Lamotrigine Solid Dispersions for Solubility Enhancement

Abstract

Aim: Lamotrigine is one of the newer antiepileptic drugs, with fewer side effects, which is marketed in the UK since 1992 and introduced in India recently. For epilepsy, it is used to treat partial seizures, primary and secondary tonic-clonic seizures, and seizures associated with Lennox-Gastaut syndrome. The low aqueous solubility of lamotrigine (0.17 g/L at 25°C) is responsible for its delayed onset of action. The purpose of the present investigation was to increase the solubility and dissolution profile of lamotrigine. Materials and Methods: In the present investigation, solubility of lamotrigine pure drug was compared in the presence of Polyethylene glycol 4000 and 6000, respectively. Physical mixture of lamotrigine with PEG 6000 was prepared. Solid dispersions (SDs) of lamotrigine with PEG 6000 were prepared using melting method and characterized for drug-carrier interaction, and SDs were then subjected to dissolution studies. Results and Discussion: On the basis of solubility studies, it was found that PEG 6000 has a more pronounced effect on increasing the solubility of lamotrigine as compared to PEG 4000. As indicated from X-ray diffraction pattern and differential scanning calorimetry thermograms, lamotrigine was in the amorphous form in the SDs, which confirmed the better dissolution rate of SDs. Conclusion: On the basis of dissolution studies, it was confirmed that the dissolution rate was substantially improved for lamotrigine in its SD as compared to the pure drug and physical mixture. Thus, the SD technique with PEG 6000 as a carrier provides a promising way to enhance the solubility and dissolution rate of lamotrigine.