INFLUENCE OF FORMULATION VARIABLES ON KETOPROFEN
DIFFUSION PROFILES FROM HYDROALCOHOLIC GELS
CORINA DALIA TODERESCU1,2#, CRISTINA DINU-PÎRVU1#, MIHAELA VIOLETA GHICA1#, VALENTINA ANUȚA1#*, DANIELA ELENA POPA1#,LAVINIA VLAIA3#, DUMITRU LUPULIASA1#
1Faculty of Pharmacy, “Carol Davila” University of Medicine and Pharmacy, 6 Traian Vuia Str., 020956, Bucharest, Romania
2Faculty of Pharmacy, Department of Pharmaceutical Sciences, ”Vasile Goldis” Western University of Arad, 86 L. Rebreanu Str.,
Arad, Romania
3Faculty of Pharmacy, “Victor Babes” University of Medicine and Pharmacy, 2 Eftimie Murgu Square, Timisoara, Romania
*corresponding author: vali_anuta@yahoo.com
#All authors have equal contribution.
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Abstract:
Ketoprofen is used to treat painful conditions such as arthritis, sprains and strains, gout, period (menstrual) pain, and pain
after surgical operations. It eases pain and reduces inflammation. After oral administration it can have side effects especially
on digestive system. That’s why it is recommended with caution. In recent years we could note an orientation towards topical
administration of NSAIDSs and hydrogels occupy one of the first places through the forms that were developed for topical
use. Five different experimental formulations coded G1 to G5 containing 1% Carbomer 940 as gel forming agent were
prepared in order to evaluate influence of both composition and preparation methodology on ketoprofen (KTP) diffusion
kinetics. Release of KTP from the various gel formulations was studied using a modified Franz diffusion cell fitted with a
standard cellophane membrane. The release profiles for all the experimental formulations as well for one commercial product
(Fastum® gel) were compared in terms of diffusion coefficients (D). The hydrogel formulated with isopropyl alcohol,
presented the slowest release of KTP, whereas the gels using ethanol and propylene glycol respectively were similar, yielding
about 60% of the incorporated substance after 5 hours. Moreover, for the preparation of the KTP gels we recommend prior
dissolution of the drug in the amount of the alcohol from the formulation. The release profile of the commercial formulation
is intermediate between those of the experimental hydrogels. To establish the drug release mechanism from the tested
hydrogels, several kinetic models were investigated: zero order, first order, Higuchi and Korsmeyer-Peppas models. For the
tested hydrogel, the release mechanism is as follows: (i) Fickian diffusional model for the commercial product; (ii) zero order
for the hydrogels G1-G4 (the release mechanism is represented by a time-independent case-II, relaxational transport); (iii) a
complex mechanism for hydrogel G5, super case-II transport, where the diffusion is associated with hydrogel network
swelling and destructuration, most probably due to its sensitivity by mechanical action during preparation. The results
obtained confirmed that the KTP in vitro release kinetics, is influenced both by the type of alcohol from the gel basis and the
preparation methodology, these variables being able to modify the bioactive compound release mechanism.

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