Nanoemulsion composition of curcumin for the treatment of inflammatory bowel diseases

Abstract

Nanoemulsion composition for the treatment of inflammatory bowel diseases, comprising: a) 1.0% (w / w) curcumin as active pharmaceutical ingredient; b) 10.0% w / w Caprylic / Capric triglycerides as oil phase; c) 15.0% w / w Tween 80 as surfactant; d) 10.0% w / w PEG 400 as co-surfactant; e) 2.0% w / w lecithin as emulsifier; f) 2.0% w / w ethanol as a solubilizer; and g) distilled water qs to 100 w / w, h) wherein the composition forms a nanoemulsion having a mean particle size in the range of 90-120 nm and a polydispersity index of less than 0.3 and provides sustained curcumin release for at least 12 hours in simulated intestinal fluid.

Description

[0001] The present invention relates to the field of pharmaceutical and nutraceutical formulations, particularly to nanoemulsion-based drug delivery systems. More specifically, it relates to a curcumin-containing nanoemulsion composition developed for targeted and enhanced delivery in the treatment of inflammatory bowel disease (IBD).

[0002] Inflammatory bowel disease (IBD), which also includes Crohn's disease and ulcerative colitis, is a chronic and recurrent inflammation of the gastrointestinal tract that severely impacts patients' quality of life. Current treatment strategies rely largely on corticosteroids, immunosuppressants, and biologics, which are often associated with significant side effects, poor tolerability, and limited long-term efficacy. Furthermore, conventional medications do not effectively target oxidative stress and the inflammatory cascade at the cellular level, necessitating the search for safer and more effective therapeutic alternatives.

[0003] Curcumin, a natural polyphenol compound from turmeric, has been extensively studied for its potent anti-inflammatory, antioxidant, and immunomodulatory properties. Despite its potential benefits in the treatment of IBD, its clinical translation is hampered by its poor water solubility, rapid metabolism, and low bioavailability, which limit its absorption and therapeutic effect in the colon. Conventional oral curcumin formulations fail to reach the inflamed intestinal mucosa in sufficient concentrations, thus undermining its therapeutic promise in the treatment of IBD.

[0004] To address these challenges, the present invention provides a novel nanoemulsion composition of curcumin that enables improved solubility, stability, and targeted intestinal delivery. By reducing the particle size to the nanoscale, the formulation increases the surface area for absorption, improves mucosal penetration, and prolongs intestinal residence time. This approach addresses the critical limitations of curcumin's bioavailability while providing a nontoxic and effective alternative for the treatment and management of IBD.

[0005] The aim of the present disclosure is to improve one or more problems of the prior art or at least to provide a useful alternative.

[0006] The aim of the present disclosure is to improve the bioavailability of curcumin for effective treatment of inflammatory bowel diseases.

[0007] Another object of the present disclosure is to provide a nanoemulsion formulation with sustained curcumin release over extended periods of time.

[0008] A further aim of the present disclosure is to enable targeted delivery of curcumin to the intestinal mucosa.

[0009] A further aim of the present disclosure is to achieve high drug entrapment efficiency with minimal drug loss.

[0010] Another object of the present disclosure is to maintain the physical and chemical stability of the formulation during storage.

[0011] Another object of the present disclosure is to reduce the need for conventional IBD medications with harmful side effects.

[0012] Another object of the present disclosure is to ensure a uniform droplet size distribution for improved absorption and therapeutic effect.

[0013] Another objective of the present disclosure is to offer a herbal, non-toxic and patient-friendly alternative for the treatment of IBD.

[0014] Further objects and advantages of the present disclosure will become apparent from the following description, which is not intended to limit the scope of the present disclosure.

[0015] The present invention relates to a novel nanoemulsion formulation of curcumin for the effective treatment and management of inflammatory bowel diseases (IBD). It addresses the long-standing problems of curcumin's poor water solubility, limited gastrointestinal absorption, and rapid metabolism by formulating it into a stable, bioavailable, and targeted nanocarrier system suitable for oral administration.

