Abstract:
The present work has been planned through rational designing to develop targeted
drug delivery system for alfuzosin HCl. Alfuzosin is basically selective antagonist of alpha 1
adrenoreceptors, indicated for treating benign prostatic hyperplasia. Its dose is 2.5 mg thrice
daily and the treatment plan includes steady-state concentration of the drug throughout course of
therapy. Due to readily absorbance and development of postural hypotension, it is not being
indicated for treatment of hypertension. Through this research project, development of targeted
systems like hydrogels and floating drug delivery system has been made in order to control the
release of drug molecule.
Regarding hydrogels; two different types of pH dependant three dimensional
polymeric networks have been developed through free radical polymerization. In first phase;
nine different formulations of pectin (Pec) have been evaluated in combination with acrylic acid
and crosslinked through glutaraldehyde. In second phase; various grades of poly (ethylene
glycol) (PEG) (Mw 400, 4000, 8000, 10000, 12000 & 20000) have been crosslinked with acrylic
acid through N,N,,-Mehtylene-bis-acrylamide (MBAAm). After development of discs, these
model systems were envisaged for various important elucidations like swelling studies, In-Vitro
drug release analysis, Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (X
RD) and Scanning Electron Microscopy (SEM). In order to predict releasing site and pattern;
both dynamic and equilibrium swelling studies were conducted and implementation of various
kinetic models has helped to elucidate kinetics of released molecule more efficiently. For both of
the systems, frequency variations indicated by FTIR spectrum revealed interaction between the
used polymers and monomers. Thermal stability has been reported by thermo gravimetric
analysis while after copolymerization; increased enthalpy characters have been reported. In pectin based formulations, release of the drug followed zero order rates while in case of PEG
based formulations; variations were reported in both rate and mechanism of drug release along
with variations of molecular weights used. In both type of formulations, the drug release data is
closely related to the swelling study’s findings and there is development of common character
i.e. release of maximum amount of drug at pH 7.5.
In floating drug delivery system, direct compression methodology has been
adopted. The study has been aimed at developing floating system with non effervescent
mechanism by using hydroxypropyl methylcellulose (HPMC) K100M, microcrystalline cellulose
(MCC) PH 102, carbopol® and three grades of poly (ethylene glycol) (MW 10,000, 12,000 and
20,000). Various pre-compressional (angle of repose, compressibility index and Hausner’s ratio)
and post compressional parameters (In-vitro buoyancy test, thickness, diameter, hardness,
friability and In-vitro dissolution test) have been conducted to evaluate the suitability of
developed dosage form for floating drug delivery system. The study is more focused towards
evaluation of three grades of PEG (MW 10000, 12000, 20000) as all other parameters have been
used as a constant quantity. Good matrix integrity has been found as all the formulations have
presented total flotation time for more than 24 hours without disintegration. The formulation
which doesn’t contain PEG has demonstrated first order along with fickian transport mechanism
while all other formulations showed variation in their kinetic profile as the quantity and type of
PEG varied.
On the bases of revealed data of hydrogel and floating drug delivery
system characterizations, it can be concluded that these systems are capable of delivering the
drug molecule to the desired site in a predetermined mode of release.