scholarly journals Crystallization from the Gas Phase: Morphology Control, Co-Crystal and Salt Formation

Proceedings ◽  
2020 ◽  
Vol 78 (1) ◽  
pp. 1
Author(s):  
Ciaran O’Malley ◽  
Patrick McArdle ◽  
Andrea Erxleben
Keyword(s):  
Gas Phase ◽  
Binary Systems ◽  
Morphology Control ◽  
Pharmaceutical Chemistry ◽  
Salt Formation ◽  
Phase Crystal ◽  
Modelling Studies ◽  
Poorly Soluble ◽  
Sublimation Rates ◽  
As Solubility

Multicomponent crystallisation is a widely studied technique in pharmaceutical chemistry to enhance physical properties of API’s such as solubility, stability and bioavailability without chemically modifying the drug moiety itself. Methods to produce multicomponent crystals are varied with solution crystallisation being the predominant method. Crystal morphologies also influence an API’s properties with needle shaped crystals dissolving slower and possessing poor flow properties compared to a more equant block shape. In this paper, we discuss the preparation of co-crystals and co-crystal salts of two poorly soluble drugs, pyrimethamine and diflunisal. In particular, we compare production of multicomponent crystals via cosublimation with the more common methods of mechanical grinding and solution crystallisation. Samples are sublimed on a laboratory scale from both ends of standard 15 × 160 mm test tubes sealed under vacuum with two heaters were used to equalize the sublimation rates of the components. We show that a range of multicomponent pharmaceutical crystals can be prepared that are not accessible via solution crystallisation, including polymorphs and ansolvates. In addition to binary systems, ternary crystals can also be obtained via this technique. Various diflunisal co-crystals crystallise as thin needles and we describe the use of tailor-made additives to obtain unprecedented morphology control of gas phase crystal growth. Finally, we discuss the formation of co-crystal salts in the absence of solvent. Salt formation was observed to occur during gas phase crystallisations in accordance with the pKa rule of 3 and modelling studies were carried out to understand the nature of proton transfer in these crystals in the absence of a solvent.

Theoretical analysis of counter-current absorption of a poorly soluble gas based on the PDE-AD model

1986 ◽  
Vol 51 (6) ◽  
pp. 1222-1239 ◽  
Author(s):  
Pavel Moravec ◽  
Vladimír Staněk
Keyword(s):  
Experimental Data ◽  
Liquid Phase ◽  
Gas Phase ◽  
Transfer Functions ◽  
Packed Bed ◽  
Packed Bed Column ◽  
Interfacial Transport ◽  
Gaseous Component ◽  
Poorly Soluble ◽  
Counter Current

Expression have been derived in the paper for all four possible transfer functions between the inlet and the outlet gas and liquid steams under the counter-current absorption of a poorly soluble gas in a packed bed column. The transfer functions have been derived for the axially dispersed model with stagnant zone in the liquid phase and the axially dispersed model for the gas phase with interfacial transport of a gaseous component (PDE - AD). calculations with practical values of parameters suggest that only two of these transfer functions are applicable for experimental data evaluation.

Gap Fill Morphology Control in Liquid-phase Crystal Growth by Use of a Magnetic Field

2011 ◽  
Vol 37 (4) ◽  
pp. 356-360
Author(s):  
Hitoshi Kato ◽  
Shigehiro Ushikubo ◽  
Masaaki Yokota ◽  
Norihito Doki ◽  
Kaoru Ogawa ◽  
...  
Keyword(s):  
Magnetic Field ◽  
Crystal Growth ◽  
Liquid Phase ◽  
Morphology Control ◽  
Phase Crystal

Crystallisation of organic salts by sublimation: salt formation from the gas phase

CrystEngComm ◽  
2020 ◽  
Vol 22 (45) ◽  
pp. 7826-7831 ◽  
Author(s):  
Jean Lombard ◽  
Vincent J. Smith ◽  
Tanya le Roex ◽  
Delia A. Haynes
Keyword(s):  
Proton Transfer ◽  
Gas Phase ◽  
Salt Formation ◽  
Organic Salts

Co-sublimation of two neutral components yields crystals of salts and co-crystals. Experiments show that during sublimation of salts, proton transfer occurs after molecules enter the gas phase.

scholarly journals Nanosuspension: A Novel Drug Delivery System

2013 ◽  
Vol 2 (4) ◽  
pp. 179-196 ◽  
Author(s):  
Bhatt Ganesh ◽  
Raturi Ankita ◽  
Kothiyal Preeti
Keyword(s):  
Matrix Material ◽  
Poorly Soluble Drugs ◽  
Wet Milling ◽  
Essential Factor ◽  
Nonaqueous Media ◽  
Poorly Soluble ◽  
Emulsification Solvent Evaporation ◽  
Novel Drug ◽  
Vehicle Size ◽  
As Solubility

