Ground Mixture Research Articles

Biopharmaceutical studies of drugs. V. Dissolution properties and bioavailability of ground mixtures of poorly water soluble drugs and soluble proteins (author's transl)

Biopharmaceutical studies of drugs. V. Dissolution properties and bioavailability of ground mixtures of poorly water soluble drugs and soluble proteins (author's transl)

Effects of grinding on the physical and chemical properties of crystalline medicinals with microcrystalline cellulose. V. Comparison with tri-O-methyl-.BETA.-cyclodextrin ground mixtures.

Ground mixtures of aspirin, benzoic acid and p-acetoxydiphenyl were prepared with tri-O-methyl-β-cyclodextrin (methyl-CD). An apparent amorphous state of methyl-CD and the medicinals after grinding was indicated by X-ray diffraction analysis. Infrared analysis also indicated that the medicinal molecules were monomolecularly dispersed in the methyl-CD ground mixtures. The infrared solution spectra of medicinals in CCl4 were compared with the solid state infrared spectra in the carbonyl stretching absorption region. It was found that in the ground mixture of aspirin with methyl-CD, the hydroxyl group of aspirin was hydrogen-bonded with the methoxyl group of methyl-CD, while the acetoxyl group of aspirin was in a free state.

Effect of grinding on physical and chemical properties of crystalline medicinals with microcrystalline cellulose. II. Retention of volatile medicinals in ground mixture.

Volatile medicinals, naphthalene, d-camphor, and p-cresol became amorphous during grinding with microcrystalline cellulose. The medicinal of interest was retained in the ground mixture even when the mixture was heated at moderately high temperature in vacuo. The close relationship was noticed between the retentivity and the state of the medicinals (amorphous or not) in the ground mixture. The amount of the medicinal remaining in the ground mixture was influenced by the medicinal content, the grinding time, and the amount of water adsorbed. The medicinals were very rapidly released from the ground mixture into water. The mechanism for these results was discussed, based on the structure of the groud mixture proposed in the previous paper as follows : the molecules of the volatile medicinals are enclosed by the cellulose molecules that were bound by hydrogen bonds between hydroxyl radicals. The system was regarded as an "entropy frozen solution" of the medicinal in cellulose molecules. By adding water to the ground mixture, the hydrogen bonds are weakened and the medicinal molecule obtains the ability of molecular movement.

Effects of grinding on physical and chemical properties of crystalline medicinals with microcrystalline cellulose. III. Infrared spectra of medicinals in ground mixtures.

Several drugs, such as benzoic acid, aspirin, salicylic acid, and methyl p-hydroxy benzoate, all of which had intermolecular hydrogen bondings, were ground with microcrystalline cellulose respectively. Each drug was ground with β-cyclodextrin too. The inclusion compounds of each drug with β-cyclodextrin were prepared from aqueous solution. When the drugs were ground with β-cyclodextrin, rapid disappearance of X-ray diffraction peaks and that of heat of fusion of drugs, compared with microcrystalline cellulose, were observed. About the inclusion compounds, it was concluded from X-ray diffraction, thermal analysis, and ultraviolet measurements that β-cyclodextrin formed 1 : 1 adduct with each drug and the drug molecules were preffered oriented. The conditions of the drug molecules in the ground mixtures and in the inclusion compounds were investigated using infrared spectroscopy, especially by monitoring the carbonyl stretching bands near 1700 cm-1. When the dispersion of drugs into matrices were completed, the distinct frequency shift of the carbonyl stretching bands was observed in the infrared spectra of these sample. From these results, it would be reasonable to consider that in the ground mixture of microcrystalline cellulose, the drug molecules were present monomolecularly, presumably interacting with cellulose molecules by hydrogen bondings.

混合摩砕によるポリ塩化ビニルのメカノケミカル分解におよぼす無機酸化物の表面活性の影響

Effect of surface activity of inorganic oxides such as silica gel, magnesia, and γ-alumina having acid or basic sites as additives on mechanochemical degradation of poly (vinyl chloride) (PVC) Powder by mechanical grinding of the mixture of oxide-PVC in an agate mortar were investigated.The mechanochemical degradation of PVC powder during grinding was much accelerated by adding oxides than PVC alone. However, its extent was mainly affected by kinds and numbers of active sites on the surface of oxides as additives. The mechanical scission of C-C bond in PVC molecules was mainly accelerated by adding magnesia having basic sites, that of C-Cl bond was accelerated by adding silica gel having acid sites and the both mechanical scission was accelerated remarkably by adding γ-alumina having both acid and basic sites.While, the hydrogen chloride disconnected from PVC in the process of grinding was catched on the active surface of oxides. Moreover, the formation of organic radical on the surface of oxides after removal of PVC powder from ground mixture was suggested by ESR spectra and the surface property was changed into hydrophobic at the same time.

