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 journal › Journal article › Research › peer-review

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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, 09.2018, p. 2420-2427.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Khan, J, Rades, T & Boyd, BJ 2018, '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', Journal of Pharmaceutical Sciences, vol. 107, no. 9, pp. 2420-2427. https://doi.org/10.1016/j.xphs.2018.04.030

APA

Khan, J., Rades, T., & Boyd, B. J. (2018). 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. Journal of Pharmaceutical Sciences, 107(9), 2420-2427. https://doi.org/10.1016/j.xphs.2018.04.030

Vancouver

Khan J, Rades T, Boyd BJ. 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. Journal of Pharmaceutical Sciences. 2018 Sep;107(9):2420-2427. https://doi.org/10.1016/j.xphs.2018.04.030

Author

Khan, Jamal ; Rades, Thomas ; Boyd, Ben J. / 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. In: Journal of Pharmaceutical Sciences. 2018 ; Vol. 107, No. 9. pp. 2420-2427.

Bibtex

@article{4d711dd4217d473ba52d11227a0f041c,
title = "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",
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.",
keywords = "ion pairing, lipid(s), poorly water-soluble drug(s), precipitation, X-ray powder diffraction",
author = "Jamal Khan and Thomas Rades and Boyd, {Ben J.}",
note = "Funding Information: This work was funded under the Australian Research Council Discovery Grant Scheme ( DP160102906 ). Publisher Copyright: {\textcopyright} 2018 American Pharmacists Association{\textregistered}",
year = "2018",
month = sep,
doi = "10.1016/j.xphs.2018.04.030",
language = "English",
volume = "107",
pages = "2420--2427",
journal = "Journal of Pharmaceutical Sciences",
issn = "0022-3549",
publisher = "Elsevier",
number = "9",

}

RIS

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.

N1 - Funding Information: This work was funded under the Australian Research Council Discovery Grant Scheme ( DP160102906 ). Publisher Copyright: © 2018 American Pharmacists Association®

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 - Journal article

C2 - 29859958

AN - SCOPUS:85049355002

VL - 107

SP - 2420

EP - 2427

JO - Journal of Pharmaceutical Sciences

JF - Journal of Pharmaceutical Sciences

SN - 0022-3549

IS - 9

ER -

ID: 299413077