title: Montelukast-loaded nanostructured lipid carriers: part I oral bioavailability improvement.
abstract: The purpose of the study was to formulate montelukast-loaded nanostructured lipid carrier (MNLC) to improve its systemic bioavailability, avoid hepatic metabolism and reduce hepatic cellular toxicity due to metabolites. MNLC was prepared using melt-emulsification-homogenization method. Preformulation study was carried out to evaluate drug-excipient compatibility. MNLCs were prepared using spatially different solid and liquid lipid triglycerides. CAE (DL-Pyrrolidonecarboxylic acid salt of L-cocyl arginine ethyl ester), a cationic, biodegradable, biocompatible surfactant was used to stabilize the system. MNLCs were characterized by FTIR, XRPD and DSC to evaluate physicochemical properties. MNLCs having a particle size of 181.4 ± 6.5 nm with encapsulation efficiency of 96.13 ± 0.98% were prepared. FTIR findings demonstrated no interaction between the drug and excipients of the formulation which could lead to asymmetric vibrations. DSC and XRPD study confirmed stable amorphous form of the montelukast in lipid matrix. In vitro release study revealed sustained release over a period of 24 h. In vivo single dose oral pharmacokinetic study demonstrated 143-fold improvement in bioavailability as compared to montelukast-aqueous solution. Thus, the result of this study implies that developed MNLC formulation be suitable to sustain the drug release with improvement in the bioavailability.
authors.affiliation: Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India.
authors.forename: Arpana
authors.initials: A
authors.lastname: Patil-Gadhe
authors.affiliation: Department of Pharmaceutics, Bharati Vidyapeeth University, Poona College of Pharmacy, Erandwane, Pune, India. Electronic address: vbpokharkar@yahoo.co.in.
authors.forename: Varsha
authors.initials: V
authors.lastname: Pokharkar
mesh_terms: D000085:Acetates / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D019540:Area Under Curve; D001249:Asthma / Q000188:drug therapy; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D003521:Cyclopropanes; D004337:Drug Carriers / Q000493:pharmacokinetics*; D008055:Lipids / Q000737:chemistry*; D008297:Male; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry; D049329:Nanostructures / Q000737:chemistry*; D010316:Particle Size; D011804:Quinolines / Q000008:administration & dosage* / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013440:Sulfides; D013501:Surface-Active Agents / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D004337:Drug Carriers; D008055:Lipids; D011804:Quinolines; D013440:Sulfides; D013501:Surface-Active Agents; C093875:montelukast
keywords: Asthma; Cationic surfactant; Montelukast; Nanostructured lipid carrier; Precirol ATO5; Systemic bioavailability