Self-emulsifying drug delivery systems: Impact of stability of hydrophobic ion pairs on drug release

Nazir, Imran; Asim, Mulazim Hussain; Dizdarević, Aida; Bernkop‐Schnürch, Andreas

doi:10.1016/j.ijpharm.2019.03.001

Cited by 51 publications

(25 citation statements)

References 32 publications

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“…The release of drug from the SEDDS mainly depended on the distribution coefficient and the stability of the ionic complexes. 13 , 38 More stable ionic complexes dissociate slowly over time, leading to a sustained drug release from the oily droplets. Drug release as a function of the drug to counterion charge ratio has also been described by Lu et al 39 Briefly, the strength of ionic complexes depended on the charge ratio of the drug to the counterion.…”

Section: Resultsmentioning

confidence: 99%

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

et al. 2020

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The aim of this study was to develop hydrophobic ionic drug polymer complexes in order to provide sustained drug release from self-emulsifying drug delivery systems (SEDDS). Captopril (CTL) was used as an anionic model drug to form ionic complexes with the cationic polymers Eudragit RS, RL, and E. Complexes of polymer to CTL charge ratio 1:1, 2:1, and 4:1 were incorporated in two SEDDS, namely FA which was 40% Kolliphor RH 40, 20% Kolliphor EL, and 40% castor oil and FB, which was 40% Kolliphor RH 40, 30% glycerol, 15% Kolliphor EL, and 15% castor oil. Blank and complex loaded SEDDS were characterized regarding their droplet size, polydispersity index (PDI), and zeta potential. Resazurin assay was performed on Caco-2 cells to evaluate the biocompatibility of SEDDS. Release of CTL from SEDDS was determined in release medium containing 0.2 mg/mL of 5,5′-dithiobis(2-nitrobenzoic acid) (DNTB) allowing quantification of free drug released into solution via a thiol/disulfide exchange reaction between CTL and DNTB forming a yellow dye. The droplet size of SEDDS FA and SEDDS FB were in the range of 100 ± 20 nm and 40 ± 10 nm, respectively, with a PDI < 0.5. The zeta potential of SEDDS FA and SEDDS FB increased after the incorporation of complexes. Cell viability remained above 80% after incubation with SEDDS FA and SEDDS FB in a concentration of 1% and 3% for 4 h. Without any polymer, CTL was entirely released from both SEDDS within seconds. In contrast, the higher the cationic lipophilic polymer to CTL ratio in SEDDS, the more sustained was the release of CTL. Among the polymers which were evaluated, Eudragit RL provided the most sustained release. SEDDS FA containing Eudragit RL and CTL in a ratio of 1:1 released 64.78 ± 8.28% of CTL, whereas SEDDS FB containing the same complex showed a release of 91.85 ± 1.17% within 1 h. Due to the formation of lipophilic ionic polymer complexes a sustained drug release from oily droplets formed by SEDDS can be achieved. Taking into account that drugs are otherwise instantly released from SEDDS, results of this study might open the door for numerous additional applications of SEDDS for which a sustained drug release is essential.

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Section: Resultsmentioning

confidence: 99%

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

et al. 2020

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“…Log P n-butanol/water determination of INS-surfactant complexes was carried out according to a procedure reported by Nazir et al 25 Complexes with a molar ratio (INS:surfactant) of 1:3 for HL, 1:4 for CL, 1:2 for OL and 1:4 for DL were selected, as these molar ratios resulted in the highest precipitation efficacies. 500 mL of water and 500 mL of n-butanol were added to 1 mg of each complex as well as to INS.…”

Section: Determination Of Log P N-butanol/water Of Insulin-surfactantmentioning

confidence: 99%

Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring

Kurpiers

Wolf

Spleis

et al. 2021

Journal of Pharmaceutical Sciences

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The aim of this study was to evaluate biodegradable cationic surfactants based on lysine. Methods: Lysine was esterified with cholesterol, oleyl alcohol and 1-decanol resulting in cholesteryl lysinate (CL), oleyl lysinate (OL) and decyl lysinate (DL). Esters were investigated regarding their log D noctanol/water , critical micelle concentration (CMC) and biodegradability. Hemolytic potential of CL, OL, DL and the already established hexadecyl lysinate (HL) was determined and complexes with insulin (INS) were formed by hydrophobic ion pairing (HIP). Lipophilic characteristics of ion-pairs were examined by analyzing their log P n-butanol/water. Results: Successful synthesis of CL, OL and DL was confirmed by IR, NMR and MS. Log D analysis revealed amphiphilic properties for the esters and a CMC of 0.01 mM, 2.0 mM and 6.0 mM was found for CL, OL and DL, respectively. Biodegradability was proven, as over 99% of OL and DL were degraded by isolated enzymes within 30 min and after 3 h 97% of CL was cleaved by membrane bound enzymes. OL as well as DL displayed no hemolytic effect and for CL cytotoxicity was significantly reduced in comparison to HL. INS/CL complex exhibited highest lipophilicity. Conclusion: Cholesterol-amino acid based surfactants seem to be promising agents for HIP.

