Pure Paracetamol for direct compression Part II. Study of the physicochemical and mechanical properties of sintered-like crystals of Paracetamol

Fachaux, J.-M.; Guyot-Hermann, A. M.; Guyot, J. C.; Conflant, P.; Drache, M.; Veesler, Stéphane; Boistelle, R.

doi:10.1016/0032-5910(94)02920-j

Cited by 18 publications

(8 citation statements)

References 4 publications

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“…The ease with which the trihydrate dehydrates is presumably the reason why this compound has not been previously reported, despite the extent to which paracetamol has been studied. Although the trihydrate has only limited thermal stability, there may be scope for processing the compound at low temperatures in a similar way to that reported for the desolvation of the 1,4‐dioxane hemisolvate to produce sintered‐like crystals of a compressible form of the monoclinic polymorph 10, 11…”

Section: List Of Hydrogen Bonds With Ha 110°amentioning

confidence: 96%

“…The interest in the orthorhombic polymorph stems from its property of undergoing plastic deformation on compaction, thereby presenting some processing advantages over the monoclinic form 9. The preparation of a dioxane hemisolvate has been previously reported as part of a study to produce sintered‐like crystals of a compressible form of the monoclinic polymorph 10, 11. Evidence for its formation was established on the basis of thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) measurements, but no further characterization was reported other than its facile loss of solvent at 50°C.…”

Section: List Of Hydrogen Bonds With Ha 110°amentioning

confidence: 99%

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Preparation and Crystal Structure of a Trihydrate of Paracetamol

McGregor

Allan

Parsons

et al. 2002

Journal of Pharmaceutical Sciences

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Section: List Of Hydrogen Bonds With Ha 110°amentioning

confidence: 96%

Section: List Of Hydrogen Bonds With Ha 110°amentioning

confidence: 99%

Preparation and Crystal Structure of a Trihydrate of Paracetamol

McGregor

Allan

Parsons

et al. 2002

Journal of Pharmaceutical Sciences

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“…Consequently, form I has to be mixed with binding agents before tabletting, which is costly in both time and materials. However, directly compressible form I has been prepared by modifying the crystallization process; for example, by the desolvation of a hemisolvate to produce sintered-like crystals 6,7 and by crystallization in the presence of 0.5% of PVP 10000 or 50000. 8 In contrast, orthorhombic paracetamol (form II) has well-developed slip planes in its crystal structure and, as a result, it undergoes plastic deformation upon compaction.…”

Section: Introductionmentioning

confidence: 99%

Physicochemical Characterization of the Orthorhombic Polymorph of Paracetamol Crystallized from Solution

Nichols¹,

Frampton²

1998

Journal of Pharmaceutical Sciences

344

383

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This paper describes a method for the laboratory-scale crystallization of the orthorhombic polymorph (form II) of paracetamol (acetaminophen) from solution. Its structure has been determined by single-crystal X-ray crystallography at 298 K (to confirm the results of data published in 1974) and at 123 K (to improve the overall accuracy of the structure determination). Despite considerable effort by many investigators, the crystallization of form II from solution, using the method given in the 1974 structure report, has been elusive. The incentive for this effort is that form II, unlike commercial paracetamol (form I), undergoes plastic deformation and is suitable for direct compression. Consequently, the ability to produce form II in quantity has attracted much interest because of the potential commercial benefits to be gained by not using binders during the manufacture of tablets. However, until now, the only method that has been reported for the bulk preparation of form II has been to grow it as polycrystalline material from fused form I. This study also compares the solid-state properties of form II with those of form I, with particular emphasis on the crystallography (both X-ray and optical), crystal morphology, thermal behavior, and compaction properties.

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“…This results in poor compression properties and therefore in the requirement of binding agents for tableting. Although improved compression properties can be obtained by varying the habit of the crystallites, 66 such a practice has problems in completely eliminating the residues of the required solvent, 67 thus being time-consuming and with an increased production cost. 68 In this respect, much attention has been focused on the production of form II.…”

Section: Paracetamolmentioning

confidence: 99%

Morphology, Polymorphism, and Co-Crystallization of Molecular Compounds

Drioli¹,

Profio²,

Curcio³

2015

Membrane-Assisted Crystallization Technology

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In classical terms, crystallization from solution can be considered a three-step mechanisms: nucleation, growth, and growth cessation, 1 as schematized in Fig. 5.1. These steps are governed by supersaturation, and the way in which each of them develops, is associated with several macroscopic crystal properties. 2 When spontaneous crystallization starts, the process can follow several pathways that inevitably result in the formation of crystals of various sizes, size distribution, shapes, purity, and structure (polymorphism); these pathways depend on the relative rates of the nucleation and the growth stages. In general, the rates of nucleation and growth increase with supersaturation at a given temperature. At high supersaturation, nucleation is the dominant mechanism, showing proportionality with the extension of the crystalline population. Furthermore, in the nucleation stage, molecular orientation and aggregation mechanisms are intimately associated with the early selection of relative organization of growth units in the crystalline lattice. Therefore, crystal density and polymorphism are features related directly to the nucleation stage.Once nuclei are formed, they can evolve into macroscopic crystals by one of the following methods: keeping their structural properties, dissolving to give rise to more thermodynamically stable aggregates, or experiencing phase change due to internal reorganizations or to liquid-mediated transitions. At this stage, 151 Membrane-Assisted Crystallization Technology Downloaded from www.worldscientific.com by NATIONAL UNIVERSITY OF SINGAPORE on 10/09/15. For personal use only.152 Membrane-Assisted Crystallization Technology Nuclei (Might or might not dissolve)

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Pure Paracetamol for direct compression Part II. Study of the physicochemical and mechanical properties of sintered-like crystals of Paracetamol

Cited by 18 publications

References 4 publications

Preparation and Crystal Structure of a Trihydrate of Paracetamol

Preparation and Crystal Structure of a Trihydrate of Paracetamol

Physicochemical Characterization of the Orthorhombic Polymorph of Paracetamol Crystallized from Solution

Morphology, Polymorphism, and Co-Crystallization of Molecular Compounds

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