Influence of operating temperature and pressure on the polymorphic transition of salmeterol xinafoate in supercritical fluids.

Precipitation of pure polymorphic forms (I and II) of salmeterol xinafoate (SX) in supercritical fluids was investigated as a function of operating pressure and temperature. It has been shown that the formation of each polymorph is governed by both thermodynamic shift and kinetic effects, which are closely associated with the extent of miscibility between the supercritical CO(2) and methanol cosolvent. In addition, the surface energetics of SX exhibit a sharp discontinuity at the transition point in concordance with the particular polymorphic form generated, being essentially independent of the temperature or pressure below and above this point.

Structure and drug release in a crosslinked poly(ethylene oxide) hydrogel.

Hydrogels are a continuously expanding class of pharmaceutical polymers designed for sustained or controlled drug release. The structure and intermolecular interactions in such systems define their macroscopic properties. The aim of this study was to investigate the mechanism of swelling, drug impregnation, and drug release from poly(ethylene oxide) (PEO) gel crosslinked by urethane bonds.

Particle engineering for pulmonary drug delivery.

With the rapidly growing popularity and sophistication of inhalation therapy, there is an increasing demand for tailor-made inhalable drug particles capable of affording the most efficient delivery to the lungs and the most optimal therapeutic outcomes. To cope with this formulation demand, a wide variety of novel particle technologies have emerged over the past decade. The present review is intended to provide a critical account of the current goals and technologies of particle engineering for the development of pulmonary drug delivery systems.

Particle size analysis in pharmaceutics: principles, methods and applications.

Physicochemical and biopharmaceutical properties of drug substances and dosage forms can be highly affected by the particle size, a critical process parameter in pharmaceutical production. The fundamental issue with particle size analysis is the variety of equivalent particle diameters generated by different methods, which is largely ascribable to the particle shape and particle dispersion mechanism involved. Thus, to enable selection of the most appropriate or optimal sizing technique, cross-correlation between different techniques may be required.

Predicting the aerosol performance of dry powder inhalation formulations by interparticulate interaction analysis using inverse gas chromatography.

Previous studies have demonstrated the utility of inverse gas chromatography (IGC) in discriminating the differences in surface energy between salmeterol xinafoate (SX) powders prepared by conventional sequential batch crystallization and micronization and by supercritical fluid crystallization. In the present study, solubility parameters derived from IGC analysis at infinite dilution (zero coverage) were further utilized to evaluate the influence of solid-solid interactions on the in vitro aerosol performance of these SX samples, with or without the inclusion of a lactose carrier. To this end, the strength of cohesive SX-SX interactions and that of adhesive SX-lactose interactions were computed for the samples from the corresponding solubility parameters, and their fine particle fractions determined using a multi-stage liquid impinger.

Nanoparticles of poorly water-soluble drugs prepared by supercritical fluid extraction of emulsions.

Purpose: The aim of the study was to develop and evaluate a new method for the production of micro- and nanoparticles of poorly soluble drugs for drug delivery applications.

Methods: Fine particles of model compounds cholesterol acetate (CA), griseofulvin (GF), and megestrol acetate (MA) were produced by extraction of the internal phase of oil-in-water emulsions using supercritical carbon dioxide. The particles were obtained both in a batch or a continuous manner in the form of aqueous nanosuspensions.

Effect of amino acids on the dispersion of disodium cromoglycate powders.

Modified disodium cromoglycate powders were prepared by co-spray drying with different concentrations of leucine, phenylalanine, tryptophan, methionine, asparagine, and arginine. Amorphous spherical particles of the same size and density where obtained which, however, exhibited different surface properties as measured by the inverse gas chromatography (IGC) and X-ray photoelectron spectroscopy (XPS) techniques. The surface energy parameters, such as the dispersive component of surface free energy of the sample, gammaSD, and the total solubility parameter, delta, were significantly lower in the presence of nonpolar chain amino acids, particularly with leucine and phenylalanine, than pure DSCG.

An improved thermoanalytical approach to quantifying trace levels of polymorphic impurity in drug powders.

