title: Enhanced bioavailability of atorvastatin calcium from stabilized gastric resident formulation.
abstract: Oral bioavailability of atorvastatin calcium (ATC) is very low (only 14%) due to instability and incomplete intestinal absorption and/or extensive gut wall extraction. When ATC is packed in the form of tablets, powders, etc., it gets destabilized as it is exposed to the oxidative environment, which is usually present during the production process, the storage of the substance, and the pharmaceutical formulation. Therefore, stabilized gastro-retentive floating tablets of ATC were prepared to enhance bioavailability. Water sorption and viscosity measurement studies are performed to get the best polymer matrix for gastro-retention. A 3(2) factorial design used to prepare optimized formulation of ATC. The selected excipients such as docusate sodium enhanced the stability and solubility of ATC in gastric media and tablet dosage form. The best formulation (F4) consisting of hypromellose, sodium bicarbonate, polyethylene oxide, docusate sodium, mannitol, crosscarmellose sodium, and magnesium stearate, gave floating lag time of 56 ± 4.16 s and good matrix integrity with in vitro dissolution of 98.2% in 12 h. After stability studies, no significant change was observed in stability, solubility, floating lag time, total floating duration, matrix integrity, and sustained drug release rates, as confirmed by DSC and powder X-ray diffraction studies. In vivo pharmacokinetic study performed in rabbits revealed enhanced bioavailability of F4 floating tablets, about 1.6 times compared with that of the conventional tablet (Storvas® 80 mg tablet). These results suggest that the gastric resident formulation is a promising approach for the oral delivery of ATC for improving bioavailability.
authors: Department of Pharmaceutics, Y. B. Chavan College of Pharmacy, Dr. Rafiq Zakaria Campus, Rauza Bagh, Aurangabad, MS, India. furkhankhan@rediffmail.com
authors: Furquan Nazimuddin
authors: FN
authors: Khan
authors: Mohamed Hassan G
authors: MH
authors: Dehghan
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000069059:Atorvastatin; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning; D002266:Carboxymethylcellulose Sodium / Q000737:chemistry; D002626:Chemistry, Pharmaceutical; D003692:Delayed-Action Preparations; D004143:Dioctyl Sulfosuccinic Acid / Q000737:chemistry; D004339:Drug Compounding; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D065347:Hypromellose Derivatives; D008297:Male; D008353:Mannitol / Q000737:chemistry; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D033362:Powder Diffraction; D011758:Pyrroles / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D012044:Regression Analysis; D017693:Sodium Bicarbonate / Q000737:chemistry; D012995:Solubility; D013229:Stearic Acids / Q000737:chemistry; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods; D014783:Viscosity; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D003692:Delayed-Action Preparations; D005079:Excipients; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D013229:Stearic Acids; D013607:Tablets; D014867:Water; D004143:Dioctyl Sulfosuccinic Acid; D065347:Hypromellose Derivatives; D008353:Mannitol; D011092:Polyethylene Glycols; C031183:stearic acid; D017693:Sodium Bicarbonate; D008747:Methylcellulose; D000069059:Atorvastatin; D002266:Carboxymethylcellulose Sodium