Use of inverse gas chromatography (IGC) to determine the surface energy and surface area of powdered materials.
Explore the source record for details and available documents.
Chromatography, Gas↗
Biomedical subjects
P York
Publications and source records attributed to P York.
The application of molecular modelling to the interpretation of inverse gas chromatography data.
The use of molecular modelling in the interpretation of inverse gas chromatography data is discussed. Crystal faces can be visualised and likely cleavage planes calculated using the surface attachment energies. Assuming that the preferred cleavage plane is the crystal face with the smallest attachment energy then the predominant crystal faces of a crystalline particle can be predicted. Surface adsorption can be modelled using Van der Waals and electrostatic interactions to evaluate the interaction energies between individual atoms of the probe molecule and atoms of the test molecule orientated as in the surface. Using examples of pharmaceutical materials, modelling has been shown to be successful in the understanding of changes in the surface energetics.
Adsorption↗
Solubility prediction of salmeterol xinafoate in water--dioxane mixtures.
The mole fraction solubility of salmeterol xinafoate was determined in various concentrations of dioxane in aqueous binary mixture. Maximum solubility was observed in 90% v/v dioxane and solubility parameter of the solute was estimated from solubility peak equal to 24.99 MPa(0.5). The predicting capability of four different cosolvency models was also evaluated employing a five data point training set. The solubility data at other cosolvent concentrations were predicted using the trained models, with percentage average errors for 28 drug solubility data sets in water-cosolvent mixtures lying between 12.5 and 15.0%. Further predictive model is proposed for accurate solubility predictions based on a minimum number of experiments. The percentage average error where tested was 10.6%.
Albuterol↗
The formation of plasmid DNA loaded pharmaceutical powders using supercritical fluid technology.
The invention of novel drugs based on biological macromolecules requires the development of specialized formulation methods. Supercritical fluid technology offers the possibility to produce dry powder formulations suitable for inhalation or needle-free injection. In this article we describe the first application of a process involving supercritical carbon dioxide for the production of plasmid DNA-loaded particles. The technique of solution enhanced dispersion by supercritical fluids (SEDS) is used to coformulate the 6.9 kb plasmid pSV beta with mannitol as excipient. After initial experiments showed a high degradation of the plasmid during powder formation, a systematic investigation of the process revealed pH effects to be crucial for the recovery of intact DNA. The application of high-buffer concentration led to an increase of the recovered supercoiled proportion from 7% to 80%.
Biotechnology↗
Time-resolved X-ray scattering using synchrotron radiation applied to the study of a polymorphic transition in carbamazepine.
The thermodynamic status of alpha-carbamazepine has been clarified using equilibrium solubility measurements, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), heated X-ray powder diffraction (XRPD), and temperature-controlled X-ray scattering techniques. alpha-Carbamazepine is the least stable of the three well-characterized anhydrous polymorphs of carbamazepine at 25 degrees C. In addition, it was confirmed that alpha-carbamazepine undergoes an exothermic transition to gamma-carbamazepine at 130 degrees C. The novel technique of time-resolved simultaneous small- and wide-angle X-ray scattering has been successfully applied to monitor this transition in situ. It was concluded that alpha-carbamazepine has a monotropic relationship with gamma-carbamazepine.
Anticonvulsants↗
Crystallization of pure anhydrous polymorphs of carbamazepine by solution enhanced dispersion with supercritical fluids (SEDS).
Pure anhydrous polymorphs of carbamazepine were prepared by solution-enhanced dispersion with supercritical fluids (SEDS). Crystallization of the polymorphs was studied. Mechanisms are proposed that consider the thermodynamics of carbamazepine, supersaturation in the SEDS process, and the binary phase equilibria of organic solvents and the carbon dioxide antisolvent. alpha-Carbamazepine was crystallized at high supersaturations and low temperatures, beta-carbamazepine crystallized from a methanol-carbon dioxide phase split, and gamma-carbamazepine crystallized via nucleation at high temperatures and low supersaturation.
Anticonvulsants↗
Solubility and precipitation of nicotinic acid in supercritical carbon dioxide.
