TRANSDERMAL DELIVERY OF LIDOCAINE AND IBUPROFEN FROM BACTERIAL CELLULOSE MEMBRANES ACROSS HUMAN SKIN

Eliane Trovatti , Carmen S.R. Freire , Armando J.D. Silvestre , Carlos Pascoal Neto , Catarina Rosado
CICECO e Departamento de Quimica, Universidade de Aveiro 3810-193, Aveiro, Portugal 2 Universidade Lusfona (CBIOS Unidade de Dermatologia Experimental), Campo Grande, 376, 1749-024, Lisboa, Portugal
1

INTRODUCTION Bacterial cellulose (BC) is a highly pure cellulose substrate produced in the form of a swollen membrane by several bacteria, mainly belonging to the Gluconacetobacter genera. The unique physical and mechanical properties of BC, arising from its tridimensional and branched nano and micro-fibrillar structure, as well as its high purity and biocompatibility triggered considerable interest on this material, particularly in the biomedical area namely as a scaffold material for tissue-engineered products for the regeneration of damaged or diseased organs, including skin. However, there are few studies addressing the use of such membranes for drug loading and controlled release. AIM The aim of this study was to investigate the potential of BC membranes as systems for topical or transdermal drug delivery. The permeation through human epidermis of a hydrophilic and a lipophilic model drug in BC and other formulation systems was compared, to assess its therapeutic applicability and feasibility. METHODS Lidocaine and ibuprofen were chosen as model drugs. A drug loading process in BC membranes was developed for both molecules, and the drug distribution was evaluated by electronic microscopy. Each drug was also included in two other systems- an HPMC gel or a single vehicle formulation. In vitro diffusion studies with Franz cells were conducted, using human epidermal membranes. Similar doses of the different formulations were placed in the donor compartment of the diffusion cells. The multiple steady-state fluxes of lidocaine and ibuprofen in each formulation system were determined. RESULTS
Cumulative amountl diffused (m2) g/cm
100 450 BC 400 gel aqueous solution

a)

b) Figure 1- SEM images of bacterial cellulose a) oven dried b)lyophilised c) oven dried with lidocaine

c)

a)

b) Figure 2- Bacterial cellulose a) pure (left), with lidocaine (middle), with ibuprofen (right) b) hydrated pure membrane

LIDOCAINE

Cumulative amountl diffused (m2) g/cm

1 h 2

) 350 m c / 300 g f ( d e s u 250 f f i d t n u 200 o m a e v 150 i t a l u m u C 100 50 0 0 1

4 Time (hour)

Figure 3- Permeation profiles of lidocaine in the different systems (mean values +SD, n=5)
120 BC gel aqueous solution

IBUPROFEN

A uniform distribution of the drug in the BC membranes was achieved (figs. 1 and 2) . Diffusion studies showed that the incorporation of lidocaine in BC membranes provided lower fluxes than those obtained with the conventional systems (figs. 3 and 5a)). The results obtained with the lipophilic drug were quite different (fig. 4). The fluxes of ibuprofen in BC were almost three times higher than those of the drug in the gel or in a PEG400 solution (fig. 5b)). CONCLUSIONS These results indicate that this technology can be successfully applied to modulate the bioavailability of drugs for dermal and transdermal administration. Such systems could be particularly advantageous in the
Flux (m2/h) g/cm
60 50 ) 1 40 h 2 m c / 30 g ( x u 20 l F 10 0 Bacterial Cellulose

1 h 2

m c / 80 g b ( d e s u f f i d 60 t n u o m a e v 40 i t a l u m u C 20

0 0 1 2 3 4 Time (hour) 5 6 7 8

Figure 4- Permeation profiles of ibuprofen in the different systems (mean values +SD, n=5)

* *

16

NS
Flux (m2/h) g/cm
)

* *

14 12
1 h 2

design of delivery systems that have, simultaneously, the ability to absorb exudates and adhere to irregular skin surfaces. Additionally, since most transdermal patches are manufactured by superimposing different materials, a system composed of fewer layers could simplify the preparation procedure and lower production costs.

10

m c / 8 g m ( x 6 u l F 4 2 0

NS

Gel

Aqueous Solution

Bacterial Cellulose

Gel

PEG400 Solution

a)

Figure 5-Steady-state fluxes (mean values +SD) *- p<0,05 a) lidocaine b)ibuprofen

b)

12th Annual Meeting of Skin Forum Frankfurt, Germany, 28 - 29 March 2011