Mathematical modelling of drug release from hydroxypropylmethylcellulose matrices: Effect of temperature

Abstract

A number of mathematical models have been used to describe the release of promethazine hydrochloride from matrices containing hydroxypropylmethylcellulose. Relationships, such as predicted by the Korsmeyer equation (M_t/M_∞ = kt_n), were considered inappropriate since the introduction of a lag period was essential to describe accurately the quantity of drug released. An equation (M_t/M_∞ = k(t − l)ⁿ + k′(t − l)²ⁿ) incorporating a lag period (l), kinetic constants (k and k′) for diffusion and erosion controlled release and a diffusional component (n) produced the best fit of the data as evaluated by information criteria and unweighted sums of squares. The kinetic constants were not normally additive, k′ becoming increasingly negative with increase in temperature. Values of n were in the range 0.563–0.764 indicating that release was controlled by both diffusion and erosion. Increasing the temperature increased the root time release rate constants from the matrices but its effect on the overall contribution to mechanisms controlling release was difficult to interpret.