Development and Evaluation of a Lamotrigine Extended-Release Mini-Tablet Dosage Form

Janaki, D (2021) Development and Evaluation of a Lamotrigine Extended-Release Mini-Tablet Dosage Form. Masters thesis, C. L. Baid Metha College of Pharmacy, Chennai.


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CHAPTER I: In this introduction chapter discussed about epilepsy, types and treatment, extended- release drug delivery system and their approaches. Also, Multi particulate drug delivery system, minitablets, types, advantages and method of manufacturing. CHAPTER II: In this Chapter the literature related to this work was surveyed and a brief discussion had been given on each literature. CHAPTER III: The objective of present investigation was to formulated and developed lamotrigine (200mg) extended-release minitablets using HPMC K4M and K100M as a release modifier. Minitablets were prepared by direct compression technique. CHAPTER IV: This Chapter gives an idea for the proposed plan of work that has to be carried out. CHAPTER V & VI: In this chapter information about the drug and the polymers used in the study was given. CHAPTER VII & VIII: This chapter deals with the materials and methods used in the study. This chapter covers the details of experimental methods, Design of experiment, including evaluation of pre formulation, in vivo, in-vitro evaluation, and release kinetics finally stability studies. CHAPTER IX: This chapter depicts the results for the all tests indicated in the chapter VIII. The results for all the parameter to be evaluated for the prepared Lamotrigine minitablet forms were given in this chapter. The In-vitro evaluation of the optimized formulation were available. Chapter VIII & X: These chapters deal with the optimization of the formulation among the 9 formulation of Lamotrigine ER minitablets. In it, the best values for different evaluation tests are found and presented. Dissolution studies of different formulation is tabulated and stability study was given. The chapter discussion involves in discussion of the better fit values of the different evaluation test to optimize the best fit values A total of 9 ER minitablet formulations were proposed by the 32 full factorial design for two independent Variables. percent drug release and tensile strength were investigated as optimised response parameters in the current study. The results of the ANOVA indicated that these models were significant for all response parameters (Table 36-37). The Design- Expert 11.1.2 software provided suitable polynomial model equations involving individual main factors and interaction factors after fitting these data. The influences of main effects (factors) on responses investigated optimized formulation fitted with selectively zero order and Peppas model to calculate the value of sum of squared residuals (SSR) and Akaike information criterion (AIC), best goodness-of-fit test (R2). High value of Mean selection criterion (MSE) was taken as criterion for selecting the most appropriate model. Accordingly, optimized formulation fitted with all dissolution model and the values found to be followed Zero-order, First order, Higuchi’ s model Korsemeyer-peppas kinetics (Table 44). The release exponent of peppas model (n=0.3) indicate Quasi-Fickian) diffusion and rates as a function of time follows zero order release. Similarly, adjusted R2 Values - 0.9910, AIC - 44.7266, some of square residues (SSR) and mean selection criterion - 2.377 were satisfied with korsemeyer-peppas model. CONCLUSION: In this study, lamotrigine extended-release mini-tablets were successfully developed by filling 8 mini-tablets into empty capsule shells (size 0), releasing almost the full dose within 12 hours. 32 full factorial design and optimization technique successfully used in the development and formulation of Minitablet. Mini tablets of lamotrigine were prepared by the direct compression method using HPMC K4 M and K100M as a release modifiers. The different formulations containing HPMC with different viscosity grades have shown differences in drug release profiles. The blend of all the formulations showed good flow properties such as the angle of repose, bulk density, tapped density. The prepared tablets showed good post-compression parameters and they passed all quality control evaluation parameters according to I.P limits. From the results it was clearly understand that as the polymer concentration increases the release rate of drug was retarded and both of these polymers can be used in combination since do not interact with the drug which may be more helpful in achieving the desired extended release of the drug for longer periods treatment of epilepsy. Lamotrigine can be used in a minitablet sustained-release drug delivery system and prolong the duration of action in the therapeutic range without reaching toxic levels as in conventional dosage forms. a valuable tool for achieving improved adherence and seizure control, and reduced toxicity. Optimum formulation F(10) was suggested by the software. Formulation F (10) were exhibited satisfactory physio-chemical characteristics and prepared with HPMC K4M (11 mg) and K100M (4.5 mg) gave 95.4 % of desired drug release in 12 hrs also stable in stability. Marketed formulation (LAMICTAL XR) showed 91.3% drug release. when compared with the optimized formulation decrease release profile.The maximum plasma concentration Cmax was 375.0 μg/mL and the time needed to reach Tmax was 4 hrs for Lamotrigine ER minitablets. The optimized formulations followed zero order kinetics while the drug release mechanism was found to be Quasi Fickian. On the basis of evaluation parameters, the formulation F10 used once a day administration in the management of epilepsy. These dosage forms have the ability to reduce the dosing frequency.

Item Type: Thesis (Masters)
Additional Information: 261910008
Uncontrolled Keywords: Development, Evaluation, Lamotrigine, Extended-Release Mini-Tablet Dosage Form.
Subjects: PHARMACY > Pharmaceutics
Depositing User: Subramani R
Date Deposited: 01 Nov 2022 02:53
Last Modified: 01 Nov 2022 02:53

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