Chargeability measurements of selected pharmaceutical dry powders to assess their electrostatic charge control capabilities.

The purpose of this study was to develop an instrument (the Purdue instrument) and the corresponding methodologies to measure the electrostatic charge development (chargeability) of dry powders when they are in dynamic contact with stainless steel surfaces. The system used an inductive noncontact sensor located inside an aluminum Faraday cage and was optimized to measure the charging capabilities of a fixed volume of powder (0.5 cc).

Effect of hydrodynamic environment on tablets dissolution rate.

The main objective of this research was to develop an experimental method to apply well-defined flow fields to solid dosage forms, to study the rate process underlying tablet dissolution, and to better understand the role of external hydrodynamic condition on mass transfer rate and film thickness during dissolution. Two drugs models, Theophylline (class 1) and Naproxen (class 2), were selected and formulated into conventional tablets containing 105 mg Theophylline or 300 mg Naproxen using the wet granulation method. Tablets were tested for dissolution using both the basket and paddle methods at different rotational speed of 25, 50, 75, and 100 rpm.

An examination of the moisture sorption characteristics of commercial magnesium stearate.

The objective of this study was to characterize the moisture sorption of magnesium stearate and the morphological changes, if any, resulting from moisture sorption. Six samples of commercial magnesium stearate USP were examined. Moisture sorption isotherms were obtained at 25 degrees C and 5% to 98% relative humidity (RH) using a moisture balance.

Prediction of tablet hardness and porosity using near-infrared diffuse reflectance spectroscopy as a nondestructive method.

The main objective of this research is to use the near-infrared diffuse reflectance method to evaluate and quantify the effects of hardness and porosity on the near-infrared spectras of tablets. To develop a model equation, validate the model and test the model predictive ability. Seven theophylline tablet formulations of the same composition but with seven different hardness values (3, 6, 8, 10, 12, 15, and 17 kp) were prepared.

Effect of magnesium stearate on the content uniformity of active ingredient in pharmaceutical powder mixtures.

The objective of this study was to determine the effect of magnesium stearate on the physical stability of polydisperse powder mixtures. The effects of concentration of magnesium stearate and the time of lubrication of mixtures with magnesium stearate on the content uniformity of the active ingredient in the mixtures were evaluated in a model mixture of lactose and aspirin. These effects were compared in a random mixture of non-interacting components and a mixture based on particle interaction.

Relationship between internal phase volume and emulsion stability: the cetyl alcohol/stearyl alcohol system.

The main objective of this study was to optimize the stability of cetyl alcohol/stearyl alcohol emulsions in terms of percentage of internal phase volume, emulsifier type and concentration, and amount of external phase (water). Creams (o/w emulsions) were prepared by phase inversion and physical properties as particle size of the internal phase, apparent viscosity, and sedimentation volume evaluated. Stability was performed at room temperature, 40 degrees C, 50 degrees C, and under stress conditions.

Polydisperse powder mixtures: effect of particle size and shape on mixture stability.

The effect of the shape and size of the components on the stability of mixtures was evaluated in binary mixtures of drug and carrier. Aspirin was used as model drug; spray-dried lactose and microcrystalline cellulose were used as carriers. The coefficient of variation (CV) of the drug in the mixture at various time intervals during mixing was used as a measure of homogeneity.

The effect of particle morphology on the physical stability of pharmaceutical powder mixtures: the effect of surface roughness of the carrier on the stability of ordered mixtures.

The effect of particle morphology of the components on the physical stability of ordered mixtures was determined for a model system comprised of a mixture of micronized aspirin and a monodisperse carrier. Spray-dried lactose, crystallized lactose, microcrystalline cellulose, and dextrate were used as carriers. The surface texture of the carriers was quantified in terms of the ratio of the perimeter of the particles to that of an idealized shape at a constant magnification.

Hydrotropic solubilization--mechanistic studies.

Purpose: This study examines the mechanism of hydrotropic solubilization using the riboflavin-nicotinamide system. The most commonly proposed mechanism for hydrotropic solubilization is complexation, and therefore, is investigated. Additionally, since nicotinamide and several other hydrotropic agents self-associate in aqueous solution, the possibility that self-association of the hydrotropic agent is important mechanistically is examined by studying the effect of temperature on hydrotropic ability.

Effect of nicotinamide and urea on the solubility of riboflavin in various solvents.

Hydrotropy is a solubilization process whereby addition of large amounts of a second solute results in an increase in the aqueous solubility of another solute. Past investigations have focused on the potential interaction of the hydrotropic agent with the solubilized solute. Conversely, this study proposes that at least some hydrotropic agents exert their solubilizing effect predominately by interacting with the solvent.

Self-association of nicotinamide in aqueous solution: light-scattering and vapor pressure osmometry studies.

Nicotinamide is a hydrotropic agent that has been reported to self-associate in aqueous solution. The objective of this study is to characterize the self-association of nicotinamide with regard to the extent of self-association as well as association constants using light-scattering and vapor pressure osmometry. Both methods allow calculation of association constants; however, while light-scattering measurements depend on the size of particles in solution, vapor pressure osmometry depends on the number of particles in solution.