[0016] One embodiment of the invention comprises a specific composition containing 1% (w / w) curcumin, 10% caprylic / capric triglyceride (MCT oil) as the oil phase, 15% Tween 80 as a surfactant, 10% PEG 400 as a co-surfactant, 2% lecithin as a stabilizer, and 2% ethanol as a solubilizer, with the remainder being 100% distilled water. This optimized ratio results in nano-sized droplets that enhance drug loading and mucosal absorption.

[0017] Another embodiment of the invention relates to the preparation method using high-speed homogenization followed by ultrasonic treatment with an amplitude of 60-80% for 10-15 minutes. This method ensures efficient reduction of the droplet size to an average of 95.6 nm with a narrow polydispersity index of 0.212, which is ideal for ensuring uniform release and stability.

[0018] Another aspect of the invention lies in its controlled-release capability. In vitro drug release studies showed that 85.6% of the curcumin was released in simulated intestinal fluid (pH 6.8) within 12 hours, indicating a sustained and long-lasting release profile ideal for chronic inflammatory diseases such as IBD, where continuous therapeutic coverage is required.

[0019] Another embodiment of the invention is the formulation, which exhibits a high entrapment efficiency of 98.2%, indicating effective incorporation of curcumin into the nanoemulsion system. This minimizes drug loss, increases bioavailability, and ensures optimal therapeutic delivery at the site of intestinal inflammation.

[0020] In another embodiment, the formulation exhibited a zeta potential of -32.4 mV, indicating strong electrostatic stability. This high surface charge prevents particle aggregation, thereby maintaining the colloidal stability of the nanoemulsion over extended periods during storage and gastrointestinal transit.

[0021] Another embodiment of the invention also demonstrated excellent storage stability. After 90 days of storage at 4°C and 25°C, there were no significant changes in particle size, drug content, or appearance, confirming that the formulation is physically and chemically stable under standard storage conditions.

[0022] Another aspect of the invention is that it provides a safe, effective and patient-friendly alternative to conventional IBD therapies such as corticosteroids and immunosuppressants.

[0023] The present invention relates to a novel nanoemulsion formulation of curcumin specifically developed for the treatment of inflammatory bowel diseases (IBD), including conditions such as Crohn's disease and ulcerative colitis. Curcumin, a natural anti-inflammatory and antioxidant compound derived from turmeric, has shown promise but suffers from poor water solubility and low gastrointestinal bioavailability. To overcome these limitations, curcumin is incorporated into a nanoemulsion system employing caprylic / capric triglyceride as the oil phase, Tween 80 and PEG 400 as surfactants and co-surfactants, as well as lecithin and ethanol to improve stability and solubilization. This nanoscale formulation ensures high drug entrapment efficiency, sustained release, and targeted delivery to the inflamed intestinal mucosa.The resulting system exhibits excellent stability, uniform particle size distribution, and effective colonic release, providing a safe, herbal, and patient-friendly alternative to conventional steroidal and immunosuppressive IBD treatments. EXAMPLE 1: Formulation Component Function Quantity (% w / w) Curcumin Pharmaceutical active ingredient 1.0% Caprylic / Capric triglyceride (MCT oil) oil phase carrier 10.0% Tween 80 (Polysorbate 80) Surfactant 15.0% PEG 400 (polyethylene glycol 400) co-surfactant 10.0% Lecithin stabilizer / emulsifier 2.0% Ethanol solubilizer (optional) 2.0% Distilled water Aqueous phase (qs up to 100%) 60.0% EXAMPLE 2: Preparation of nanoemulsion-based curcumin nanocarriers

[0024] First, the oil phase is prepared by dissolving 1.0 g of curcumin in 10.0 g of caprylic / capric triglyceride (MCT oil) with gentle stirring and gentle heating to 40-45 °C to ensure complete solubilization. In a separate container, a surfactant mixture is prepared by mixing 15.0 g of Tween 80 and 10.0 g of PEG 400 with 2.0 g of lecithin, which acts as a natural emulsifier to improve the stability and bioadhesive properties of the nanoemulsion. Optionally, 2.0 g of ethanol can be added to assist the initial dissolution of curcumin and reduce viscosity.

