Roland Boistelle

The initial phases of calcium and magnesium phosphates precipitated from solutions of high to medium concentrations

The precipitation of calcium and magnesium phosphates is performed at 25°C by mixing solutions of ammonium phosphate and solutions of calcium and magnesium chlorides under the condition [P] = [Ca] + [Mg] in large pH intervals. Before any nucleation the phosphate concentration ranges from 0.50M to 0.01M. The phases first precipitated are CaHPO4·2H2O (brushite), CaHPO4 (monetite), Ca3(PO4)2·xH2O (amorphous calcium phosphate), MgNH4PO4·6H2O (struvite), and MgHPO4·3H2O (newberyite). The precipitation fields of each phase are determined and discussed as a function of pH, composition and supersaturation. The solutions are even supersaturated with respect to several other calcium phosphates but they never occur first even if their supersaturation is the highest.

Crystallization of gypsum from hemihydrate in presence of additives

The crystallization of gypsum (CaSO 4 . 2H 2 O) from a suspension of calcium sulphate hemihydrate is well-known as the setting of plaster. In this paper we present results concerning the crystallization of gypsum in the presence of different acids. The influence of additives on the crystallization kinetics and on the morphology of gypsum crystal have been studied. The rate retarding effect was determined by recording, versus time, the conductivity of suspension of hemihydrate. The amount of additives adsorbed was measured by capillary electrophoresis. The results are well-related to the amount of adsorbed and incorporated additives during the crystallization. The influence of different additives on the morphology of a crystal of gypsum was also investigated and discussed. Their efficiency is related to the presence of calcium on the faces (120) and (111) and to the correspondence between distances between the carboxylic groups of the additives and between the adsorption sites at the surface of the crystal.

Growth units and nucleation: the case of calcium phosphates.

Abstract Calcium phosphates are precipitated at 37°C from solutions the pH of which ranges from 5.0 to 11.0. Despite the fact that the supersaturations of hydroxyapatite HAP, octocalcium phosphate OCP and brushite B are often in the order HAP⪢OCP⪢B, brushite nucleates more easily than OCP and HAP at low pH, while OCP nucleates more easily than HAP at mean to high pH. These facts cannot be explained, as usually, by the only differences in the surface free energies of the three solid phases. On the other hand, they may be explained by assuming that the values of the kinetic coefficients change as a function of the concentration in the proper growth units which have to integrate in the nuclei of either phase. In the model we propose, the kinetic coefficients of OCP and HAP are smaller than that of B by 10 and 18 orders of magnitude at pH=6.5, differences which reduce to 3 orders of magnitude at pH=10.0. Accordingly, nucleation of OCP and HAP is favoured with increasing pH.

Pure Paracetamol for direct compression Part I. Development of sintered-like crystals of Paracetamol

Abstract The widespread distribution of Paracetamol on the market is the reason why it would be preferable to use the fastest, simplest and least expensive method of preparing Paracetamol tablets, that is, through direct compression. Yet, it is well known that this drug exhibits bad flow properties, and poor compression ability which causes capping. Several manufacturers have prepared Paracetamol powders for direct compression. Unquestionably these materials have good compressibility but all these Paracetamols for direct compression are not pure Paracetamol. They are mixtures of Paracetamol with either starch, carboxymethylstarch, pre-gelatinized starch, PVP or gelatin added. After noting the good compression ability of some sintered-like crystals, we prepared a pure Paracetamol for direct compression (FGH Paracetamol) through the recrystallizing of crystals from a dioxane solution or suspension. The Paracetamol interacts with this solvent to form a ‘solvate’. The desolvation of these solvate crystals led to the production of sintered-like crystals exhibiting a polyhedric habit.

Comparison of solubilities and molecular interactions of BPTI molecules giving different polymorphs

The solubility of the monoclinic modification of BPTI was determined at different temperatures in solutions at three KSCN concentrations (250, 300 and 350 mM) and five (NH4)2SO4 concentrations (1.4, 1.5, 1.6, 1.75 and 1.85 M). In both cases, the solubility decreases with increasing ionic strength. Moreover, in KSCN solutions it increases with increasing temperature whereas it decreases in (NH4)2SO4 solutions. Quasi-elastic light scattering and small-angle X-ray scattering experiments were carried out at constant protein concentration (15 mg ml−1) for KSCN and (NH4)2SO4 concentrations ranging from 0 to 350 mM and from 0 to 1.85 M, respectively. They showed that the solutions are monodispersed, but not monomeric, in the vicinity of the solubility curve, whereas they are polydispersed at lower concentration. Under crystallization conditions, the molecular interactions change from repulsive to attractive once the KSCN concentration was higher or equal to 250 mM. In KSCN, (NH4)2SO4 and also in NaCl solutions the scatterers have the same size (Rh ≈ 23 A) suggesting that they are BPTI tetramers. As a consequence, it was not possible to predict which polymorph was going to nucleate and grow on the basis of the scatterers size since in NaCl solutions a hexagonal modification occurs instead of the monoclinic modification which occurs in the two other solutions.

