A NEW PURE PARACETAMOL FOR DIRECT COMPRESSION - THE ORTHORHOMBIC FORM

The poor compression ability of paracetamol is well known. The paracet amols for direct compression that can be found on the market are all c ompounds of paracetamol with gelatin, PVP, starch or starch derivative s. A pure paracetamol for direct compression, in keeping with the Phar macopoeia monograph would be particularly convenient. In a previous pa per, we reported the preparation of a new pure paracetamol for direct compression: it was recrystallized from a dioxane solution and its cry stals exhibited a sintered-like texture favourable to compression. The disadvantage of this paracetamol was the difficulty in obtaining comp lete elimination of residual solvent. In this work we have investigate d the polymorphs of paracetamol. The usual form is the monoclinic form . The arrangement of the molecules inside the crystal presents a stiff construction, consequently its compression ability is poor. We prepar ed form II which crystallizes in the orthorhombic system. Its physical structure contains possible sliding planes. This is the reason why th is polymorph exhibits good compression ability. We investigated this n ew form as far as its physical, technological and stability properties are concerned, using X-ray powder diffraction, thermal analysis, and an instrumented tablet machine. Tablets were formulated and their mech anical, biopharmaceutical and stability properties were studied.