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 - Sep 2018 |
Keywords
- ion pairing
- lipid(s)
- poorly water-soluble drug(s)
- precipitation
- X-ray powder diffraction
Cite this
}
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. / Khan, Jamal; Rades, Thomas; Boyd, Ben J.
In: Journal of Pharmaceutical Sciences, Vol. 107, No. 9, 2420-2427, 09.2018.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - 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
AU - Khan, Jamal
AU - Rades, Thomas
AU - Boyd, Ben J.
PY - 2018/9
Y1 - 2018/9
N2 - 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.
AB - 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.
KW - ion pairing
KW - lipid(s)
KW - poorly water-soluble drug(s)
KW - precipitation
KW - X-ray powder diffraction
UR - http://www.scopus.com/inward/record.url?scp=85049355002&partnerID=8YFLogxK
U2 - 10.1016/j.xphs.2018.04.030
DO - 10.1016/j.xphs.2018.04.030
M3 - Article
VL - 107
JO - Journal of Pharmaceutical Sciences
JF - Journal of Pharmaceutical Sciences
SN - 0022-3549
IS - 9
M1 - 2420-2427
ER -