DEVELOPMENT OF MULTIPARTICULATE FORMULATION AND EVALUATION OF COLON TARGETED DRUG DELIVERY SYSTEM OF KETOPROFEN: IN VIVO STUDY WITH INDUCED COLITIS MODEL IN RATS AND GAMMA SCINTIGRAPHY

Abstract

Objectives: To develop a multiparticulate containing chitosan and guar gum for the treatment of ulcerative colitis.
Methods: The formulation of multiparticulate was done by extrusion spheronization method using Eudragit L-100 and Eudragit S-100 as a coating
solution and Ketoprofen as a model drug.
Results: Preliminary trial batches were previously assessed for physicochemical characterization, in vitro release, ex vivo mucoadhesion study,
swelling studies, and in vivo evaluation and showed that the formulations appeared to be a good candidate to deliver the drug to the colon. BoxBehnken
design was
used to
statistically
optimize the formulation
parameters
and
evaluate
the main effects,
interaction
effects,
and quadratic

effects
of the
process
parameters
of
enteric
coated
multiparticulate
on drug
polymer
ratio
and coat composition. In
this work,
the effectiveness
of

optimized
batch
(K10) in
the treatment
of inflammatory
bowel
disease was
evaluated.
Experimentally,
colitis was
induced by
rectal
instillation
of
2,
4,

6,
trinitrobenzene
sulfonic
acid
into
male
Wistar rats.
The histological
evaluations
were
done
as
inflammatory
indices.
In
vivo
gamma
scintigraphy

studies
of multiparticulate
without drug demonstrate
degradation
of multiparticulate
whenever
they
reach
the colon.
Conclusion: Results of studies like Gamma Scintigraphy and Histological study of optimized formulation (K10) clearly indicate that there is a great
potential in the delivery of Ketoprofen to the colonic region. The animals treated with Ketoprofen (K10) formulation had an improvement in pathology
and may be useful for the treatment of inflammatory bowel disease.
Keywords: Chitosan, Guar gum, Ketoprofen, Gamma scintigraphy, Histology, Ulcerative colitis, Box-Behnken design.