A new application for the Antoine equation in formulation development.

Characterization of formulation components in pre-formulation and formulation studies will be made easier if a rapid method to evaluate the evaporation characteristics of an ingredient in the formulation is developed. This study aims at providing a simple and rapid thermogravimetric method for estimating the vapor pressure characteristics using the Antoine equation as the analytical tool. The heat treatment for the majority of benzoic acid derivatives follows zero-order rate processes that are in good correlation with their evaporation process. The optimum conditions for the rising temperature experiments were found when the heating rate was 10 degrees C/min in an atmosphere of dry nitrogen (100 ml/min). Methyl paraben was taken as the calibration compound since its Antoine constants are reported in the literature, and its selected thermodynamic parameters were evaluated using the Langmuir equation. The coefficient of vaporization (k macro) was determined to be 124,525+/-0.8, with units being reported in the S.I. system. The corresponding vapor-pressure plots were obtained for the remaining compounds and their Antoine constants calculated.

A high-performance liquid chromatography assay for yohimbine HCl analysis.

The analysis used yohimbine HCl solution prepared from commercially available yohimbine HCl powder. Stability-indicating high-performance liquid chromatographic (HPLC) assay procedures were established and utilized to analyze the concentration of the drug. The method proved to be a simple model since it does not contain a buffer system. The mobile phase used, a methanol:water 70:30 ratio, was similar to that suggested by the manufacturer for the storage of the column. Therefore, the solvent system saves analytical processing time since it does not require a change in the mobile phase before and after the analysis. The analytical method has been shown to be stability indicating. The assay method showed a retention time for yohimbine of 4.2 min; for caffeine, the internal standard, it was 2.3 min. The standard deviation and the coefficient of variation were under acceptable limits of 2% and were specifically 1.51% and 1.35% for within-day and between-day samples, respectively. The results showed that the degradation products obtained from stressing yohimbine HCl by heat and extremes in pH did not interfere with the yohimbine HCl peak, although the internal standard, caffeine, did show some interference due to having a retention time similar to the degradation products.

An improved high-performance liquid chromatography assay for spironolactone analysis.

This study prepared an extemporaneously formulated liquid suspension dosage form (5 mg/ml) from commercially available 25 mg tablets. Stability-indicating HPLC assay procedures were established and utilized to analyze the concentration of the drug. The method proved to be a simple model since it does not contain a buffer system. The mobile phase used was the same as that suggested by the manufacturer for the storage of the column. Therefore, the solvent system saves analytical processing time, since it does not require a change in the mobile phase before or after the analysis. The analytical method has been shown to be stability-indicating. The results have shown that there is no interference from any of the degradation products obtained from stressing spironolactone by heat and extremes in pH or with the internal standard, hydrocortisone 21-acetate.

The formulatiion development and stability of spironolactone suspension.

The purpose of this study was to extemporaneously formulate a liquid dosage form from commercially available tablets and establish the chemical stability of the drug. A suspension of spironolactone (5mg/mL) was formulated from 25-mg spironolactone tablets. Stability-indicating, high perfpromance liquid chromatography assay procedures were used to analyze the concentration of the drug. Chemical stability was predicted using accelerated stability studies. The stability studies were conducted at four temperatures, namely 5*, 30*, and 50*, and 60*C. The spironolactone suspension showed less than 10% degradation at all four temperatures for a period of three months. It appears that the formulation may be stable for longer periods of time; however, the investigation did not extend past this timeline and no recommendation should be implied.

The formulation development and stability of metronidazole suspension.

The purpose of this study was to extemporaneously formulate a liquid dosage form from commercially available tablets and establish the chemical stability of the drug. A suspension of metronidazole (15 mg/mL) was formulated from 500-mg metronidazole tablets. Stability-indicating, high-performance liquid chromatography assay procedures were utilized to analyze the concentration of the drug. Chemical stability was predicted using accelerated stability studies conducted at four temperatures, namely, 40 deg, 50 deg, 60 deg, and 70 deg C for metronidazole. The Arrhenius plot was used to predict the shelf-life of the metronidazole suspension at room temperature. The shelf-life was calculated from the initial concentration and k0 was found to be 73 years. Howwever, it would be more reasonable to expect that a quantity lasting no more than 90 days should be prepared and dispensed.

A comparative study of the degradation of different starches using thermal analysis.

Four starches obtained from different sources were treated to thermal analysis and their mechanisms of degradation were deciphered using a rising temperature method of evaluation. A comparison of the solid state reactivity between the four starches was made, using a method known as the alpha(s)-alpha(r) method. By this method, it was possible to differentiate between four starches of completely different plant origin. Potato starch and rice starch were found to have the highest reactivity.

Influence of dielectric constant on sedimentation rate of concentrated suspensions of aluminum and magnesium hydroxides.

Sedimentation of dilute pharmaceutical suspensions obeys Stokes's law, which assumes that there is no interaction between particles. The behavior of concentrated pharmaceutical suspensions is generally interpreted by use of modifications of Stokes's law that do not consider chemical interaction between particles. Properties of the medium itself, such as dielectric constant and surface tension, have not been included in the established equations. The present work shows that the dielectric constant of the medium has a distinct effect on the rate of sedimentation of the systems investigated.

Interpretation of the hindered settling of calcium carbonate suspensions in terms of permeability.

Many pharmaceutical formulations are produced in the form of concentrated suspensions. Calcium carbonate suspensions are used in this study and interpreted as the "model" for the behavior of such suspensions. The behavior of concentrated suspensions of powders in a liquid medium cannot be treated by the simple application of the normal principles of free fall and the use of Stokes Law pertaining to the viscous resistance offered by the surrounding fluid to fall. A single particle operating by the Stokes principle obeys this relationship. This law applies to the behavior of particles at low concentration in a liquid medium and is the basis for particle size distribution methods. At higher concentrations, however, the particles do not enjoy the freedom of unhindered fall. The system subsides "en bloc," and it is common practice to offer a modification to the Stokes equation which takes into consideration some function of the porosity of the system. There have been a considerable number of equations developed and modified based on this principle. However, an alternative method is to approach the problem by dealing with the permeability of a bed of powders in a liquid in which the bed is slowly altering with time. This is best achieved by the use of the permeability equation developed and presented by Kozeny-Carmen. This equation, as well as the Richardson-Zaki expression, are related to show that the Kozeny parameter K varies with the suspension porosity under sedimentation conditions. The values of K are often larger than the value normally reported (i.e., approximately 5). The data and treatment outlined here are extended to include not only the calcium carbonate suspensions, but other systems previously mentioned in the literature.

Stability of aspirin in solid mixtures.

It has been shown that the degradation of aspirin in mixtures may be monitored by thermal analytical techniques. The methodology employed differential scanning calorimetry and thermal gravimetric analysis by standard techniques providing simple and rapid analysis for screening the stability of aspirin in mixtures. The degradation was found to depend on the nature of the additive but, in particular, the presence of acidic or basic groups within its structure.