Effect of pH, polymer concentration and molecular weight on the physical state properties of tolfenamic acid

Abstract

Tolfenamic acid (TA) has been transformed from crystalline to amorphous state through freeze-drying by using varying ratios of polyacrylic acid (PA) at various pH values. The characterization of the films has been carried out using X-ray diffraction, differential scanning calorimetry, Fourier transform infrared (FTIR) spectrometry and scanning electron microscopy. The results showed a gradual change in the solid state properties of TA and a complete transformation into its amorphous form in 1:8, 1:4, 1:2 and 1:1 ratios at pH 3, 4, 5 and 6, respectively. FTIR spectrometry reveals the formation of a yellow polymorphic form of TA. Polymer molecular weight has also been observed to affect the drug transformation and interaction as the low molecular weight PA (M_w ∼ 1800) was found to be most effective followed by its medium (M_v ∼ 450 000) and high molecular weight (M_v ∼ 3 000 000) forms. No signs of recrystallization in the TA–PA films were noted during the 12-week storage period. PA of low molecular weight has also been found more effective in inhibiting the recrystallization of the melt upon cooling thus proving a valuable polymer in producing stable amorphous solid dispersions of TA.

• Amorphous
• characterization
• freeze-drying
• polyacrylic acid
• recrystallization

Acknowledgements

The authors are highly grateful to Mr Paul Bennett and Mr Chris Truman of Centre for Food Innovation, Sheffield Hallam University for providing the freeze-drying facilities. The authors are also thankful to Ms Beverly Lane, Ms Joanna, Dr Nik Reeves-McLaren and Dr Le Ma for providing analytical facilities. The authors are highly grateful to the Higher Education Commission of Pakistan and Baqai Medical University, Karachi for their kind support.

Declaration of interest

The authors report no declarations of interest.