Influence of the preparation procedure and chitosan type on physicochemical properties and release behavior of alginate-chitosan microparticles.

BACKGROUND: The potential for use of chitosan-treated alginate microparticles as a vehicle for oral phenytoin delivery has not been thoroughly exploited. AIM: We studied the influence of preparation procedure and chitosan type on physicochemical properties and release behavior of alginate-chitosan microparticles. METHOD: The total number of 24 microparticles formulations prepared by varying contents of calcium gelling ions and varying contents and type of chitosan was examined. As an additional variable, two different hardening times (1 and 24 hours) were employed. Possible interactions of components, surface morphology of microparticles as well as release profile of phenytoin were studied. RESULTS: Both series of formulations with regard to hardening times, irrespective of the chitosan type and/or concentration employed appeared to be highly loaded with the model drug (above 90%). The drug release studies showed that the kinetics of phenytoin cannot be straightforwardly predicted based on the molecular weight of chitosan alone. On the other hand, prolonging the hardening time from 1 to 24 hours had significantly improved phenytoin kinetics, and gave rise to a formulation with the liberation half-time of about 2.5 hours. CONCLUSION: This study showed that the latter formulation is eligible for further modifications aimed at improving the regularity of phenytoin absorption.

Preparation and characterisation of phenytoin-loaded alginate and alginate-chitosan microparticles.

We aimed to prepare and investigate microparticles with the varying contents of calcium gelling ion, loaded with phenytoin, a standard antiepileptic agent, in its acidic form. Two different methods of alginate-based microparticles preparation were used: with and without treatment with chitosan. Furthermore, two standard procedures, the one-stage and the two-stage, were applied. Microparticle size of 12 one-stage formulations ranged from 466 to 636 mum. Both types of formulations, chitosan-treated and nontreated, appeared to be highly loaded with the model drug (91-96%). The chitosan-coated alginate-based microparticles prepared by the one-stage procedure exhibited kinetics of phenytoin liberation comparable to a similar sustained release system that had been tested at pH 6.8, as published earlier. As the gel erosion of alginate-based microparticles should be potentiated by the higher pH (used in the present study at pH 7.4), the most favorable of 12 formulations, with the liberation half-time of about 2 hr, seemed to be eligible for further modifications. Counterintuitively, the applied two-stage procedure did not appear to beneficially affect the dissolution behavior of phenytoin when tested in two formulations, which makes further modifications necessary.

Chemometrically assisted development and validation of LC-UV and LC-MS methods for simultaneous determination of torasemide and its impurities.

Complete evaluation of chromatographic behavior and establishment of optimal experimental conditions for determination of torasemide and its four impurities are determined by experimental design. Fractional factorial and 3(n) full factorial design were employed for efficient and rapid optimization of liquid chromatography-ultraviolet and liquid chromatography-mass spectrometry (LC-MS) methods. Separation is achieved on a Zorbax SB C(18) analytical column (250 x 4.6 mm, 5 µm) with mobile phase consisting of acetonitrile and 10 mM ammonium formate (pH 2.5 with formic acid) in gradient mode. The flow rate is 1 mL min(-1), the temperature of the column is 25 °C and UV detection is performed at 290 nm. The efficiency of ionization in electrospray ionization is higher than in atmospheric pressure chemical ionization mode; therefore, it is further used for analysis of torasemide and its impurities. Both methods meet all validation criteria. The calibration curves show high linearity with the coefficients of correlation (r) greater than 0.9982. The obtained recovery values (95.78-104.92%) and relative standard deviation values (0.12-5.56%) indicate good accuracy and precision. Lower limit of detection (LOD) and limit of quantitation (LOQ) values are obtained with the LC-MS method, indicating higher sensitivity of the proposed method.