Solubilities of a model compound (nicotinic acid) in pure supercritical carbon dioxide (SC-CO(2)) and SC-CO(2) modified with methanol have been measured in the pressure range of 80-200 bar and between temperatures of 35 and 90 degrees C. On-line ultraviolet detection enabled a simple and relatively fast measurement of very low levels of solubility (10(-7) mol fraction) with good accuracy in pure and modified SC-CO(2). The solute solubility in both pure SC-CO(2) and SC-CO(2) modified with methanol increased with pressure at all investigated temperatures. A retrograde solubility behavior was observed in that, at pressures below 120 bar, a solubility decrease on temperature increase occurred. Solubility data were used to calculate supersaturation values and to define optimum operating conditions to obtain crystalline particles 1-5 microm in diameter using the solution-enhanced dispersion by supercritical fluids (SEDS) process, thereby demonstrating the feasibility of a one-step production process for particulate pharmaceuticals suitable for respiratory drug delivery.
Aluminum↗
The changes in surface energetics with relative humidity of carbamazepine and paracetamol as measured by inverse gas chromatography.
The surface energetic parameters of carbamazepine and paracetamol have been studied using inverse gas chromatography modified to produce dry and ambient conditions within the column. The values of the dispersive component of the surface free energy (gamma(S)D) do not change significantly at the increased relative humidity. In contrast the specific component of the free energy of adsorption (-DeltaG(A)SP) as measured by polar probes, can either remain constant or decrease by up to 10%, depending on the material and the probe. This indicates that an increase in the relative humidity causes a decrease in the surface energetics of the powder surface. It is proposed that where the water molecules are adsorbing to the same sites as the polar probes, the interaction of these probes with the surface is decreased. To identify these sites, the preferential interaction of each probe, including water, with the drug molecule has been modelled.
Acetaminophen↗
Process control and scale-up of pharmaceutical wet granulation processes: a review.
In this paper the techniques for process control and scale-up of pharmaceutical wet granulation processes are reviewed. For wet granulation in high-shear mixers, specific methods based on the liquid saturation and the consistency of the wet mass are described. Both parameters can be used to quantify the deformability of the wet granules, and relate well with the particle size of the end granules. In practice, the power consumption of the high-shear mixer is used for the monitoring of the wet granulation process, whilst for scale-up, it is helpful to use the underlying relationship between power consumption and saturation level or wet mass consistency. In fluid bed granulation the granulation process is different and the moisture content in the bed is the key parameter to control. This can be monitored directly by near infrared probes or indirectly with temperature probes. As a large number of inter-related variables can be adjusted to modify the process, computerized techniques have become popular for fluid-bed process control--fuzzy logic, neural networks, and models based on experimental design techniques are several examples. In addition, engineering techniques based on particle size population balance modelling are under development for both fluid bed and high-shear granulation.
Particle Size↗
Characterization of two polymorphs of salmeterol xinafoate crystallized from supercritical fluids.
PURPOSE: To characterize two polymorphs of salmeterol xinafoate (SX-I and SX-II) produced by supercritical fluid crystallization. METHODS: SX-I and SX-II were crystallized as fine powders using Solution Enhanced Dispersion by Supercritical Fluids (SEDS). The two polymorphs and a reference micronized SX sample (MSX) were characterized using powder X-ray diffractometry (PXRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), aqueous solubility (and dissolution) determination at 5-40 degrees C, BET adsorption analysis, and inverse gas chromatography (IGC). RESULTS: Compared with SX-I, SX-II exhibited a lower enthalpy of fusion, a higher equilibrium solubility, a higher intrinsic dissolution rate, a lower enthalpy of solution (based on van't Hoff solubility plots), and a different FTIR spectrum (reflecting differences in intermolecular hydrogen bonding). Solubility ratio plot yielded a transition temperature (-99 degrees C) below the melting points of both polymorphs. MSX showed essentially the same crystal form as SX-I (confirmed by PXRD and FTIR), but a distinctly different thermal behaviour. Mild trituration of SX-I afforded a similar DSC profile to MSX while prolonged grinding of SX-I gave rise to an endotherm at -109 degrees C, corresponding to solid-solid transition of SX-I to SX-II. Surface analysis of MSX, SX-I, and SX-II by IGC revealed significant differences in surface free energy in terms of both dispersive (nonpolar) interactions and specific (polar) acid-base properties. CONCLUSIONS: The SEDS-processed SX-I and SX-II display high polymorphic purity and distinctly different physical and surface properties. The polymorphs are related enantiotropically with SX-I being the thermodynamically stable form at room temperature.
