Growth kinetics and mechanism of glycine crystals

Growth rate of the {001} and {010} faces of glycine crystals was measured as a function of supersaturation in a flow cell system. A growth mechanism was identified by comparing the results with theoretical models and by calculating the [alpha]-factors. The BCF equations fits the growth data well. Thus, crystals growth of glycine can be explained by the screw dislocation mechanism.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29988/1/0000355.pd

Phenytoin crystal growth rates in the presence of phosphate and chloride ions

Phenytoin crystal growth kinetics have been measured as a function of supersaturation in pH 2.2 phosphoric acid and pH 2.2 hydrochloric acid solutions. Two different methods were used for the kinetic analysis. The first involved a zone-sensing device which provided an analysis of the distribution of crystals in a batch crystallizer. Crystal growth rates were calculated from the increase in the size of the distribution with time. In the second method, growth rates were evaluated from the change in size with time of individual crystals observed under an inverted microscope. The results from each method compare favorably. The use of both techniques provides an excellent opportunity to exploit the strengths of each: an average growth rate from a population of crystals from batch crystallization and insight into the effect of growth on the morphology of the crystals from the individual crystal measurements.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29867/1/0000215.pd

The mechanism of phenytoin crystal growth

Phenytoin crystal growth kinetics have been measured as a function of pH, supersaturation and temperature in phosphate buffer. Incorporation of growth units into the crystal lattice was not influenced by diffusion from the bulk to the solid surface. Thus, the rate limiting step for phenytoin growth is surface integration. Phenytoin crystal growth is via a screw-dislocation mechanism; this mechanism explains the observed dependence of growth rate on supersaturation and the increase in growth rate with pH.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30628/1/0000269.pd

Phase transition and heterogeneous/epitaxial nucleation of hydrated and anhydrous theophylline crystals

Theophylline crystallizes in the anhydrous or monohydrate form. The solubility of the anhydrous form exceeds the solubility of the monohydrate form below 60[deg]C. The anhydrous: hydrate phase transition of theophylline in buffered suspensions has been studied by measurement of the supersaturation profile and the crystal size distributions. The role of crystallographic parameters in the nucleation and growth of monohydrate crystals, during dissolution of the anhydrous phase, has been investigated. A solvent-mediated route has been identified and can be described in terms of the dissolution kinetics of the anhydrous phase and the nucleation and growth kinetics of the hydrated phase. The growth rate of the monohydrate crystals depends on the square of the supersaturation and is independent of the stirring rate, which suggests a surface-controlled growth process. The dissolution rate of the anhydrous crystals depends on the 1.5 order of the undersaturation and is inversely proportional to the square root of the crystal size. Anhydrous theophylline crystals act as heterogeneous nucleation substrates for the crystals of the monohydrate phase and these grow epitaxially on the anhydrous crystals. Based on the kinetic equations for dissolution of the anhydrous form and crystallization of the monohydrate form, a computer simulation has been developed that predicts the changes in the concentration of theophylline in solution during the phase transition.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29838/1/0000185.pd

The Potential of Raman Spectroscopy as a Process Analytical Technique During Formulations of Topical Gels and Emulsions

Purpose. The primary objective of this study is to investigate the possibility of using Raman spectroscopy as a process analytical technique (PAT) for quality control during manufacturing of topical dosage forms.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41503/1/11095_2004_Article_493747.pd

A microfluidic device for investigating crystal nucleation kinetics

We have developed an original setup using microfluidic tools allowing one to produce continuously monodisperse microreactors ($\approx 100$ nL), and to control their temperatures as they flow in the microdevice. With a specific microchannels geometry, we are able to apply large temperature quenches to droplets containing a KNO$_3$ solution (up to 50$^{\circ}$C in 10 s), and then to follow nucleation kinetics at high supersaturations. By measuring the probability of crystal presence in the droplets as a function of time, we estimate the nucleation rate for different supersaturations, and confront our results to the classical nucleation theory

