Donaduzzi C.M.,Donaduzzi and Cia Ltda
Arzneimittel-Forschung/Drug Research | Year: 2010
The purpose of this study is to compare the bioavailability of two itraconazole (CAS 84625-61-6) capsule formulations. An open, randomized, two-period crossover study with a 7-day washout interval was conduced in 32 healthy volunteers. The plasma samples were obtained up to 96 h after drug administration. A sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of itraconazole in human plasma. Itraconazole and ketoconazole (internal standard) were extracted from the plasma by liquid-liquid extraction using diethylether : dichloromethane (70 : 30) as extraction solvent and separated on a C 8 analytical column (150 mm×4.6 mm I.D.) maintained at 40 °C. The elution was performed by a constant flow rate of 1.2 mL/min and the mobile phase consisted of acetonitrile and acetic acid 0.1% (85 : 15 v/v). The mass spectrometer equipped with an electrospray source in positive mode, was set up in multiple reaction monitoring, to detect parent → product ion 705.0 → 392.0 (itraconazole) and 531.0 → 81.70 (ketoconazole). The chromatographic separation was obtained within 3.5 min and was linear in the concentration range of 5 to 600 ng/mL. Bioequivalence between the products was determined by calculating 90%confidence intervals for the ratio of C max (95.02%-109.48 %), AUC 0-t (81.41%-107.77 %) and AUC 0-inf (80.85%-106.86%). These values for the test and reference products are within the 80-125% interval, proposed by FDA and EMEA. It was concluded that the proposed method was successfully applied to a pharmacokinetic study in healthy human volunteers, and results showed that the two itraconazole formulations are bioequivalent in their rate and extent of absorption. © ECV · Editio Cantor Verlag, Aulendorf (Germany).
Stability study of prednisolone sodium phosphate in conditions of thermal and oxidative stress in oral formulation [Estudo de estabilidade do fosfato dissódico de prednisolona em condições de estresse oxidativo e térmico, em formulação oral]
Lindino C.A.,West Parana State University |
Mitsui M.L.,Donaduzzi and Cia Ltda. |
Ortiguara R.,Donaduzzi and Cia Ltda. |
Felin D.,Donaduzzi and Cia Ltda. |
And 2 more authors.
Ecletica Quimica | Year: 2010
This work was to investigate the process of degradation of the drug Prednisolone Sodium Phosphate (FSP) in oral solution dosage form through the degradation experiments, evaluating the parameters in accordance with Resolution 899/2003 ANVISA and the degradation process of the drug. The method by high performance liquid chromatography (HPLC) developed for the determination of the drug was validated to demonstrate its applicability as an indicator of stability, ensuring reliability. After the method be validated to study the degradation of the drug, it was shown that drastic conditions of oxidative stress (H2O2 30%) and temperature 60°C, the degradation of the drug is dependent on its concentration (first order kinetics). The results were satisfactory, showing that this method is suitable to investigate the formation of degradation products in oral dosage form solution.