LAYERED EXCIPIENT SUPPOSITORIES - THE POSSIBILITY OF MODULATING DRUG AVAILABILITY

The release rate of a drug dose from suppositories is affected by char acteristics of the excipient (melting temperature and rate, viscosity at rectal temperature, hydro-lipophilic characteristics). Release kine tics from excipients commonly available do not always respond to clini cal requirements, even after the introduction of auxiliary agents. Rel ease curves which were differentiated and adaptable to therapeutic con ditions were obtained by vehicling a drug in suppositories of two supe rimposed layers of lipophilic excipients with different characteristic s and hence with a difference in drug availability. The two distinct e xcipient layers release the drug from these suppositories contemporane ously but independently. The amount of drug released in the time cours e is the sum of the single amounts individually released by the two su ppository layers. By previously mixing the two excipients, release rat e becomes uniform in the suppository body overall and is conditioned o nly by the assumed characteristics of the mixture. The release mechani sm for superimposed layer suppositories is confirmed by the good agree ment between experimental and calculated curves. By using a pair of ex cipients with different characteristics in superimposed layers between which the drug is distributed, it is possible to modulate drug releas e kinetics by regulating the reciprocal ratio between the two supposit ory fractions. (C) 1997 Elsevier Science B.V.