Sferična kristalizacija zdravilnih učinkovin

Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions of these techniques. By controlling process parameters during crystallization, such as temperature, stirring rate, type and amount of solvents, or excipient selection, it is possible to control the formation of agglomerates and obtain spherical particles of the desired size, porosity, or hardness. Researchers have reported that the particles produced have improved micromeritic, physical, and mechanical properties, which make them suitable for direct compression. In some cases, when additional excipients are incorporated during spherical crystallization, biopharmaceutical parameters including the bioavailability of drugs can also be tailored.Sferična kristalizacija je postopek izdelave večjih delcev z aglomeracijo manjših med samo kristalizacijo. Najpogosteje uporabljeni tehniki za izdelavo takšnih delcev sta sferična aglomeracija in kvaziemulzija z difuzijo topila. Sistem z difuzijo amoniaka in kristalo-ko-aglomeracija sta razširitvi teh dveh metod. Z nadzorovanjem procesnih parametrov med kristalizacijo, kot sta temperatura in hitrost mešanja, z izbiro lastnosti in množine topil ter z izbiro pomožnih snovi, lahko vplivamo na nastanek aglomeratov in izdelamo sferične delce želenih velikosti, primerne poroznosti ali trdote. Raziskovalci poročajo, da imajo izdelani delci izboljšane pretočne lastnosti, izboljšane druge fizikalne in mehanske lastnosti zaradi česar so primerni za direktno tabletiranje. V nekaterih primerih lahko ob vgradnji ustreznih pomožnih snovi, ki jih dodamo med procesom sferične kristalizacije, izboljšamo tudi biofarmacevtske lastnosti zdravilnih učinkovin vključno s povečanjem biološke uporabnosti

Growth and Morphology of L-Alanine Crystals: Influence of Additive Adsorption

The effect of L-amino acids, as additives, on the crystal growth and morphology of L-alanine crystals has been studied. The crystal growth of L-alanine is described by the spiral growth mechanism. From examining the growth rate dependence on supersaturation at constant additive concentration, it is concluded that there is no change in the growth mechanism due to the presence of the different additives. L-Alanine crystals were grown both in the absence and in the presence of additives. The crystal morphology was characterized by optical goniometry assigning the different Miller indices to the well-developed crystal faces. The addition of L-amino acids selectively inhibits the development of certain L-alanine crystal faces. L-Alanine crystals grown in the presence of nonpolar amino acids, such as L-leucine, L-phenylalanine, and L-valine, at concentrations as low as 0.20 m (0.3%, w/w) develop the {120} faces, whereas the {010}, {110}, and {210} faces are not developed. The effect of these additives on the morphology of L-alanine is explained at the molecular level based on crystallographic considerations. The molecular structure of a face will determine the availability of sites that favor the adsorption of the additives. The availability of sites and their energy, on a particular crystal face, will determine the extent of adsorption. The growth rate of a crystal face is decreased by the adsorption of the additive. The inhibitory effect of these additives can be explained by a Langmuir isotherm, assuming that the inhibition of the growth rate is proportional to the degree of surface coverage and that the crystal surface is homogeneous with respect to the energy of adsorption sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/41434/1/11095_2004_Article_304897.pd

The Relation between Adsorption of Additives and Crystal Growth Rate of L-Alanine

The growth kinetics of L-alanine from solution in the presence and absence of L-phenylalanine and L-leucine has been studied. L-Alanine crystal growth, from crystal size distribution measurements, is independent of the agitation rate suggesting that the growth mechanism is surface controlled. The dependence of growth rate on supersaturation at constant additive concentration suggests that there is no change in the growth mechanism of L-alanine due to the presence of additive. The growth rate of L-alanine is reduced by 50% with a mol fraction of 5 x 10-5 of L-phenylalanine and 2 x 10-4 of L-leucine. The solubility of L-alanine is not significantly affected by the presence of these additives in solution. The effect of these additives on the growth kinetics is due to their adsorption onto the growing L-alanine crystals. The extent of this effect is satisfactorily explained assuming both that (i) the inhibition of the growth rate is proportional to the degree of surface coverage and that (ii) the crystal surface is homogeneous with respect to the energy of adsorption sites.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30862/1/0000525.pd

Multiple-component solid phases containing at least one active pharmaceutical ingredient

The subject invention concerns a method for identifying complementary chemical functionalities to form a desired supramolecular synthon. The subject invention also pertains to binary phase compositions comprising one or more pharmaceutical entities and methods for producing such compositions