Formulation and Evaluation of a Nanoemulsion-Based Drug Delivery System to Enhance the Oral Performance of Curcumin

Abstract

Poor aqueous solubility limits the in vitro dissolution performance of many drugs, among them curcumin which is a bioactive compound with great therapeutic potential but with poor dissolution in gastrointestinal fluids. This study aimed to develop a curcumin nanoemulsion to improve in vitro dissolution performance and physicochemical stability of the curcumin solution. Nanoemulsions were made with the following three emulsifiers: Capryol ® 90, Tween ®80, and polysorbate 400 (PEG 400), and were characterized by measuring droplet size, polydispersity index, and zeta potential. In vitro dissolution performance was evaluated and compared with that of pure curcumin and physical stability was studied under different storage conditions. Data visualization techniques were used to bring integration of formulation attributes. The optimized nanoemulsion had a nanoscale droplet size in a narrow distribution with sufficient electrostatic stability. For nanoemulsion, dissolution efficiency was found to be significantly increased in vitro compared to pure curcumin in all time points, and the optimized formulation tested showed greater and consistent performance. Stability evaluation showed little variation in size under normal storage conditions, with an anticipated size increase at high temperature. In conclusion, the nanoemulsion system enhanced the dissolution behaviour of curcumin to a great extent with an acceptable physicochemical stability, and may therefore support its potential as an oral delivery platform for poorly water-soluble drugs.

Introduction

The most common way of drug administration is oral administration due to its convenient, non-invasive way of administration and because it usually complies with high patient adherence. However, it has been observed that oral delivery of most of the active pharmaceutical ingredient (APIs) is limited by a poor level of aqueous solubility and, hence, a slow rate of dissolution in the gastrointestinal (GI) fluids resulting in low and unpredictable absorption. The problem is very widespread in the contemporary drug development; a significant proportion of approved drugs, and even a higher percentage of development candidates are poorly soluble in water, solubility improvement has been a consistent concern among formulation scientists [1].

A wide variety of formulation strategies have been developed for enhancing dissolution and oral bioavailability of poorly water-soluble drugs, including cosolvents, solubilization using surfactants, salt formations and cyclodextrin complexes, amorphous solid dispersions and lipid-based carriers [2]. Recent comprehensive reviews highlight the need to select between these approaches based on the physicochemical properties of the drug (e.g. lipophilicity, melting point, and crystallinity), the desired dosage form and the possibility of obtaining clinical translation. Among the modern alternatives, lipid-based systems (self-emulsifying systems and nano-enabled lipids) are being continuously mentioned as viable alternative platforms for solubilizing hydrophobic compounds and enhancing their oral absorption potential [3].

Nanoemulsions are kinetically stable, colloidal dispersions (usually oil in water for oral administration), in which the internal phase is dispersed as drops in the nanometer size range. Their pharmaceutical relevance is highly related to (i) high interfacial surface area, (ii) efficient solubilization of lipophilic payloads in the oil phase and (iii) the capacity to present the drug in a pre-solubilized form which has the potential to enhance apparent dissolution and absorption processes. Recent reviews however also highlight that the performance of nanoemulsions is critically dependent on the formulation composition (oil/surfactant/co-surfactant choice) and manufacturing method (high energy techniques (ultrasonication or high pressure homogenization) or low energy methods), as those factors govern the droplet size distribution, physical stability and drug loading capacity. To this end, physicochemical characterization, in particular, droplet size, polydispersity index (PDI) and zeta potential are still considered to be the keys to stability prediction, as well as to reproducible oral delivery conduct [4].

Curcumin (a polyphenol constituent of Curcuma longa) is a popularly studied bioactive component has been widely investigated for its reported anti-inflammatory, antioxidant, and anticancer. Though such pharmacological promise exists, the oral translation of curcumin is limited by its very low aqueous solubility and low stability in GI-relevant conditions and is rapidly bio transformed, and such characteristics represent major barriers to achieving adequate systemic exposure following conventional oral dosing of curcumin [5]. A recent systematic review on advanced oral delivery systems for curcumin concluded that nano- and micro-scale carrier systems (lipid-based approaches, among others) are commonly used to improve the bioavailability of curcumin after oral administration, when compared with unformulated curcumin, but also highlighted that formulation development and evaluation is not always optimized and that formulations vary greatly[ 6]. To add to this, an oral curcumin methodological review of systematic reviews that paid particular attention to the bioavailability differences between products was identified in the year 2024 as a determinant of observed results – although not always well managed in evidence synthesis – with a need to have rigorously characterised and reproducible formulations to achieve publishable and interpretable results [6].

