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

Abstract

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.

Gelatin-Graphene Oxide Nanocomposite Hydrogels for Kluyveromyces lactis Encapsulation: Potential Applications in Probiotics and Bioreactor Packings

“…Polymeric materials, particularly hydrogels, have been described as the preferred choice due to characteristics such as hydrophilic porous matrix, flexibility, high biocompatibility and biodegradability, prolonged consistency, userfriendliness, low cost, and ease of access [20][21][22]. To aid in finding its optimal parameters, there have been several experimental and in silico studies that confirm a strong dependency on solubility, high degree of functional design space, surface multivalency, facile chemical modification, high stability, and ease of integration with other materials such as lipids and nanoparticles [23][24][25][26]. For instance, Mdlovu et al designed a magnetic nanocarrier composed of iron oxide magnetic nanoparticles coated with Pluronic F127 for the delivery of the chemotherapeutic drug doxorubicin (DOX) in neuroblastoma where the drug release profile showed a pH-dependent drug release where more DOX was released under acidic environments than in neutral conditions [27].…”

A deep eutectic-based, self-emulsifying subcutaneous depot system for apomorphine therapy in Parkinson’s disease

“…Self-emulsifying drug delivery systems (SEDDS) are homogeneous mixtures of oils, surfactants, and cosolvents that emulsify upon aqueous dilution to improve lipophilic drug solubility, absorption, and controlled release ( 28 , 29 ). The majority of SEDDS have been developed to increase oral bioavailability, including FDA-approved Sandimmune Neoral.…”

The Evaluation of Drug Delivery Nanocarrier Development and Pharmacological Briefing for Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…The use of GRAS-type excipients with the least possible surfactant and cosurfactant (or co-solvent) ratios should be taken into consideration to assure that the final formulation is cytocompatible. As with other lipid-based formulations, the particle size relies on the excipients’ hydrophile–lipophile balance (HLB) value, where it is usually found that the higher the HLB value is, the lower the PS and Đ are, while the ZP charge is usually negative due to the presence of anionic surfactants and fatty acids unless specific lipids that grant the positive charge to the developed system are specifically employed, such as cationic surfactants, namely, tertiary amine surfactant, oleylamine, and the quaternary ammonium surfactants or polymers (e.g., Eudragit RS or RL) [ 196 , 197 ]. Incipient reports suggested that SEDDs could increase materials’ liver uptake [ 198 , 199 ], with further studies recommended on the cytocompatibility and mechanism behind such increment.…”