PMID: 11902798Mar 21, 2002Paper

Crystallization conditions and formation of orthorhombic paracetamol from ethanolic solution

The Journal of Pharmacy and Pharmacology
N Al-ZoubiS Malamataris

Abstract

Orthorhombic paracetamol exhibits far better tabletability than the monoclinic form and its bulk crystallization from solution attracts much interest. In this study, temperature changes in supersaturated ethanolic solution have been recorded after seeding with orthorhombic crystals under different cooling temperatures (Tc) and agitation rates (AR). Average cooling rate (CR), time for maximum temperature deviation (tmax) and area confined between curves of measured and reference temperature plots (AUC) were calculated and correlated with crystal yield (Y). The micromeritic (size and shape) and the compression properties, the density and the orthorhombic content of the crystalline product were evaluated and related to the main crystallization conditions applied (Tc and AR). Conditions for optimal crystal yield and orthorhombic content were elucidated. It was found that crystal yield (Y) increased with AR and decreased with Tc. The ratio tmax/CR provided good prediction of crystal yield (Y = 58.92-1.386 tmax/CR, r2 = 0.964 and P = 0.0001). Tc and AR linearly affected crystal size and the size distribution, probably due to alterations in supersaturation, but they did not affect the crystal shape significantly. Density and compressi...Continue Reading

References

Jun 11, 1998·Journal of Pharmaceutical Sciences·G Nichols, C S Frampton
Aug 4, 1998·Pharmaceutical Research·E JoirisJ C Guyot
Jan 7, 1999·Drug Development and Industrial Pharmacy·F N de WetT G Dekker
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Nov 7, 2000·International Journal of Pharmaceutics·H A GarekaniA R Rajabi-Siahboomi

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Citations

Jan 10, 2008·Pharmaceutical Research·Kyriakos KachrimanisUlrich J Griesser
Oct 3, 2002·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·N Al-ZoubiS Malamataris
Dec 15, 2015·International Journal of Pharmaceutics·Stevanus HiendrawanRaymond R Tjandrawinata
Jun 15, 2007·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Jonathan C BurleyRanko M Vrcelj
Aug 29, 2006·Journal of Pharmaceutical and Biomedical Analysis·Kyriakos KachrimanisUlrich J Griesser
Aug 22, 2017·The Journal of Physical Chemistry Letters·Joshua T DamronAyyalusamy Ramamoorthy

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