title: Co-milling of telmisartan with poly(vinyl alcohol)--An alkalinizer free green approach to ensure its bioavailability.
abstract: The aim of this study was to enhance the dissolution and bioavailability of telmisartan (TLM), a poorly water soluble drug by co-milling approach. Physical mixtures of TLM and poly(vinyl alcohol) (PVA) were co-milled in a planetary micro mill in a dry condition by varying process parameters such as drug to polymer weight ratio, ball-to-powder weight ratio, and rotational speed. The co-milled products offered cumulative percentage dissolution of TLM above 75% in 30 min (CG 1 and CG2). These samples were characterized using field emission scanning electron microscopy (FE-SEM), powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and Raman spectra analysis. Well-dispersed acicular shaped particles of TLM were observed in co-milled products. A mixture of crystalline and amorphous TLM with a particle size less than 1 μm was present in CG1. The particle size of TLM observed in CG2 was less than 2 μm. In addition to crystalline and amorphous form of TLM, defective/disordered crystals of TLM were also present in CG 2. Therefore, CG2 tablets exhibited poor stability. CG 1 tablets were found to be stable under accelerated stability test conditions. The relative bioavailability of TLM of CG 1 containing tablets in comparison with Micardis® was 93.92±12.84% (in rabbits). Thus, co-milling of TLM with PVA proves to be a promising "alkalinizer free green approach" to ensure the dissolution and bioavailability of poorly water soluble TLM.
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215, India.
authors.forename: Jinu
authors.initials: J
authors.lastname: Isaac
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215, India.
authors.forename: Swastika
authors.initials: S
authors.lastname: Ganguly
authors.affiliation: Department of Pharmaceutical Sciences and Technology, Birla Institute of Technology, Mesra, Ranchi, Jharkhand 835215, India. Electronic address: aghosh@bitmesra.ac.in.
authors.forename: Animesh
authors.initials: A
authors.lastname: Ghosh
mesh_terms: D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry* / Q000493:pharmacokinetics*; D001565:Benzoates / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D004339:Drug Compounding / Q000379:methods*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D011108:Polymers / Q000737:chemistry*; D011143:Polyvinyl Chloride / Q000737:chemistry*; D011208:Powders / Q000737:chemistry; D011817:Rabbits; D012995:Solubility; D013607:Tablets / Q000737:chemistry / Q000493:pharmacokinetics; D000077333:Telmisartan; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D001562:Benzimidazoles; D001565:Benzoates; D011108:Polymers; D011208:Powders; D013607:Tablets; D011143:Polyvinyl Chloride; D000077333:Telmisartan
keywords: Co-milling; Disordered crystals; Green pharmaceutical formulation; Poly(vinyl alcohol); Telmisartan