Kinetic Mechanism of Drug Release

Drug release kinetics is a QTTP that should be considered in the development of a formulation, allowing the definition of in vivo–in vitro correlations [82,83]. In vitro drug release was analyzed by fitting the results to four mathematical kinetics models [72,83]: zero order (1), first order (2), Higuchi model (3), and Korsmeyer–Peppas (4) models. The correlation coefficient (*R* 2 ) was determined to compare the precision of these models as it presents the highest *R* <sup>2</sup> value, which was selected to describe the drug release kinetics. The value of the diffusion release exponent (*n*) obtained by the Korsmeyer–Peppas model was used to characterize the drug release mechanism [84,85]: *n* ≤ 0.43 means a Fickian release, where the drug diffusion is proportional to the concentration; *n* = 0.85 represents a non-Fickian release, i.e., a zero-order release, where the drug diffusion is independent from the concentration; 0.43 < *n* < 0.85 defines an anomalous transport route, which is a combination of non-Fickian release and Fickian release; *n* > 0.89 is a case II transport (relaxation-controlled release). The Microsoft Excel® software was used to calculate the *R* <sup>2</sup> and the model parameters of the following equations [86]:


*M* represents the amount of drug released at time *t*, *M*<sup>0</sup> corresponds to the drug concentration at time 0, *k* is the rate constant, and *n* is the diffusion release exponent.
