Objective: Epilepsy is a common neurodegenerative disorder characterized by spontaneous and repeated attacks of convulsions. It requires immediate pharmacotherapy to prevent its progression to status epilepticus. However, most of the anticonvulsant drugs are poorly water-soluble and demonstrate the delayed onset of action. Thus there is a need to improve its solubility for the better pharmaceutical profile. The objective of the present investigation was to enhance the solubility of lamotrigine incorporating soya lecithin as a phospholipid carrier by solid dispersion technique Methods: Solid dispersions of lamotrigine were prepared with soya lecithin by the solvent method. The effect of concentration of phospholipid and solvents on aqueous solubility and dissolution profile of lamotrigine was analyzed.Results: Ethanol increased lamotrigine solubility with soya lecithin in ratio 5:1. X-ray diffraction and scanning electron micrograph indicated a smaller crystallite size of lamotrigine with fairly uniform size distribution in the lamotrigine-soya lecithin solid dispersion. The resultant solid dispersion also significantly delayed the onset of clonic convulsion (875.8 s) as compared to control (85.5 s) and offered complete protection (100%) against the pentylenetetrazole induced seizures in the rat as compared to control (33.33%). Also, solid dispersion with maximum drug content (77.68%) and dissolution rate (91.40%) was formulated as an orodispersible tablet and characterized for its pharmaceutical properties. Conclusion:It can be concluded that the solid dispersion of lamotrigine incorporated with soya lecithin demonstrated enhanced solubility and dissolution rate may have potential clinical application. I In nt te er rn na at ti io on na al l J Jo ou ur rn na al l o of f A Ap pp pl li ie ed d P Ph ha ar rm ma ac ce eu ut ti ic cs s
Objective: The presence of tight junctions in blood-brain barrier creates a major problem for the delivery of drugs and severely affects adequate therapeutic concentration to reach the brain. For the treatment of epilepsy, oral route of administration is most convenient but shows delayed absorption. Moreover, in emergency cases, parenteral administration is not possible as it requires medical assistance. Thus, an alternative route of drug delivery is highly desirable for an effective outcome. Methods: In the present study, bioadhesive chitosan nanoparticles of topiramate for intranasal administration were prepared by ionotropic gelation method using chitosan as bioadhesive polymer and sodium tripolyphosphate as the crosslinking agent. The prepared nanoparticles were evaluated for physicochemical properties like particle size, surface morphology, drug content, entrapment efficiency, thermal behavior and crystallinity, in vitro drug diffusion, ex vivo bio adhesion, and ex vivo biocompatibility studies in excised sheep nasal mucosa. Results: Differential scanning calorimetry and x-ray diffraction study showed molecular dispersion of drug into the polymer matrices and conversion of it into an amorphous form. Nanoparticles obtained were discrete in nature (size 313.5 nm) and appropriate for intranasal administration. The topiramate nanoparticles revealed high encapsulation efficacy, strong bioadhesion potential and high ex vivo permeation and did not exhibit any deformity to the nasal mucosa. In vitro drug diffusion of optimized formulation showed 92.91% release of drugs after 180 min. Ex-vivo permeation of drugs across nasal mucosa was 89.03 % after 180 min. Conclusion: Hence, the intranasal administration of topiramate using chitosan can be a promising alternative for brain targeting and the treatment of epilepsy.
Aim: Due to the presence of rich blood circulation and non-invasive nature of administration, the nasal route has been established as valuable therapeutic alternatives. This study was designed with the basic objective to formulate mucoadhesive microspheres of anticonvulsant drug, lamotrigine (LT) for intranasal delivery and to carry out its pharmacodynamic investigations to benefit the emergency cases of epileptic seizures. Materials and Methods:The microspheres were prepared by ionotropic gelation method and characterized for morphology scanning electron microscopy, particle size, drug entrapment efficiency, thermal behavior (differential scanning calorimetry), and crystallinity (X-ray diffraction), in vitro swelling studies, in vitro drug diffusion, ex vivo bioadhesion, and ex vivo biocompatibility studies in excised sheep nasal mucosa. The resultant LT loaded chitosan (CH) microspheres were further evaluated for pharmacodynamic efficacy in pentylenetetrazol (PTZ) induced seizures in mice. Result and Discussion: Results demonstrated that the microspheres were discrete, smooth, and spherical in shape with size 24.5 ± 2.62 to 48.52 ± 2.34 µm, appropriate for nasal drug delivery. The CH-based nasal LT microspheres demonstrated high encapsulation efficacy, strong bioadhesion potential, and high permeation without any signs of morphological toxicity in excised sheep nasal mucosa. Importantly the intranasal administration of LT microspheres delayed the onset of clonic convulsion and offered complete protection against the PTZ induced seizures in mice compared to its peripheral administration. Conclusion: Thus, the formulation of LT loaded CH mucoadhesive microspheres offers promising advantages over conventional dosage with its immediate onset of action.
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