Influence of crystallization conditions on the physical properties of acetaminophen crystals: evaluation by multiple linear regression

Abstract

The comparative influence of the following 3 aqueous crystallization variables on various physical properties of acetaminophen (paracetamol, P) has been appraised statistically by multiple linear regression analysis: the concentration of the additive, p-acetoxyacetanilide, A, in the solution (PAA), the stirring speed (SPEED) and the initial supersaturation of P (SIGMA) in the solution. The following properties of the crystals have been studied: the uptake of A and water during crystallization, the length-to-width ratio and the entropy of fusion ( ΔS f). The uptake of A depends almost exclusively on PAA, and much less so, on SPEED and/or on SIGMA. The length-to-width ratio also depends chiefly on PAA and, to some extent, on SIGMA but only in the presence of A, i.e. SIGMA only plays a mediating role. The uptake of water, however, is determined, in descending order of significance, by SIGMA, SPEED, and PAA. Comparison of the multiple r 2 and residual mean-square values suggests that both the additive uptake and the length-to-width ratio are governed mainly by the crystallization conditions while the water content is less so. On the other hand, the entropy of fusion is partially linked to the crystallization conditions possibly via the density of growth defects.