Curcumin-loaded self-nanomicellizing solid dispersion system: part I: development, optimization, characterization, and oral bioavailability

Abstract

Curcumin (CUR) is considered as one of the most bioactive molecules ever discovered from nature due to its proven anti-inflammatory and antioxidant in both preclinical and clinical studies. Despite its proven safety and efficacy, the clinical translation of CUR into a useful therapeutic agent is still limited due to its poor oral bioavailability. To overcome its limitation and enhance oral bioavailability by improving its aqueous solubility, stability, and intestinal permeability, a novel CUR formulation (NCF) was developed using the self-nanomicellizing solid dispersion strategy. From the initial screening of polymers for their potential to improve the solubility and stability, Soluplus (SOL) was selected. The optimized NCF demonstrated over 20,000-fold improvement in aqueous solubility as a result of amorphization, hydrogen bonding interaction, and micellization determined using differential scanning calorimetry, X-ray diffraction, scanning electron microscopy, Fourier transform infrared spectroscopy, nuclear magnetic resonance, dynamic light scattering, and transmission electron microscopy. Moreover, the greater stabilizing effect in alkaline pH and light was observed. Furthermore, significant enhancement of dissolution and permeability of CUR across everted sacs of rat small intestine were noticed. Pharmacokinetic studies demonstrated that the oral bioavailability of CUR was increased 117 and 17-fold in case of NCF and physical mixture of CUR and SOL compared to CUR suspension. These results suggest NCF identified as a promising new approach for repositioning of CUR for pharmaceutical application by enhancing the oral bioavailability of CUR. The findings herein stimulate further in vivo evaluations and clinical tests of NCF.

Formulation and Optimization of Curcumin Solid Dispersion Pellets for Improved Solubility

“…The solid dispersion formulation showed mean size of micelles in the range 721.4 to 1311.7 nm and PDI in range 0.409 to 1.612. Parikh et al [15] reported similar nanomicellizing formulations where the size of micelles was obtained as 63.05±5.24 nm with polydispersity index of 0.09±0.04. In these formulations they used Soluplus and Solutol HS-15 as polymers.…”

“…Nanomicellization is achieved with the help of amphiphilic carrier that can solubilize the drug in its hydrophobic core and also helps in improving the drug stability and solubility. Parika et al [15] Reported self nanomicellizing SD of Cu using soluplus as the carrier. However, the use of a high amount of polymer in the selfnanomicellizing SD may pose a problem in handling and dispensing of this formulation.…”

Curcumin Can Decrease Tissue Inflammation and the Severity of HSV-2 Infection in the Female Reproductive Mucosa

“…This approach is complicated by the fact that crude curcumin contains a large fraction of insoluble curcumin that may not be accessible to the FGT epithelial tissues. We therefore also utilized 2 known polymers, PVP-K30 and Soluplus ® , to increase the solubility of crude curcumin by preparing solid dispersion formulations [29]. Groups of 4-6 mice received IVAG either PBS or 1 mg of crude curcumin in PBS or 100 µg curcumin in either solvent, 6 h before infection with a lethal dose of HSV-2.…”

“…Furthermore, following oral and intraperitoneal (IP) delivery, nanocurcumin therapy can delay the progression of cataract development [26], protect against inflammatory markers and lipid metabolism in streptozotocin-induced diabetes, and have significant benefit in other disease models [27]. In addition, solid dispersion formulations of curcumin greatly increased its bioavailability and were shown to decrease cognitive impairment in an animal model of Alzheimer's disease [28,29].…”

Curcuminoids: Implication for inflammation and oxidative stress in cardiovascular diseases

“…Although active curcumin metabolites have many advantageous targets, they have low oral bioavailability due to their extensive first‐pass metabolism and poor aqueous solubility (Bayomi et al, ). Their poor chemical stability, permeability in vivo, aqueous solubility, and high first‐pass metabolism have been indicated as the potential factors contributing to its poor bioavailability overall (Parikh, Kathawala, Song, Zhou, & Garg, ). Thus, a series of synthetic modification, phosphatidylcholine formulations, lipid complexes, solid dispersions, prodrugs, microspheres, analogues, derivatives, and nanoscale formulations, to curcumin have been intensively studied in order to develop a molecule with enhanced bioactivities (Markatou et al, ; Paradkar, Ambike, Jadhav, & Mahadik, ; Sivasami & Hemalatha, ).…”