ABSTRACT
Rheumatoid arthritis (RA) is an immune-mediated disease that necessitates a thorough understanding of its intricate pathophysiological mechanism for precise and effective therapeutic targeting. The European League Against Rheumatism (EULAR) has established guidelines for RA treatment, endorsing monotherapy or combination therapy with corticosteroids and synthetic disease-modifying antirheumatic drugs (sDMARDs). This review delves into clinical trials and research outcomes related to combination drug delivery, with an emphasis on the role of natural products in combination with synthetic drugs. Given the significant adverse effects associated with systemic administration, topical delivery has emerged as an alternative avenue for effective management of RA.
ABSTRACT
The current study aimed to develop a topical emulgel of dasatinib (DTB) for rheumatoid arthritis (RA) treatment to reduce systemic side effects. The quality by design (QbD) approach was employed to optimize DTB-loaded nano-emulgel using a central composite design (CCD). Emulgel was prepared using the hot emulsification method, and then the particle size (PS) was reduced using the homogenization technique. The PS and % entrapment efficiency (% EE) were found to be 172.53 ± 3.33 nm (0.160 ± 0.014 PDI) and 95.11 ± 0.16%, respectively. The nano-emulsion (CF018 emulsion) in vitro drug release profile showed sustained release (SR) up to 24 h. MTT assay results from an in vitro cell line study revealed that formulation excipients had no effect, whereas emulgel showed a high degree of internalization. Furthermore, emulgel treatment significantly reduced LPS-induced TNF-α production in RAW 264.7 cells. The spherical shape was depicted in FESEM images of optimized nano-emulgel (CF018 emulgel) formulation. Ex vivo skin permeation was significantly increased when compared to the free drug-loaded gel (FDG). In vivo data revealed that the optimized CF018 emulgel is a non-irritant and is safe. In terms of paw swelling, the FCA-induced arthritis model demonstrated that the CF018 emulgel reduced paw swelling percentage compared to adjuvant-induced arthritis (AIA) control group. Following clinical testing in the near future, the designed preparation could be a viable alternative treatment for RA.
ABSTRACT
Nano-emulgel is an emerging drug delivery system intended to enhance the therapeutic profile of lipophilic drugs. Lipophilic formulations have a variety of limitations, which includes poor solubility, unpredictable absorption, and low oral bioavailability. Nano-emulgel, an amalgamated preparation of different systems aims to deal with these limitations. The novel system prepared by the incorporation of nano-emulsion into gel improves stability and enables drug delivery for both immediate and controlled release. The focus on nano-emulgel has also increased due to its ability to achieve targeted delivery, ease of application, absence of gastrointestinal degradation or the first pass metabolism, and safety profile. This review focuses on the formulation components of nano-emulgel for topical drug delivery, pharmacokinetics and safety profiles.
ABSTRACT
Sorafenib tosylate (SFNT) is the first-line drug for hepatocellular carcinoma. It exhibits poor solubility leading to low oral bioavailability subsequently requiring intake of large quantities of drug to exhibit desired efficacy. The present investigation was aimed at enhancing the solubility and dissolution rate of SFNT using complexation method. The binary inclusion complex was prepared with ß-cyclodextrin (ß-CD). The molecular docking studies confirmed the hosting of SFNT into hydrophobic cavity of ß-CD, while the phase solubility studies revealed the stoichiometry of complexation with a stability constant of 735.8 M-1. The ternary complex was prepared by combining the SFNT-ß-CD complex with PEG-6000 and HPMC polymers. The results from ATR-IR studies revealed no interaction between drug and excipients. The decreased intensities in ATR-IR peaks and changes in chemical shifts from NMR of SFNT in complexes indicate the possibility of SFNT hosting into the hydrophobic cavity of ß-CD. The disappearance of SFNT peak in DSC and XRD studies revealed the amorphization upon complexation. The ternary complexes exhibited improved in vitro solubility (17.54 µg/mL) compared to pure SFNT (0.19 µg/mL) and binary inclusion complex (1.52 µg/mL). The dissolution profile of ternary inclusion complex in 0.1 N HCl was significantly higher compared to binary inclusion complex and pure drug. In cytotoxicity studies, the ternary inclusion complex has shown remarkable effect than the binary inclusion complex and pure drug on HepG2 cell lines.
