A Customized Screening Tool Approach for the Development of a Self-Nanoemulsifying Drug Delivery System (SNEDDS)

The present study focused on establishing a novel, (pre-)screening approach that enables the development of promising performing self-nanoemulsifying drug delivery systems (SNEDDSs) with a limited number of experiments. The strategic approach was based on first identifying appropriate excipients (oils/lipids, surfactants, and co-solvents) providing a high saturation solubility for lipophilic model compounds with poor aqueous solubility. Excipients meeting these requirements were selected for SNEDDS development, and a special triangular mixture design was applied for determining excipient ratios for the SNEDDS formulations. Celecoxib and fenofibrate were used as model drugs.

Formulations were studied applying a specific combination of in vitro characterization methods. Specifications for a promising SNEDDS formulation were self-imposed: a very small droplet size (< 50 nm), a narrow size distribution of these droplets (PDI < 0.15) and a high transmittance following SNEDDS dispersion in water (> 99% in comparison with purified water). Excipients that provided a nanoemulsion after dispersion were combined, and ratios were optimized using a customized mapping method in a triangular mixture design. The best performing formulations were finally studied for their in vitro release performance. Results of the study demonstrate the efficiency of the customized screening tool approach. Since it enables successful SNEDDS development in a short time with manageable resources, this novel screening tool approach could play an important role in future SNEDDS development.

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Schmied, FP., Bernhardt, A., Engel, A. et al. A Customized Screening Tool Approach for the Development of a Self-Nanoemulsifying Drug Delivery System (SNEDDS). AAPS PharmSciTech 23, 39 (2022). https://doi.org/10.1208/s12249-021-02176-7

Materials

Celecoxib and fenofibrate were used as model drug substances. Celecoxib was obtained from Aarti Drugs Ltd. (Mumbai, India) and fenofibrate from D.K. Pharma Chem PVT Ltd. (Maharashtra, India). Polyoxyethylene (80) sorbitan monooleate (Tween^® 80), d-α-tocopherol polyethylene glycol 1000 succinate (d-TPGS, Tocophersolan), isopropyl myristate (IPM-100), polyoxyl-(23) lauryl ether (Brij^® 35), castor oil, oleic acid, corn oil, olive oil, peanut oil, soybean oil, polyoxyl-40 hydrogenated castor oil (Cremophor^® RH 40), sorbitan sesquioleate (Span^® 83), polyoxyethylene sorbitan monolaurate (Tween^® 20), and tetraethylene glycol (Tetra EG) were purchased from Sigma Aldrich (Steinheim, Germany). Lauroyl polyoxyl-32 glycerides (Gelucire^® 44/14), oleoyl polyoxyl-6 glycerides (Labrafil^® M 1944 CS), linoleoyl polyoxyl-6 glycerides (Labrafil^® M 2125 CS), caprylocaproyl polyoxyl-8 glycerides (Labrasol^®), propylene glycol monolaurate (type II) (lauroglycol™ 90), propylene glycol monolaurate (type I) (Lauroglycol™ FCC), glyceryl monolinoleate (Maisine™ CC), glyceryl monooleate (Peceol™), polyglyceryl-3 dioleate (Plurol^® Oleique CC 497), glyceryl tricaprylate/tricaprate (Labrafac™ lipophile WL 1349), propylene glycol dicaprylate/dicaprate (Labrafac™ PG) and diethylene glycol monoethyl ether (Transcutol^® HP) were kindly donated by Gattefossé S.A.S (Saint Priest, France). Medium-chain triglycerides (Miglyol^® 812) and polyethylene glycol 400 were obtained from Caesar & Loretz GmbH (Hilden, Germany). Ethyl oleate (Crodamol™ EO), sorbitan monolaurate (Span^® 20), sorbitan monooleate (Span^® 80) and propane-1,2,3-triol were provided by Merck KGaA (Darmstadt, Germany). Polyoxyl-35 hydrogenated castor oil (Kolliphor^® EL) and polyoxyl-15 hydroxystearate (Kolliphor^® HS 15) were obtained from BASF SE (Ludwigshafen, Germany). Propylene glycol was purchased from VWR International GmbH (Darmstadt, Germany). Fish oil (EPA/DHA) is an in-house product of Evonik Operations GmbH (Hanau, Germany). All other chemicals and solvents were of analytical grade and purchased commercially.