title: 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 (Mw ∼ 1800) was found to be most effective followed by its medium (Mv ∼ 450 000) and high molecular weight (Mv ∼ 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.
authors.affiliation: Department of Materials Science and Engineering, The Kroto Research Institute, University of Sheffield , North Campus, Broad Lane, Sheffield , UK.
authors.forename: Muhammad Ali
authors.initials: MA
authors.lastname: Sheraz
authors.forename: Sofia
authors.initials: S
authors.lastname: Ahmed
authors.forename: Ihtesham
authors.initials: I
authors.lastname: Ur Rehman
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D004355:Drug Stability; D004356:Drug Storage; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D008855:Microscopy, Electron, Scanning; D008970:Molecular Weight; D011108:Polymers / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D014961:X-Ray Diffraction; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000180:Acrylic Resins; D000894:Anti-Inflammatory Agents, Non-Steroidal; D011108:Polymers; D062367:ortho-Aminobenzoates; C009500:tolfenamic acid; C006903:carbopol 940
keywords: Amorphous; characterization; freeze-drying; polyacrylic acid; recrystallization