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“…Oleic acid 38,89 Oil in water (o/w) nanoemulsication solvent extraction to form PLA-PEG NPs using in situ HIP 38,89 1-Hydroxy-2-naphthoic acid 38,89 Cholic acid 38,89 Sodium deoxycholate 38 Docusate sodium 38,89 56 Double emulsion 56 CM-PEG 56 Single emulsion 56 Sodium dodecyl sulfate 56 Taurocholic acid 56 Sodium docusate 56 Double emulsion 56 Single emulsion 56 SEDDS 169 Dextran sulfate 91 Solid in oil in water (S/O/W) to form PLGA NPs 91 Sodium deoxycholate 165 SEDDS 165 Sodium laurate 165 Sodium stearoyl glutamate 165 Pamoic acid disodium 165 Bromothymol blue Tetrabutylammonium bromide 66 Encapsulated into polystyrene microparticles using compressed carbon dioxide 66 Tetrahexylammonium bromide 66 Tetraoctylammonium bromide 66…”

Section: Azd2811mentioning

confidence: 99%

“…Arginine-nonyl ester 41 Idarubicin Dextran sulfate 95 Warm wax microemulsion solvent evaporation 95 Homogenization and stabilization with SDS 53 Dimyristoyl phosphatidyl glycerol 42 SNEDDS 42 Oleic acid 58,102,162 S/O/W emulsion 58 PLGA NPs by emulsion solvent diffusion 102,162 Pamoic acid disodium 165 SEDDS 165 Sodium laurate 165 Sodium stearoyl glutamate 165 Sodium deoxycholate 80,93,165 PLGA NPs by emulsion solvent diffusion 93 S/O/W emulsion 80 SEDDS 165 Sodium docusate 84,86 SEDDS 86 Stearic acid coacervation 84 Sodium dodecyl sulfate 49,84,111,177,178 Stearic acid coacervation 84 PLGA NPs by emulsion solvent diffusion 111,177,178 Electrospray with stearic or pamoic acid 49 Irinotecan Sodium docusate 98 Sodium stearyl sulfate 98 Taurocholic acid 98…”

Section: Doxorubicinmentioning

confidence: 99%

“…Oleic acid 94,101 PLGA microspheres by O/W emulsion 101 SMEDDS 94 Sodium deoxycholate 165 SEDDS 165 Sodium laurate 165 Sodium stearoyl glutamate 165 Pamoic acid disodium 165 Sodium docusate 45,84,86,172 SEDDS 45,86 Stearic acid coacervation 84 Oligosaccharide ester microparticles by spray drying 172 Solid lipid nanoparticles and nanostructured lipid carriers by high pressure homogenization 110 Sodium dodecyl sulfate 11,84 Stearic acid coacervation 84 Hydrogen bonding complexation between polyacrylic acid and Pluronic F68 (ref. 11) Sodium stearate 87 Solid lipid NPs by: solvent diffusion 87 Oil-in-oil (O/O) emulsion-evaporation 87 Loperamide 56 Single emulsion 56 CM-PEG 56 Double emulsion 56 Single emulsion 56 Dextran sulfate 59 Emulsion solvent diffusion 59 Oleic acid 57,58 PLGA NPs by emulsion diffusion 57 S/O/W emulsion 58 Sodium docusate 56 Double emulsion 56 Single emulsion 56 Sodium dodecyl sulfate 18,57 PLGA NPs by emulsion diffusion 57 when one species is only partially ionized.…”

Section: Leuprolidementioning

confidence: 99%

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Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

2019

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Self-emulsifying drug delivery systems: Impact of stability of hydrophobic ion pairs on drug release

Cited by 51 publications

References 32 publications

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

Self-Emulsifying Drug Delivery Systems: Hydrophobic Drug Polymer Complexes Provide a Sustained Release in Vitro

Lysine-Based Biodegradable Surfactants: Increasing the Lipophilicity of Insulin by Hydrophobic Ion Paring

Hydrophobic ion pairing: encapsulating small molecules, peptides, and proteins into nanocarriers

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