title: Production of Irbesartan Nanocrystals by High Shear Homogenisation and Ultra-Probe Sonication for Improved Dissolution Rate.
abstract: Irbesartan (IRB) is a BCS class II drug with poorly aqueous solubility and its absorption is dissolution rate limited. In the present study solubility and dissolution rate of IRB were improved by nanonization and using two poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) amphiphiles, namely Pluronic® F127 and Pluronic® F68, as nanosuspension stabilisers. In addition, the role of these surfactants in the solubilization of the drug was assessed. The nanocrystals were produced by two top-down techniques- high shear homogenisation and ultra-probe sonication. The nanocrystals were characterized for particle size, size distribution and zeta potential and compared to the unprocessed drug by FTIR, thermal analysis, scanning electron microscopy, solubility and dissolution rate. IRB nanocrystals showed greater solubility and faster dissolution rate than the original drug, solubility being higher for formulations prepared with F127 than those with F68. Presence of an endothermic peak of drug in the formulation confirmed its crystalline nature, regardless of the use of two energetic methods. SEM of the nanocrystals revealed a small rod-shaped morphology and the substantial decrease of the particles size. Overall results support these nanonization techniques as a simple, cost-effective and scalable approach to improve the aqueous solubility of drugs such as IRB that are classified into Class II of the Biopharmaceutic Classification System (BCS).
authors.forename: Karthik
authors.initials: K
authors.lastname: Sridhar
authors.affiliation: Department of Pharmaceutics, PSG College of Pharmacy, Coimbatore 641004, Tamilnadu, India. hablet1@gmail.com.
authors.forename: Habibur
authors.initials: H
authors.lastname: Rahman
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sosnik
authors.forename: Uditta
authors.initials: U
authors.lastname: Mukherjee
authors.forename: Tamilselvan
authors.initials: T
authors.lastname: Natarajan
authors.forename: Karthik
authors.initials: K
authors.lastname: Siram
authors.forename: Balakumar
authors.initials: B
authors.lastname: Krishnamoorthy
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004339:Drug Compounding; D000077405:Irbesartan; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D012995:Solubility; D013010:Sonication; D017550:Spectroscopy, Fourier Transform Infrared; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D013777:Tetrazoles / Q000737:chemistry*; D014465:Ultrasonics
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D013777:Tetrazoles; D020442:Poloxamer; D000077405:Irbesartan