[0025] Once both the oil phase and the surfactant phase are ready, they are thoroughly mixed with continuous stirring for 15-20 minutes to create a pre-emulsion. This pre-emulsion is then slowly added dropwise to 60.0 g of distilled water (at room temperature) under high-speed mechanical stirring (10,000-12,000 rpm) over 10 minutes to form a coarse emulsion. The temperature is maintained at 30-35°C during this process to prevent curcumin degradation and promote uniform dispersion.

[0026] Finally, the coarse emulsion is subjected to high-energy ultrasound for 10-15 minutes using a sonicator (amplitude 60-80%, pulse 5 s on / 5 s off) to reduce the droplet size to the nanoscale (20-200 nm) and form a stable nanoemulsion. The resulting curcumin-loaded nanocarriers are then stored in light-protected vials at 4 °C. EXAMPLE 3: Particle size and polydispersity index (PDI)

[0027] To determine particle size and polydispersity index (PDI), a small volume of the nanoemulsion (1 ml) was diluted with 10 ml of distilled water and analyzed using a dynamic light scattering (DLS) instrument, such as a Malvern Zetasizer. The sample was placed in a disposable cuvette, and measurements were taken at 25 °C. The average particle diameter and PDI were recorded to assess droplet uniformity and dispersion quality, and to ensure suitability for mucosal absorption.

[0028] The results show that the optimized curcumin nanoemulsion had an average particle size of 95.6 nm, which is within the desirable nanometer range for efficient intestinal absorption. The polydispersity index (PDI) was 0.212, indicating a narrow size distribution and a homogeneous droplet population. These values ​​confirm the effectiveness of the surfactant-to-cosurfactant ratio and the use of high-energy ultrasound in producing a stable and uniform nanoemulsion suitable for therapeutic use. EXAMPLE 4: Zeta Potential

[0029] Zeta potential analysis was performed using the same DLS instrument equipped with a zeta cell. The nanoemulsion sample (1 mL) was diluted with 9 mL of deionized water and added to the zeta cell to measure the surface charge of the droplets. The measurement was performed at 25 °C to evaluate the electrostatic stability of the formulation. A zeta potential of more than ±30 mV indicates a physically stable nanoemulsion, as the droplets exhibit sufficient repulsion.

[0030] The results show that the zeta potential measurement yielded a value of -32.4 mV, indicating good electrostatic stabilization of the nanoemulsion. This negative surface charge prevents aggregation of the nanodroplets during storage and transport through the gastrointestinal tract. The use of Tween 80 and lecithin contributed to the negative zeta potential and ensured that the formulation remained physically stable over extended periods without phase separation. EXAMPLE 5: Drug content and entrapment efficiency

[0031] To determine the active ingredient content, 1 ml of the nanoemulsion was mixed with 10 ml of methanol to break the emulsion and completely dissolve the curcumin. The solution was filtered and analyzed by UV spectrophotometry at 420 nm against a methanol blank. The entrapment efficiency was calculated by comparing the amount of curcumin actually incorporated into the formulation (measured absorbance) with the theoretical amount originally added: Entrapment efficiency (%) = (actual drug concentration / theoretical drug concentration) × 100.

[0032] UV spectrophotometric analysis revealed that the formulation contained 98.2 mg of curcumin out of the originally used 100 mg, corresponding to an active ingredient content of 98.2%. The entrapment efficiency was calculated to be 98.2%, indicating that almost all of the curcumin was successfully encapsulated within the nanoemulsion droplets. This high efficiency can be attributed to the effective solubilization of curcumin in the oil phase and the stabilization provided by the surfactant system. EXAMPLE 6: In vitro release study

[0033] The release profile of curcumin from the nanoemulsion was investigated using a dialysis bag diffusion method. A specific volume of the nanoemulsion (2 mL) was placed into a presoaked dialysis membrane (MWCO 12,000-14,000 Da), sealed, and immersed in 100 mL of simulated intestinal fluid (pH 6.8) at 37 ± 0.5°C. The medium was continuously stirred at 100 rpm. At specific time intervals (e.g., 0.5, 1, 2, 4, 6, 8, 12, 24 hours), 5 mL samples were withdrawn and replaced with fresh buffer. The samples were analyzed spectrophotometrically at 420 nm to quantify the released curcumin.

