Ward Gh

Process-Induced Crystallinity Changes in Albuterol Sulfate and Its Effect on Powder Physical Stability

Pharmaceutical powders are often milled to achieve the optimum particle size. These size reduction processes can introduce dislocations and/or defects onto particle surfaces affecting the overall crystallinity of the powder. If enough energy is imparted, amorphous regions on the particle surfaces may be produced. These amorphous regions have the propensity to absorb significant quantities of water. In this study the effect of sorbed water on the physical characteristics of albuterol sulfate is investigated. Physical properties of this compound are studied in both micronized and unmicronized states using scanning electron microscopy, differential scanning calorimetry, powder x-ray diffraction, solution microcalorimetry, laser diffraction particle size analysis and water vapor sorption analysis. Subtle differences in crystallinity induced by air jet micronization are detected by several analytical methods. Amorphous to crystalline conversions are observed, the kinetics of which are found to be both temperature and relative humidity dependent. These experiments show the dynamic nature of micronized albuterol sulfate and aid in the determination of the actual physical state of this pharmaceutical powder.

AQUAFAC 1: Aqueous functional group activity coefficients; application to hydrocarbons

Abstract A simple group-contribution method for the estimation of aqueous activity coefficients is introduced. The AQUAFAC method derives group values directly from aqueous data. This work shows the fundamental background of how AQUAFAC group values (q-values) are generated. Group values for alkanes, polycyclic aromatic hydrocarbons and alkyl aromatics are given. It is shown that aromatic alkyl substituents contribute differently to the aqueous activity coefficient than do corresponding aliphatic alkyl substituents.

Aquafac: Aqueous Functional Group Activity Coefficients

Abstract AQUAFAC, a new group contribution method for estimating aqueous activity coefficients, has been applied to a large set of organic compounds. The current work introduces 27 new group values for hydrocarbon, halogen, and non-hydrogen bond donating oxygen groups. Group values (q-values) have been derived from a data set of 621 compounds representing over 1700 individual solubility values. No correction factors were used in generating the current group values. AQUAFAC was found to give acceptable results when applied to some environmentally important compounds.

Increase in the Specific Surface Area of Budesonide During Storage Postmicronization

AbstractPurpose. To evaluate an anomalous increase in the specific surface area of budesonide during storage postmicronization. Methods. Budesonide was micronized using a conventional air-jet mill. Surface areas and total pore volumes were measured using nitrogen sorption. Porosity was measured using mercury intrusion porosimetry. Particle size was measured using laser diffraction. Results. Budesonide exhibited a surface area increase of 22 ± 2% when stored at 25°C following micronization. The rate of surface area increase was lower at 20°C, suggesting a temperature-dependent stress relaxation mechanism for the micronized particles. The increase in surface area was accompanied by: (a) an increase in total pore volume; (b) a shift of the pore size distribution to smaller pore sizes; (c) a decrease in size of particles above ∼1 μm; and (d) an increase in rugosity/surface roughness. Conclusions. Freshly micronized budesonide exhibited an unusual and significant postmicronization increase in specific surface area upon storage under ambient conditions. Postmicronization stress-relief by intraparticle crack formation, crack propagation with time, and particle fracture seems to be the primary mechanism behind this surface area increase.

Precipitation of pH solubilized phenytoin

Abstract Precipitation of phenytoin often occurs as it is diluted by blood after intravenous injection. The presence and the amount of precipitate depend upon the initial pH and buffer capacity of the formulation vehicle. The prediction of phenytoin precipitation can be carried out in vitro using isotonic Sorensens phosphate buffer (SPB) to simulate blood. An equation is developed to calculate the change in solubility resulting from the change in pH due to dilution. This equation is very difficult to solve analytically because it involves a high order polynomial. However, it can be solved numerically using a spreadsheet program. The relationship between pH or solubility and dilution can then be presented graphically. Therefore, the precipitation of any pH solubilized drug due to dilution under various conditions can be easily predicted. This is illustrated for several aqueous phenytoin solutions.

STUDIES IN PHLEBITIS : DETECTION AND QUANTITATION USING A THERMOGRAPHIC CAMERA

A new method for the detection of acute phlebitis in superficial veins is investigated. A thermographic camera is utilized for the quantitation of temperature changes in a rabbit ear model. A control group receiving no injection is compared against each of five treatment groups receiving these commercially available parenterals: amiodarone hydrochloride, phenytoin sodium, mechlorethamine hydrochloride, cephalothin sodium, and diazepam. The vehicles of the above-mentioned drugs as well as several commonly used organic cosolvents are also investigated. Local tissue responses to the parenteral challenges are measured and a good correlation between the visual and the thermographic data was seen.