Accurate quantification of impurities existing as separate crystalline phases at trace levels in drug materials is an important issue in the pharmaceutical industry. In the present study, a thermoanalytical approach previously developed for quantifying trace levels of polymorphic impurity (form II metastable nuclei) in commercial salmeterol xinafoate powders has been successfully applied with slight modifications to ribavirin, an antiviral drug exhibiting roughly similar polymorph-dependent crystallization kinetics in melts to that of salmeterol xinafoate. Essentially, the approach involved modeling of the crystallization kinetics of both tested and reference drug materials in melts using the Avrami-Erofe'ev (AE) rate expression, derivation of a mathematical equation for relating the AE kinetic constant to the composition of reference polymorph mixtures, and the use of this derived equation (in the form of a calibration curve) to calculate the impurity contents of the tested samples from their computed AE constants.

Surface characterization of salmeterol xinafoate powders by inverse gas chromatography at finite coverage.

In our previous studies, surface analysis by inverse gas chromatography (IGC) at infinite dilution (zero coverage) was performed on four salmeterol xinafoate (SX) powdered samples, viz, two supercritical CO2-processed Form I (SX-I) and Form II (SX-II) polymorphs, a commercial granulated SX (GSX) raw material and its micronized product (MSX). Both GSX and MSX are also of the same Form I polymorph. To further probe the differences in surface properties between the samples, the present study has extended the IGC analysis to the finite concentration range of selected energy probes.

Optimisation of powders for pulmonary delivery using supercritical fluid technology.

Supercritical fluid technology exploited in this work afforded single-step production of respirable particles of terbutaline sulphate (TBS). Different crystal forms of TBS were produced consistently, including two polymorphs, a stoichiometric monohydrate and amorphous material as well as particles with different degrees of crystallinity, size, and morphology. Different solid-state and surface characterisation techniques were applied in conjunction with measurements of powder flow properties using AeroFlow device and aerosol performance by Andersen Cascade Impactor tests.

Thermal analysis of trace levels of polymorphic impurity in salmeterol xinafoate samples.

Purpose: To quantify trace levels of polymorphic impurity in two salmeterol xinafoate (SX) Form I samples: granular SX (GSX) produced by fast-cooling crystallization and micronized SX (MSX) prepared from GSX by micronization.

Methods: SX-I and SX-II produced by solution enhanced dispersion by supercritical fluids (SEDS) were the reference polymorphs (100% pure) used for quantitative comparison. The percentage of polymorphic conversion, alpha, of each Form I sample to Form II was measured by differential scanning calorimetry (DSC) as a function of time (i.

Amplitude and phase microscopy for sizing of spherical particles.

We describe a numerical vector diffraction model based on Mie theory that describes the imaging of spherical particles by bright-field, confocal, and interferometric microscopes. The model correctly scales the amplitude-scattered field relative to the incident field so that the forward-scattered and incident light can be interfered to correctly model imaging with copolarization transmission microscopes for the first time to our knowledge. The model is used to demonstrate that amplitude and phase imaging with an interferometric microscope allows subwavelength particle sizing.

Influence of polymorphism on the surface energetics of salmeterol xinafoate crystallized from supercritical fluids.

Purpose: To characterize the surface thermodynamic properties of two polymorphic forms (I and II) of salmeterol xinafoate (SX) prepared from supercritical fluids and a commercial micronized SX (form 1) sample (MSX).

Methods: Inverse gas chromatographic analysis was conducted on the SX samples at 30, 40, 50, and 60 degrees C using the following probes at infinite dilution: nonpolar probes (NPs; alkane C5-C9 series); and polar probes (PPs; i.e.

Solubility prediction in supercritical CO(2) using minimum number of experiments.

The correlation ability and solubility prediction in supercritical carbon dioxide of a proposed equation were studied. The work involved the solubilities of nicotinic acid and p-acetoxyacetanilide in supercritical carbon dioxide using a dynamic flow solubility system at 35-75 degrees C and 100-200 bar. The generated experimental solubility data together with 21 data sets collected from the literature were used to evaluate the correlation ability of available empirical equations.