Albuterol↗
Polymorph control of sulfathiazole in supercritical CO2.
PURPOSE: Sulfathiazole was used to investigate polymorph control in liquid and supercritical CO2. Conventional techniques require a variety of solvents and techniques to produce different polymorphs. The present approach involves precipitation from an organic solution with liquid or supercritical CO2 using the SEDS process. METHODS: Sulfathiazole was precipitated from methanol or acetone solutions. Experiments were carried out within a temperature range of 0-120 degrees C. Composition of the fluid phase was varied between x(CO2) = 0.27-0.99. Pressure was constant at 200 bar. Samples obtained were analyzed using SEM, DSC, and XRPD. RESULTS: Pure polymorphs were obtained at different temperatures and flow rate ratios of CO2/solvent. With methanol Form I, III, and IV and their mixtures could be crystallized. With acetone Form I or a mixture of Form I and amorphous sulfathiazole was obtained. The fluid composition was used as a control parameter to define the process areas (T-x diagram) where the pure forms or mixtures of different forms could be obtained. CONCLUSIONS: The experiments enabled the relationship between flow and temperature for each polymorph to be determined. The crystallization method developed proved to be a simple and efficient technique for reproducible and consistent isolation of sulfathiazole polymorphs.
Acetone↗
Drug-fatty acid salt with wax-like properties employed as binder in melt granulation.
The tacky and deformable properties of a wax-like drug-fatty acid salt, propranolol oleate (POA), make particle size reduction and separation challenging. The aim of this study was to investigate the use of POA as binder in a melt granulation procedure to improve processing properties. POA is a suitable candidate for binder phase in melt granulation with a melting temperature of 50-56 degrees C. Small batches (ca 30 g) were manufactured using a high shear mixer with lactose monohydrate as the substrate phase. Optimum uniformity of drug content and minimum friability were found at 10% w/w POA binder concentration. POA melt granules exhibited a >10-fold increase in the rate of in vitro dissolution at pH 7.4 with 0.2% w/v sodium lauryl sulphate compared with raw POA. The increased drug surface area in granular form was thought to be responsible for the change in dissolution behaviour. This study has demonstrated that melt granulation using POA as binder is a viable process which leads to beneficial changes in dissolution behaviour for the lipophilic drug-fatty acid salt.
Adrenergic beta-Antagonists↗
Characterization of oleic acid and propranolol oleate mesomorphism using (13)C solid-state nuclear magnetic resonance spectroscopy (SSNMR).
Lipids regularly exhibit complicated thermotropic and lyotropic phase behavior. In this study, the utility of (13)C solid-state nuclear magnetic resonance spectroscopy (SSNMR) in characterizing the phase properties of pharmaceutical lipids was investigated. Variable temperature (13)C SSNMR spectra and spin-lattice relaxation times (T(1)(C)) were obtained for high-purity oleic acid (OA) and propranolol oleate (POA). Spectral changes took place following OA gamma-to-alpha phase transition that indicated increased nuclear inequivalence of aliphatic chain carbons in the alpha phase. T(1)(C) data for the alpha phase demonstrated considerable conformational changes throughout the aliphatic chain, not solely in the methyl side chain as previously reported. These data support alpha-OA classification as a conformationally disordered crystalline phase. The prevalence of low T(1)(C) values in both POA I and II suggested the absence of a rigid crystalline molecular lattice, so both phases were described as conformationally disordered crystalline phases. A two-phase mixture of POA I and II was also identified, emphasizing the sensitivity of this technique. (13)C SSNMR provided valuable information regarding the nuclear environment of specific functional groups in lipid crystalline and mesomorphic structures. Understanding phase behavior at the molecular level can aid selection of appropriate formulation strategies for lipids by allowing prediction of processing properties, and physical and chemical stability. (13)C SSNMR is a powerful technique for pharmaceutical lipid characterization.
Adrenergic beta-Antagonists↗
Supercritical fluid processing of proteins. I: lysozyme precipitation from organic solution.
