Implementing Central Composite Design for Developing Transdermal Diacerein-Loaded Niosomes: Ex vivo Permeation and In vivo Deposition

Abstract

Background: Niosomes are surfactant-based vesicular nanosystems that proved their efficiency in transdermal delivery by overcoming skin inherent anatomic barrier; startum corneum. Central composite design is an efficient tool for developing and optimizing niosomal formulations using fewer experiments.

Objective: The objective of this study was to prepare niosomes as a transdermal delivery system of diacerein using film hydration technique, employing central composite design, for avoiding its oral gastrointestinal problems.

Methods: Three-level three-factor central composite design was employed for attaining optimal niosomes formulation with the desired characteristics. Three formulation variables were assessed: amount of salt in hydration medium (X1), lipid amount (X2) and number of surfactant parts (X3). DCNloaded niosomes were evaluated for entrapment efficiency percent (Y1), particle size (Y2), polydispersity index (Y3) and zeta potential (Y4). The suggested optimal niosomes were subjected to further characterization and utilized as a nucleus for developing elastic vesicles for comparative ex vivo and in vivo studies.

Results: The values of the independent variables (X1, X2 and X3) in the optimal niosomes formulation were 0 g, 150 mg and 5 parts, respectively. It showed entrapment efficiency percentage of 95.63%, particle size of 436.65 nm, polydispersity index of 0.47 and zeta potential of -38.80 mV. Results of ex vivo permeation and skin deposition studies showed enhanced skin permeation and retention capacity of the prepared vesicles than drug suspension.

Conclusion: Results revealed that a transdermal niosomal system was successfully prepared and evaluated using central composite design which will result in delivering diacerein efficiently, avoiding its oral problems.

Keywords: Diacerein; central composite; ex vivo permeation; niosomes; optimization; skin deposition studies..

Fig. (1)

Response 3-D plots for the effect of amount of salt in hydration medium (X₁), lipid amount (X₂) and number of surfactant parts (X₃) on (a) entrapment efficiency percent (EE%) and (b) particle size (PS) of DCN-loaded niosomes.

Fig. (2)

Response 3-D plots for the effect of amount of salt in hydration medium (X₁), lipid amount (X₂) and number of surfactant parts (X₃) on (a) polydispersity index (PDI) and (b) zeta potential (ZP) of DCN-loaded niosomes.

Fig. (3)

Transmission electron micrograph of the optimal niosomes formulation.

Fig. (4)

DSC thermograms of (a) DCN, (b) CH, (c) Span 60, (d) physical mixture of DCN with niosomal components and (e) the optimal niosomes formulation.

Fig. (5)

Cumulative amount of DCN permeated per unit area across excised rat's skin via elastic vesicles and optimal niosomes formulation compared to drug suspension.

Fig. (6)

In vivo skin deposition profiles of DCN versus times from elastic vesicles, optimal niosomes formulation and drug suspension after topical application.