Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme

For many years, researchers have been making efforts to find a manufacturing technique, as well as a drug delivery system, that will allow for oral delivery of biopharmaceuticals to their target site of action without impairing their biological activity. Due to the positive in vivo outcomes of this formulation strategy, self-emulsifying drug delivery systems (SEDDSs) have been intensively studied in the last few years as a way of overcoming the different challenges associated with the oral delivery of macromolecules. The purpose of the present study was to examine the possibility of developing solid SEDDSs as potential carriers for the oral delivery of lysozyme (LYS) using the Quality by Design (QbD) concept.

LYS was successfully ion paired with anionic surfactant, sodium dodecyl sulphate (SDS), and this complex was incorporated into a previously developed and optimized liquid SEDDS formulation comprising medium-chain triglycerides, polysorbate 80, and PEG 400. The final formulation of a liquid SEDDS carrying the LYS:SDS complex showed satisfactory in vitro characteristics as well as self-emulsifying properties (droplet size: 13.02 nm, PDI: 0.245, and zeta potential: −4.85 mV). The obtained nanoemulsions were robust to dilution in the different media and highly stable after 7 days, with a minor increase in droplet size (13.84 nm) and constant negative zeta potential (−0.49 mV). An optimized liquid SEDDS loaded with the LYS:SDS complex was further solidified into powders by adsorption onto a chosen solid carrier, followed by direct compression into self-emulsifying tablets. Solid SEDDS formulations also exhibited acceptable in vitro characteristics, while LYS preserved its therapeutic activity in all phases of the development process. On the basis of the results gathered, loading the hydrophobic ion pairs of therapeutic proteins and peptides to solid SEDDS may serve as a potential method for delivering biopharmaceuticals orally.

2.1. Materials

Lyophilized LYS from chicken egg white (Mw: 14.3 kDa) (MedChemExpress, Monmouth, NJ, USA) was used as a model protein. Lyophilized Micrococcus lysodeikticus (Sigma-Aldrich, St. Louis, MO, USA) was used as Gram-positive bacteria to investigate LYS enzymatic activity. Sodium dodecyl sulphate (SDS) (Molar Chemicals Ltd., Budapest, Hungary) was used as counterion for HIP and sodium hydroxide and hydrochloric acid (Ph. Eur.) as pH adjusters. Tween 80^® (polysorbate 80) (Merk KgaA, Darmstadt, Germany), PEG 400 (polyethylene glycol 400) (Molar Chemicals Ltd., Budapest, Hungary), and Miglyol 812^® (medium-chain triglycerides) (Sasol Germany GmbH, Witten, Germany) were used in preparation of liquid SEDDS. Neusilin^® UFL2 (magnesium aluminometasilicate) (Fuji Chemical Industries Co., Ltd. Kamiichi, Nakaniikawa, Toyama, Japan), Syloid^® 244 FP, and Syloid^® AL-1 FP (Grace Davison, Worms, Germany) were used as solid carriers in preparation of solid SEDDS. Vivapur 102^® (microcrystalline cellulose) and Vivasol^® (croscarmellose sodium) (JRS PHARMA GmbH & Co. KG, Rosenberg, Germany) were used in tablet formulation as diluent and disintegration agents, respectively. Salts used to prepare the phosphate buffer as well as all the other reagents were of analytical grade.

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Šahinović, M.; Hassan, A.; Kristó, K.; Regdon, G., Jr.; Vranić, E.; Sovány, T. Quality by Design-Based Development of Solid Self-Emulsifying Drug Delivery System (SEDDS) as a Potential Carrier for Oral Delivery of Lysozyme. Pharmaceutics 2023, 15, 995.
https://doi.org/10.3390/pharmaceutics15030995