Addition of Cationic Surfactants to Lipid-Based Formulations of Poorly Water-Soluble Acidic Drugs Alters the Phase Distribution and the Solid-State Form of the Precipitate Upon In Vitro Lipolysis

Research output: Contribution to journalJournal articleResearchpeer-review

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 languageEnglish
JournalJournal of Pharmaceutical Sciences
Issue number9
Pages (from-to)2420-2427
Number of pages8
Publication statusPublished - Sep 2018

Bibliographical note

Funding Information:
This work was funded under the Australian Research Council Discovery Grant Scheme ( DP160102906 ).

Publisher Copyright:
© 2018 American Pharmacists Association®

    Research areas

  • ion pairing, lipid(s), poorly water-soluble drug(s), precipitation, X-ray powder diffraction

ID: 299413077