Change search
ReferencesLink to record
Permanent link

Direct link
Sandwich crystals of butyl paraben
KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology, Transport Phenomena. Solid-State Research Group, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, United Kingdom .ORCID iD: 0000-0001-7413-5571
KTH, School of Chemical Science and Engineering (CHE), Chemical Engineering and Technology, Transport Phenomena. University of Limerick, Department of Chemical and Environmental Science, Materials and Surface Science Institute, Ireland .
2014 (English)In: CRYSTENGCOMM, ISSN 1466-8033, Vol. 16, no 37, 8863-8873 p.Article in journal (Refereed) Published
Abstract [en]

Butyl paraben crystals having a porous layer in between two solid non-porous layers have been produced by cooling crystallization in mixtures of ethanol and water. The outer layers are transparent and fully crystalline, while the middle layer appears to be polycrystalline and is full of pores of various dimensions, down to below 0.1 mu m diameters. The thickness of the porous layer reaches about 40% of the whole crystal. The crystals contain one polymorph only and appear to be essentially fully crystalline. They are stable for more than a year when stored on the shelf at room temperature. When the crystals dissolve, the porous layer dissolves faster, leaving the outer layers for slower dissolution. The sandwich crystals are easily cleaved through the middle layer parallel to the (100) plane. This type of sandwich crystals may provide new useful properties to pharmaceutical solids, e. g. larger specific surface area, higher dissolution rates and improved compaction properties.

Place, publisher, year, edition, pages
2014. Vol. 16, no 37, 8863-8873 p.
National Category
Pharmaceutical Sciences Organic Chemistry Analytical Chemistry
URN: urn:nbn:se:kth:diva-122220DOI: 10.1039/c4ce01320dISI: 000341359200032ScopusID: 2-s2.0-84906871652OAI: diva2:621399

Updated from manuscript to article.

QC 20141003

Available from: 2013-05-14 Created: 2013-05-14 Last updated: 2014-10-03Bibliographically approved
In thesis
1. Crystallization of Parabens: Thermodynamics, Nucleation and Processing
Open this publication in new window or tab >>Crystallization of Parabens: Thermodynamics, Nucleation and Processing
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

In this work, the solubility of butyl paraben in 7 pure solvents and in 5 different ethanol-water mixtures has been determined from 1 ˚C to 50 ˚C. The solubility of ethyl paraben and propyl paraben in various solvents has been determined at 10 ˚C. The molar solubility of butyl paraben in pure solvents and its thermodynamic properties, measured by Differential Scanning Calorimetry, have been used to estimate the activity of the pure solid phase, and solution activity coefficients.

More than 5000 nucleation experiments of ethyl paraben, propyl paraben and butyl paraben in ethyl acetate, acetone, methanol, ethanol, propanol and 70%, 90% ethanol aqueous solution have been performed. The induction time of each paraben has been determined at three different supersaturation levels in various solvents. The wide variation in induction time reveals the stochastic nature of nucleation. The solid-liquid interfacial energy, free energy of nucleation, nuclei critical radius and pre-exponential factor of parabens in these solvents have been determined according to the classical nucleation theory, and different methods of evaluation are compared. The interfacial energy of parabens in these solvents tends to increase with decreasing mole fraction solubility but the correlation is not very strong. The influence of solvent on nucleation of each paraben and nucleation behavior of parabens in each solvent is discussed. There is a trend in the data that the higher the boiling point of the solvent and the higher the melting point of the solute, the more difficult is the nucleation. This observation is paralleled by the fact that a metastable polymorph has a lower interfacial energy than the stable form, and that a solid compound with a higher melting point appears to have a higher solid-melt and solid-aqueous solution interfacial energy.

It has been found that when a paraben is added to aqueous solutions with a certain proportion of ethanol, the solution separates into two immiscible liquid phases in equilibrium. The top layer is water-rich and the bottom layer is paraben-rich. The area in the ternary phase diagram of the liquid-liquid-phase separation region increases with increasing temperature. The area of the liquid-liquid-phase separation region decreases from butyl paraben, propyl paraben to ethyl paraben at the constant temperature.

Cooling crystallization of solutions of different proportions of butyl paraben, water and ethanol have been carried out and recorded using the Focused Beam Reflectance Method, Particle Vision and Measurement, and in-situ Infrared Spectroscopy. The FBRM and IR curves and the PVM photos track the appearance of liquid-liquid phase separation and crystallization. The results suggest that the liquid-liquid phase separation has a negative influence on the crystal size distribution. The work illustrates how Process Analytical Technology (PAT) can be used to increase the understanding of complex crystallizations.

By cooling crystallization of butyl paraben under conditions of liquid-liquid-phase separation, crystals consisting of a porous layer in between two solid layers have been produced. The outer layers are transparent and compact while the middle layer is full of pores. The thickness of the porous layer can reach more than half of the whole crystal. These sandwich crystals contain only one polymorph as determined by Confocal Raman Microscopy and single crystal X-Ray Diffraction. However, the middle layer material melts at lower temperature than outer layer material.

Place, publisher, year, edition, pages
Stockholm: KTH Royal Institute of Technology, 2013. xvi, 67 p.
Trita-CHE-Report, ISSN 1654-1081 ; 2013:20
Nucleation, Induction time, Interfacial energy, Ethyl paraben, Propyl paraben, Butyl paraben, Methanol, Ethanol, Propanol, Acetone, Ethyl acetate, Solubility, Thermodynamics, Activity, Activity coefficient, Liquid-liquid phase separation, Ternary phase diagram, Melting point, Boiling point, Polarity, Cooling crystallization, Sandwich crystal, Porous, Particle Vision and Measurement, Focused Beam Reflectance Method, Infrared Spectroscopy, Confocal Raman Microscopy, X-Ray Diffraction, Differential Scanning Calorimetry
National Category
Pharmaceutical Sciences Organic Chemistry Physical Chemistry
Research subject
SRA - E-Science (SeRC)
urn:nbn:se:kth:diva-122228 (URN)978-91-7501-723-5 (ISBN)
Public defence
2013-05-30, K1, Teknikringen 56, KTH, Stockholm, 10:00 (English)
investigate nucleation and crystallization of drug-like organic molecules
Swedish e‐Science Research Center

QC 20130515

Available from: 2013-05-15 Created: 2013-05-14 Last updated: 2013-05-15Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textScopus

Search in DiVA

By author/editor
Yang, HuaiyuRasmuson, Åke
By organisation
Transport Phenomena
Pharmaceutical SciencesOrganic ChemistryAnalytical Chemistry

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 36 hits
ReferencesLink to record
Permanent link

Direct link