Rheology and molecular mobility of amorphous blends of citric acid and paracetamol

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 71; no. 1; pp. 55 - 63
• Main Authors: Hoppu, Pekka, Hietala, Sami, Schantz, Staffan, Juppo, Anne Mari
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 2009
• Subjects: Acetaminophen - chemistry; Amorphous; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical - methods; Citric Acid - chemistry; Crystallization; Drug Stability; Drug Storage; Molecular mobility; Phase Transition; Physical stability; Rheology; Solid dispersion; Temperature; Thermodynamics; X-Ray Diffraction; Amorphous; Solid dispersion; Rheology; Molecular mobility; Physical stability
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2008.06.029

The aim of this study was to investigate the rheological properties, molecular mobility and crystallization tendency of pure citric acid and paracetamol or blends of them. Amorphous samples were produced by ethanol-evaporation or by melt-quenching. Enthalpy recovery, glass fragility and heat capacity were determined by differential scanning calorimetry (DSC). Other physical characterization methods were rheology and the crystallization tendency using X-ray powder diffraction (XRPD) and DSC. All the samples behaved as Newtonian liquids and they were fragile glasses. The 50/50 (w/w, %) blend had good physical stability upon consecutive shearing regardless of the preparation method. All the samples were stable for at least one year in dry conditions at −20 °C. The melt-produced blends containing 25% or 50% paracetamol were stable at least two years in dry ambient conditions. The good physical stability at ambient temperature cannot be explained by molecular mobility because molecular mobility of the model material is less than 100 s in ambient conditions. Thus other factors, such as the thermodynamic and crystallization driving forces or formation of degradation products, must determine the physical stability of the blends. The composition and processing method have an impact on the physical stability of the sample.