Abstract
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.Graphical abstract
Highlights
The majority of new drug candidates in current research and development pipelines are associated with poor aqueous solubility
The aim of the present study was to establish a novel and tailored screening tool approach for the initial, rapid development of promising self-nanoemulsifying drug delivery systems (SNEDDSs) formulations which should be based on the triangular mixture design and provide SNEDDS mixtures that fit with a set of selfimposed specifications such as providing very small nanodroplets (< 50 nm) that are narrowly distributed (polydispersity index (PDI) < 0.15) and provide a highly translucent (> 99%), stable nanoemulsion after dispersion in aqueous fluids
First, to each SNEDDS sample was added 10–15 ml mobile phase described in the sections “high-performance liquid chromatography (HPLC) Method for Analyzing Celecoxib” and “HPLC Method for Analyzing Fenofibrate”, and the mixture was subjected to ultrasonic treatment for 5 min
Summary
The majority of new drug candidates in current research and development pipelines are associated with poor aqueous solubility. The aqueous solubility of “grease ball” molecules is substantially limited by their pronounced lipophilic character (LogP > 3), while “brick dust” molecules are characterized by very high melting points (Tm > 200 °C) resulting in a high crystal lattice energy that severely impedes the drugs’ solubility behavior [5, 6]. In view of this growing number of poorly soluble drug candidates, it is proving necessary to establish formulation approaches to counteract the solubility issues of these drugs. The variety of components that can be used for SNEDDS reveals the complexity of these systems and the
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