Ikuo Johno

Effects of hardness on the disintegration time and the dissolution rate of uncoated caffeine tablets

The effects of hardness on disintegration and dissolution characteristics of uncoated caffeine tablets made at eight different pressure levels were studied. The disintegration times were determined using the J.P. VIII procedure with disks and the dissolution rate measurements were performed with the U.S.P. XVIII procedure (U.S.P. method) and the J.P. VIII disintegration test apparatus (J.P. method). A good correlation between the hardness and the disintegration times was obtained. The dissolution rate constants were determined from the equation of Noyes & Whitney (1897) and a good correlation between the hardness and the dissolution rate constants was obtained. The hardness governed the dissolution over all the stages from tablet to the smallest particles after the breakage by disintegration. The dissolution rates of the J.P. method were greater than those of the U.S.P. method.

Interpretation of dissolution rate data from in vitro testing of compressed tablets

To find if theoretically and experimentally a relation existed between the dissolution rate theory of Kitazawa, Johno & others (1975) and that of Wagner (1969), a study was undertaken with uncoated caffeine, aspirin and proxyphylline tablets using two dissolution methods. Although the original treatment for surface area of drug available for dissolution was quite different between the two dissolution theories, the dissolution rate constants obtained were in fair agreement. Hence it might not be always necessary to take into consideration changes in the surface area as a function of dissolution rate, and the 1n W∞/ (W∞ ‐ W) versus time plot devised by Kitazawa & others might be a useful and simple means of obtaining the dissolution rate constant of an active ingredient from a dosage form such as compressed tablet.

Comparative evaluation of microultrafiltration devices for determination of protein binding.

The free fraction of drugs was determined comparatively with new microultrafiltration devices, Molcut II (Catalogue No. SJGC type) (MLII) and (Catalogue No. PLGC type) (NML: a device derived by changing the membrane component of MLII), which were developed by Nihon Millipore Ltd., Tokyo, Japan. The results obtained with the device are compared with those of MPS-1 (MPS), which is commercially available from Amicon Co., Danvers, MA, U.S.A. Drugs tested are phenytoin, carbamazepine, valproic acid, the ophylline, phenobarbital, and gliclazide, In five of six drugs the free fraction by MLII shows lower values, although that by NML is in good agreement with MPS. The lower values of free fraction of drugs obtained with MLII may be caused by adsorption to the device. The adsorption increase is relatively correlated to increasing lipophilicity of drugs. The results suggest that physicochemical properties of each drug, especially hydrophobicity, should be taken into account, when a new device is used to examine protein binding of drugs. The NML, which is less expensive and is convenient because no special instrument is needed, is a reliable and satisfactory device for routine therapeutic free drug monitoring.

Determination of Cefpiramide in Plasma by High-Performance Liquid Chromatographic with Internal Surface Reversed-Phase Silica Column

Abstract We investigated the isolation of cefpiramide (CPM), cephem antibiotics, from human plasma proteins by high-performance liquid chromatography with a new column, PinkertonR column (Regis Chemical Co., Illinois, U.S.A.), and discussed whether the column is applicable to routine clinical determination. In condition of our studies, CPM could be analyzed without any pretreatment. The chromatograms of CPM obtained were single, sharp peaks. Proteins and endogenous compounds in plasma did not interfere with the assay. And, the precise free fraction of CPM could be obtained. The effect on the isolation by the different flow direction was also studied since the column could be used reversibly. There were significant differences (p < 0.01) between two slopes of the calibration curves by the different flow direction. It is suggested that calibration curves for both flow directions are required. The analytical procedures outlined in this study may be applicable to routine clinical use since this is a simple an...

Protein binding of cefpiramide in the plasma of various species.

Abstract— The plasma protein binding of cefpiramide in man, dog, rabbit and rat was examined. Cefpiramide was more strongly bound to human plasma than to animal plasma and was exclusively bound to albumin. The characteristics of the protein binding of cefpiramide is one of the factors influencing the extrapolation of drug disposition from animals to man.

