Pharmaceutical Development and Technology 2015-03-01

Solid-state stability and compatibility studies of clavulanate potassium.

Judyta Cielecka-Piontek, Magdalena Paczkowska, Przemysław Zalewski, Kornelia Lewandowska, Bolesław Barszcz

Index: Pharm. Dev. Technol. 20(2) , 146-52, (2015)

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Abstract

The kinetic and thermodynamic parameters of degradation of clavulanate potassium in the solid state were studied by using a reversed phase high performance liquid chromatography (RP-HPLC) method. The degradation of clavulanate potassium was a first-order reaction depending on the substrate concentration at an increased relative air humidity (RH) and in dry air. The dependence ln k = f(1/T) became the ln k = (0.026 ± 166.35)-(2702.82 ± 1779.43)(1/T) in dry air and ln k = (1.65 ± 100.40) × 10(3)-(5748.81 ± 3659.67)(1/T) at 76.4% RH. The thermodynamic parameters Ea, ΔH(≠a), ΔS(≠a) of the degradation of clavulanate potassium in the solid state were calculated. The dependence ln k = f (RH%) assumed the form ln k = (8.78 ± 5.75) 10 (-2) (RH%) + (2.64 × 10(-8 )± 40.41). The compatibility of clavulanate potassium with commonly used excipients was studied at an increased temperature and in dry air. The geometric structure of molecule, highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) orbitals were also determined in order to predict the structural changes and reactive sites in clavulanate potassium during degradation and compatibility studies in the solid state. The ultraviolet (UV), Fourier transform infrared spectroscopy (FT-IR) and Raman spectra of degraded samples of the compound were analyzed.