Layered excipient suppositories: The possibility of modulating drug availability

Abstract

The release rate of a drug dose from suppositories is affected by characteristics of the excipient (melting temperature and rate, viscosity at rectal temperature, hydro-lipophilic characteristics). Release kinetics from excipients commonly available do not always respond to clinical requirements, even after the introduction of auxiliary agents. Release curves which were differentiated and adaptable to therapeutic conditions were obtained by vehicling a drug in suppositories of two superimposed layers of lipophilic excipients with different characteristics and hence with a difference in drug availability. The two distinct excipient layers release the drug from these suppositories contemporaneously but independently. The amount of drug released in the time course is the sum of the single amounts individually released by the two suppository layers. By previously mixing the two excipients, release rate becomes uniform in the suppository body overall and is conditioned only by the assumed characteristics of the mixture. The release mechanism for superimposed layer suppositories is confirmed by the good agreement between experimental and calculated curves. By using a pair of excipients with different characteristics in superimposed layers between which the drug is distributed, it is possible to modulate drug release kinetics by regulating the reciprocal ratio between the two suppository fractions.