RESEARCH ENVISAGED
Thiocolchicoside is a muscle relaxant with anti-inflammatory and analgesic effects. It acts as a competitive GABAA receptor antagonist and also glycine receptor antagonist with similar potency and nicotinic acetylcholine receptors to a much lesser extent. It has powerful convulsant activity and should not be used in seizure prone individuals.
Thiocolchicoside is having a half-life of 5-6 hrs. The bioavailability of Thiocolchicoside tablets is approximately 25% absorbed with first pass metabolism and the serum concentration touches its peak within 1-2 hrs after oral administration.
Due to inherent draw backs of Thiocolchicoside an alternative drug delivery systems is needed to accomplish maximum therapeutic efficiency add to reduce dose dependent side effects and to develop patient compliance. The physicochemical properties of Thiocolchicoside like smaller dose, partial hydrophilicity, stability at GIT pH, shorter biological half-life, how molecular weight etc, makes it an ideal applicant for administration by oral route.
Hence, the attempt is to formulate sustained drug delivery system in the form of matrix tablets which will overcome inherent conventional drawbacks like poor patient compliance, shorter half-life and poor bioavailability.
Polysaccharides may always be a better alternate for the semi-synthetic polymer being non-toxic, biodegradable, and non-carcinogenic with least regulatory issues. So, the main object of proposed work is to focus on the possibilities of using this polysaccharides as Guar Gum and Okra Gum for the development of extended release drug delivery system of Thiocolchicoside.
In present, work we have tried to explore the matrixing ability of Okra Gum, and Guar Gum polymers for the development of extended release drug delivery system of Thiocolchicoside, which have very little half-life and number of adverse effects are associated with it. So it may be a good applicant for such delivery.
PLAN OF WORK
In the current studies it was proposed to design a matrix forming drug delivery for Thiocolchicoside. The plan of work can be outlined as follows:
1.
Literature review of research articles
and patents
2.
Procurement of drug
3.
Extraction and isolation of okra gum
polysaccharide
4.
Pre-formulation studies and drug analysis
Ø Characterization
of drug sample
·
UV Spectroscopic analysis
·
IR Spectroscopy
·
Differential Scanning Calorimetry
Ø Solubility
profile
Ø Drug
excipient interaction study
5.
Formulation and Optimization of Thiocolchicoside
loaded Matrix Tablet
Ø Selection
of polymer and its concentration
Ø Selection
of channeling agent and its concentration
Ø Comparison
of formulation based on guar gum and okra gum
6.
Evaluation of matrix tablet
·
Pre-compression parameter
·
Angle of repose
·
Bulk density
·
Tapped density
·
Carr’s index
·
Hausner’s ratio
·
Post compression parameter
·
Hardness test
·
Friability test
·
Uniformity test
·
Drug content uniformity
·
In vitro dissolution test
7.
Data treatment of the result obtained to predict release behaviour
8.
Optimization studies for the concentration of Guar Gum
9.
Optimization studies for the concentration of Okra mucilage
10.
Evaluation of various batchces sof matrix tablet
LITERATURE REVIEW
Murakami H et. al.
(2000) had reported the
long-acting matrix tablets by direct compression of the mixture of drug and
poly (DL-lactide-co-glycolide) nanoparticles and to explain the effects of such
factors as polymer species, mixing ratio of nanoparticles with different molecular
weights, and the tablet weight on the drug release and to discuss the mechanism
of drug release from matrix tablets. This structure had advantages in terms of
simplicity in design and predictability of drug release rate and may be useful
as an implantable dosage form.
Nath B. S. et. al
(2000) had prepared the in
vitro release date showed that 30 percent w/w total matrix component gave
extended release of Theophylline for more than 8 hours. Analysis of drug
release rate from the matrix system showed that the drug was released by
anomalous diffusion obeying first order rate kinetics.
Baumgartner S et. al.
(2000) had prepared the floating
matrix tablets, which are designed to prolong the gastric residence time,
increase the drug bioavailability and reduce the side effects of irritating
drugs. The drug released from those tablets was sufficiently sustained (more
than 8 h) and non-Fickian transport of the drug from tablets was confirmed.
AmaralM et. al.
(2001) had showed that an
increased amount of HPMC or hydrogenated castor oil resulted in reduced drug
release, the inclusion of buffers in the HPMC matrix tablets enhanced Naproxen
release. The presence of lactose on HPMC tablets did not show different result
from that comprising dibasic calcium phosphate as filler. For the tablet of HCO
the presence of lactose enhanced the Naproxen release rate.
HijareA et. al.
(2004) had designed and evaluated
sustained release tablets of diltiazem hydrochloride by using guar gum, sodium
CMC and HPMC polymer, various physical characteristics drug-polymer
interactions in vitro drug release and stability were evaluated.
Yunqi W et. al.
(2005) had reported a optimized
validated simple spectrophotometric method for determination of glucosamine
released from sustained release (SR) hydrophilic matrix tablet based on
reaction with ninhydrin. Determination of glucosamine release from tablet
dosage form was developed based on the diketohydrindamine-diketohydrindylidene
color formation. Dissolution studies of sustained release glucosamine
formulations caused in reproducible dissolution profiles.
Kalu V et. al. (2006) had
reported an okra gum was evaluated as a controlled-release agent in modified
release matrices in comparison with sodium carboxymethylcellulose (NaCMC) using
aspirin as the model drug. Tablets were produced by direct compression and the
in vitro drug release was assessed under conditions similar to those in the
gastrointestinal system for a period of 6 years. They had concluded that the
okra gum is suitable for the sustained release of water soluble drugs.
ShoailM et. al. (2006) had
developed a once-daily sustained release matrix table of ibuprofen using
hydroxypropyl methylcellulose (HPMC) as release controlling factor and
evaluated the drug release parameters as per various release kinetic models.
They concluded that the drug release mechanism was found as a complex mixture
of diffusion, swelling and erosion.
Corti G et. al. (2007) had
reported the sustained release Matrix Tablet of metformin hydrochloride in combination
with tri acetyl-cyclodextrin. They concluded that the combination of the drug
with a hydrophobic cyclodextrin, such as TABCD, and its dispersion in a
suitable polymeric matrix, was effective and adequately modulating the drug
release rate.
Barakat N et. al. (2008) had
examined the release of carbamazepine from hydrophobic and
hydrophilic-hydrophobic matrix combination. Hydrophobic matrix tablets had
ready by hot fusion technique, while hydrophilic-hydrophobic matrix tablets had
ready by wet granulation technique. They concluded that the both matrix
formulation show higher relative bioavailability of CBZ than the reference
Tegretol tablet.
Praveen S. H. et. al. (2008) had developed oral controlled release matrix tablet formulations of
Isoniazid using Hydroxypropyl methylcellulose (HPMC) as a hydrophilic release
retardant and in-vitro release characteristics of the drug. The formulations
was settled using wet granulation technology. They concluded the hydrophilic
polymer like HPMC could be used as a matrix material to design CR formulations
of a water-soluble drug Isoniazid with desired quality and release
characteristics. The tablet manufacturing method was relatively simple and can be easily adopted in conventional tablet manufacturing
units in industries on a commercial scale. A series of CR formulations of
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