Andrey Yu. Manakov

A New Method of Producing Monoclinic Paracetamol Suitable for Direct Compression

ABSTRACTPurposeTo develop a technique of obtaining monoclinic polymorph of paracetamol suitable for direct compression without excipients.MethodsPreparation 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.ResultsThe preparation technique gave fine monoclinic paracetamol powder containing agglomerates (30–200xa0μm) composed of flat particles (linear sizes 1–10xa0μm, the thickness 60–150xa0nm). 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.ConclusionsThe 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.

Nucleation of gas hydrates in multiphase systems with several types of interfaces

Isothermal nucleation of gas hydrates in two-layer water–organic liquid systems was studied with the use of Sapphire Rocking Cell RCS6 with six transparent sapphire cells by thermal analysis under gas pressure. The experiments were conducted at constant supercooling (about 20.2xa0°C). Decane (both with and without surfactants Surfynol 420 and Span 80) and crude oils were used as organic liquids. It was observed that gas hydrate nucleation occurred at water–stainless steel–gas and water–sapphire–organic liquid three-phase contact lines rather than at water–gas or water–organic liquid interfaces. The empirical survival curves were constructed for the entire set of data. Two series of experiments for the system of water–decane–Surfynol 420–methane with the same sample were also conducted. The series of experiments differed with cell angle relative to the horizontal (45° and 14°). Comparison of the observed thermal effects with data of visual examination for this system allowed nucleation rates of methane hydrate on the different nucleation sites to be determined.