Projects per year
Abstract
It has been previously shown that the interaction of some weakly basic drugs with oppositely charged fatty acids during digestion can influence the solid-state form of the drug if it precipitates. The present study hypothesized the opposite effect for weakly acidic drugs. Tolfenamic acid (TA) and an oppositely charged cationic surfactant, didodecyldimethylammonium bromide (DDAB) were combined in a model medium chain lipid formulation. The phase distribution upon in vitro lipolysis was determined using HPLC and the solid-state form of precipitated TA was determined using X-ray diffraction and crossed polarized light microscopy. TA precipitated in a different polymorphic crystalline form to the starting reference material in the absence of DDAB but precipitated in an amorphous form when DDAB was included in the same formulation. The solubility of TA upon dispersion and digestion of the formulation was considerably higher in the presence of DDAB. The findings point to ionic interactions between TA and DDAB as the reason for the improved drug solubility throughout digestion, and precipitation of drug in an amorphous salt form, analogous to what has been observed in the past for some poorly water-soluble weakly basic drugs with anionic co-formers.
Original language | English |
---|---|
Article number | 2420-2427 |
Number of pages | 8 |
Journal | Journal of Pharmaceutical Sciences |
Volume | 107 |
Issue number | 9 |
DOIs | |
Publication status | Published - Sept 2018 |
Keywords
- ion pairing
- lipid(s)
- poorly water-soluble drug(s)
- precipitation
- X-ray powder diffraction
Projects
- 2 Finished
-
Understanding and implications of formation of lipid nanostructures in milk
Boyd, B. (Primary Chief Investigator (PCI)) & Hawley, A. M. (Partner Investigator (PI))
Australian Research Council (ARC), Monash University, Australian Synchrotron (Australia)
1/01/16 → 31/12/19
Project: Research
-
ARC Centre of Excellence in Convergent Bio-Nano Science and Technology
Davis, T. (Primary Chief Investigator (PCI)), Boyd, B. (Chief Investigator (CI)), Bunnett, N. (Chief Investigator (CI)), Porter, C. (Chief Investigator (CI)), Caruso, F. (Chief Investigator (CI)), Kent, S. (Chief Investigator (CI)), Thordarson, P. (Chief Investigator (CI)), Kearnes, M. (Chief Investigator (CI)), Gooding, J. (Chief Investigator (CI)), Kavallaris, M. (Chief Investigator (CI)), Thurecht, K. J. (Chief Investigator (CI)), Whittaker, A. K. (Chief Investigator (CI)), Parton, R. (Chief Investigator (CI)), Corrie, S. R. (Chief Investigator (CI)), Johnston, A. (Chief Investigator (CI)), McGhee, J. (Chief Investigator (CI)), Greguric, I. D. (Partner Investigator (PI)), Stevens, M. M. (Partner Investigator (PI)), Lewis, J. S. (Partner Investigator (PI)), Lee, D. S. (Partner Investigator (PI)), Alexander, C. (Partner Investigator (PI)), Dawson, K. (Partner Investigator (PI)), Hawker, C. (Partner Investigator (PI)), Haddleton, D. (Partner Investigator (PI)), Thierry, B. (Chief Investigator (CI)), Prestidge, C. A. (Chief Investigator (CI)), Meyer, A. (Project Manager), Jones-Jayasinghe, N. (Project Manager), Voelcker, N. (Chief Investigator (CI)), Nann, T. (Chief Investigator (CI)) & McLean, K. (Partner Investigator (PI))
Australian Research Council (ARC), Monash University, University of Melbourne, University of New South Wales (UNSW), University of Queensland , University of South Australia, Monash University – Internal Faculty Contribution, University of Wisconsin Madison, Memorial Sloan Kettering Cancer Center, University of California System, University College Dublin, Imperial College London, University of Warwick, Sungkyunkwan University, Australian Nuclear Science and Technology Organisation (ANSTO) , University of Nottingham
30/06/14 → 29/06/21
Project: Research