IN-VITRO IN-VIVO STUDIES OF LAMOTRIGINE TABLETS PREPARED BY HOT MELT EXTRUSION TECHNIQUE
Keywords:
Lamo, HME, In vivo, Kollidon VA64, PermeabilityAbstract
Objective: Present study deals with improvement in dissolution and bioavailability of poorly water soluble Lamotrigine (Lamo), an antiepileptic drug (AED) of phenyltriazine class. Formulation of poorly water soluble drug for oral delivery is one of the biggest challenge. Amongst all the approaches, the novel solid dispersion (SD) technique known as hot melt extrusion (HME) has found to be the most widely used method in improving dissolution and bioavailability.
Methods: Dissolution enhancement of Lamo were done by HME technology where crystalline form of API is converted to amorphous form using hydrophilic polymer Kollidon VA64. Plasticizers like Polyethylene glycol (PEG 4000), polyoxyl 35 castor oil (Cremophor EL) and Sorbiton monolaurate (Montane 20PHA) were used. Physical blends of drug, polymer and plasticizer were prepared in the ratio of 1:1:0.1. These physical mixtures were subjected to melt and the resultant formulations were subjected to physical characterization, dissolution, permeability and in vivo testing. Pharmacokinetics of Lamo was studied in rats. Drug efflux pump like P-glycoprotein (P-gp) was recognized to posses' functional role in determining the pharmacokinetics of drugs.
Results: Drug release showed the similar profile for all the HME formulations while the permeability studies showed improved permeability of formulations containing Montane 20PHA. In comparison to Non HME, HME formulations showed a significant enhancement in permeability. SD prepared by Cremophor EL resulted in 765.22% enhancement in extent of absorption.
Conclusion: HME technology could be a promising formulation approach to enhance the dissolution and bioavailability of Lamo.
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