbonyltheophylline (7-AC-Th) prodrugs have been synthesized by known methods and characterized. All of the members in both series were much more soluble in isopropyl myristate (S(IMP)) (10-200 times) and in each series, at least one member was more soluble in pH 4.0 buffer (S(AQ)) than Th. However, in the 7-AC-Th series, only the acetyl member, 2, which exhibited about 90% of the S(AQ) of Th, was sufficiently stable to be evaluated - it gave four times the flux of Th/IPM (isopropyl myristate). In the 7-AOC-Th series, all the members were sufficiently stable to be evaluated but the member which exhibited the greatest S(AQ), 6 (methyloxycarbonyl), did not exhibit the greatest flux. Instead, 8 (propyloxycarbonyl), which exhibited the second greatest S(AQ) (about 80% of the S(AQ) of Th), but exhibited over ten times the S(IPM) of 6 gave the greatest flux - two times the flux of Th/IPM. Thus, good biphasic solubility was the best predictor of increased flux. All of the prodrugs delivered only Th through the mouse skin. Only 2/IPM actually delivered more Th into the skin than Th/IPM which correlated with its ability to increase the flux of Th through the skin. |
| Pmid | 11000542 |
| Is Certified Translation | No |
| Dupe Override | No |
| Is Public | Yes |
| Language Text | English |