Novel mathematical method for quantitative expression of deviation from the Higuchi model

Abstract

A simple mathematical method to express the deviation in release profile of a test product following Higuchi's kinetics from an ideal Higuchi release profile was developed. The method is based on calculation of area under the curve (AUC) by using the trapezoidal rule. The precision of prediction depends on the number of data points. The method is exemplified for 2 dosage forms (tablets of diltiazem HCl and microspheres of diclofenac sodium) that are designed to release the drug over a 12-hour period. The method can be adopted for the formulations where drug release is incomplete (<100%) or complete (100%) at last sampling time. To describe the kinetics of drug release from the test formulation, zero-order, first-order, Higuchi's, Hixson-Crowell's, and Weibull's models were used. The criterion for selecting the most appropriate model was based on the goodness-of-fit test. The release kinetics of the tablets and microspheres were explained by the Higuchi model. The release profiles of the test batches were slightly below the ideal Higuchi release profile. For the test products, observed percentage deviation from an ideal Higuchi profile is less than 16% for tablets and less than 11% for microspheres. The proposed method can be extended to the modified release formulations that are designed to release a drug over 6, 18, or 24 hours. If the data points are not evenly separated, the ideal drug release profile and AUC are calculated according to the specific sampling time. The proposed method may be used for comparing formulated products during the research and development stage, for quality control of the products, or for promoting products by comparing performance of the test product with that of the innovator's product.

Preparation of Novel Hydrolyzing Urethane Modified Thiol-Ene Networks

“…Although the indirect assessment offered by the film hardness study suggests that the rate of water uptake, K eq H 2 O, is tunable in the thiol-ene hydrolyzing networks by changing the molecular functionality of the constituents, no direct rate of hydrolysis is measured. A well-known kinetic model exists for the quantitative comparison among polymer networks used for the controlled-release/drug-delivery applications of pharmaceuticals [25]. The theoretical model, referred to as the Higuchi model, accounts for the relative water permeability of the networks and the concentrations, solubility, and diffusion of agents in the network.…”

Goodness of fit Model Dependent Approaches of Controlled Release Matrix Tablets of Zidovudine.

“…20 The predicted percent of cumulative drug released (CDR) versus square root of time was considered as the reference line. The average absolute difference between AUCs (AADA) in 12 hr system for residual was calculated by using equation 12. Where n is the difference between two successive sampling points, t 100 is the time to 100% drug release and α is the percent deviation.…”

Goodness-of-Fit Model-Dependent Approach for Release Kinetics of Levofloxacin Hemihydrates Floating Tablet

“…Regression analysis was adopted to compute the constants. Gohel et al proposed a mathematical approach for the determination of deviation in Higuchi release profile (17). The rationale behind this study was to select an optimized batch by evaluating the deviation of dissolution data using an AUC-based mathematical approach as well as goodness of fit to the kinetic models.…”

“…A novel approach of deviation from Highchi model proposed by Gohel et al (17) was used to evaluate deviation between predicted and observed dissolution profile of floating formulations. The predicted percentage CDR at each time point was back-calculated using the regression equation of Higuchi model.…”