Is free fraction measurement of phenytoin always necessary in pediatric epileptic patients

Sixty-two serum samples from 28 pediatric epileptic patients under treatment with phenytoin [diphenylhydantoin (DPH)] were obtained to study the correlation between total and free serum DPH concentrations. The effect of coadministered antiepileptic drugs on DPH protein binding was also studied. Binding of DPH to serum protein was assessed by ultrafiltration, and total and free DPH concentrations were determined by fluorescence polarization immunoassay. A strong correlation existed between the total and free concentrations [r = 0.958, p < 0.001, standard error of estimate (± 1Sγ) = 0.214]. The mean value for the DPH free fraction was 8.9% (range 5.7–16.3%). The samples obtained from patients on combination therapy with valproic acid (VPA) showed a larger DPH free fraction and greater variation. Exclusion of the 16 samples from patients concomitantly taking DPH and VPA yielded a better correlation (n = 46, r = 0.983, p < 0.001, ± 1Sγ = 0.145). The mean free fraction in the patients not taking VPA was 7.7% (range 5.7–9.0%). The effect of VPA on the protein binding of DPH was also studied by addition of the same antiepileptic drugs to normal human plasma; the results were similar to those obtained for epileptic patients. These findings suggest that the free DPH fraction can be predicted from the total concentration, even when the drug is coadministered with other antiepileptic drugs, the sole exception being VPA

The Storage and Management of Plasma Fractionation Products at Kishiwada City Hospital.

In september 1997 the Ministry of Health and Welfare started to require the documentation and management of blood formulations in each medical facility, investigated all blood formulations in use. These blood formulations included the products of blood transfusion and plasma fractionation. Our Department manages the plasma fractionation products while the rest are controlled by the Division of Transfusion in Clinical Laboratory Department.This report was concerned about the documentation and management of plasma fractionation products using an original personal computer program developed in our Department. The outstanding characteristics of the management were the use of our original number, to name the individual products and each product never applied to different patients. A follow-up study of the management for about one year was carried out and the oversight by medical staff in each clinic was 2.1%(165/7, 752). The particular follow-up and training for medical members were performed by pharmacists and the omission was decreased from 165 to 20, thus resalting in 0.2%.For the rational use and management of plasma fractionation products, the role of pharmacists is therefore considered to be important and indispensable.

An estimation of pharmacokinetic parameters for each dosing at unequal doses and dosing intervals

The calculations of pharmacokinetic parameters for each dosing at unequal doses and dosing intervals were proposed. Systemic clearance of a drug following one-compartment open model can be determined by the product of the apparent first-order elimination rate constant and the apparent volume of distribution. The determination of maximum plasma concentration (Cmax) and the time required for the Cmax at each dosing were also presented here. These theoretical considerations are applicable to multicompartment open model.

A comparison of the dissolution rates of caffeine tablets in a rotating‐basket with those in a Sartorius dissolution tester

Uncoated caffeine tablets of four different hardnesses were tested for dissolution rate by the Sartorius (S.S. method) and by the rotating basket method of the U.S.P. XVIII. In both methods the dissolution rate decreased with increasing hardness, and the rate obtained with the S.S. method was always less than that by the U.S.P. method. This result cannot be explained as being due only to the difference in the volume of dissolution medium. Also it was difficult to ensure that the characteristic changes in the process of dissolution paralleled the curves obtained from a plot of % caffeine dissolved vs time. Accordingly, the dissolution rate constants were calculated from the slope of each straight line in a plot of In W∞/(W∞ ‐ W) vs time.

Effects of blood glucose and plasma osmolality on transmucosal fluid movement and intestinal drug absorption.

It had been clarified in our previous study that the transmucosal fluid inflow and the absorption of sulfanilamide in alloxan diabetic rats were increased significantly than in control rats using the in situ recirculating perfusion method. The present study was designed to elucidate further in full the effects of diabetes on these intestinal absorptions. Plasma osmolality was increased with increasing blood glucose and a good correlation was obtained over a wide range of the blood glucose. The increase of blood glucose resulted in the increment of the transmucosal fluid inflow and the absorption of the drug. To examine these effects of blood glucose, rats having hyperglycemia, one of physiological characteristics in diabetic animals, were prepared by the administration of D-glucose. The fluid movement and the drug absorption in the glucose administered rats were significantly increased than in the controls and were not found significant difference compared to those of the diabetics on the basis of dry-weight of the small intestine of the experimental animal. From the results obtained in the present study and in our previous findings, it might be able to conclude that a possible mechanism on the increase of the drug absorption in the diabetics would be that the enhancement of plasma osmolality due to the hyperglycemia caused the increment of the transmucosal fluid inflow to compensate the abnormal high osmolality in blood and this inflow might lead the drug absorption increase consequently.