Preparation and In-vivo Pharmacokinetic Study of a Novel Extended Release Compression Coated Tablets of Fenoterol Hydrobromide

摘要

The aim of this study was to formulate extended release compression coated core tablets of fenoterol hydrobromide, a selective β2 adrenergic receptor agonist, in an attempt to prevent nocturnal asthma. Two hydrophilic polymers viz Kollidon® SR, Polyox® WSR 303 and a hydrophobic one (Precirol® ATO5) were employed. Compression coated tablets were formulated by preparing a core tablet containing 7.5 mg drug and various amounts of polymer and Emcompress® then compressed coated with the same polymeric materials. For comparison purpose different matrix tablets were also prepared employing the same polymers. In-vitro release studies were carried out at different pH (1.2 and 6.8). Pharmacokinetics of extended release tablets as well as commercially available immediate release tablets (Berotec®) were studied after oral administration to beagle dogs using a new developed LC-MS/MS method with a lower limit of quantification of 1 ng/ml. Fenoterol release from compression coated tablets was significantly lower than matrix tablets. The mechanism of release was changed with the nature and content of polymer. The release pattern of drug from F16 containing 40 mg Kollidon® SR divided in the core tablet (15 mg) and the rest in the compressed coat (25 mg) showed a typical zero order release kinetic that could extend drug release >10 h and reasonable time for 75% to be released (t75) (8.92 h). When compared to immediate release Berotec® tablet the MRT was significantly extended from 7.03 ± 0.76 to 10.93 ± 1.25 h (P < 0.001) and HVDt 50%Cmax was also significantly extended from 2.71 ± 0.68 to 6.81 ± 0.67 h with expected prevention of nocturnal asthma.