Zero order drug delivery from double-layered porous films: release rate profiles from ethyl cellulose, hydroxypropyl cellulose and polyethylene glycol mixtures

Abstract

Abstract Laminated double-layered films comprising a drug-containing and drug-free layer were prepared using tripelennamine, barbitone, salicylic acid and caffeine dispersed in hydroxypropylcellulose (HPC) attached to ethyl cellulose (EC) films containing various proportions of polyethylene glycol (PEG) or HPC to enhance permeability. Drug release in vitro followed zero-order kinetics, rate constants being dependent on the thickness of the drug-free membrane, which was rate-controlling. Thickness-corrected zero order constants were independent of drug-loading, which did, however, control the duration of release. Permeability coefficient measurements on the same rate-controlling films used as single barrier membranes enabled the effective drug concentration (Co) at the interface between the laminated membranes to be estimated; Co was independent of drug loading and was of the order expected from the aqueous solubilities of the drugs. Release rates were enhanced by addition of hydrophilic polymer to the rate-controlling membranes, either linearly with fraction of additive for PEG to 0·6 or HPC to 0·4, or logarithmically for HPC from 0·4 to 0·8. Enhancement coefficients, which were different for each system, reflected the different mechanisms of hydrophilic polymer action. PEG was leached out rapidly, pores being formed in the matrix. In contrast, HPC was largely retained, so that the enhancement was less. The logarithmic enhancement stemmed from formation of swollen hydrated channels, which, unlike the low HPC fractions or the PEG systems, allowed entry of buffer ions, so that only in these channel systems were the release rates altered by change of the external pH.