ELASTIC NANOVESICLES AS STEROID HORMONES TRANSDERMAL
DELIVERY SYSTEM. PREPARATION, CHARACTERIZATION AND IN VITRO
EVALUATORY STUDIES
Cristina Hlevca1, Cristina Dinu Parvu2 , Luigi Silvestro3, Alina Ortan4 , Elena Patrut1, Rasit Iuksel1, Minerva Panteli1
1National
Institute for Chemical Pharmaceutical Research and Development, Bucharest
3S.C. Pharma Serv International S.R.L, Bucharest
INTRODUCTION
Drospirenone is a new antimineralocorticoid progestin, also with
an antiandrogenic activity, used for contraception and management
of menopausal symptoms (1).
At present, on the market there are only oral formulations with
drospirenone (DRS). This oral administration has certain
disadvantages, which can be eliminated by transdermal
formulation.
One of the problems encountered in transdermal drug delivery is
the low permeability of drugs through the skin barrier. This
problem can be solved by using elastic vesicles as drug delivery
systems (2).
2University
of Medicine and Pharmacy, “Carol Davila”, Bucharest
4 University of Agricultural Sciences and Veterinary Medicine, Bucharest
Stability studies for ethosomes and transferosomes
The studies were performed during a period of 2 month; the
entrapment efficiency and size distribution were determined.
The results indicated a good stability for transferosomes and
ethosomes; the entrapment efficiency decreased insignificantly
(table 1) and vesicles’ size distribution was approximately
constant for two months.
In Vitro release study
In vitro drug release studies were conducted with a modified
Frantz diffusion cell where a standard cellophane membrane was
fitted. The receptor medium consisted of phosphate buffer in
hydroalcoholic solution. The DRS released through the cellophane
membrane was spectrophotometrically analyzed at 274 nm.
Series1
METHODS AND RESULTS
Series2
Series3
Series4
Series5
Series6
100
Preparation of elastic vesicles
90
80
70
60
50
40
30
20
10
0
0
Entrapment Efficiency Determination
0.2 ml from liposomal suspensions were separated by
centrifugation at 12000 rpm at 10ºC for 60 min. Drospirenone
was analyzed spectrophotometrically.
Table 1.The influence of transferosomes and ethosomes
composition on the entrapment efficiency
-
Percentage of
entrapment after
preparation
(%)
78.57
Percentage of
entrapment
after 1 month
(%)
77.92
Percentage of
entrapment
after 2 months
(%)
76.33
100 : 15 : 20
-
98
97.3
96.89
EDRS II
-
44 : 56
74.5
74.12
73.20
EDRS II
-
30 : 70
78.13
77.32
76.85
EDRS III
-
20 : 80
80.4
79.2
78.44
Type of
vesicles
Ratio m/m/m
PC : Co : DRS
(g)
Ratio V/V
ethanol : water
(%)
TDRS I
100 : 20 : 20
TDRS II
Size Distribution
Size distribution was determined with Mastersizer 2000 – Malvern
instrument
The size determinations showed a large polydispersion of the
elastic vesicles, with a higher percentage between 70 and 150 nm
in case of the analyzed MLV ethosomes, and between 180-500 nm
in case of the MLV transpherosomes.
10
15
20
25
30
Fig 3. Released procentage of DRS in 24 h
Fig 2. The mechanism of
ethosomes preparation by
Touitou method (4)
Fig 1. The mechanism of transferosomes
preparation by hydration of the lipidic
film method (3)
5
EDRS I
EDRS II
EDRS III
TDRS I
TDRS II
DRS solution
CONCLUSIONS
 After sonication, the dimensions of transferosomes population
were between 50 – 90 nm, and for ethosomes between 20-70 nm;
these values were approximately constant for 2 months.
 The conducted experiments showed that the molar ratios of
DRS, phosphatidyl choline (PC) and sodium cholate influence the
drug entrapment of the transferosomes. In case of ethosomes, the
entrapment efficiency was affected by the percentage of ethanol,
PC and DRS in the formulation.
 The release rate was also influenced by the composition of
ethosomes and transferosomes: lower percentage of sodium cholate
determined higher release rate in case of transferosomes,
respectively higher percentage of ethanol resulted in higher release
rate. Ethosomes and transferosomes formulations released 40-86 %
DRS in 24h, compared with a hydroalcoholic solution of DRS,
which released 96% in 2h.
REFERENCES
1. Sitruk-Ware R. (2006) Human Reproduction Update 12, 169-178
2. Honeywell-Nguyen P. L., Bouwstra J. (2005) Drug discovery
Today: Technologies, 267-74.
3. Elsayed M. M. A., Abdallah O. Y., Naggar V., F., Khalafalah N.,
M. (2006) International Jurnal of Pharmaceutics, 322, 60-66.
4. Touitou E., Godin B.and Weiss C. (2002), Drug Develop .Res.
50, 406-415.
A 10-a editie a
Seminarului National de nanostiinta si nanotehnologie
18 mai 2011
Biblioteca Academiei Romane