Studies On Pharmacokinetics Of Sustained-Release Pellets Of Clamthromycin, Clamthromycin Citrate And Cyclodextrin Complex

Objective: One of the main goals in pharmaceutical technological field was to improve solubility and dissolution rate of poorly water-soluble drugs in vitro, which affected the uptake in vivo directly. Two kinds of film-coated pellets of clarithromycin would be prepared and pharmacokinetic test performed in healthy volunteers. In order to improve the solubility, clarithromycin citrate and ternary complex were to be made. The pharmacokinetic profiles of the citrate and ternary complex were to be obtained in Beagle dogs.Methods: Citric acid was added to the clarithromycin core to enhance the drug solubility and dissolution at alkaline medium. Two kinds of film-coated pellets of clarithromycin were prepared: formulation-1 (F-1) was prepared by incorporating three kinds of pH-dependent gradient-release coated pellets into capsules, formulation-2 (F-2) was prepared by coated with an insoluble semiosmotic film which was made by blending Eudragit(?) RL30D with Eudragit(?) RS30D, pore former PEG6000 was added.Pharmacokinetic profiles of two formulations were obtained in three healthy male volunteers and compared to commercially available immediate release (IR) tablets. Clarithromycin concentration in plasma was determined by means of liquid chromatography-tandem mass spectrometry method. Thermo Hypersil-Keystone-C₁₈, 5 μm,150×3.0 mm column (Thermo, USA) was used for separation at a flow-rate of 0.5 ml/min. The mobile phase consisted of methanol: water: formic acid (80:20:1, v/v). HPLC system was equipped with LC-10ADvp pump (Shimadzu), attached to an autosampler injection valve (America Agilent). Detection was performed by a TSQ triple-quad mass spectrometer in the selected reaction monitoring mode using TurboIonSpray electrospary ionization source (Finnigan, USA) and monitoring the transition of protonated for CLA at m/z158.2. The relative collision energy was set at 35 eV. Argon was used as the collision gas at a pressure of approximately 1.4 mTorr. The mass spectrometer was interfaced to a computer workstation running Xcalibur 1.1 software. Roxithromycin was used an internal standards. The standard curve was found to be linear (r = 0.9995) over the concentration range of 10-5000 ng/ml. The analytical method was validated in relation to accuracy,...