Low bioavailability is the major problem associated with poorly soluble drugs. The problem is more complex for drugs which are poorly soluble in both aqueous and nonaqueous media, as solubility is an essential factor for drug absorption, independent of the route of administration. Nanosuspensions have emerged as an attractive and promising approach to improve stability and bioavailability of poorly soluble drugs. These are very finely colloid, biphasic, dispersed, solid drug particles in an aqueous vehicle, size below 1?m, without any matrix material, stabilized by surfactants and polymers. Techniques such as wet milling, high-pressure homogenization, emulsification-solvent evaporation and supercritical fluid have been used in the preparation of nanosuspension. Nanosuspension can be delivered by oral, parenteral, pulmonary and ocular routes. DOI: http://dx.doi.org/10.3329/ijpls.v2i4.17117 International Journal of Pharmaceutical and Life Sciences Volume 2, Issue 4: October 2013; 179-196

scholarly journals Model for acid-base chemistry in nanoparticle growth (MABNAG)

2013 ◽  
Vol 13 (3) ◽  
pp. 7175-7222 ◽  
Author(s):  
T. Yli-Juuti ◽  
K. Barsanti ◽  
L. Hildebrandt Ruiz ◽  
A.-J. Kieloaho ◽  
U. Makkonen ◽  
...  
Keyword(s):  
Particle Size ◽  
Sulfuric Acid ◽  
Gas Phase ◽  
Organic Compounds ◽  
Particle Growth ◽  
Particle Phase ◽  
Vapor Pressures ◽  
Salt Formation ◽  
Acid Base ◽  
Nanoparticle Growth

Abstract. Climatic effects of newly-formed atmospheric secondary aerosol particles are to a large extent determined by their condensational growth rates. However, all the vapors condensing on atmospheric nanoparticles and growing them to climatically relevant sizes are not identified yet and the effects of particle phase processes on particle growth rates are poorly known. Besides sulfuric acid, organic compounds are known to contribute significantly to atmospheric nanoparticle growth. In this study a particle growth model MABNAG (Model for Acid-Base chemistry in NAnoparticle Growth) was developed to study the effect of salt formation on nanoparticle growth, which has been proposed as a potential mechanism lowering the equilibrium vapor pressures of organic compounds through dissociation in the particle phase and thus preventing their evaporation. MABNAG is a model for monodisperse aqueous particles and it couples dynamics of condensation to particle phase chemistry. Non-zero equilibrium vapor pressures, with both size and composition dependence, are considered for condensation. The model was applied for atmospherically relevant systems with sulfuric acid, one organic acid, ammonia, one amine and water in the gas phase allowed to condense on 3–20 nm particles. The effect of dissociation of the organic acid was found to be small under ambient conditions typical for a boreal forest site, but considerable for base-rich environments (gas phase concentrations of about 1010 cm−3 for the sum of the bases). The contribution of the bases to particle mass decreased as particle size increased, except at very high gas phase concentrations of the bases. The relative importance of amine versus ammonia did not change significantly as a function of particle size. While our results give a reasonable first estimate on the maximum contribution of salt formation to nanoparticle growth, further studies on, e.g. the thermodynamic properties of the atmospheric organics, concentrations of low-volatility organic acids and amines, along with studies investigating the applicability of thermodynamics for the smallest nanoparticles are needed to truly understand the acid-base chemistry of atmospheric nanoparticles.

scholarly journals Investigations on the Solubility of Vortioxetine Based on X-ray Structural Data and Crystal Contacts

Crystals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 536
Author(s):  
Xian-Rui Zhang ◽  
Lei Gao ◽  
Gui-Yuan He ◽  
Chao-Jie Chen
Keyword(s):  
Hydrogen Bonds ◽  
Structural Data ◽  
Pharmaceutical Chemistry ◽  
X Ray Diffraction ◽  
Dihydroxybenzoic Acid ◽  
X Ray ◽  
Crystal Contacts ◽  
Poorly Soluble ◽  
Xrd Techniques ◽  
Solid Form

Investigation on the solid-state pharmaceutical chemistry has been known as an intriguing strategy to not only modify the physicochemical properties of drugs but also expand the solid form landscape. Vortioxetine (VOT) is an effective but poorly soluble antidepressant. To improve the solubility of vortioxetine and expand possible solid forms, in this paper, four novel solid forms of vortioxetine with dihydroxybenzoic acids (VOT-23BA, VOT-24BA-TOL, VOT-25BA, and VOT-26BA, 23BA = 2,3-dihydroxybenzoic acid, 24BA = 2,4-dihydroxybenzoic acid, 25BA = 2,5-dihydroxybenzoic acid, 26BA = 2,6-dihydroxybenzoic acid, and TOL = toluene) were synthesized first by a solvent evaporation method and then characterized by single-crystal X-ray diffraction (SCXRD), thermal, and XRD techniques. VOT-24BA-TOL, VOT-25BA, and VOT-26BA, showed similar [2+2] tetrameric R 4 4 (12) hydrogen bonds by acid-piperazine heterosynthon. In the VOT-23BA-H2O salt, the VOT cation and 23BA anion interacted through protonated piperazine-hydroxyl N-H···O hydrogen bonds, not protonated piperazine-deprotonated carboxylic acid N-H···O hydrogen bonds. Solubility studies were carried out in purified water and it was found that the VOT-23BA-H2O, VOT-25BA, and VOT-26BA salts exhibited an increase in water compared to pure VOT. The solubility of the stabilized salt formations followed the order of VOT-25BA > VOT-26BA > VOT-23BA-H2O in purified water.

