Double layer suppositories (D-15) of nifedipine (NF), prepared by using a solid dispersion system of polyethylene glycol 4000 as a water-soluble carrier and cellulose acetate phthalate as a poorly water-soluble-carrier, were administered to healthy volunteers, and their sustained-release characteristics, bioavailability and clinical utility were investigated. It was found that D-15 was able to maintain a therapeutically effective level of NF from 30 min to 10 h without causing an excessively high peak level and offered good bioavailability. From the results of pharmacokinetic analysis by using the compartment model method, it appeared that the plasma concentration-time course after rectal administration of D-15 is satisfactorily accounted for by a one-compartment model with first-order release and absorption steps. The value of release rate constant of D-15 obtained was smaller than that of absorption rate constant, and the sustained-release effect was apparently attributed to the slow release of NF from the suppository.
The plasma level of NF rapidly decreased as removing D-15, and the plasma level showed hardly any irregularities arising from the removal and the renewal of suppositories.
Accordingly, it was concluded that D-15 is an effective sustained-release dosage from and represents a convenient mode of therapy with reduced frequency of drug administration and reduced risk of side-effects.