| abstract |
Pharmaceutical compositions for administration of an active substance to or through a damaged or undamaged skin or mucosal surface or to the oral cavity including the teeth of an animal such as a human. The composition has advantageous properties with respect to release of the active substance from the composition and, furthermore, the composition is bioadhesive. The composition comprises the active substance and an effective amount of a fatty acid ester which, together with a liquid phase, is capable of generating a liquid crystalline phase in which the constituents of the composition are enclosed, the active substance having a solubility in the liquid crystalline phase of at most 20 mg/g at 20 °C, and a solubility in water of at most 10 mg/ml at 20 °C, the water, where applicable, being buffered to a pH substantially identical to the pH prevailing in the liquid crystalline phase (pH about 3.6-9). The composition is particularly suited for administration of substances which have a very low water solubility and which are to be supplied in an effective amount in a localized region over a period of time. Active substances of particular importance are antiherpes virus agents including antiviral drugs and prodrugs thereof, such as nucleosides, nucleoside analogues, phosphorylated nucleosides (nucleotides), nucleotide analogues and salts, complexes and prodrugs thereof; e.g. guanosine analogues, deoxyguanosine analogues, guanine, guanine analogues, thymidine analogues, uracil analogues and adenine analogues. Especially interesting antiherpes virus agents for use either alone or in combination in a composition according to the present invention are selected from acyclovir, famciclovir, deciclovir, penciclovir, zidovudin, ganciclovir, didanosin, zalcitabin, valaciclovir, sorivudine, lobucavir, brivudine, cidofovir, n-docosanol, ISIS-2922, and prodrugs and analogues thereof. |