In this study, the enhancing effect of artichoke extract containing cynaropicrin on the in

vitro and in vivo percutaneous absorption of ketoprofen from gels has been investigated

Alamanni, Maria Cristina Paolina

Cossu, Massimo

Gavini, Elisabetta

Giunchedi, Paolo

Rassu, Giovanna

Sanna, Vanna Annunziata

Sechi, Gabriella

English

UnissResearch

                                            
SardiniaChem 2006 
GIORNATA DI STUDIO DEDICATA ALLA CHIMICA ORGANICA 
DELLE MOLECOLE BIOLOGICAMENTE ATTIVE 
5 Giugno 2006, Complesso Universitario di Monserrato, Cagliari 
 
COMITATO ORGANIZZATORE: 
Salvatore Cabiddu - Università di Cagliari, Giovanna Delogu - CNR Sassari, 
Pier Paolo Piras - Università di Cagliari, Giampaolo Giacomelli - Università di Sassari 
HANNO CONTRIBUITO ALLA REALIZZAZIONE DEL CONVEGNO: 
UNIVERSITÀ DI CAGLIARI; UNIVERSITÀ DI SASSARI-Dipartimento di Chimica; CNR-Istituto di 
Chimica Biomolecolare, Sezione di Sassari; SIGMA-ALDRICH Srl; EXACTA+OPTECH Sardegna S.r.l., 
CARLO ERBA REAGENTI; VWR INTERNATIONAL s.r.l. 
 
O
NHO
OH
H3C
OH
CH3
CH3
O
O
O
CH3
O
O
O
H
OH
CH3
OO
O
H3C
P48 
 120
IN VITRO AND IN VIVO STUDIESOF ARTICHOKE EXTRACT (CYNARA 
SCOLYMUS L.)AS KETOPROFEN SKIN PENETRATION ENHANCER 
G.Sechi, E.Gavini, V.Sanna, M.Cossu, G.Rassu, M.C.Alamanni, P.Giunchedi1 
1Dipartimento di Scienze del Farmaco, University of Sassari, Italy. 
The most difficult aspect of transdermal delivery system is to overcome the barrier of 
stratum corneum. Various skin permeation enhancers have been screened for their effects 
on ketoprofen skin permeability [1]. Terpenes, monoterpenes as well as larger terpene 
molecules, sesquiterpenes, have also been evaluated as enhancers for molecules permeating 
human skin membranes [2]. The artichoke leaves present a high content of sesquiterpene 
lactones among which cynaropicrin is the principal (3). 
In this study, the enhancing effect of artichoke extract containing cynaropicrin on the in 
vitro and in vivo percutaneous absorption of ketoprofen from gels has been investigated. 
Artichoke leaves have been extracted by a Soxhlet using methylene chloride; after 
evaporation, the residue obtained has been dissolved into a solution of water–methanol, 
washed using ether and then evaporated to obtain finally a dried green extract. The 
cynaropicrin content was determined as follows: an exact amount of extract has been 
dissolved in methanol and injected in HPLC to find the amount of cynaropicrin.  
Fastum® gel (A) is an Italian commercial product; it has been used as comparison and as 
the base for the preparation of the other different gels (B-E). It contains 2.5% (w/w) of 
ketoprofen. Gels B-D have been obtained from A to which 1.0, 2.0 or 3.0 % (w/w) of 
extract has been added respectively. Gel E has been prepared by incorporation of 0.5% 
(w/w) of cynaropicrin standard to A. 
The in vitro permeation studies have been performed by Franz diffusion cells, using 
phosphate buffer (pH 7.4, 37°C, magnetic stirring) as receptor fluid. At set time points 
(from 0 to 3.5 h) the amount of ketoprofen permeated has been determined by UV 
spectrophotometer at 254 nm. 
The stripping test has been employed to perform the in vivo studies. The formulations A, B 
and E have been chosen on the basis of the previous results. The drug penetrated through 
the stratum corneum has been determined spectrophotometrically. 
P48 
 121
The extraction method employed is suitable to obtain an extract rich in cynaropicrin (45% 
w/w). 
The in vitro results demonstrate that the cumulative amount of the ketoprofen permeated is 
dependent on the composition of the formulation and particularly on the cynaropicrin 
content (Figure 1).  
0
200
400
600
800
1000
1200
1400
1600
1800
0.0 0.5 1.0 1.5 2.0 2.5 3.0 3.5
Time (hrs)
cu
m
ul
at
iv
e 
am
ou
nt
 o
f d
ru
g 
pe
rm
ea
te
 ( µg
)
A B C D E
 
Figure 1. Cumulative amount of ketoprofen permeated in vitro 
The results from the in vivo tests show that B and E gels (containing 0.5% w/w of 
cynaropicrin as extract and standard respectively) are characterized by significant 
differences in the amount of drug recovered in the stratum corneum, compared to the 
formulation A (without cynaropicrin). The drug permeated corresponds to less than 100 mg 
in case of A and about 125 and 122 mg in case of B and E respectively. This indicates that 
the amount of the drug able to penetrate the stratum corneum depends on the amount of 
cynaropicrin in the gel regardless how it has been added to the gel (as extract or as 
standard). However, the use of the extract results economically more advantageous than 
cynaropicrin as pure material: in fact due to the difficulties in the extraction and 
purification process, cynaropicrin is not easy to find as standard in the market and thus it is 
also very expensive. 
In conclusion, the artichoke extract might be proposed as potential penetration enhancer for 
the percutaneous absorption of ketoprofen. 
References 
[1]Valenta C, Wanka M, Heidlas J. J Control Release. 2000;63(1-2):165-173.  
[2]Williams AC and Barry BW. Adv Drug Deliv Rev. 2004; 56:603-618. 
[3]Pedretti M. Erboristeria domani. Studio edizione S.a.s. Dic. 1986; 47-58. 


In vitro and in vivo studies of artichoke extract (Cynara scolymus L.) as ketoprofen skin penetration enhancer

<i>In vitro</i> and <i>in vivo</i> studies of artichoke extract (<i>Cynara scolymus</i> L.) as ketoprofen skin penetration enhancer

Abstract

Similar works

Full text

Available Versions

UnissResearch