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A New Method of Producing Monoclinic Paracetamol Suitable for Direct Compression

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ABSTRACT

Purpose

To develop a technique of obtaining monoclinic polymorph of paracetamol suitable for direct compression without excipients.

Methods

Preparation of spongy monoclinic paracetamol was based on quench-cooling of paracetamol solutions in water-acetone mixtures sprayed into a vessel with liquid nitrogen followed by removal of solvents by freeze-drying. X-ray powder diffraction was used to study annealing of quench-cooled solutions in “paracetamol-acetone-water” and “acetone-water” systems and to find optimum conditions for obtaining fine particles of pure monoclinic paracetamol. Samples were characterized by electron microscopy; compression properties were measured.

Results

The preparation technique gave fine monoclinic paracetamol powder containing agglomerates (30–200 μm) composed of flat particles (linear sizes 1–10 μm, the thickness 60–150 nm). The spongy sample was suitable for direct compression without excipients, stable on storage, and mechanically robust. Mechanically stable tablets pressed from the spongy sample were better soluble in water than commercially available tablets of paracetamol with excipients.

Conclusions

The proposed method gave spongy monoclinic paracetamol samples with improved properties. For inexpensive paracetamol, the method may not yield economic advantage. However, the same method based on freeze-drying solutions in mixed aqueous-organic solvents can be used to prepare new improved forms of other molecular solids for pharmaceutical applications.

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ACKNOWLEDGMENTS & DISCLOSURES

This work was supported by RUX0-008-NO-06, the Program “Fundamental Science for Medical Applications,” FASI State Contract of RF no. 02.740.11.5102, the Project 21.44 of the Program “Nanomaterials” of the Presidium of RAS, the Integration Projects no. 13 and no. 109 of SB RAS, and Russian Ministry of Education and Science (State Contract of RF no. 14.740.11.1023). A.G.O. and A.I.A. thank CRDF (projects Y5-C-08-09, Y5-C-08-01) for financial support. We thank Dr. M.S. Melgunov for the specific surface area measurements.

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Authors and Affiliations

  1. REC-008 “Molecular Design and Ecologically Safe Technologies”, Novosibirsk State University, ul. Pirogova 2, Novosibirsk, 630090, Russia

    Andrey G. Ogienko, Elena V. Boldyreva, Andrey Yu Manakov, Vladimir V. Boldyrev, Alexander S. Yunoshev, Anna A. Ogienko, Svetlana A. Myz, Alexei I. Ancharov, Andrey F. Achkasov & Tatiana N. Drebushchak

  2. Nikolaev Institute of Inorganic Chemistry SB RAS, Lavrentieva 3, Novosibirsk, 630090, Russia

    Andrey G. Ogienko & Andrey Yu Manakov

  3. Institute of Solid State Chemistry and Mechanochemistry SB RAS, ul. Kutateladze 18, Novosibirsk, 630128, Russia

    Elena V. Boldyreva, Vladimir V. Boldyrev, Svetlana A. Myz, Alexei I. Ancharov & Tatiana N. Drebushchak

  4. Lavrentiev Institute of Hydrodynamics SB RAS, Lavrentieva 15, Novosibirsk, 630090, Russia

    Alexander S. Yunoshev

  5. Institute of Cytology and Genetics SB RAS, Lavrentieva 10, Novosibirsk, 630090, Russia

    Anna A. Ogienko

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  1. Andrey G. Ogienko
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  2. Elena V. Boldyreva
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  3. Andrey Yu Manakov
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  4. Vladimir V. Boldyrev
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  5. Alexander S. Yunoshev
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  6. Anna A. Ogienko
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  7. Svetlana A. Myz
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  8. Alexei I. Ancharov
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  9. Andrey F. Achkasov
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  10. Tatiana N. Drebushchak
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Correspondence to Elena V. Boldyreva.

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Ogienko, A.G., Boldyreva, E.V., Yu Manakov, A. et al. A New Method of Producing Monoclinic Paracetamol Suitable for Direct Compression. Pharm Res 28, 3116–3127 (2011). https://doi.org/10.1007/s11095-011-0502-x

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  • DOI: https://doi.org/10.1007/s11095-011-0502-x

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