Polymer-mediated disruption of drug crystallinity.
Ibuprofen (IB), a BCS Class II compound, is a highly crystalline substance with poor solubility properties. Here we report on the disruption of this crystalline structure upon intimate contact with the polymeric carrier cross-linked polyvinylpyrrolidone (PVP-CL) facilitated by low energy simple mixing. Whilst strong molecular interactions between APIs and carriers within delivery systems would be expected on melting or through solvent depositions, this is not the case with less energetic mixing. Simple mixing of the two compounds resulted in a significant decrease in the differential scanning calorimetry (DSC) melting enthalpy for IB, indicating that approximately 30% of the crystalline content was disordered. This structural change was confirmed by broadening and intensity diminution of characteristic IB X-ray powder diffractometry (PXRD) peaks. Unexpectedly, the crystalline content of the drug continued to decrease upon storage under ambient conditions. The molecular environment of the mixture was further investigated using Fourier transform infrared (FT-IR) and Fourier transform Raman (FT-Raman) spectroscopy. These data suggest that the primary interaction between these components of the physical mix is hydrogen bonding, with a secondary mechanism involving electrostatic/hydrophobic interactions through the IB benzene ring. Such interactions and subsequent loss of crystallinity could confer a dissolution rate advantage for IB.
Rawlinson
Clare F
CF
Drug Delivery Group, School of Pharmacy, University of Bradford, Richmond Road, Bradford BD7 1DP, UK.
Williams
Adrian C
AC
Timmins
Peter
P
Grimsey
Ian
I
D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D004355:Drug Stability; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D007052:Ibuprofen / Q000737:chemistry*; D007700:Kinetics; D015394:Molecular Structure; D004364:Pharmaceutical Preparations / Q000737:chemistry; D011108:Polymers / Q000737:chemistry; D011205:Povidone / Q000737:chemistry*; D012995:Solubility; D013056:Spectrophotometry, Ultraviolet; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D014867:Water / Q000737:chemistry; D014961:X-Ray Diffraction
D004364:Pharmaceutical Preparations; D011108:Polymers; D014867:Water; D011205:Povidone; D007052:Ibuprofen