FORMULATION AND EVALUATION OF FLOATING TABLET OF ZOLMITRIPTAN TABLET

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ISSN: 2005-4238 IJAST 825

FORMULATION AND EVALUATION OF FLOATING TABLET OF ZOLMITRIPTAN TABLET

* Satya Prakash ¹, Dr. Sachin Kumar², Dr. Manoj Kumar Sagar³

1Research Scholar, ²Professor, ³Principal,

1N.K.B.R College of Pharmacy & Research Centre, Meerut

2,3Department of Pharmaceutical Sciences, NKBR College of Pharmacy & Research Centre Meerut U.P.

ABSTRACT

The present investigation was performed to find out floating tablets of Zolmitriptan tablet by wet granulation method. Zolmitriptan in floating tablets by using various Viscosity grades of Hydroxy Propyl Methyl Cellulose, HPMC K15 M and Ethyl cellulose. The Sodium bicarbonate also added in different concentrations as an agent of gas generating to improve floating capacity of tablet. All the tablets were studied for their parameters for Pre-compression Bulk density, Tapped density, Carr’s index, Hausner’s ratio and Angle of repose and Post-compression Hardness, Thickness, Friability, Weight variation and Content uniformity. Tablets are also evaluated in-vitro shows best release range of 12 hours. The release kinetics of some formulation like F2, 3, 4, 5 and 9 followed Higuchi model, formulation F1, 5, 6, 7 and 8 followed the Zero order and formulation F1 and 5 followed 1^st-order. There is no change in colour, but change in Hardness, occur in evaluation of formulation 4. Various studies were taken place (in-vitro) which increase the gastric residence time and improved bioavailability of the drug. Hence in the present investigation floating tablets have been synthesized to overcome drawbacks associated with Antimigraine tablet of Zolmitriptan.

Keywords:- Investigation, Floating, Treatment, Gastro-retention, Zolmitriptan, Tablet, Drug, Administration.

Introduction

Outline of Introduction

The study of floating drug delivery systems should be especially designed to achieve huge bioavailability.

At present lot of scientists are engaged in the development of the ideal FDDS. This system have an advantage of single dose for the whole course of treatment and it deliver the active form of drug in target site. Scientists have developed a system and that system provoke other scientists to form control release tablet. Control release means control in the drug release in target site and minimize the effect of drug with less and lower dose. Gastro-retention drug delivery systems can be maintained in the stomach which can help increase long-term drug delivery that has an absorption window in certain GI regions. These system help in releasing the drug till drug reaches the suction window, result in good bioavailability. The broadest route of administration is oral route. Which are used know a days in different dosage forms. The gastro-retention drug delivery system can be retained in the stomach and help prolong gastric retention time and optimal in absolute bioavailability with improving patient compliance in migraine treatment.

These systems help in releasing drug into gastric fluid before absorption and, hence guard the bioavailability of drugs that have strength and better solubility in gastric fluids¹. Gastrointestinal disease are the result of migraine, headache including nausea and vomiting. Survey should be performed to know about the difference in normal head ache to migraine. Frequent headaches are the result of chronic

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disorder². Migraine headache is followed by sensory warning symptom such as flashes of light, blind spots and legs, distaste, emit, and increased sensitivity to light and sound. Delayed triggers, controlling indication and taking drugs on migraine treatment and precaution. OTC medications such as naproxen, ibuprofen, acetaminophen and other analgesics such as caffeine with aspirin are often the first abortive therapies to eliminate a headache or significantly less pain. Activation of trigeminal sensory nerve result in the release of vasoactive neuropeptides which react with dural blood vessels to promote vasodilatation and dural plasma extravasations resulting in neurological inflammation^3-4. In the treatment of migraine Zolmitriptan act as a neurotransmitter receptor agonist. Zolmitriptan past through metabolism and get dissolve in to show its result^5-6. Zolmitriptan is an agonist for a member of the vascular 5- hydroxytryptamine receptor subtype having only a weak sympathy for the 5-HT1A and 5-HT7 receptors and no significant pharmacological activity at the 5-HT2, 5-HT3 receptor subtypes at alpha-1, alpha-2, dopamine-1, dopamine-2, muscarinic. So an attempt has been made to bypass hepatic first pass metabolism by increasing bioavailability^7-10.