[0034] The results show that approximately 85.6% of the total curcumin was released within 12 hours, indicating a sustained release profile suitable for chronic conditions such as inflammatory bowel disease. The nanosize of the droplets and the presence of PEG 400 contributed to maintaining a slow and controlled drug diffusion rate, supporting their use for prolonged therapeutic effects. EXAMPLE 7: Stability studies

[0035] Stability testing was performed by storing the nanoemulsion in sealed amber glass vials at various temperatures: 4°C (refrigerator), 25°C (room temperature), and 40°C (accelerated conditions). Samples were analyzed at intervals of 0, 15, 30, 60, and 90 days for changes in appearance, phase separation, particle size, PDI, and drug content. UV spectroscopy and DLS were used for quantitative assessment, while visual observations were recorded for physical stability, such as creaming or turbidity.

[0036] After 90 days of storage, the nanoemulsion remained physically and chemically stable at 4°C and 25°C, with no signs of phase separation, color change, or significant changes in particle size. At 4°C, the particle size remained at 96.3 nm and the drug content at 96.5%, while at 40°C, a slight increase in particle size to 112.3 nm and a slight decrease in the drug content to 91.4% were observed. Examples

[0037] 1.Nanoemulsion composition for the treatment of inflammatory bowel diseases, comprising: - 1.0% (w / w) curcumin as active pharmaceutical ingredient; - 10.0% w / w Caprylic / Capric triglycerides as oil phase; - 15.0% w / w Tween 80 as surfactant; - 10.0% w / w PEG 400 as co-surfactant; - 2.0% (w / w) lecithin as emulsifier; - 2.0% w / w ethanol as a solubilizer; and - distilled water qs to 100 w / w, wherein the composition forms a nanoemulsion with an average particle size in the range of 90-120 nm and a polydispersity index of less than 0.3 and provides sustained curcumin release for at least 12 hours in simulated intestinal fluid

Claims

[1] Nanoemulsion composition for the treatment of inflammatory bowel diseases, comprising: a) 1.0% (w / w) curcumin as active pharmaceutical ingredient; b) 10.0% w / w Caprylic / Capric triglycerides as oil phase; c) 15.0% w / w Tween 80 as surfactant; d) 10.0% w / w PEG 400 as co-surfactant; e) 2.0% w / w lecithin as emulsifier; f) 2.0% w / w ethanol as a solubilizer; and g) distilled water qs to 100 w / w, h) wherein the composition forms a nanoemulsion having a mean particle size in the range of 90-120 nm and a polydispersity index of less than 0.3 and provides sustained curcumin release for at least 12 hours in simulated intestinal fluid. [2] The composition of claim 1, wherein the nanoemulsion has a zeta potential in the range of -30 to -35 mV to ensure electrostatic stabilization and physical stability. [3] The composition of claim 1, wherein the entrapment efficiency of curcumin in the nanoemulsion is greater than 95%. [4] The composition of claim 1, wherein the curcumin is completely solubilized in the oil phase prior to emulsification. [5] The composition of claim 1, wherein the nanoemulsion is prepared by high-speed homogenization followed by ultrasonication at 60-80% amplitude for 10-15 minutes. [6] The composition of claim 1, wherein the release of curcumin in simulated intestinal fluid at pH 6.8 is at least 80% over a period of 12 hours [7] The composition of claim 1, wherein the nanoemulsion remains stable for a period of at least 90 days when stored at 4°C and 25°C without significant change in particle size, drug content or phase separation.