ve plateaus due to a number of factors, depending on the type of matrix used (Reza, Quadir and Haider). Most matrices tend to swell and/or buckle, which may impede drug release; there may be an ionic interaction between the drug and the matrix, impeding release; the matrix may become saturated with the drug molecules which will impede movement through the matrix; or the drug may cause changes in the matrix which alter its flow characteristics; and over time, the drug concentration becomes depleted.
Higuchi was the first to derive an equation to describe the release of a drug from an insoluble matrix as the square root of a time-dependent process. It is based on the Fick diffusion equation, which is as follows for skin absorption:
where dM/Sdt (I) is the steady-state flow across the stratum corneum, D is the diffusion coefficient or diffusivity of drug molecules, delta c is the drug concentration gradient across the stratum corneum layer, K is the partition coefficient of the drug between the skin and the formulation medium, and h is the stratum corneum thickness (Mehdizadeh, Toliate, Rouini, Abashzadeh and Dorkoosh 308-309). Thus, the rate of drug transport depends not only on its aqueous solubility, but is also directly proportional to its oil/water partition coefficient.
The Higuchi equation is as follows:
Qt =[2DSÇ[A-0.5SÇ])0.5xt0.5 = kH /1
where Qt is the amount of drug released in time t, D is the diffusion coefficient of the drug, S is the solubility of the drug in the dissolution medium, Ç is the porosity of the matrix, A is the drug content per cubic centimeter of matrix, and kH is the release rate constant for the Higuchi model (Gobel, Panchal
Plotting the cumulative amount of drug transported per unit area (micrograms/cm-2) against the square root of time according to the Higuchi equation yields a straight line, and the slope of the regression line re...