April Journal-2009.p65 - Association of Biotechnology and Pharmacy

Current Trends in Biotechnology and Pharmacy
Vol. 3 (2) 188-196, April 2009. ISSN 0973-8916
A-HCl is well absorbed after oral
administration with peak plasma concentrations
in 1 to 2 hours after a dose. Bioavailability is about
94% in poor metabolisers but only 63% in
extensive metabolisers. Atomoxetine is
metabolized primarily via the cytochrome P450
isoenzyme CYP2D6 to the active metabolite 4-
hydroxyatomoxetine; a minority of the population
are poor metabolisers and experience plasma
concentrations about 5 times those in extensive
metabolisers. The half life of atomoxetine is about
5.2 hours in extensive and 21.6 in poor
metabolisers (9). A-HCl due to its low therapeutic
dose (10-100 mg) and substantial
biotransformation in liver becomes it ideal
candidate for design and development of
transdermal therapeutic system. A-HCl in
transdermal formulations provides sustained blood
levels over a prolonged period, which is required
for control of ADHD.
In spite of several advantages offered by
transdermal route, only a few drug molecules are
administered transdermally because the
formidable barrier nature of stratum corneum.
Two major approaches to increase transdermal
permeation rate include physical techniques
(iontophoresis, electroporation, sonophoresis, and
microneedles) and use of chemical penetration
enhancers (PE) such as solvents, surfactants,
fatty acids, and terpenes.
Propylene glycol (PG) is the most commonly
used pharmaceutical excipients and have been
widely employed to enhance the transdermal flux
of many drugs (10-14). Various mechanisms of
action have been attributed to the PG for its
penetration enhancement capabilities such as
increased thermodynamic activity (15), increased
skin/vehicle partitioning of the drug (16), and
alteration of barrier property by interacting with
skin components. PG may reduce barrier property
of skin by causing conformational changes either
in lipid acryl chains (17) or protein domains (18)
or by partial lipid extractions (19).
189
The objective of this study was to formulate
transdermal patches of A-HCl and to evaluate
the effect of PG in drug release.
Materials and Methods
Materials
Atomoxetine HCl, Eudragit RL 100 (ERL)
(Rohm Pharma GmbH, Germany) and Eudragit
RS 100 (ERS) (Rohm Pharma GmbH, Germany)
were procured from Aurobindo Pharmaceuticals
(Hyderabad, India). Liquid mercury, dibutyl
phthalate (DBP), hydroxypropyl methyl cellulose
(HPMC), propylene glycol (PG), disodium
hydrogen phosphate, potassium dihydrogen
phosphate, sodium chloride were purchased from
S.D. Fine Chemicals Limited, India. All the
materials used were of analytical grade.
Preparation of TDDS
The composition of various formulations is
given in Table 1. The polymeric solution (10% w/
v) was prepared by dissolving ERL-100/ ERS-
100 and HPMC in different ratios, along with A-
HCl, DBP and PG in ethanol. The solution was
poured into a glass ring placed on the surface of
liquid mercury kept in a petridish. The solvent
was allowed to evaporate under ambient
conditions (temperature 32 0 C and relative humidity
45%) for 24 hours. Aluminum foil was used as
backing film. The polymer was found to be self
sticking due to the presence of eudragit polymers
along with plasticizer. The patches were cut to
give required area and stored in airtight container
till further use.
Physicochemical Evaluation
Thickness and Weight Variation
The thickness of the patches was
assessed at 6 different points using screw gauze.
For each formulation, three randomly selected
patches were used. For weight variation test, 3
films from each batch were weighed individually
and the average weight was calculated (Table
2).
Mamatha et al