Biopharmaceutical Relevance of Dissolution Profile Comparison: Proposal of a Combined Approach

Abstract

The aims of the present study were to evaluate the performance of the main methods proposed for the comparison of percentage dissolved versus time curves and to recommend a more biorelevant combined approach for the comparison of dissolution profiles of multisource drug products. In vitro dissolution tests of four brands of oxcarbazepine (OxCBZ) tablets were performed, and the resulting profiles were compared by model-independent, model-dependent, and ANOVA-based statistical methods. After a careful analysis of the results, some methods were chosen and applied to the comparison of dissolution profiles of four brands of carbamazepine (CBZ) tablets and two brands of phenytoin (PHT) capsules. Finally, these in vitro results were qualitatively correlated with the corresponding in vivo results previously obtained with the same CBZ and PHT products assayed in healthy volunteers. The analysis of the dissolution data obtained with OxCBZ tablets allowed discarding the ANOVA-based statistical methods since in all cases they were over-discriminating from a biopharmaceutical point of view. The remaining comparison methods were applied to in vitro profiles of CBZ and PHT products and the results correlated with in vivo data. The most suitable methods for the biopharmaceutical comparison of in vitro dissolution profiles were the model-independent ones, and among them, the best correlations were the f 2 similarity factor along with a measure of the dissolution extent (e.g., area under the curve). This combined approach gives a robust and informative result with the most biopharmaceutical relevance.

Electrospun nanofibers: A nanotechnological approach for drug delivery and dissolution optimization in poorly water-soluble drugs

“…Because of that, the dissolution test has extended its application not only to solid pharmaceutical dosage forms but to novel drug delivery systems such as electrospun nanofibers. It is well known that solubility is greatly dominated by the nature of the substance functional groups and their interactions with those of the solvent [ 162 ]. Electrospinning has allowed the production of nanofibers with poorly water-soluble drugs embedded in hydrophilic polymers, which enhances their dissolution rate [ 163 , 164 ].…”

Conventional and Multivariate Statistical Methods for Evaluation of <i>In vitro</i> Dissolution Similarity of Bisoprolol Film-coated Tablets

“…In this case, out of the original solubility data in the case of the test and reference samples, we have derived the set of α and β parameters for each set of measurements (each F=f(t) curve). The mean (average) -vectors and the covariance matrices are further computed in a manner analogous to that described by (6) - (8) and the pooled covariance matrix is computed by (9) and the Mahalanobis distance by (10). The limiting value -D M,lim.…”

“…Since the 90s, regulatory agencies and scientific researchers have increasingly suggested the use of new mathematicalstatistical methods to prove in vitro dissolution similarity [8]. Hence, in cases when the f 2 statistics is not applicable, the guidelines address the possibility for using alternative statistical methodologies for dissolution profiles comparison, using model-dependent or model-independent methods [9,10].…”

Understanding and predicting the impact of critical dissolution variables for nifedipine immediate release capsules by multivariate data analysis

“…Dissolution profiles can be analysed using model-dependent methods (experimental data are fitted using mathematical equations), model-independent methods (single values such as mean dissolution time, area under dissolution curve etc. are used for the evaluation of the data) and statistical methods (like ANOVA and multivariate statistics) (Costa and Sousa Lobo, 2001;Ruiz and Volonte, 2014;Yuksel, 2000). Multivariate approaches have been used to assess the impact of formulation composition and manufacturing method on dissolution (Andersson et al, 2007;Huang et al, 2009;Kaul et al, 2011;Maggio et al, 2009;Nagarwal et al, 2009;Ring et al, 2011), to compare dissolution profiles of various pharmaceutical dosage forms (Adams et al, 2002(Adams et al, , 2001Enăchescu, 2010;Huang et al, 2011;Maggio et al, 2008), to quantify the drug release during dissolution (Hernandez et al, 2016), to develop in vitro dissolution methods for pure substance or several formulation types (Eaton et al, 2007;Fish et al, 2009;Graffner et al, 1996;Persson et al, 2010;Petruševska et al, 2015), and to define the in vivo predictive in vitro dissolution set-up based on the modification of the polarity of the dissolution medium with the use of ethanol (Abuzarur-Aloul et al, 1998a, 1998b.…”