Andrographolide-loaded ethosomal gel for transdermal application: Formulation and in vitro penetration study

Abstract

Background: Andrographolide is a phytoconstituent with anti-inflammatory activity, however, the compound’s poor oral bioavailability has hindered its effective formulation for oral administration. This study, therefore, aims to develop an ethosome for improving andrographolide penetration through the transdermal delivery system. Methods: This study developed 3 ethosome formulas with different andrographolide-phospholipid weight ratios (1:8, 1:9; 1:10), using the thin-layer dispersion-sonication method. Subsequently, the ethosomes were evaluated for particle size, polydispersity index, zeta potential, morphology, as well as entrapment efficiency, and incorporated into a gel dosage form. Subsequently, an in vitro penetration study was performed using Franz diffusion cells for 24 hours and the stability of the gels at 5 ± 2°C, 30 ± 2°C, and 40 ± 2°C, were studied for 3 months. Results: The results showed the optimal formula was E2, a 1:9 weight ratio formula of andrographolide and phospholipid. Based on the transmission electron micrograph, E2 possessed unilamellar, as well as spherical-shaped vesicles, and exhibited superior characteristics for transdermal delivery, with a particle size of 89.95 ± 0.75 nm, polydispersity index of 0.254 ± 0.020, a zeta potential of -39.3 ± 0.82 mV, and entrapment efficiency of 97.89 ± 0.02%. Furthermore, the cumulative andrographolide penetration and transdermal flux for the ethosomal gel of E2 (EG2) were 129.25 ± 4.66 µg/cm2 and 5.16 ± 0.10 µg/cm2/hours, respectively. All the ethosomal gel formulations exhibited improved penetration enhancement of andrographolide, compared to the nonethosomal formulations. Also, the andrographolide levels in the ethosomal and nonethosomal gels after 3 months ranged from 98.13 to 104.19%, 97.93 to 104.01%, and 97.23 to 102.26% at storage temperatures of 5 ± 2°C, 30 ± 2°C/RH 65% ± 5%, and 40 ± 2°C/RH 75% ± 5%, respectively. Conclusions: This study concluded that encapsulation into ethosome enhances andrographolide delivery through the skin.

Advances in Ameliorating Rheumatoid Arthritis by Andrographolide Ethosome-Based Gel: Pharmacokinetic and Activity Study in Rats

“…Based on the results, the EE (%) values of the andrographolide ethosomes were greater than 97%, and this is consistent with the previous study on the EG2 formula [17]. Increasing the phospholipid concentration tends to enhance the size and strength of the vesicle membrane, thereby leading to an increased number of entrapped drugs [23,25].…”

“…The dynamic light scattering (DLS) approach yielded vesicle size measurements of less than 300 nm. The PDI value generated when the sizing was determined using DLS, and this is consistent with Martihandini et al [17]. This value indicates the degree of heterogeneity in a dispersed system based on the particle.…”

“…The development of the AEG formula has been previously carried out by Martihandini et al [17], where andrographolides formulated in ethosomes with an andrographolide-phospholipid ratio of 1:9 increased drug penetration through the skin using transdermal delivery in an in vitro study. Therefore, in this study, the formula and method of preparation as well as characterization was performed based on the method in Martihandini et al [17].…”

“…The ethosomal suspension containing andrographolides and phospholipids with a weight ratio of 1:9, w/w was prepared using the thin layer hydration method, as proposed by Martihandini et al [17]. Subsequently, it was formulated into a gel preparation containing 10 mg andrographolides/g gel, and another sample was prepared without ethosomes for comparison.…”

“…Their high alcohol content tends to disorganize and alter the permeability of the stratum corneum's lipid bilayer structure, thereby enhancing transdermal penetration [16]. A recent study by Martihandini et al [17] revealed that andrographolide encapsulated on ethosome has a vesicle size range of 92.27-123.00 nm, zeta potential>±30 mV, and entrapment efficiency of 97.10%-97.93%. The results also revealed that there was an improvement in skin penetration.…”