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Studies on Tolfenamic Acid–Chitosan Intermolecular Interactions: Effect of pH, Polymer Concentration and Molecular Weight

Abstract

Solid-state properties of tolfenamic acid (TA) and its complexes with chitosan (CT) have been studied. Effect of medium pH, molecular weight of polymer and its different concentrations on these TA–CT complexes were studied in detail. Low and medium molecular weight CT have been used in different ratios at pH ranging from 4 to 6 and freeze-drying technique has been employed to modify the appearance of crystalline TA. Physical properties of the formed complexes have been studied by employing X-ray diffraction, differential scanning calorimetry and scanning electron microscopy; chemical structure has been studied using Fourier transform infrared spectroscopy. The results showed that both forms of the polymer exhibited complete conversion in 1:8 ratio at pH 4, 1:4 at pH 5 and 1:1 at pH 6 indicating a marked effect of pH on drug–polymer complexation. The percent crystallinity calculations indicated low molecular weight CT slightly more effective than the other form. No changes in the complexes have been observed during the 12 week storage under controlled conditions. Both forms of CT at different pH values indicated retardation of recrystallization in TA during cooling of the melt from 1:1 ratios exhibiting formation of strong intermolecular hydrogen bonding between the drug and the polymer.

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ACKNOWLEDGMENTS

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.

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The authors declare no conflicts of interest.

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Correspondence to Ihtesham Ur Rehman.

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Ahmed, S., Sheraz, M.A. & Rehman, I.U. Studies on Tolfenamic Acid–Chitosan Intermolecular Interactions: Effect of pH, Polymer Concentration and Molecular Weight. AAPS PharmSciTech 14, 870–879 (2013). https://doi.org/10.1208/s12249-013-9974-9

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  • DOI: https://doi.org/10.1208/s12249-013-9974-9

KEY WORDS

  • amorphous
  • chitosan
  • effect of pH and molecular weight
  • freeze-drying
  • recrystallization
  • tolfenamic acid