A new pure paracetamol for direct compression: The orthorhombic form

The poor compression ability of paracetamol is well known. The paracetamols for direct compression that can be found on the market are all compounds of paracetamol with gelatin, PVP, starch or starch derivatives. A pure paracetamol for direct compression, in keeping with the Pharmacopoeia monograph would be particularly convenient. In a previous paper, we reported the preparation of a new pure paracetamol for direct compression: it was recrystallized from a dioxane solution and its crystals exhibited a sintered-like texture favourable to compression. The disadvantage of this paracetamol was the difficulty in obtaining complete elimination of residual solvent. In this work we have investigated 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 prepared form II which crystallizes in the orthorhombic system. Its physical structure contains possible sliding planes. This is the reason why this polymorph exhibits good compression ability. We investigated this new 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 mechanical, biopharmaceutical and stability properties were studied.