The solution enhanced dispersion by supercritical fluid (SEDS) process was used to evaluate the effect of the processing variables on the biological and physicochemical characteristics of lysozyme protein particles produced from an organic solution of dimethylsulfoxide (DMSO) using an experimental design procedure. The processing variables were temperature, pressure, solution concentration and the flow-rates of supercritical carbon dioxide and a protein solution. Solutions of hen egg lysozyme (0.5-1%, w/v) in DMSO were dispersed using supercritical carbon dioxide as the antisolvent, and particles precipitated in a particle formation vessel. The morphology, particle size and size distribution and biological activity of the protein were determined. The precipitates were also examined with high sensitivity differential scanning calorimetry (HSDSC) and high-performance cation-exchange chromatography. The amount of residual DMSO was determined using headspace gas chromatography. Particle size measurements showed the precipitates to be agglomerates with primary particles of size 1-5 microm, containing <20 ppm of residual solvent. The activity of the precipitates varied between 44 and 100% depending on the experimental conditions. The similarity of HSDSC data for unprocessed and processed samples indicated that the SEDS process does not cause major denaturation of lysozyme when prepared from DMSO solutions. By optimising of working conditions, the SEDS process can produce micron-sized particles of lysozyme with minimal loss of biological activity.
Carbon Dioxide↗
Interpretation of the differences in the surface energetics of two optical forms of mannitol by inverse gas chromatography and molecular modelling.
Inverse gas chromatography (IGC) has been successfully used to characterise the nature of the surface of two optical forms of mannitol, DL and betaD. This has shown that the surface energetics of the two forms are significantly different with the DL form having higher values for the interactions with the dispersive and basic probes. Molecular modelling was used to predict the slip planes by utilising attachment energy calculations and so the dominant faces exposed upon milling could be predicted. Imaging these faces showed that the orientation of the molecules at these surfaces differed between the two forms. A visual comparison of the faces indicated that the DL form had a higher density of acidic and dispersive sites exposed at the surfaces than the betaD form. The results from the modelling agreed with the trends seen in the changes in surface energetics as measured by IGC. This suggests that the components of the surface energetic terms reflect the density of exposed groups at the particle surfaces.
Chemical Phenomena↗
Applicability of a scale-up methodology for wet granulation processes in Collette Gral high shear mixer-granulators.
This study investigates the extension of a scale-up methodology based on dimensionless power relationships, to a series of vertical mixer-granulators in which the bowl is removable, i.e. both impeller and chopper blades are mounted on top-driven vertical shafts positioned through the lid. Granulation runs were carried out in several bowl sizes belonging to the series of Collette Gral mixer-granulators, ranging from 8 to 600 l capacities. It was shown that under certain conditions a common scale-up master curve could be drawn from the data gathered for each bowl, thus permitting the use of such a curve for the determination of mixer-granulator power consumption at a defined granulation end-point. The results also helped to clarify the concept of similitude, both geometrical and dynamic, which is implied in the methodology. The importance of wall slippage (as promoted by the insertion of a PTFE lining into the bowls) and batch size are illustrated.
Algorithms↗
Strategies for particle design using supercritical fluid technologies.
Major advances in drug delivery and targeting over recent years have highlighted the limitations of conventional particle formation and pretreatment processes in fine-tuning the characteristics required. The alternative strategy of using supercritical fluid technologies for crystal and particle engineering of pharmaceutical materials and drug delivery systems shows great promise in this area. The design of particles for specific drug delivery needs - such as particle size control or polymorphic purity - is increasingly seen as a viable option. In describing recent progress in this field, this review provides a perspective of the current position of this platform technology and considers the possibilities and challenges for future applications and developments.
Journal Article↗
Process control in a high shear mixer-granulator using wet mass consistency: the effect of formulation variables.
This work investigates the relationships between the wet mass consistency/viscosity of samples prepared in a mixer-granulator and physical properties of the dry granules produced from the wet mass; namely, size distribution, bulk density (Hausner ratio), friability, and flow avalanching behavior. The correlation between the consistency of the wet mass and the downstream dry granule properties confirms that consistency is the key parameter to control in wet granulation by mechanical agitation. Variations in the formulation affect the dimensionless power relationship of the mixer-granulator considered; that is, the equivalence between wet mass consistency and mixer net power consumption, which is actually the parameter used to monitor the wet granulation process. The same variations in formulation also affect the relationships between wet mass consistency and dry granule properties.
Algorithms↗