Masanori Kayano

Evaluation of the correlation between in vivo and in vitro release of phenylpropanolamine HCl from controlled-release tablets

Abstract The dissolution behavior of two controlled-release matrix tablets, formualtions A and B, containing phenylpropanolamine HCl as a model drug was studied using a paddle method and a paddle-beads procedure. The paddle-beads method involves a system in which polystyrene beads are inserted into the dissolution medium to cause mechanical destruction or frictional force. These tablets have the advantages of pH- and agitation-independent release performance in vitro using the paddle method. These matrices and solution were orally administered to six beagle dogs, and the results were analyzed by deconvolution. In vitro dissolution curves using the paddle method did not coincide with the in vivo profiles in the fasted condition, while in vitro release using the paddle-beads method was similar to the in vivo profile in the fasted condition in dogs. The paddle-beads method may be useful for investigating in vivo/in vitro correlation of controlled-release dosage forms.

Determination of a new H+—K+ ATPase inhibitor (E3810) and its four metabolites in human plasma by high-performance liquid chromatography

A method for the simultaneous determination of E3810, 2-[(4-(3-methoxypropoxy)-3-methyl pyridine-2-yl)methyl sulfinyl]-1H-benzimidazole sodium salt and its four metabolites, demethylated-E3810 (DM), demethylated thioether-E3810 (DMTE), sulfone-E3810 (S), and thioether-E3810 (TE), in human plasma by high-performance liquid chromatography (HPLC) with UV absorbance detection has been established. The correlation coefficient for all the standard curves was 0.998 or greater. The quantitation limit was 5 ng/ml for E3810 and 20 ng/ml for each of its four metabolites. The recovery of E3810 and its four metabolites from human plasma was high, being greater than 80% when 100 ng of each substance was added per tube, except for DM (74.1%). The stability of E3810 and its four metabolites was evaluated and the following results were obtained: (1) when samples were centrifuged within 20 min after collection, there was no loss of E3810 or its metabolites; (2) when 100 microliters of a 1% aqueous solution of diethylamine was added within 20 min after plasma isolation, there was no loss of E3810 or its metabolites; and (3) there were no stability problems during storage for a period of 10 months at -20 degrees C.

Effect of moisture on crystallization of theophylline in tablets

AbstractNeedle-like crystals appeared on the surface of theophylline tablets containing anhydrous theophylline, hygroscopic materials such as potassium, and other formulation ingredients, when stored under conditions of high relative humidity. X-ray powder diffraction studies on these crystals showed that anhydrous theophylline was converted to the hydrate.Crystal growth was accelerated by increased moisture uptake in tablets containing the hygroscopic materials polyethylene glycol 6000 or sodium chloride. The appearance of needle-like crystals on the surface of tablets resulted in a decrease in the rate of release of theophylline.

Formation and structure of stably dispersed small particles composed of phosphatidylcholine and ubiquinone-10: Coexistence of emulsion particles with bilayer vesicles

Stable aqueous dispersions of ubiquinone-10 (Q 10 ) were produced by cosonication with egg yolk phosphatidylcholine (PC) in a Q 10 mole fraction range of lipid mixture of 0.1–0.7. Electron microscopic and dynamic light scattering measurements showed the diameter of the dispersed particles to be 65–75 nm. The trapped aqueous volume inside the particles was determined fluorometrically with an aqueous space marker, calcein. Trapped volume decreased remarkably with the addition of Q 10 into small unilamellar vesicles of PC. The decline in the fraction of vesicular particles was also confirmed by 1 H-NMR measurements of the choline methyl of PC in the presence of a paramagnetic cation, Pr 31 . These results indicate that the excessive amount of Q 10 separated from PC bilayers is stabilized as emulsion particles by the PC monolayer on the surface. Monolayer-bilayer equilibrium of the PC-Q 10 mixture was estimated by measurements of spreading and collapse pressures. Results show that the coexistence of the emulsion particles (surface monolayer of PC + core of Q 10 ) with the vesicular particles (PC bilayers) is responsible for the maximum surface pressure of the monolayer. The coexistence is probably critically important to the production of stably dispersed particles of the lipid mixture.

Preparation of a novel type of controlled-release carrier and evaluation of drug release from the matrix tablet and its physical properties

Abstract Solved mixtures of hydrogels (SMH), composed of hydroxypropylcellulose (HPC), a pseudo-hydrogel, and ethylcellulose, a water-insoluble polymer, were prepared by solvent evaporation. Phenylpropanolamine hydrochloride was used as a model drug. The amount of drug released from a matrix tablet containing SMH powder and the drug increased with decreasing weight fraction of HPC (WFH) in SMH. SMH showed improved properties compared to HPC alone, for example, flowability and hydroscopicity. These properties increased with decreasing WFH. The sorption apparatus described in this study is capable of an immediate, sensitive and accurate response to initial moisture sorption. The kinetics of moisture sorption measurement using this apparatus is useful for a preliminary study.

Effect of Crystallization of Theophylline on Physical Properties of Tablets

AbstractTablets containing anhydrous theophylline, a hygroscopic material such as magnesium chloride or potassium acetate, and other constituents were stored for 4 and 12 weeks under 90% relative humidity at 37°C. During storage, whisker-like crystals appeared on the surface of the tablets. The crystals were observed under a scanning electron microscope. Changes were found in the physical properties of these tablets: crushing strength, friability, disintegration time and dissolution rate.

Inclusion Complex of Cinnarizine with β-Cyclodextrin in Aqueous Solution and in Solid State

Inclusion complex formation of cinnarizine(CN) with s-cyclodextrin (s-CD) in aqueous solution and in solid state was confirmed by the solubility method, powder X-ray diffractometry, differential scanning calorimetry(DSC) and proton nuclear magnetic resonance(1H-NMR) spectroscopy. The apparent stability constant, K’, of the complex in water at 20°C was estimated as 6.2x103M-1. The stoichiometry of the complex was given as the ratio 1:2 of CN to s-CD. The dissolution rate of CN/s-CD complex which could be prepared three different methods, coprecipitation method, neutralization method and spray-drying method, was much more rapid than intact CN, i.e., about 30 times or more. The degradation of CN in acidic solution was found to be of pseudo first-order reaction. The pseudo first-order rate constant with s-CD decrease with an increase in concentration of s-CD at pH 1.20. The inclusion complex prepared by spray-drying method was very stable under heating conditions and under high humid conditions. There was no difference in the bioavailability of CN between oral administration of s-CD complex and that of CN alone. The absorption of CN decreased significantly when CN administered with NaHCO3. However, there was observed no decrease in the case of CN/s-CD inclusion complex.