Crystallization and dissolution of pharmaceutical compounds: An experimental approach

In pharmaceutical industry growth and dissolution are important stages for different reasons. In industrial processes crystallization is an important operation which controls the physical properties of the material such as the crystal habit, crystal size distribution and polymorphism. For economic and technical reasons before patenting a drug it is important to search all the possible polymorphs. In the case of organic drugs which are slightly soluble in gastrointestinal fluids, the dissolution rate of the solid dosage form is an important factor determining the rate of absorption. The kinetics of solubilization will depend mainly on the crystal habit, crystal size distribution and on the polymorphs. This paper presents a laboratory study of the dissolution of crystals of an organic drug in a crystallizer equipped with an in situ conductivity probe and an UV analyzer on-line. The rate of dissolution and evolution of the crystal size distribution are measured. A solution mediated phase transition of the drug is observed. The final objective is to model the dissolution process from kinetic data and determine the influence on the dissolution of under-saturation, temperature, crystal habit and crystal size distribution.

The influence of additives on the crystal habit of gibbsite

Abstract Crystallization of gibbsite (Al(OH) 3 ) is an important stage of the Bayer process, production of alumina from bauxite ores. In both pure or industrial supersaturated sodium aluminate solutions, gibbsite crystals are always agglomerated. In the present paper, we present results of a study concerning the influence of different polycarboxylic acids as crystal habit modifier for gibbsite. In pure solution, agglomerated hexagonal plates are observed. Whereas acicular and tabular morphologies are found in the presence of different additives. These results are discussed referring to the crystallographic structure of gibbsite. It is found that only oxygen atoms are present on gibbsite surface. This observation leads us to propose an additive way of acting by formation of a molecular complex between the growth unit and the carboxylic groups of the additive.

Solubility, phase transition, kinetic ripening and growth rates of porcine pancreatic α-amylase isoenzymes

Abstract Two polymorphic modifications, A and B, of porcine pancreatic α-amylase were grown between 4 and 30°C. A and B crystals are made up by two isoenzymes so that four crystal varieties (AI, AII, BI, BII) exist. A and B are easily distinguished due to their typical crystal habits but there is no difference between AI and AII or BI and BII respectively at least as concerns their unit cells, crystal habits and solubilities for instance. On the other hand, the growth rates are somewhat different, even if the overall rate determining step is volume diffusion. The transition temperature between A and B polymorphs is 18°C, A being stable above this temperature. A and B can undergo a phase transition by slightly changing the temperature around the transition point. Kinetic ripening experiments show that ripening can be used for growing larger crystals at the expenses of smaller ones.

About supersaturation and growth rates of hydrargillite Al(OH)3 in alumina caustic solutions

Abstract Growth rates of hydrargillite crystals, Al(OH) 3 , growing from concentrated caustic solutions, are traditionally plotted and discussed as a function of the difference between actual concentration and solubility of alumina. This way to express supersaturation is probably due to practical or technical reasons, as hydrargillite is mainly grown in industrial plants. However, as the solubility of hydrargillite is greatly affected by the presence of caustic soda there are as many growth rate curves as there are solutions at different soda concentrations, if supersaturation is expressed as a concentration difference. In the present paper we show that all growth rates, measured in different caustic solutions, lie on a single curve if supersaturation is normalized with respect to solubility, i.e. expressed as a ratio of actual concentration over solubility. Accordingly, growth rates become independent of the caustic concentrations when growth takes place at the same supersaturation.

Growth kinetics of hydrargillite Al(OH)3 from caustic soda solutions

Abstract The growth rates of hydrargillite (alumina trihydroxide) from caustic alumina solutions were studied in a semi-continuous crystallizer as a function of temperature and supersaturation. If supersaturation is expressed as β = C / C 0 , where C 0 is the solubility at given temperature and caustic soda concentration, then the growth rates can be described by the model G (μm/h) = k 0 (β-β c ) 2 exp(-δ G / RT ), where k 0 = 1.92 × 10 19 μm/h is independ ent of temperature and caustic soda concentration, and δ G = 120.7 kJ/mol. The term β c , which normally is 1 in pure systems, arises from the fact that there are dead zones at low supersaturation where growth is inhibited, probably by Fe ions. Accordingly, β c is a critical supersaturation which must be exceeded for growing the crystals. The model we propose also describes pretty well the results of previous works where the kinetic coefficients of the growth rate equations are dependent not only on temperature but also on caustic soda concentration.