Material and Methods

Table:-1 List of Chemicals

S. No. Chemicals Brand

1 Drug ( Zolmitriptan) Jubilant Life Sciences Roorkee

2 HPMC Nova Polychem Karol Bagh, New Delhi

3 HPMC K15M S.D Fine chemicals Ltd, Mumbai, India

4 Ethyl cellulose Bio-Sols Pvt. Ltd., Mumbai India 5 Sodium Bicarbonate S.D Fine chemicals Ltd, Mumbai, India 6 Magnesium Stearate S.D Fine chemicals Ltd, Mumbai, India

7 Talc S.D Fine chemicals Ltd, Mumbai, India

Preformulation Studies:- Standardization of Drug:-

UV Spectrophotometric method for Zolmitriptan:-

5mg of Zolmitriptan was analyzed by using (Lab India UV 3000) spectrophotometer heaving double beam detector configuration. Calibration curve of Zolmitriptan was plotted in 0.1N HCl at maximum wavelength of 284nm¹¹.

Physical drug Excipients Compatibility Studies:- Fourier transforms infrared spectroscopy:-

FTIR study was performed to verify pure drug and polymer interaction. The study of pure drug Zolmitriptan and HPMC, HPMC K 15 M and Ethyl cellulose. It was performed by KBr pellet method.

The pure drug powder with KBr and pellet was prepared by high pressure to 100kg/cm for 2min. The obtained tablet was analyzed in (FTIR 8400S, Shimadzu, Japan). KBr was obtained initially before analysis of test samples. The procedure was repeated for the analysis of drug and excipients¹².

Determination of melting point:-

Melting point determination was done by using capillary method (Kumar and Sindhuri 2014).

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Solubility:-

Slightly soluble in water (1.3 mg/mL) at 250°C however shows bigger solubility in 0.1M acid (Panda et.al., 2015).

Micrometry study of Powder:- Bulk density and tapped density:-

Both bulk and tapped density were calculated a quantity of powder from each formula, previously light shaken for break any amount formed, was introduced into the 10ml of measuring cylinder. After initial volume was observed the cylinder was allowed to fall down its own weight from the hard surface from a height of 2.5cm at 2sec Intervals. The tapping was continued until no further change in the volume was noted LBD and TBD were calculated using the following formulas.

LBD = Wt of powder/Vol of powder ……. (4.1) TBD = Powder wt/Tapped vol powder …….. (4.2) Carr’s index:-

The floability of powder can be determined by differentiate the (LBD) and (TBD) of powder and the value at which it crowded depressed ¹³.

Carr’s index is calculated by formula

Carr’s index (%) = ^TBD−LBD_TBD × 100 ……. (4.3) Hausner’s ratio:-

The Hausner’s can be determined by the following equation¹³. Hausner’s ratio = ^TBD

LBD ……. (4.4) Where,

TBD= Tapped bulk density LBD= Loose bulk density Angle of repose:-

Angle of repose was determined by using funnel method of following formula¹³.

Tanθ = ^h_r ……. (4.5) Where,

θ = angle of repose h = height of the pile r = radius of the pile base

Preparation of Matrix Tablets of Zolmitriptan:-

Floating matrix tablet containing Zolmitriptan were prepared by wet granulation method by using various concentrations of different grades of polymers with NaHCO3. Zolmitriptan and polymers were mixed completely using mortar and pestle. Alcohol was utilized as granulating medium. Granules were ready by passing the wet coherent mass through # 18 sieves. The granules were dried in hot air oven at a temp of 60°C for 1 hour. Dried granules were sifted along # 20 sieves & lubricated, Mg stearate and talc simply 4- 5 min before compression.

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Table:-2 All the formulation composition of floating tablet Zolmitriptan

S.No. Ingredients (mg) No. of Formulation

1.

Zolmitriptan

F1 F2 F3 F4 F5 F6 F7 F8 F9

5 5 5 5 5 5 5 5 5

2. HPMC 50 45 40 40 35 30 30 25 20

3. HPMC K 15 M 15 20 25 15 20 25 15 20 25

4. Ethyl cellulose 15 15 15 15 15 15 15 15 15

5 Sodium Bicarbonate 10 10 10 20 20 20 30 30 30

6 Magnesium Stearate 3 3 3 3 3 3 3 3 3

7 Talc 2 2 2 2 2 2 2 2 2

Total Weight 100 100 100 100 100 100 100 100 100

Evaluation Parameters of Post-compression Tablet:- Tablet Hardness:-

The Zolmitriptan floating tablets hardness was determined by using Monsanto hardness tester. From each batch the crushing strength of ten floating tablets with known weight was note in kg/cm2 and hardness of tablets was determined¹².

