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The Mission of this research is to formulate and enhance the release of Diclofenac sodium utilising Tamarind Kernel Gum (TKG) as natural polymer. The study investigated the potential of TKG by comparing with Hydroxy Propyl Methyl Cellulose (HPMC) and Sodium Carboxy Methyl Cellulose (Na CMC). Nine formulations were designed, three of which incorporated TKG, HPMC and Sodium CMC. Wet Granulation Technique was employed for the formulation of Diclofenac sodium matrix tablets and evaluation tests were performed to check the performance of tablets. The study sought to examine the effect of various matrix formers on the release retardant property The formulations, comprised of tamarind kernel gum, had a longer duration release profile, as demonstrated by invitro studies and kinetic analysis In conclusion, the use of natural polymer in diclofenac sodium tablet formulation offers the promise of sustained release medications.
ABSTRACT:
The Mission of this research is to formulate and enhance the release of Diclofenac sodium utilising Tamarind Kernel Gum (TKG) as natural polymer. The study investigated the potential of TKG by comparing with Hydroxy Propyl Methyl Cellulose (HPMC) and Sodium Carboxy Methyl Cellulose (Na CMC). Nine formulations were designed, three of which incorporated TKG, HPMC and Sodium CMC. Wet Granulation Technique was employed for the formulation of Diclofenac sodium matrix tablets and evaluation tests were performed to check the performance of tablets. The study sought to examine the effect of various matrix formers on the release retardant property The formulations, comprised of tamarind kernel gum, had a longer duration release profile, as demonstrated by invitro studies and kinetic analysis In conclusion, the use of natural polymer in diclofenac sodium tablet formulation offers the promise of sustained release medications.
KEYWORDS: Diclofenac Sodium, Tamarind Kernel Gum, Hydroxy Propyl Methyl Cellulose, Sodium CMC, Wet Granulation, Sustained Release.
INTRODUCTION:
Ninety percent of the intake of medicine presumably occurs by the oral route. Oral dosage formulations are the most often used drug delivery route1. This is evidenced by the fact that in comparison to other oral dosage forms, Tablets are the manufacturer's favoured form because of its greater stability, virtually tamper-resistant, and fairly low cost of production, packing and distribution2. The design of controlled release formulations is of great interest in pharmaceutical research especially for NSAID like Diclofenac sodium.
Diclofenac sodium is well known for its properties that provide relief from pain and reduce inflammation, on the other hand due to its short half-life, frequent dosage is required, that could trigger gastro intestinal adverse effects3. controlled release formulation development may eliminate these challenges by ensuring a constant medication release at a zero order in nature by perpetually releasing a quantity proportional to the amount the body eliminates over time4. Matrix type of approach is suitable for the formulation that has a homogenous dispersion of the API inside hydrophilic or hydrophobic polymers that prolong the release rate5. Polymers have been widely used for medication delivery due to their unique features that cannot be mirrored by material alternatives. Natural Polymers are intriguing because of their affordability, versatility to various chemical alterations and numerous dervitizable groups6. Natural Gums feature as one of the most common hydrophilic polymers. Natural gums are biodegradable, obnoxious in recognition of this reason, the utilization of natural gums are considerably taken contemplated in the formulation of Controlled Release matrix tablets7, Tamarind kernel gum, a galactoxyloglucan polysaccharide extracted from Tamarindus indica L. seeds has been explored for its potential utilisation as release retardant to enhance the dissolution properties of diclofenac sodium8
MATERIALS AND METHODS:
Materials:
Giftsample of Diclofenac Sodium was acquired from Bangalore Pharmaceuticals Research Laboratory Ltd, Bangalore.
Tamarind was purchased from the grocery
HPMC K15M from Colorcon
Na Carboxyl methyl cellulose High Viscosity Grade
All further materials used were of Pharmacopeial grade
Method:
Gum Isolation from Tamarind Seed:
Tamarindus indica (TI) crushed kernels were immersed in water for a whole day, subsequently heated for 60 minutes and set aside for 120 minutes to allow resin to settle into the water. To remove marc from the filtrate, the soaked seeds were strained through a cotton bag. To precipitate the gum, an equivalent amount of 100% ethanol was added to the filtrate9. Filtration was used to separate the gum. The insoluble residue was not dumped, but rather exposed for numerous extractions with diminishing quantities of solvent for extraction. Hot air oven at 40°C was used to dry the gum. The gum which was previously dried was pulverised and kept in sealed containers at room temperature10.
Physicochemical Characterization of Tamarind Kernel Gum (TKG)11 :
The Detached TKG has undergone evaluation for various physicochemical characterization. TKG generated from TI seeds, was cream to off-white coloured powder. 1% aqueous dispersion showed a viscosity of 450cps, implying that colloidal nature of gum complying with Non-Newtonian substances that refuse to settle down rapidly.
Phytochemical Characterization of Tamarind Kernel Gum12
Gum when tested with FeCl3 gave dark precipitate indicated the presence of tannin. Ruthenium red gave pink colour and benzidine solution gave blue colour indicating the presence of mucilage. The gum was exposed to a few drops of hydrogen peroxide to check for the presence of peroxidases enzymes, which are typically present in gum acacia. No blue coloring appeared, indicating the absence of enzymes.
