Formulation of Extended-Release Beads of Lamotrigine Based on Alginate and Cassia fistula Seed Gum by QbD Approach

Aim: This study was focused on the formulation of the multi-unit extended-release peroral delivery device of lamotrigine for better management of epilepsy. Background: The single-unit extended-release peroral preparations often suffer from all-or-none effect. A significant number of multi-unit delivery systems have been reported as a solution to this problem. But most of them are found to be composed of synthetic, semi-synthetic or their combination having physiological toxicity as well as negative environmental impact. Therefore, fabrication and formulation of multi-emit extended-release peroral preparations with natural, non-toxic, biodegradable polymers employing green manufacturing processes are being appreciated worldwide. Objective: Lamotrigine-loaded extended-release multi-unit beads have been fabricated with the incorporation of a natural polysaccharide Cassia fistula seed gum in calcium-cross-linked alginate matrix employing a simple green process and 2(3) full factorial design. Methods: The total polymer concentration, polymer ratio and [CaCl2] were considered as independent formulation variables with two different levels of each for the experiment-design. The extended-release beads were then prepared by the ionotropic gelation method using calcium chloride as the crosslinker-ions provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANO-VA of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant and dissolution similarity factor (f(2)) was done by 2(3) full factorial design using Design-Expert software along with numerical optimization of the independent variables in order to meet USP-reference release profile. Results: The optimized batch showed excellent outcomes with DEE of 84.7 +/- 2.7 (%), CPR2h of 8.41 +/- 2.96 (%), CPR5h of 36.8 +/- 4.7 (%), CPR12h of 87.3 +/- 3.64 (%) and f(2) of 65.9. Conclusion: This approach of the development of multi-unit oral devices utilizing natural polysaccharides might be inspiring towards the world-wide effort for green manufacturing of sustained-release drug products by the QbD route.