Physicochemical properties and intestinal absorption of a ground mixture of chloramphenicol palmitate with microcrystalline cellulose (author's transl

The ground mixtures of chloramphenicol palmitate and microcrystalline cellulose were prepared using Form A (stable form) and Form B (metastable form) chloramphenicol palmitates. In spite of the difference in the original crystal structure, X ray diffraction and differential scanning calorimetry showed that almost the same micro-dispersed or "amorphous" state of the drug was obtained by the grinding. Dissolution and enzymatic hydrolysis rates of the drug in the ground mixtures were greater than that of Form A. Enzymatic hydrolysis rate of Form B was as fast as those of the ground mixture, even when its dissolution rate was not very greater than that of Form A. The four preparations, Form A, Form B, Form A ground mixture, and Form B ground mixture, were administered in a random crossover fashion to five human subjects, and drug absorption was assessed from urinary excretion data of the metabolites. After oral administration of the ground mixtures, the drug was found to be better and more uniformly absorbed. Especially, in the case of Form A, 20-fold increase in the amount of drug absorbed was observed by the grinding.

Effects of grinding on physical and chemical properties of crystalline medicinals with microcrystalline cellulose. I. Some physical properties of crystalline medicinals in ground mixtures.

Effects of grinding on physical and chemical properties of crystalline medicinals with microcrystalline cellulose. I. Some physical properties of crystalline medicinals in ground mixtures.

Dissolution behavior and bioavailability of phenytoin from a ground mixture with microcrystalline cellulose.

The ground mixture of phenytoin and microcrystalline cellulose was prepared by grinding in a vibrational ball mill. The X-ray diffraction patterns indicated the amorphous nature of the ground mixture. Comparative studies were made concerning the in vitro dissolution and in vivo absorption of fine phenytoin powder, phenytoin sodium powder, and the ground mixture. The ground mixture showed a greater dissolution rate than the fine powder and attained supersaturation in the pharmacopeial disintegration media at pH 1.2 and 7.4. In vivo absorption studies of each preparation were carried out in five subjects, using a crossover design, by measuring the urinary excretion rate of a main metabolite, 5-(p-hydroxyphenyl)-5-phenylhydantoin. The blood levels of phenytoin and the corresponding urinary excretion patterns of the metabolite were determined in two subjects. The ground mixtures significantly improved the bioavailability of phenytoin. The drug was completely and rapidly absorbed after oral administration of the ground mixture. The vibrational ball milling technique for a poorly water-soluble drug with microcrystalline cellulose provides a promising way of improving the in vivo drug absorption.

Increasing Polyunsaturation of Milk Fats by Feeding Formaldehyde Protected Sunflower-Soybean Supplement

A practical means of protecting fats of a feed concentrate containing high polyunsaturated fatty acids is described. A ground mixture of 30% soybeans and 70% sunflower seeds was treated with 1% formaldehyde to protect the unsaturated lipids from microbial hydrogenation in the rumen. This was fed as a supplement to two Holstein cows in amounts that were doubled weekly. These ranged from 524 to 8384g/day and provided successively increasing intakes of 100, 200, 400, 800, and 1600g of linoleic acid daily. Percent milk fat increased by more than one, and linoleic acid (C18:2) of milk fat increased from 2.5 to 20% with compensatory declines in myristic (C14:0) and palmitic (C16:0) acids. Cholesterol and vitamin E of plasma both doubled at the highest supplementation. Milk yield, solids-not-fat, protein, and milk cholesterol were unaltered. Fat in feces doubled from about 3 to 6%. Daily linoleic acid content of feces increased from 25g to 120g, indicating a dietary loss of 7 to 10% of this polyunsaturated acid. These cheaper feed ingredients elevated the polyunsaturated fats in milk as effectively as the expensive purified casein and safflower oil supplements in previous experiments.

Dissolution rate and bioavailability of griseofulvin from a ground mixture with microcrystalline cellulose.

A ground mixture of griseofulvin and microcrystalline cellulose was prepared by grinding them in a vibrational ball mill. The dissolution rate and bioavailability of griseofulvin from the ground mixture were shown to be significantly greater than those from a micronized griseofulvin powder.

Mechanochemical Effect on the Solid State Reaction between Barium Carbonate and Titanium Dioxide

The influence of structural distortion and microscopically homogeneous mixing etc., given to powder material as mechanochemical effect by mechanical grinding, on velocity of solid state reaction have been studied in the system of BaCO3-TiO2-. When BaCO$ and TiO2 (anatase) were ground independently in air or in vacuum and together in air, remarkable structural changes were not seen on X-ray diffraction patterns. Whereas, when both compounds were mixed and ground for 48 hours in vacuum (10-2 mmHg), the clear change into amorphous phase by distruction and the rapid growth of secondary particles by strong aggregation occurred between both distorted surfaces were shown. However, the formation of BaTiO, was not confirmed. The formation velocities of 13aTiO0 by heating the ground mixture of J3aCO3 and TiO2 were studied through the X-ray diffraction patterns at high temperature '(10°C/min) and it was found that the formation of BaTiOs were much accelerated by mechanochemical effect. The formation of BaTiO3 started at 500°C and ended at 800°C in the case of the mixture ground for 48 hours in vacuum, while it began at 750°C and terminated at 1100°C in the case of the simple mixture without grinding. Arrhenius plots of some ground mixtures were expressed as a bended line, caused on the difference between reactivity of distorted BaCO3 on the surface and that of undistorted BaCO3 in the center of a particle.

