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ABSTRACT
The purpose of this research was to develop hydro dynamically balanced systems of Ranolazine, an anti-anginal drug which are designed to increase the
gastric residence time, thus prolonging the drug release. In the present study, the tablets were prepared by direct compression technique using different
polymers like HPMC (K4M, K15M, and K100M), Carbopol 934P, Chitosan and sodium bicarbonate as the gas generating agent. The prepared tablets were
evaluated with different parameters like hardness, friability, uniformity of weight, content uniformity, in-vitro buoyancy studies, swelling characteristics and
in-vitro dissolution study. The tablets containing Ranolazine released 75.19 to 99.44% of drug at the end of 12th hr by in-vitro release study. The formulation
RF8 was selected as an optimized formulation because it gave the best result in terms of the required in-vitro buoyancy study, good floating integrity, drug
release in sustained release manner and best fitted to Korsmeyer-Peppas model with R2 value of 0.983. As the n value for the Korsmeyer-Peppas model was
found to be less than 0.89, it follows case-2 transport. In-vivo radiographic studies revealed that the tablets remain in the stomach for 300±10 mins which
indicates the increase in the gastric residence time. Short-term stability studies indicated no appreciable changes in the drug content and In-vitro drug release
rates of formulation RF8
INTRODUCTION
Novel oral controlled dosage form that is retained in the
stomach for prolonged and predictable period is of major
interest among academic and industrial research groups. One
of the most feasible approaches for achieving prolonged and
predictable drug delivery profile in the GI tract is to control
gastric residence time (GRT)10. Various gastro retentive
techniques were used including floating system, raft systems,
expanding systems, swelling systems, bioadhesive systems
and low density systems. Gastric retention ensures the
delivery of drugs with narrow residence time in the small
intestine region11. Floating systems having low density
systems that have sufficient buoyancy to float over the gastric
contents and remain in the stomach without affecting the
gastric emptying rate for a prolonged period16. While the
systems float over the gastric contents, the drug is released
slowly at the desired rate, which results in increased gastric
retentive time and reduces fluctuation in plasma drug
concentration.
MATERIALS AND METHODS
Ranolazine was a generous gift sample from Micro Labs Ltd,
Hosur, India. Hydroxy propyl methyl cellulose (HPMC K4M,
HPMC K15M and HPMC K100M), Carbopol 934P were
purchased from Yarrow Chem Products Mumbai, India.
Chitosan was gifted from Cochin fisheries dept, Kerala. All
other chemicals used were of analytical grade.
Preparation of floating tablets of Ranolazine
Floating tablet of Ranolazine was prepared by direct
compression method14. All the ingredients were accurately
weighed and mixed properly. The drug and polymer were
blend in mortar followed by the addition of sodium
bicarbonate, MCC, talc and magnesium stearate, finally
compressed into tablets using a rotary punching machine.
Evaluation of floating tablets14, 24
Physical evaluation of floating tablet of Ranolazine
Hardness test: The crushing strength (Kg/cm2) of tablet was
determined by using Monsanto hardness tester (Monsanto,
Japan).
Friability test: This was determined by weighing 10 tablets
after dusting, placing them in the friabilator (Roche
friabilator) and rotating vertically at 25 rpm for 4min. After
revolutions the tablets were dedusted and weighed again the
percent friability was calculated by the formula
%F= {1-Wt/W} ×100
Uniformity of weight: 20 tablets were selected at random
and weighed individually. The average weight of each batch
of tablet was calculated. Individual weights of the tablets
were compared with the average weight. Since the tablets
weighed over 500 mg, I.P specifies that the tablets pass the
test if not more than two of the individual weights deviate
from the average weight by more than 5%.
Content uniformity: Randomly select 10 tablets were
weighed and make powdered individually. Take powder of
individual tablet which is equivalent to 100 mg was weighed
and dissolved in 100ml of Methanol, then the solution was
sonicated for 15 minutes, then undissolved matter was
removed by filtration through Whattman No.1 filter paper,
then serial dilutions were carried out. The absorbance of the
diluted solutions was measured at 272nm. The concentration
of the drug was computed from the standard curve of the
Ranolazine.
Thickness and diameter: Five tablets were randomly
selected for the determination of thickness and diameter with
the help of vernier calipers (Mitutoyo Corporation, Japan).
In-vitro buoyancy study: The test was performed using
dissolution testing apparatus USP type-1. The test for all the
formulation was carried out in 900 ml 0.1 HCL at basket
rotation of 100 rpm at 37±0.50C. The time required for the
tablet to rise to the surface of the dissolution medium and the
duration of time tablet constantly floated on the dissolution
medium was noted as floating lag time and total floating time
respectively.
Swelling characteristics (Water uptake study): The
swelling properties of the tablets were determined by placing
the tablet in dissolution test apparatus (LabIndia DS 8000), in
900 ml of 0.1 N HCl at 37±0.50C. The tablets were removed
periodically from the dissolution medium after draining free