Optimization study on the formulation of roxithromycin dispersible tablet using experimental design

Abstract

This study set out to improve the physical and pharmaceutical characteristics of the present formulation using an appropriate experimental design. The work described here concerns the formulation of the dispersible tablet applying direct compression method containing roxithromycin in the form of coated granules. In this study 2(3) factorial design was used as screening test model and Central Composite Design (CCC) associated with response surface methodology was used as optimization study model to develop and to optimize the proper formulation of roxithromycin dispersible tablet. The three independent variables investigated were functional excipients like binder (X1), disintegrant (X2) and lubricant (X3). The effects of these variables were investigated on the following responses: hardness (Y1), friability (Y2) and disintegration time (Y3) of tablet. Three replicates at the center levels of the each design were used to independently calculate the experimental error and to detect any curvature in the response surface. This enabled the best formulations to be selected objectively. The effect order of each term to all response variable was X3> X2> X1> X1*X2> X2*X2> X2*X3> X3*X3> X1*X3> X1*X1 and model equations on each response variables were generated. Optimized compositions of formula were accordingly computed using those model equations and confirmed by following demonstration study. As a result, this study has demonstrated the efficiency and effectiveness of using a systematic formulation optimization process to develop the tablet formulation of roxithromycin dispersible tablet with limited experiment.

Review of Disintegrants and the Disintegration Phenomena

“…The DoE approach was applied to find the binder-disintegrant combination for optimized roxithromycin dispersible tablet formulations. 101 After accomplishing the central composite design study along with response surface methodology, researchers concluded that vinylpyrrolidone or vinyl acetate copolymer (binder) and crospovidone (disintegrant) made the best combination. As disintegrants function by different mechanisms, there is the possibility of synergism between disintegrants.…”

Dissolution Efficiency and Design Space for an Oral Pharmaceutical Product in Tablet Form

“…The critical formulation attributes are the mass fractions of three excipients. The acceptable ranges of the latter are determined by multivariate models, such as Mixture Design analysis, − the Bayesian method, and neural networks . The Mixture Design analysis is the method of choice for data that are complete and lack a correlation structure.…”

Ειδικά Προβλήματα Ποιότητας Φαρμάκων Χορηγούμενων Από Το Στόμα

“…Η αξιολόγηση της μεθόδου και των ορίων του μη-γραμμικού Χώρου Σχεδιασμού έγινε μέσω της συσχέτισης των συντελεστών με τη μέθοδο της διασταυρούμενης επικύρωσης (leave-one-out cross-validation, LOOCV) [70]. Παράλληλα, στη βιβλιογραφία υπάρχουν και περιπτώσεις όπου συνδυάζονται τα παραγοντικά πειράματα και τα πειράματα Επιφανειακής Απόκρισης για βελτιστοποίηση της διεργασίας, όπως στην περίπτωση των Weon et al, όπου μελετάται ο σχεδιασμός δισκίων με άμεση δισκιοποίηση και μεταβλητές σχεδιασμού τα επίπεδα τριών εκδόχων, μέσω παραγοντικού σχεδιασμού και Κεντρικού Σύνθετου (Central Composite) σχεδιασμού [71].…”