Lorazepam-loaded solid lipid nanoparticles: preparation, and intestinal permeability investigation

Abstract

Introduction and Background: Lorazepam, a benzodiazepine specifically used as an anti-epilepsy, anxiolytic, hypnotic and sedative, has been shown to be an effective anticonvulsant with minimum depressive effects on respiration and circulation in children status epilepticus disorder. Moreover, it is highly unstable and susceptible of being hydrolyzed in aqueous media therefore it is impossible to prepare aqueous solutions of this compound for oral or other routs of administration. In the present investigation, we are going to prepare and characterize SLNs of Lorazepam with suitable size and drug entrapment efficiency. The intestinal absorption characteristics of prepared nanoparticles will be assessed to estimate the in vivo bioavailability of the preparations. This would lead to controlled release oral dosage forms which is the best tolerated for children with status epilepticus.Aim: Preparation and in vitro-in vivo evaluation of lipid nanoparticles for controlled oral delivery of lorazepam.Methods: SPIP was performed in isolated jejunal segment at three Formulation of LORAZEPAM (SLN and NLC) to compare intestinal permeability changes against ofsimple solution of Lorazepam. Phenol red was used as a non-absorbable marker. Stability studies were conducted to ensure that the loss of Lorazepam could be attributed to intestinal absorption. Outlet samples were analysed using the developed HPLC method and effective permeability values were calculated by respected formula.Results: The effective permeability value of Lorazepam simple solution in the jejunum was 5.57×10-4. Also the effective permeability values of SLN7-SLN8-NLC Lorazepam nanoemolsoinwere found to be 7.18×10-4, 2.98×10-4 and 0.71×10-4cm/sec. Discussion and conclusion:In conclusion,New techniques have shown that the use of nanoparticles like SLN can dramatically increase intestinal permeability.