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.
Subject(s)
Acetaminophen/chemistry , Analgesics, Non-Narcotic/chemistry , Chemistry, Pharmaceutical/methods , Acetone/chemistry , Freeze Drying , Porosity , Powder Diffraction , Solvents/chemistry , Water/chemistry , X-Ray DiffractionABSTRACT
Glycine is used to treat various health problems and is efficient in the treatment of the negative symptoms of schizophrenia. Since glycine exists as a few polymorphs, the aim of this work is to compare the effects of the alpha- and gamma-forms of glycine on the behavior of the genetic catalepsy (GC) strain of rats. Both polymorphs of glycine have been administered to rats orally as pure solid chemicals, and cataleptic behavior and behaviors in the open-field, elevated plus-maze, and light-dark box tests were studied. Both the alpha- and gamma-polymorphs of glycine increased exploratory activity in the open-field test, but only the gamma-polymorph had beneficial effects on catalepsy and exploratory activity in the light-dark box and reduced anxiety in the elevated plus-maze.