Unprecedented morphology control of gas phase cocrystal growth using multi zone heating and tailor made additives

2020 ◽  
Vol 56 (42) ◽  
pp. 5657-5660 ◽  
Author(s):  
Ciarán O’Malley ◽  
Andrea Erxleben ◽  
Seamus Kellehan ◽  
Patrick McArdle
Keyword(s):  
Gas Phase ◽  
Morphology Control ◽  
Highly Effective

Cocrystallization from the gas phase in the presence of tailor-made additives proceeds with highly effective morphology control.

scholarly journals Model for acid-base chemistry in nanoparticle growth (MABNAG)

2013 ◽  
Vol 13 (24) ◽  
pp. 12507-12524 ◽  
Author(s):  
T. Yli-Juuti ◽  
K. Barsanti ◽  
L. Hildebrandt Ruiz ◽  
A.-J. Kieloaho ◽  
U. Makkonen ◽  
...  
Keyword(s):  
Particle Size ◽  
Sulfuric Acid ◽  
Gas Phase ◽  
Organic Compounds ◽  
Growth Rates ◽  
Particle Growth ◽  
Particle Phase ◽  
Salt Formation ◽  
Acid Base ◽  
Nanoparticle Growth

Abstract. Climatic effects of newly-formed atmospheric secondary aerosol particles are to a large extent determined by their condensational growth rates. However, all the vapours condensing on atmospheric nanoparticles and growing them to climatically relevant sizes are not identified yet and the effects of particle phase processes on particle growth rates are poorly known. Besides sulfuric acid, organic compounds are known to contribute significantly to atmospheric nanoparticle growth. In this study a particle growth model MABNAG (Model for Acid-Base chemistry in NAnoparticle Growth) was developed to study the effect of salt formation on nanoparticle growth, which has been proposed as a potential mechanism lowering the equilibrium vapour pressures of organic compounds through dissociation in the particle phase and thus preventing their evaporation. MABNAG is a model for monodisperse aqueous particles and it couples dynamics of condensation to particle phase chemistry. Non-zero equilibrium vapour pressures, with both size and composition dependence, are considered for condensation. The model was applied for atmospherically relevant systems with sulfuric acid, one organic acid, ammonia, one amine and water in the gas phase allowed to condense on 3–20 nm particles. The effect of dissociation of the organic acid was found to be small under ambient conditions typical for a boreal forest site, but considerable for base-rich environments (gas phase concentrations of about 1010 cm−3 for the sum of the bases). The contribution of the bases to particle mass decreased as particle size increased, except at very high gas phase concentrations of the bases. The relative importance of amine versus ammonia did not change significantly as a function of particle size. While our results give a reasonable first estimate on the maximum contribution of salt formation to nanoparticle growth, further studies on, e.g. the thermodynamic properties of the atmospheric organics, concentrations of low-volatility organics and amines, along with studies investigating the applicability of thermodynamics for the smallest nanoparticles are needed to truly understand the acid-base chemistry of atmospheric nanoparticles.

scholarly journals How Does the CO2 in Supercritical State Affect the Properties of Drug-Polymer Systems, Dissolution Performance and Characteristics of Tablets Containing Bicalutamide?

Materials ◽  
2020 ◽  
Vol 13 (12) ◽  
pp. 2848
Author(s):  
Agata Antosik-Rogóż ◽  
Joanna Szafraniec-Szczęsny ◽  
Krzysztof Chmiel ◽  
Justyna Knapik-Kowalczuk ◽  
Mateusz Kurek ◽  
...  
Keyword(s):  
Particle Size ◽  
Binary Systems ◽  
Morphological Changes ◽  
Solid Dispersions ◽  
Drug Dissolution ◽  
Scanning Calorimetry ◽  
State Affect ◽  
Poorly Soluble ◽  
Increasing Demand ◽  
Size And Morphology

The increasing demand for novel drug formulations has caused the introduction of the supercritical fluid technology, CO2 in particular, into pharmaceutical technology as a method enabling the reduction of particle size and the formation of inclusion complexes and solid dispersions. In this paper, we describe the application of scCO2 in the preparation of binary systems containing poorly soluble antiandrogenic drug bicalutamide and polymeric excipients, either Macrogol 6000 or Poloxamer®407. The changes in the particle size and morphology were followed using scanning electron microscopy and laser diffraction measurements. Differential scanning calorimetry was applied to assess thermal properties, while X-ray powder diffractometry was used to determine the changes in the crystal structure of the systems. The dissolution of bicalutamide was also considered. Binary solid dispersions were further compressed, and the attributes of tablets were assessed. Tablets were analyzed directly after manufacturing and storage in climate chambers. The obtained results indicate that the use of supercritical CO2 led to the morphological changes of particles and the improvement of drug dissolution. The flowability of blends containing processed binary systems was poor; however, they were successfully compressed into tablets exhibiting enhanced drug release.

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