Characterisation of blends of paracetamol and citric acid.
The purpose of this study was to characterise physically stable amorphous blends that were sticky (low glass transition temperature) in ambient conditions. The effects of composition, melting time and melting temperature were evaluated with respect to physical and chemical property. Citric acid anhydrate and paracetamol were melt-quenched as binary mixtures and as pure materials. Bulk samples were characterised by differential scanning calorimetry, X-ray powder diffractometry, and Raman and Fourier transform infrared spectroscopy. The composition and the sample exposure to moisture affected significantly the physical stability of samples. The extreme melting conditions, coupled with long exposure to heat and a high melting temperature, lowered the overall crystallisation rate. Paracetamol had a stronger tendency to crystallise from the blends than did citric acid. The 50:50% (w/w) blend was physically stable for at least 27 weeks in dry conditions and was partly crystalline after 4 weeks of storage at a relative humidity of 43%. The result of the physical stability of blends is discussed in terms of hydrogen bonding interaction between paracetamol and citric acid and in relation to degradation products formed in a mixing state.
Hoppu
Pekka
P
Faculty of Pharmacy, Division of Pharmaceutical Technology, P.O. Box 56, FIN-00014 University of Helsinki, Finland. pekka.hoppu@helsinki.fi
Jouppila
Kirsi
K
Rantanen
Jukka
J
Schantz
Staffan
S
Juppo
Anne M
AM
D000082:Acetaminophen / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D019343:Citric Acid / Q000737:chemistry*; D003460:Crystallization; D004338:Drug Combinations; D004355:Drug Stability; D006813:Humidity; D006860:Hydrogen Bonding; D013057:Spectrum Analysis; D044366:Transition Temperature; D014961:X-Ray Diffraction
D004338:Drug Combinations; D019343:Citric Acid; D000082:Acetaminophen