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-unit 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 23 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 crosslinkerions
provider. The beads were then evaluated for drug encapsulation efficiency and drug release. ANOVA
of all the dependent variables such as DEE, cumulative % drug release at 2h, 5h, 12h, rate constant
and dissolution similarity factor (f2) was done by 23 full factorial design using Design-Expert software
along with numerical optimization of the independent variables in order to meet USP-reference release
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 (f2) 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.