Investigation of formulation variables influencing the drug release rate from immediate release lamotrigine tablets by experimental design

permeability and low solubility, the formulation composition is very important for the release of the active principle. Interactions between lamotrigine and excipients can cause fl uctuations in blood concentration of lamotrigine, which may lead to adverse eff ects [1]. The objective of this study was to evaluate the eff ects of excipients (fi ller, disintegrant and lubricant) and storage humidity conditions on physical characteristics and dissolution rates of lamotrigine immediate release tablets. MATERIALS AND METHODS: A 23 full factorial
design (3 factors on 2 levels) was used in analyzing the eff ects of formulation composition (lactose or microcrystalline cellulose used as fi llers, magnesium stearate as lubricant, sodium starch glycolate as disintegrant). Formulations were tested according to the 9th European Pharmacopoeia. In vitro dissolution test was performed in two media pH 1.2 and pH 6.8 (USP40), content analysis was carried out by UV/VIS spectrophotometry at 267 and 304 nm [2]. ANOVA test was used for results comparison.
RESULTS: Tablet formulations with microcrystalline cellulose (MCC) exerted bett er compressibility,
friability and disintegration. Lactose formulations, in both media, released more than 85% of lamotrigine in the fi rst 15 minutes, except T3 (high disintegrant, low lubricant content). MCC formulations showed lower release of lamotrigine, as only T8 (high lubricant and high disintegrant content) released more than 85% of lamotrigine in
the fi rst 15 minutes, in both media. In reduced (30%) and elevated (75%) humidity conditions, MCC tablets showed reduced dissolution rate of lamotrigine, while no signifi cant changes were observed for lactose tablets. CONCLUSION: Low concentrations of magnesium stearate and sodium starch glycolate led to slightly higher dissolution rate of lamotrigine, lower strength, friability and disintegration for lactose tablets. However, for MCC tablets this led to higher dissolution rates and strengths and had no signifi cant eff ect on friability and disintegration. The obtained results demonstrate the importance of understanding interactions of excipients
and active substances.