Dasatinib-Loaded Topical Nano-Emulgel for Rheumatoid Arthritis: Formulation Design and Optimization by QbD, In Vitro, Ex Vivo, and In Vivo Evaluation

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.

Development and preclinical assessment of nanoemulgel loaded with phytoconstituents for the management of rheumatoid arthritis

“…The stable formulations were further evaluated in freezethaw cycles. Three freeze-thaw cycles between − 21°C and + 25°C were performed at each temperature for not less than 48 hour and examined for changes in homogeneity and color [19,29].…”

Continuous Manufacturing of Solvent-Free Cyclodextrin Inclusion Complexes for Enhanced Drug Solubility via Hot-Melt Extrusion: A Quality by Design Approach

“…The drug content of all the samples ranged from 93.6% to 104.2% of labeled claims. According to the USP, a range of 90–110% for the labeled claim is acceptable [ 53 ]. Therefore, all the TIC formulations are accepted to be within the specified range of USP.…”

Comprehensive insights into rheumatoid arthritis: Pathophysiology, current therapies and herbal alternatives for effective disease management

“…A 2022 study revealed the potential role of a microbial dye in combination with multiple low doses of gamma radiation exhibiting anti‐inflammatory effects and reducing disease severity in adjuvant induced arthritis rats (Abdel‐Rafei et al, 2022). Alternatively, nano‐carriers have also been explored for drug delivery against chronic inflammatory diseases (Oshi et al, 2022; Gorantla et al, 2020; Donthi et al, 2023). Recently, dendrimers have gained attention for their narrow polydispersity index (Dubey et al, 2021).…”

“…However, there have been advancements in the surgical sector such as prophylactic antibiotics and laminar airflow on the wound to prevent contamination, reducing joint infection incidences to a low 2%-2.4% (Goodman, 2015b). Alternatively, nano-carriers have also been explored for drug delivery against chronic inflammatory diseases (Oshi et al, 2022;Gorantla et al, 2020;Donthi et al, 2023). Recently, dendrimers have gained attention for their narrow polydispersity index (Dubey et al, 2021).…”