Pulmonary delivery of free and liposomal insulin.

The effects of oligomerization and liposomal entrapment on pulmonary insulin absorption were investigated in rats using an intratracheal instillation method. The results indicated that both dimeric and hexameric insulins can be rapidly absorbed into the systemic circulation, producing a significant hypoglycemic response. Intratracheal instillation of insulin in two different oligomerized states has not resulted in any significant difference in the duration of hypoglycemic effect.

Pulmonary biotransformation of insulin in rat and rabbit.

In vitro biodegradation of insulin in rabbit and rat lung homogenates was investigated. Insulin can be sequentially metabolized into two primary fragments in rabbit lung homogenate by an aminopeptidase. The amino acid sequences of the fragments were found to be the des-Phe-InsulinB1 (Metabolite I) and des-Phe-Val-InsulinB1-2 (Metabolite II).

Insulin aggregation in aqueous media and its effect on alpha-chymotrypsin-mediated proteolytic degradation.

Self-association of zinc-insulin monomers into dimers and hexamers may lead to enhanced protection of the peptide from proteolytic degradation. The present study has been undertaken to investigate the relationship, if any, between the rate of enzymatic degradation of insulin by a protease, alpha-chymotrypsin, and the extent of insulin aggregation in aqueous solutions. Insulin solutions (0.

Thermorheologic properties of aqueous solutions and gels of Tetronic 1508.

The rheologic properties of aqueous solutions and gels of Tetronic 1508 were investigated as a function of polymer concentration and temperature utilizing rotational viscometry. Below the sol-gel transition temperature the polymer solutions were low in viscosity and exhibited Newtonian rheologic behavior even at concentrations of 20 and 25% (w/w). Upon sol-gel transition, the more concentrated polymer solutions underwent a dramatic four- to five-orders of magnitude increase in viscosity, resulting in the formation of a rigid gel structure.

Beta-cyclodextrin/steroid complexation: effect of steroid structure on association equilibria.

Molecular associations of beta-cyclodextrin (beta-CyD) with four steroids (cortisone, hydrocortisone, progesterone, and testosterone) have been studied using phase-solubility and spectroscopic techniques. Phase solubility diagrams could be categorized as B type. The complexes are formed at the stoichiometric ratios of 1:2 (drug:beta-CyD).

Preparation and characterization of methotrexate-immunoglobulin conjugates.

In the targeting of chemotherapeutic agents to specific cells via covalent conjugation of the agent to monoclonal antibodies, conjugation methods which lead to maximum binding capacity with minimum loss of activity (for both drug and antibody) are essential. A model system for evaluation of various conjugation procedures is described. Rabbit anti-bovine serum albumin immunoglobulin (IgG) was used to represent the antibody, and methotrexate (MTX) was used as the targeting agent.

Reversal of acetaminophen intoxication with an N-acetylcysteine-liposome preparation.

An N-acetyl-l-cysteine (NAC)-liposome drug delivery system was assessed for its ability to reverse acetaminophen toxicity. Positively charged NAC-liposomes, as compared to neutral and negatively charged preparations, were highly effective in reversing acetaminophen-induced lethality in mice. The positively charged liposome preparation, when administered at a dose equivalent to 50 mg/kg NAC, increased the LD50 of acetaminophen from 840 to 1507 mg/kg; free NAC (50 mg/kg) did not significantly alter the LD50 (829 mg/kg).

Paired-ion high-performance liquid chromatographic assay for sulfinpyrazone in plasma.

A specific and sensitive liquid chromatographic method is reported for the assay of sulfinpyrazone in plasma utilizing ion pairing between the tetrabutylammonium cation and the sulfinpyrazone anion. The method is rapid in that conventional extraction procedures are avoided in favor of using disposable cartridges packed with an octade-cylsilane bonded phase as a means of separating the drug from plasma. The samples were chromatographed on a C18 reversed-phase column using a mobile phase consisting of 0.

Application of immersional calorimetry to investigation of solid-liquid interactions: microcrystalline cellulose-water system.

A comprehensive characterization of the specific solid-liquid interaction for microcrystalline cellulose and water is presented. The procedure consisted of a conjoint vapor adsorption and immersional wetting experiment. The following information was obtained with respect to the solid.

Nonisothermal aqueous calorimetry: computation of process-dependent temperature change and aspects of calorimeter design.

A general method for determining the process-dependent (intrinsic) temperature change in a nonisothermal calorimeter is presented. The nonisothermal approach to calorimetric investigations requires an estimate of the magnitude of the process independent (extrinsic) temperature change during the reaction period. The proposed method can be applied to any calorimeter whose output is a discrete or continuous temperature--time profile.

Determination of energy change associated with dissolution of a solid.

The dissolution of a solid immersed in a solvent was considered as a consecutive process, consisting of a primary surface interaction leading to the production of a new surface at the solid-liquid interface, solvation of the solid at the interface, and transfer of the solvated solid into the bulk of the solution. The energy changes involved in each step were studied for the dissolution of m-tolylacetamide in hexane and heptane. An energy diagram was constructed according to the proposed dissolution mechanism.