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  • Title: Compression behavior of orthorhombic paracetamol.
    Author: Joiris E, Di Martino P, Berneron C, Guyot-Hermann AM, Guyot JC.
    Journal: Pharm Res; 1998 Jul; 15(7):1122-30. PubMed ID: 9688070.
    Abstract:
    PURPOSE: Orthorhombic crystals of paracetamol exhibit good technological properties during compression. The purpose of this study was to investigate the compression behavior of this substance and to compare it to that of monoclinic paracetamol. From the crystal structure, it could be hypothesized that sliding planes are present in the orthorhombic form, and could be responsible for an increase in crystal plasticity. METHODS: Compression of pure orthorhombic or monoclinic paracetamol tablets was carried out on a fully instrumented single punch machine. Data was used to establish Heckel's profiles. Images of compressed crystals were obtained by scanning electron microscopy. RESULTS: Tabletability of the orthorhombic crystals was far better than that of the monoclinic ones, and capping was not observed even at high compression pressure. Compared to the monoclinic form, orthorhombic paracetamol exhibited greater fragmentation at low pressure, increased plastic deformation at higher pressure, and lower elastic recovery during decompression. Plastic behavior was confirmed by SEM - micrographs showing that crystals folded under pressure. A compactibility study showed that the nature of interparticle bonds was similar for both polymorphs, the number of bonds being greater for orthorhombic paracetamol. CONCLUSIONS: Unlike the monoclinic form, orthorhombic paracetamol is suitable for the direct compression process. The crystalline structure accounts for its better compression behavior, because of the presence of sliding planes.
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