Estimation of the nucleation kinetics for the anti-solvent crystallisation of paracetamol in methanol/water solutions

Ó'Ciardha, Clifford Thomás; Frawley, Patrick J.; Mitchell, Niall A.

doi:10.1016/j.jcrysgro.2011.06.017

Cited by 53 publications

(48 citation statements)

References 16 publications

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“…Attempts to change the crystal habit and the workability of drugs using alternative crystallization procedures of drugs has been published; for example ibuprofen (Gordon and Amin, 1984), hexamethylmelamine (Gonda, 1985), nitrofurantoin (Marshall and York, 1989) and paracetamol (Ó'Ciardhá et al, 2011). Although, more general influence of several different shapes and sizes of a single API on flowability and compressibility has not yet been presented.…”

Section: Introductionmentioning

confidence: 99%

Comparison of Compression and Material Properties of Differently Shaped and Sized Paracetamols

Šimek

Grünwaldová²,

Kratochvíl

2017

KONA

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Paracetamol is well-known API (active pharmaceutical ingredient) for its bad flow and compression abilities. To improve the compressibility, a high amount of excipient is commonly mixed with paracetamol to create better compressible material. Conversely, we used modified crystallization procedures to prepare plate, irregular and spherical particles from original raw paracetamol to prepare directly compressible API. To expand our screening, several sizes of each shape were prepared and material properties analyzed, mainly the flow and compression abilities, and significant variation of the properties presented; from very poor properties of raw paracetamol to excellent properties of spherical crystals which exhibited ability to be directly compressed without excipient. The analysis also showed very small effect of the size modification on tablet compression and material behavior as the main contribution had the shape alteration and compression force.

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Section: Introductionmentioning

confidence: 99%

Comparison of Compression and Material Properties of Differently Shaped and Sized Paracetamols

Šimek

Grünwaldová²,

Kratochvíl

2017

KONA

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“…The drugs receive regulatory approval for only single crystal form or polymorph. For the production of these drug materials, crystallization from solution is a vital unit operation which is highly responsible for achieving the chemicals with high purity and to produce the desired final crystal form . Solubility, crystallinity and crystal properties of an active pharmaceutical ingredient (API) play a crucial role in the worth series of pharmaceutical development, manufacturing and formulation .…”

Section: Introductionmentioning

confidence: 99%

Understanding the effect of solvent polarity on the habit modification of monoclinic paracetamol in terms of molecular recognition at the solvent crystal/interface

Sudha

Srinivasan

2014

Crystal Research and Technology

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The habit change of monoclinic paracetamol crystallized from solutions with different solvents such as water, ethanol, methanol, acetone, isopropyl alcohol, tetrahydrofuran, cyclohexanone, acetonitrile and 1, 4 ‐ dioxane was investigated. Change in solubility, pH and nucleation time of paracetamol in these solvents at ambient condition was studied. The polymorphic form of the nucleated paracetamol was observed under in‐situ optical microscopy. Solutions with different solvents having different chemical nature and polarity yielded paracetamol crystals with different habits: columnar morphology from polar protic water and prismatic morphology from other selected polar protic, aprotic and in non‐polar solvents. The significant differences on the growth rate of various crystal habit faces of the monoclinic paracetamol grown from different solvents are attributed in context with the solubility of the solute, solvent polarity, evaporation number of the solvent, rate of generation of supersaturation and the role of hydrogen bonding interaction between the solvent molecules and protruding solute molecules on the crystal surface. Among the solution with different solvents, bulk monoclinic paracetamol single crystal was grown from ethanolic solution using seed rotation technique by controlled cooling method.

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“…ese values are smaller than literature values, which are 2.16×10 9 #/m 3 for cooling crystallization (Mitchell et al, 2011) and 1.50×10 6 #/kg for antisolvent crystallization (Ó'Ciardhá et al, 2011). e reason for this di erence was discussed in Section 3.1.4. e primary nucleation rate parameters are also substantially the same because the same detection method and the same compound were used.…”

Section: Rate Parameters In Antisolvent and Coolingmentioning

confidence: 70%

“…In our study, this number density was estimated by combining experimental results and numerical calculations to properly distinguish between primary and secondary nucleation. We employed a sensitive detection method for primary nucleation, i.e., visual detection; therefore, our estimated number density at the detection point was smaller than that determined by other research groups (Ó'Ciardhá et al, 2011;Kodera et al, 2019b). is method can also be applied to cooling crystallization.…”

Section: Introductionmentioning

confidence: 99%

Nucleation Kinetics Estimated by Using the Modified Induction Time in Cooling Crystallization and the Applicability to the Combined Process of Antisolvent and Cooling Crystallization

Kodera

Kobari

Hirasawa

2020

J. Chem. Eng. Japan

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A previously proposed method for estimating antisolvent crystallization kinetics has been successfully applied to cooling crystallization to yield kinetic parameters for simulating the crystallization process. In particular, the primary nucleation kinetics were analyzed using the modi ed induction time data, essentially as proposed by Kubota. The number density at the detection point, (N/M) det , is an important value in the kinetic analysis but is di cult to estimate experimentally. Therefore, the numerical optimization was used to estimate the value of (N/M) det in the same manner as for antisolvent crystallization. Primary nucleation was detected for both antisolvent and cooling crystallization with a sensitive detection method, visual detection, to reduce the e ects of secondary nucleation. As a result, the (N/M) det values for each method are small and almost identical (approximately 200 #/kg-solvent). The secondary nucleation and growth rate parameters for cooling crystallization were also successfully determined by numerical optimization. All the kinetic parameters determined for cooling crystallization were evaluated with experimental data. Consequently, it is con rmed that these rate parameters can simulate trends in concentration as well as the nal number mean diameter of the product crystals with acceptable accuracy. Moreover, the crystallization rate parameters determined for both antisolvent and cooling crystallization were validated with simulations and experimental data from combined crystallization, where antisolvent crystallization is followed by cooling crystallization. The simulation and experimental results for the concentration trend and number mean diameter of the produced crystal were in good agreement. The applicability of our estimation method to both antisolvent and cooling crystallization indicates the broad utility of this method for various crystallization process in the pharmaceutical industry.

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Estimation of the nucleation kinetics for the anti-solvent crystallisation of paracetamol in methanol/water solutions

Cited by 53 publications

References 16 publications

Comparison of Compression and Material Properties of Differently Shaped and Sized Paracetamols

Comparison of Compression and Material Properties of Differently Shaped and Sized Paracetamols

Understanding the effect of solvent polarity on the habit modification of monoclinic paracetamol in terms of molecular recognition at the solvent crystal/interface

Nucleation Kinetics Estimated by Using the Modified Induction Time in Cooling Crystallization and the Applicability to the Combined Process of Antisolvent and Cooling Crystallization

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