In lipid-based system, nano primal formation and glibness on dilution in GI fluids are highly dependent on bilayer selection of excipients. Studies involving self-nanoemulsifying systems (closely related to nanoemulsions formed in situ on aqueous dispersion) indicate that the use of medium-chain lipid excipients and non-ionic surfactants are often preferred because they can offer high solubilization capacity of the drug and high emulsification speed, resulting in small droplet sizes and narrow size distribution under optimized conditions [7]. Likewise, studies of curcumin focused nanoemulsion have shown that stability can be condition-dependent (for example, studies of the effects of pH on the state of interfacial charge and the integrity of droplets) to support the case of studying nanoemulsion formulations under multiple storage and GI relevant conditions as opposed to a single time point or environment [8].

Despite extensive research on nanoemulsion-based systems in order to improve the delivery of curcumin to the oral cavity, the formulation performance is strongly determined by the choice of excipients and, therefore, the resulting physicochemical profile. In this regard, the nanoemulsion systems, precisely made up of Capryol® 90 (oil phase) and Tween® 80 (surfactant) and PEG400 (co-surfactant), are under-characterized, especially with regard to the integrated evaluation of (i) dissolution enhancement and (ii) physicochemical stability under various storage conditions. This restriction of the available conclusions to formulation-specific applications demonstrates that a systematic formulation and evaluation scheme is necessary for this combination of ingredients. Can a curcumin nanoemulsion loaded with Capryol® 90, Tween® 80 and PEG 400 improve in vitro dissolution performance, while having acceptable physicochemical stability for oral delivery?

The current experiment is intended to design and test a nanoemulsion with curcumin. Particularly, the research is aimed at the creation of curcumin nanoemulsions with the help of high-energy emulsification, the description of their physicochemical characteristics in terms of droplet size, polydispersity index (PDI), and zeta potential, and the comparison between the in vitro outcomes of nanoemulsions in terms of the dissolution of pure curcumin. Besides, physical stability of the formulations in varying storage conditions is investigated. Lastly, formulation performance is graphically visualized using integrative graphical techniques that do not have the redundancy effect.

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Materials

As the model poorly water-soluble compound, curcumin was used. Capryol® 90 (oil phase), Tween® 80 (surfactant) and PEG 400 (co-surfactant) were chosen as the major formulation components, and all of them are of pharmaceutical grade. Capryol® 90 consists mainly of propylene glycol mono caprylate (C8) mono esters, and it is often chosen as lipid excipient in oral lipid-based delivery systems because of its suitability in solubilization of lipophilic drugs [9].

Tween® 80 (as a non-ionic surfactant), PEG 400 as the hydrophilic co-surfactant were used to aid in the formation of fine dispersions, and in the stabilization of the interface. Similar surfactant/co-surfactant strategies (also in the form of Tween® and PEG combinations), are often reported in nanoemulsion/SNEDD’s formulation frameworks [9]. particularly when aiming to achieve droplet sizes in the nanometer range and acceptable distribution uniformity [10].

Purified (deionized) water was used for nanoemulsion preparation as well as dilution steps (aqueous phase). The materials were all stored and handled in accordance with the recommendations of the manufacturers [11].

Dissolution profiles were statistically analyzed using two-way ANOVA (formulation × time) followed by Sidak/Tukey multiple comparisons test. Significance was set at p < 0.05.

Source: Oday Sajjad Alsawad, Ahmed Abduljabbar, Journal of NAnostructures, Formulation and Evaluation of a Nanoemulsion-Based Drug Delivery System to Enhance the Oral Performance of Curcumin, Volume 16, Issue 4, October 2026, Pages 5017-5026, doi: 10.22052/JNS.2026.04.045