Solid Acidity of Ground Mixture of Gibbsite-Hydrous Silica

In an attempt to apply surface activity of mechanochemicai dehydrate to catalytic property, the behavior of gibbsite-hydrous silica mixture during mechanical grinding were investigated.Gibbsite, Al(OH), , and hydrous silica, SiO2.n H20, were mixed in the ratio 10/90 (SiO2/AlxO3) and ground. r-A1203 of imperfect spinel structure and amorphous silica were formed by mechanochemical dehydration, and a considerable amount of solid acidity appeared on th surface through substitutiort (AIS eSi) between both particles. However, the acidity was not developed strongly (the highest value was O.2mrnol/g) because of the growth of secondary particles by aggregation and the adsorption of water from atmosphereoccurred during further grinding, Whereas, when the adsorped surface was cleanedup by heating, the amount of acidity in the range of high temperature from 800 to 1000 C was increased rapidly (the highest yalue was O.9mmol/g) and became almost equal to that ef commercial silica-alumina catalyst having same composition.On the other hand, when the mixture was ground in vacuum- to prevent the adsorption of water, ev-A120s was formed rapidly by accerelation of mechaRochemical dehydration.It was suggested that the rapid increase in acidity was caused by elevatihg thermal stability of r-A1203 in high temperature ranges.

Study of Grinding Reaction of the System of Fine Particle Silica and Basic Zinc Carbonate by X-Ray Silicon K-Emission Band Spectra

Abstract Usefulness of X-ray emission spectrometry was demonstrated in a study of the grinding reaction of the system of fine particle silica and basic zinc carbonate. SiKα bands of the ground mixtures shifted toward the lower energy side relative to that of the fine particle silica, whearas SiKβ bands toward the opposite side. These band shifts were regarded as a measure of the reaction progress. The SiKβ band shift was shown more distinctly than the Kα band shift and explained as come from a decrease in the s-character of the bond caused by the chemical bonding of the zinc atom with the fine particle silica. The Kβ band shift was also correlated with the destabilization energy relative to the fine particle silica after C. G. Dodd and G. L. Glen. The band shifts indicated that the final product of this grinding reaction was amorphous zinc silicate-like compound. The correspondence of the X-ray band shifts with the infrared spectral shifts was also shown.

939 Dichlorobenzene: Urinary metabolite as index of occupational exposure: Pagnotto, L. D. & Walkley, Janet E. (1965). Urinary dichlorophenol as an index of paradichlorobenzene exposure. Am. ind. Hyg. Ass. J.26, 137

The mechanochemical adsorption of 3,5-dichlorophenol by laponite, saponite, montmorillonite, beidellite, and vermiculite was studied. Mixtures containing dichlorophenol and clay in the ratio 6:10 were manually ground for 1–10 min. The ground mixtures were then analyzed by thermo-IR-spectroscopy. Depending on the surface acidity of the clay two different associations between interlayer cations, water, and dichlorophenol were identified. In these associations dichlorophenol acts either as a proton acceptor or donor (configurations I and II, respectively). In laponite, montmorillonite and saponite the surface acidity of interlayer water is high; in beidellite and vermiculite it is low. Consequently, mainly configuration I was obtained for the first group of minerals and configuration II for the second group.

THE INCREASED DURATION OF INSULIN ACTION BY THE USE OF PROTAMINE ZINC INSULIN IN PELLET FORM1

BEST (1) has reviewed the numerous attempts to prolong the action of insulin. Many recent experiments have shown the increased effectiveness of compressed pellets of estrone, testosterone propionate and desoxycorticosterone implanted subcutaneously (2, 3). We are reporting experiments on the effect of compressed subcutaneous pellets of crystalline Zn insulin3 and mixtures of crystalline Zn insulin with protamine, on the blood sugar concentration of dogs. Adult dogs were depancreatized under nembutal anesthesia, and stabilized on a diet of lean meat 250 gm., cane sugar 25 gm., and pancreas 50 gm., given at 9 A.M. and 4 P.M. daily. The dogs received 10 u of insulin daily, except on the day before each experiment. Pellets were made of crystalline Zn insulin and carefully ground mixtures of Zn insulin and protamine, in an apparatus made for this purpose. The apparatus has two steel plates (fig. 1) with opposing surfaces that are machine ground. These can be fastened firmly together.