QbD Approach for the Development of Tea Tree Oil-Enhanced Microemulgel Loaded with Curcumin and Diclofenac for Rheumatoid Arthritis Treatment

Abstract

Rheumatoid arthritis, a chronic autoimmune disorder affecting millions worldwide each year, poses a significant threat due to its potential for progressive joint damage and debilitating pain if left untreated. Topical anti-inflammatory and analgesic treatments offer localized relief with reduced systemic side effects compared to conventional oral therapies, making them a promising option for managing rheumatoid arthritis. Therefore, the current study endeavored to formulate a microemulsion gel formulation loaded with diclofenac and curcumin for topical administration in the management of rheumatoid arthritis, utilizing Tea tree oil. The ratio of surfactant and cosurfactant was 4:1, assessed by pseudoternary phase diagram on the basis of the maximum emulsification region. The microemulsion underwent optimization using a Central Composite Rotatable Design (CCRD) with constraints of minimum particle size, polydispersity index, and maximum transmittance. The Curcufenac-T microemulsion had a particle size, polydispersity index (PDI), and transmittance of 151.82 ± 15.9 nm, 0.287 ± 0.021, and -5.78 ± 0.26 mV, respectively. DSC analyses confirmed the stability and compatibility of diclofenac and curcumin within the formulation. The microemulsion was changed into gel form by incorporating 1% carbopol-934. Skin permeation analysis revealed that the percentage of diclofenac permeated at 0.5 h from Curcufenac-T microemugel and the conventional gel was 12.1% and 3.9%, respectively, while at 12 h, the rates were 82.6% and 34.2%, respectively. In vitro permeability demonstrated significant potential for the effective delivery of diclofenac and curcumin to targeted sites, compared to conventional gel. Therefore, it was deduced that the Tea tree oil integrated diclofenac and curcumin microemulsion gel could enhance the effectiveness of diclofenac and serve as a promising vehicle for rheumatoid arthritis treatment.

Keywords: QbD; central composite rotatable design; curcumin; diclofenac; microemulsion gel; tea tree oil.

Figure 1

Pseudoternary phase diagrams constructed for various Smix ratios.

Figure 2

Response surface plots showing the effect of oil and Smix on (A) particle size, (B) PDI, and (C) percentage transmittance.

Figure 3

Particle size of Curcufenac-T.

Figure 4

Zeta potential of Curcufenac-T.

Figure 5

Morphological determination using TEM of Curcufenac-T.

Figure 6

DSC of (A) diclofenac, (B) curcumin, and (C) lyophilized Curcufenac-T.

Figure 7

Drug release profile of diclofenac from conventional formulation and microemulsion gel.

Figure 8

Drug release profile of curcumin from conventional formulation and microemulsion gel.