Biomedical subjects
Publications and source records attributed to M A Zoglio.
According to theory, "capping" (visible lamination) occurs at the uniaxial relaxation stage at the point at which the upper punch pressure is released. A method is described whereby the stress in a tablet prone to a "capping" problem can be released in a triaxial manner.
To explore the relative absorbabilities of different ionic forms of cephalosporins, the absorption rates of four compounds were measured in the pH 5-9 region using an in situ rat gut technique. Cephalexin, cephradine, and cephaloglycin have some oral activity, while 3-[(acetyloxy)methyl]-8-oxo-7-[[(4-oxo-1(4H-pyridinyl)acetyl]-amino]-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid (I) has insignificant oral activity. The pH-species profiles calculated from their ionization constants showed that cephalexin, cephradine, and cephaloglycin have a large proportion of uncharged molecules plus zwitterions in the pH range of the small intestine, while I exists as the anion throughout this range. When the species profiles are compared with the pH-absorption rate profiles for cephalexin, cephradine, and I, the results are consistent with a model in which the zwitterionic and/or uncharged forms of the molecules are well absorbed, whereas the anions show little or no absorption. Although it has a pH profile for zwitterions plus uncharged molecules similar to cephalexin, cephaloglycin shows poor absorption, suggesting that the ratio of uncharged molecules to zwitterions may be important in absorption.
When granules are milled in a ball mill, the size decrease follows a modification of Kick's law. The Briggsian decay constant, here denoted as the attritional crushing strength, shows correlation with the Harwood-Pilpel crushing strength. Both crushing strengths show a correlation with the amount of granulating agent (povidone) added to the granulation, i.e., the more povidone added, the harder the granule.
The apparent first-order breakdown of the medicinally active agent 3-(p-chlorophenyl)-2-ethyl-2,3,5,6-tetrahydroimidazo[2,1-b]thiazol-3-ol was studied in aqueous solutions where dehydration gave the unsaturated compound 3-(p-chlorophenyl)-5,6-dihydro-2-ethylimidazo[2,1-b]thiazole. This thiazole was the primary solvolytic product produced in approximately quantitative yields for the temperature range studied and ostensibly underwent no further reaction in acidic media even on prolonged heating. Investigations were carried out at various pH values in standard buffers at constant ionic strength. The ionization constants of the compounds are reported as well as the apparent activation energies for the degradation in acid and acetate buffers. The influence of ionic strength on the velocity constant was determined.
Granulations were made at various air speeds and various rates of addition of granulating liquid in a spray-granulatin assembly. The ensuring particle sizes were log-normal, and the data substantiate that the process is of the nature previously described. The mean diameter obtained was approximately proportional to the liquid flow rate squared but was independent of air rate. The standard deviation was independent of both parameters.
The kinetics of wetting during the process of making tablet granulations were studied; the process progresses through an intermediate (overwetted) nonequilibrium granule to a final, equilibrated granule. In systematic formulation changes, there is an optimum composition from the point of view of hardness and content of equilibrium granules.
The microionization constants for two zwitterionic compounds were determined by incorporating two experimental techniques. These compounds have chromophoric changes dependent upon the solution pH. By combining the spectrophotometric measurements with potentiometric mmeasurements, all four microionization constants were calculated. The method used is completely general and is applicable to all diprotic compounds that exhibit this spectrophotometric behavior. The observed pKa's had differences of at most 1.2 units for either compound and were in the 1-4 range. A comparison of the results with each compound and similar compounds indicates that the values are resonable.
Evidence is presented that excessive blending in a wet granulation process shifts the packing arrangement of the wet granule, causing it to become dense and nonporous. With prolonged kneading, a large amount of the water-soluble excipients dissolves in the granulating fluid, and these two factors make the drying slower. This result, coupled with the previous finding that a certain time is required to attain an equilibrium size granule, explains why there exists an optimum kneading time for a wet granulation from a mechanical performance point of view.
A continuous nonisothermal-isothermal method for stability prediction was developed. The approach yields all necessary parameters for prediction, including reaction order. The experimental procedure involves changing the temperature of the samples being studied until degradation is rapid enough to proceed at a convenient isothermal rate for a sufficient number of half-lives with adequate analytical sensitivity so that the reaction order can be unambiguously determined. The analytical information obtained during the nonisothermal and isothermal portions of the experiment is utilized without curve matching in calculating the activation energy and determining the reaction order, reaction rate, and stability prediction at any desired temperature. Model experiments include the acid-catalyzed hydrolysis of acetylcholine bromide and the inversion of sucrose.
A sucrose-lactose-starch granulation was used to study particulate motion and attrition in a fluid bed dryer. There is some classification of material in the dryer as drying proceeds; fine particles are dried faster and become less dense, and the less dry but denser large particles show some (although not great) accumulation tendencies in the lower central area. Unlike countercurrent rotary drying, fluid bed drying cannot be accounted for by water diffusion inside the granule as the rate-limiting step. In its place, a model of external water vapor diffusion is proposed and is supported by vapor-concentration curves and by the linear dependence of the rate constants on the linear air velocities. The dried granulation exhibits the same trend as does countercurrent dried material in that larger particles have higher moisture contents than do smaller particles. Quantitative relationships between content of moisture and size were developed and are supported by experimental data. The granulation, upon storage, does not equilibrate, indicating that this type of water distribution is a problem in batch process granulations as well as in the earlier reported case of granulations for continuous production.