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.
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.
Authors: Joshua S Boateng; Kerr H Matthews; Anthony D Auffret; Mike J Humphrey; Howard N Stevens; Gillian M Eccleston Journal: Int J Pharm Date: 2009-05-27 Impact factor: 5.875
Authors: Andrey G Ogienko; Svetlana A Myz; Andrey A Nefedov; Anna A Ogienko; Tatyana P Adamova; Olga M Voronkova; Svetlana V Amosova; Boris A Trofimov; Vladimir V Boldyrev; Elena V Boldyreva Journal: Pharmaceutics Date: 2022-02-24 Impact factor: 6.321