Biomedical subjects

Henry H Y Tong

Publications and source records attributed to Henry H Y Tong.

7 recordsLinked to original sources

PubMed2006

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. This review offers an in-depth discussion on particle size analysis pertaining to specific pharmaceutical applications and regulatory aspects, fundamental principles and terminology, instrumentation types, data presentation and interpretation, in-line and process analytical technology. For illustration purposes, special consideration is given to the analysis of aerosols using time-of-flight and cascade impactor measurements, which is supported by a computational analysis conducted for this review.

Aerosols↗

PubMed2006

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. It was found that the aerosol performance of SX could be substantially improved by the addition of lactose carrier only if the adhesive SX-lactose interactions were stronger than the cohesive SX-SX interactions. The difference in strength between these two forms of interactions also displayed a significant correlation with the increase in fine particle fraction after the addition of lactose carrier. These results suggest that IGC-based interparticulate interaction measurements may serve as a useful means for predicting the aerosol performance of dry powder inhalation formulations.

Administration, Inhalation↗

PubMed2005

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. For ribavirin, modification of the latter equation by incorporation of an empirical exponent was found necessary to account for the composition-dependent changes in crystallization kinetics of the reference mixtures. Such modification has made possible the determination of polymorphic impurity content of as low as 0.004% (w/w) in ribavirin samples induced by different forms of grinding treatment.

Calibration↗

PubMed2005

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. The adsorption isotherms of the SX samples were constructed using (nonpolar) octane, (polar acidic) chloroform, and (polar basic) tetrahydrofuran as liquid probes. Type II adsorption isotherms with weak knees were observed with each probe for all SX Form I samples. The extents of probe adsorption by the samples at various relative pressures follow the rank order: SX-II > GSX approximately MSX > SX-I, indicating that the SX-I has fewer high-energy adsorption sites than GSX and MSX. Type III isotherms were observed for SX-II with the two polar probes, indicative of weak adsorbate-adsorbent interactions. The additional information generated shows that IGC analysis at finite coverage is a valuable complementary tool to that at infinite dilution.

Adsorption↗

PubMed2005

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. However no quantitative relationship between these parameters, the additive concentrations, and the fine particle fractions, FPF, determined for different inhalers and air flow rates, was observed. The FPF significantly increased with addition of leucine and this effect was attributed to reduced intermolecular interactions between leucine and disodium cromoglycate molecules, as indicated by the difference in corresponding Hansen solubility parameters. Decrease of interparticle interactions for leucine-containing powders also led to a lesser dependence of FPF on the flow rate and inhaler type.

Aerosols↗

PubMed2003

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.e., at different scanning speeds). The data were analyzed by the Avrami-Erofe'ev (AE) equation using an iterative fitting computer program. SX-I samples containing 1.24, 4.41, and 13.47% (w/w) of SX-II as physical mixtures were subjected to similar analysis and data treatment. A mathematical relationship based on an instantaneous nucleation model was derived to relate the AE rate constants, k, of pure SX-I and physical mixtures to weight percentage of SX-II. This relationship was then used to calculate the percentage polymorphic impurity of GSX and MSX from their k values. For relative comparison of the Form-II nuclei present, the k values of SX-I, GSX, and MSX were used to calculate their differences in free energy of nucleation. RESULTS: The AE equation affords good (r2 approximately equal to 0.81) to excellent (r2 approximately equal to 0.99) fits of data for the samples. The levels of polymorphic impurity in GSX and MSX are 0.16 and 0.62% (w/w), respectively. Based on the free energy differences of nucleation between the reference SX-I material and the other samples, the number (and size) of the Form II nuclei present in the samples rank in the order: MSX > GSX > SX-I. CONCLUSIONS: DSC is a useful tool for assessing the polymorphic purity of SX materials and possibly other enantiotropic pairs showing similar thermal behavior.

Albuterol↗

PubMed2002

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., dichloromethane, chloroform, acetone, ethyl acetate, diethyl ether, and tetrahydrofuran). Surface thermodynamic parameters of adsorption and Hansen solubility parameters were calculated from the retention times of the probes. RESULTS: The free energies of adsorption (- deltaG(A)) of the three samples obtained at various temperatures follow this order: SX-II > MSX approximately/= SX-I for the NPs; and SX-II > MSX > SX-I for the PPs. For both NPs and PPs, SX-II exhibits a less negative enthalpy of adsorption (deltaH(A)) and a much less negative entropy of adsorption (ASA) than MSX and SX-I, suggesting that the high -AGA of SX-II is contributed by a considerably reduced entropy loss. The dispersive component of surface free energy (gammas(D)) is the highest for MSX but the lowest for SX-II at all temperatures studied, whereas the specific component of surface free energy of adsorption (-deltaG(A)SP) is higher for SX-II than for SX-I. That SX-II displays the highest -deltaG(A) for the NP but the lowest gammasD of all the SX samples may be explained by the additional -AGA change associated with an increased mobility of the probe molecules on the less stable and more disordered SX-II surface. The acid and base parameters, K(A) and K(D) that were derived from deltaH(A)SP reveal significant differences in the relative acid and base properties among the samples. The calculated Hansen solubility parameters (deltaD, deltap, and deltaH) indicate that the surface of SX-II is the most polar and most energetic of all the three samples in terms of specific interactions (mostly hydrogen bonding). CONCLUSIONS: The metastable SX-II polymorph possesses a higher surface free energy, higher surface entropy, and a more polar surface than the stable SX-I polymorph.

Albuterol↗