Formulation of Controlled Release Tablets:
Diclofenac sodium controlled release matrix tablets were developed using different ratios of drug to polymer (1:1, 1:2, and 1:3), with TKG, HPMC, and Sodium CMC as the matrix agents. The active pharmaceutical ingredient and matrix agents were mixed thoroughly in a mortar using the serial dilution method. A binder solution, made from equal parts methanol and filtered water, was incorporated to form a dough-like mass. This mixture was then sieved through a #12 sieve to create moist granules and dried at 60°C13. The dried granules were then sieved through a #16 sieve to break up any clumps. To the dried granules, talc and magnesium stearate (each at 2%) were added after being sieved through a #20 sieve.
This blend was stored in a self-sealed cover. The granules were then compacted into tablets using a compression machine, with 9mm round flat punches, achieving a hardness of 5-7kg/sq.cm. The formulae were tabulated
Post Compressional Evaluation of Diclofenac sodium Controlled release matrix tablets: Physical Appearance14:
The overall look of the tablet were evaluated through visual inspection. The tablet was spherical, unstained, smooth and odor-free
Hardness15:
The rigidity of tablets was examined with a Monsanto Hardness Tester. The test has been executed triplicate on all batches in accordance with the USPXXIV monograph on uncoated tablets
Friability16:
Tablets from all batches have been applied to test friability as per USPXXIV monograph. Friability testing was carried out utilising a Roche Friabilator with triplicate readings
Disintegration Time (DT):
Thermonic Tablet Disintegration Test Machine was utilized to measure the disintegration time by employing aqueous, acidic and alkaline solvents as disintegrating fluids.
Estimation of drug in Diclofenac Tablets17:
Formulated tablets were crushed down, and the tablet powder containing 50mg equivalent weight was meticulously measured and placed into a 100ml volumetric flask (VF). The solution in the VF was then filtered and was diluted suitably and diclofenac content was measured at 276nm employing a UV-Visible Spectrophotometer.
RESULTS AND DISCUSSION:
UV-Visible Spectrophotometer is employed for analysing diclofenac sodium concentration at 276nm absorbance in 0.1N HCl and 6.8 Phosphate buffer. Calibration curve was generated to examine for linearity, accuracy, precision and interference via Beer's rule at the amount ranging from 10 to 50µg/ml. The strategy's repeatability was assured with low RSD values (<1.21%)
FTIR investigations were utilised in determining drug and excipient compatibility. The spectral studies shows no chemical interaction between drug and excipient.
Table 4 illustrates the physical characteristics of matrix tablets of diclofenac sodium. The level of hardness of formulated tablets was ranging from 5.5-7.0 kg/sq.cm. The drop in weight through the friability test was not more than 0.10% in all instances. Formulated diclofenac sodium tablets are within 100±3% labelled claim. The Disintegration test confirmed that diclofenac sodium matrix tablets remain intact in aqueous, acidic as well as in alkaline nature
Diclofenac release matrix tablets were monitored using an 8-station dissolving test device (Lab India, Disso 2000) operated at 50RPM utilising stirrer (Paddle) and 37±1°C. The dissolving media was a 900ml 7.4 phosphate buffer. Over an interval of 12hours, 5ml samples of each individual were collected at various points of time. Drug release profiles are displayed in Figure 2.
Formulation F1, F2, F3 were designed with Tamarind kernel gum as matrix forming agents at a concentration of 50%, 100%, 150%. Drug release of 99.1%, 98.1%, 99.8% was identified at 6hours, 7hours and 12hours with F1, F2, and F3 respectively.
Formulation F5, F6, F7 were prepared with HPMC at 50%, 100%, 150% concentration as matrix agents. F5, F6, and F7 exhibited drug release of 61.1%, 54.11%, and 46.2% at 12hours respectively.
Sodium CMC was used as matrix agent in formulation F7, F8, and F9 at concentration of 50%, 100%, 150%. With F7, F8 and F9 a drug release of 85.8%, 82.1%, and 79.1% at an interval of 12hours was noted, respectively. The release data was evaluated using the zero order, first order, Higuchi model, korsemeyer-peppas kinetic models. Coefficient of Regression values determined through the analysis of release data using kinetic models. Apart from F1,F2, and F3 all matrix tablet formulations followed first order kinetics.
All formulated matrix tablets illustrated Diffusion controlled drug release mechanism as indicated by Higuchi Model Data18. The drug release data was evaluated using the korsemeyer-peppas equation, for characterization of drug release mechanism19. The release exponent 'n' was found was observed with values ranging from 0.598 - 0.765 indicating Non- Fickian Diffusion
CONCLUSION:
It may be stated that to extend the drug release, dosage form employing tamarind kernel gum can be put forth and results illustrated that the formulations containing various concentrations of tamarind kernel gum especially F3 exhibits a release upto 12hours.
CONFLICT OF INTEREST:
The authors have no conflicts of interest regarding this investigation.
ACKNOWLEDGMENTS:
Authors must be thankful to the Management and Principal of KVSR Siddhartha College of Pharmaceutical Sciences for providing the necessary facilities.
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