Matrix-type transdermal films to enhance simvastatin ex vivo skin permeability

Abstract

This study aimed at employing Plackett-Burman design in screening formulation variables that affect quality of matrix-type simvastatin (SMV) transdermal film. To achieve this goal, 12 formulations were prepared by casting method. The investigated variables were Eudragit RL percentage, polymer mixture percentage, plasticizer type, plasticizer percentage, enhancer type, enhancer percentage and dichloromethane fraction in organic phase. The films were evaluated for physicochemical properties and ex vivo SMV permeation. SMV initial, delayed flux, diffusivity and permeability coefficient were calculated on the delayed flux phase with constraint to minimize the initial flux and approaching steady-state flux. The obtained results revealed flat films with homogeneous distribution of SMV within the films. Thickness values changed from 65 to 180 μm by changing the factors' combinations. Most of the permeation profiles showed sustained release feature with fast permeation phase followed by slow phase. Analysis of variance (ANOVA) showed significant effects (p < 0.05) of the investigated variables on the responses with Prob > F values of 0.0147, 0.0814, 0.0063 and 0.0142 for the initial and delayed fluxes, permeability coefficients and diffusivities, respectively. The findings of screening study showed the importance of the significant variables to be scaled up for full optimization study as a promising alternative drug delivery system.

Optimized vinpocetine-loaded vitamin E D-&alpha;-tocopherol polyethylene glycol 1000 succinate-alpha lipoic acid micelles as a potential transdermal drug delivery system: in vitro and ex vivo studies

“…Hence, the use of PG allowed for more water absorption by the film, thus facilitating VNP diffusion. 32,52 This result was in accordance with Vora et al who observed a permeation-enhancing effect of PG when used as a plasticizer in carvedilol transdermal systems. 53…”

“…The prepared films were evaluated for elongation percent as previously described. 32 Briefly, rectangular film strips of 1×4 cm were fixed in such a way that the length of the film between the jaws was 2 cm under a weight of 200 g for a minute. The elongation percent was calculated according to equation 1.…”

“…This finding on increasing the elongation percent of films by the action of PG is in accordance with the previously reported data. 32,44,45 effect on initial drug permeation after 2 hours (Y 2 )…”

Development of Pomegranate Extract-Loaded Solid Lipid Nanoparticles: Quality by Design Approach to Screen the Variables Affecting the Quality Attributes and Characterization

“… 12 Several studies had been utilizing PBD in screening the formulation and/or processing variables in development of various dosage forms and drug delivery systems such as controlled release matrix tablets, 13 hot melt sustained release extrudates, 14 liposomes, 15 niosomes, 16 transferosomes, 17 protein loaded PLGA nanoparticles, 18 PLGA-based nanoparticles, 19 alginate-reinforced chitosan nanoparticles, 20 Eudragit microspheres, 21 and matrix-type transdermal films. 22 …”

“…For these reasons, Plackett–Burman design (PBD) is considered as a highly efficient tool to screen a number of formulation and/or processing variables and explore the most significant variables that can be used in optimization of the process and fix the other insignificant at a low level . Several studies had been utilizing PBD in screening the formulation and/or processing variables in development of various dosage forms and drug delivery systems such as controlled release matrix tablets, hot melt sustained release extrudates, liposomes, niosomes, transferosomes, protein loaded PLGA nanoparticles, PLGA-based nanoparticles, alginate-reinforced chitosan nanoparticles, Eudragit microspheres, and matrix-type transdermal films …”