Tablet thickness:-

The thickness of floating tablets was determined, five tablets were used and average value was calculated by using Vernier caliper¹².

Friability:-

Friability of tablet was stand determined by using Roche Friability tester. Firstly twenty tablets taken and weight accurately and transfer into Friability tester. The tester was operated at 25 rpm for 4 min or run up to 100 revolutions. The tablets were loss weighed; % friability was calculated by following formula¹². F = Initial wt - Final wt/Initial wt × 100 ……. (4.7) Weight variation: -

This method is performed as weight variation of tablets. Twenty tablets were individually weighed in (gm) on electronic balance. After that calculated the average weight of tablet and checked for weight variation of tablets.

Calculation of percentage weight deviation

% Variation = Individual wt - Average wt/Average wt × 100 ……. (4.8) Content uniformity:-

This test is performed by taking 20 tablets weighed and powder. A quantity of powdered tablet equal to 100mg of Zolmitriptan tablet was dissolved in 0.1N HCl solution. It was diluted and absorbance was

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measured 284nm by using Zolmitriptan pacify was uniform by using UV Spectroscopy (Lab India UV 3000) at 284nm 0.1N HCl solution and % drug content was estimated¹².

Floating lag/time study:-

The tablets were transferred in a 100ml, beaker containing 0.1N HCL. The time required for the tablet to increase to the surface and float was performed as floating lag time and total duration of time by which dosage form remain buoyant is called total floating time.

In Vitro Drug Release Studies:-

In-vitro drug release study for the prepared matrix tablets were manage for a amount of 12hrs by using USP equipment II (Paddle type) at temp. 37±.5ºC. The studies were performed with 100rpm using 900ml of 0.1N HCl. 10ml of samples were withdrawn at one hrs intervals and replace equal volume of buffer.

The Zolmitriptan release was measured at 284nm by using an ultraviolet visible spectrophotometer (Lab India UV 3000)¹².

Dissolution parameters:-

Medium : 0.01N Hydrochloride

Type : USP apparatus II (Paddle type) RPM : 100

Quantity : 900ml

Temperature : 37 ºC ± 0.5 ºC Duration : 12 hrs

Sampling time : 1-12hrs.

Kinetic Parameter:-

The kinetic in-vitro release study data was applied to kinetic model like as- Zero order:-

The rate of those zero order reaction does not very with neither increasing nor decreasing reactants concentration. This implies that the speed of reaction is up to the speed constant, (k) of the reaction following equation^14-16.

M= Mo – Kot ……. (4.10) Where,

M= drug amount release.

Mo= total release drug amount.

Kot= rate constant.

First order:-

First order is defined as that proceeds at a rate that on linearly on single reactant concentration.

It is given by equation¹⁴.

Log C= Log Co – Kt/2.303 ……. (4.11) Where,

C= drug release amount.

Co= total release drug amount.

K= rate constant.

Korsmeyer-Peppas model:-

The Korsmeyer-Peppas model empirical related the function of time for diffusion controlled mechanism.

It is given by this equation.

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Mt/M∞ = ktn …….. (4.12) Where,

Mt / M∞ = could be a selection of drug release time Kt = Constant release rate

n = Exponent release Higuchi model:-

The release of a drug from a drug delivery system involves dissolution. Higuchi equation has become a kinetic equation¹⁴.

Ft = Kht1/2 ……... (4.13) Where,

Ft = amount release drug t = time

Kh = constant rate release Stability studies:-

The stability studies of optimised formulation (F4) were carried out according to ICH guideline. The correct formulation was subjected to stability at 40±2°C/75±5% RH for 90 days. After then duration the product was evaluated for colour, Hardness, Drug content & In-vitro drug release¹².

Result and Discussion:- Preformulation Study- UV Spectroscopy-

After scanning of the sample drug, the wave length was obtained about 284nm 0.1N HCl was utilized in the study of Zolmitriptan.

