Journal of Pharmaceutical Research and Opinion 3: 6 (2013) 28 - 35.
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JOURNAL OF PHARMACEUTICAL RESEARCH AND OPINION
Journal homepage: http://www.innovativejournal.in/index.php/jpro
28
FUROSEMIDE LOADED SUPERPOROUS HYDROGEL COMPOSITE AS A CONTROLLED
RELEASE DEVICE: DIFFERENT STRATEGIES FOR DRUG LOADING
Latif R.*
1
Abdel Halim S.A
1
Abdel Kader O.M
1
1
Department of Pharmaceutics, Faculty of Pharmacy, Cairo University
ARTICLE INFO ABSTRACT
Received 18
th
June 2013
Accepted 25
th
June 2013
Corresponding Author:
Latif R
Department of
Pharmaceutics, Faculty of
Pharmacy, Cairo University,
Egypt
latifranda@yahoo.co.uk
Keywords: controlled release
formulation, gastroretentive
device, super porous
hydrogel composite,
furosemide.
The aim of the present work was to develop controlled release, gastroretentive device
using superporous hydrogel composite (SPHC). Furosemide was chosen as good
candidate for such system due to its narrow absorption window, low bioavailability
and short half-life. Plain hydrogel was evaluated with respect to swelling ratio,
apparent density and floating time. Scanning electron micrographs of SPHC showed
large interconnected pores and extensive capillary insertion. Prepared Microspheres
were tested for drug content, and tablets evaluated with respect to quality control
tests. All loaded formulae inside SPHC were tested for drug release profile.
Microspheres, tablets and drug solutions were tested for loading inside SPHC. Kinetic
treatment of release data revealed that soaked drug solution was unable to control
drug release, where it gave a t
1/2
(0.5hrs) very similar to that of the free drug (0.6hrs).
Loaded microspheres showed only a slight retardation in release t
1/2
to 1.06 hrs along
with a high percent of flush (~30mg %). However, loaded tablet demonstrated a
promising sustained effect corresponding to a release t
1/2
= 6hrs and a low percent of
initial flush (~1.2mg %). Therefore, the applicability of SPHC as a controlled release
device proved to be largely dependent on the type of dosage form included.
©2013, JPRO, All Right Reserved.
INTRODUCTION
Since drug delivery technology
1
is an equivalent component in drug development, a design of delivery systems that can
target a candidate drug to its absorption site is a successful achievement
2-3
.
Among the different systems and devices used to control the drug delivery to the GIT, gastroretentive dosage forms have
attracted much attention of academic researchers
4
. Those systems are advantageous in case of drugs characterized by a
narrow absorption window. They provide a prolonged intimate contact with the absorbing membrane; thereby, increasing
efficacy
5
.
For a successful development of a gastroretentive system, the selected dosage form must be able to reside for a time
necessary to release the entire drug included before the normal physiology of the stomach can clear up the dosage form to
the intestine
6
.
Many attempts have been made to attain gastroretention through different systems including bioadhesion
7
or
mucoadhesion to gastric mucosa
8-10
, high density systems
11
, floating systems
12-15
, and expandable systems
16
. In our
study, we focused specifically on superporous hydrogel systems, as the fast swelling
17
highly porous nature
18-20
of these
devices made them excellent candidate materials for gastroretentive delivery of many drugs
5
.
Owing to their unique properties, when applied as drug carriers, superporous hydrogels swell to a volume much larger
than the opening of the pylorus
21
; thus, remaining in the stomach for the time necessary to release the loaded drug within
their matrices before they begin to degrade
22
.
The new technology found extensive pharmaceutical application. Dorkoosh etal succeeded to prepare superporous
hydrogel polymers loaded with peptide drugs such as buserelin, octreotide and insulin, and proved that these devices
were promising systems for peroral peptide drug delivery
23-24
. Later on, Yin etal were able to improve the intestinal
absorption of insulin using superporous hydrogel containing interpenetrating polymer network (IPN)
25
. A more recent
study achieved by Gümüşderelioğlu etal demonstrated the superiority of superporous polyacrylate/chitosan
interpenetrating network hydrogels for protein delivery. Bovine serum albumin was taken as a model protein. Loading
was performed by the soaking method before and after IPN formation
26
.The method of soaking superporous hydrogels in
drug solutions was also employed in loading rosiglitazone maleate on swelled polymeric matrix
27
. Mahmoud etal
incorporated a self-nanoemulsifying drug delivery system into the SPHC matrix
28
. The incorporation of ranitidine
hydrochloride and release retardant polymers in SPHC through a central hole was demonstrated by Chavda etal. A piece of
SPHC was used to close the hole by the aid of biodegradable glue. The whole system was used to sustain the delivery of the
drug over 17 hours
29
.
Furosemide, a famous "high ceiling" loop diuretic, suffers from a short half-life (1-2hrs) and short duration of action
(~2hrs), besides a narrow absorption window. All these factors together provided a good rationale for its relatively low