Table:-3 Standard Calibration Curve of Zolmitriptan

S.No. Concentration (μg/ml) Absorbance (284nm)

I. 02 0.152

II. 04 0.323

III. 06 0.512

IV. 08 0.694

V. 10 0.818

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Fig:-1 Standard Calibration Curve of Zolmitriptan 5.2 Physical drug Excipients Compatibility Studies:-

Fig:-2 FTIR spectra of Zolmitriptan

y = 0.1703x - 0.0111 R² = 0.9955

0 0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8 0.9

2 4 6 8 10

Calibration curve

calibration curve Linear (calibration curve)

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Fig:-3 FTIR Scop of Zolmitriptan+HPMC K15M

Fig:-4 FTIR spectrum of Zolmitriptan+HPMC

Fig:-5 FTIR spectrum of Zolmitriptan+Ethyl Cellulose Discussion FTIR Spectroscopy:-

The FTIR spectra of pure drug Zolmitriptan show design due to Nitrogen-Hydrogen extending at 3241.42/cm, Carbon=Oxygen extending at 1731.03/cm and C=Carbon stretching at 1551.0/cm. These assay were meeting the arrive values. The FTIR scope of optimised formulation F9 (Zolmitriptan+Material) reveal peak N-H stretching at 3244.70/cm, Carbon=Oxygen extending at 1734.05/cm, C=C stretching at 1546.09/cm.

Evaluation of Powders for Matrix Tablet:-

Table:- 4 Evaluation of Powders for matrix tablets of Zolmitriptan 5mg Formulation

Code

Angle of Repose

Bulk density (gm/ml)

Carr’s index (%)

Tapped density (gm/cc)

Hausner’s ratio

F1 25.20±0.10 0.228±0.02 26.15±0.9 0.312±0.04 1.45±0.14

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F2 22.36±0.06 0.299±0.12 24.36±0.6 0.375±0.06 1.39±0.18 F3 20.86±0.02 0.270±0.05 20.50±1.2 0.310±0.06 1.26±0.23 F4 23.25±0.10 0.215±0.08 30.68±0.8 0.310±0.05 1.48±0.20 F5 22.54±0.12 0.226±0.09 26.09±0.7 0.275±0.02 1.28±0.18 F6 23.74±0.04 0.245±0.10 20.50±0.8 0.309±0.09 1.35±0.13 F7 22.40±0.12 0.260±0.06 16.95±1.2 0.320±0.08 1.26±0.14 F8 21.71±0.14 0.282±0.12 21.72±1.4 0.331±0.012 1.15±0.06 F9 20.60±0.08 0.276±0.03 14.76±0.6 0.345±0.03 1.19±0.09 Values are expressed as mean ±standard deviation SD (n=3)

Discussion:-

The physical mixtures for matrix tablet were evaluated with respect to Angle of repose was found between 20.60±0.08 to 25.20±0.10and Carr’s index values were found between 14.76±0.6 to 30.68±0.8%

the powder of all batches indicating excellent to poor flow ability and compressibility. Hausner ratio was found to be range 1.15±0.06 to 1.48±0.20. Bulk density ratio was found to be range 0.215±0.08 to 0.299±0.12 and tapped density ratio 0.275±0.02 to 0.375±0.06 for all the batches indicating that possible and poor flow properties.

Fig:-6 Graphical representation of Carr’s index and angle of repose found in different batches of formulation

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Fig:-7 Graphical representation of bulk density and tapped density found in different batches of formulation

Evaluation Parameters of Post-compressed Tablet:-

Table:-5 Evaluation of Post-compressed floating tablet of Zolmitriptan 5mg Formulation

Code

Weight variation Average wt in

(mg)

Floating Lag/Time

(Sec)

Hardness (Kg/cm2)

Friability (%)

Thickness in (mm)

Drug content uniformity

(%)

F1 204±3.5 42±2.0 3.80±0.4 0.56±0.04 3.18±0.1 98.45±0.9

F2 206±2.5 35±3.5 4.46±0.6 0.65±0.03 3.34±0.4 97.37±1.5

F3 203±3.0 36±4.0 4.54±0.7 0.68±0.06 3.19±0.6 97.79±1.0

F4 205±2.6 25±1.5 4.18±0.4 0.71±0.02 3.25±0.2 98.60±1.6

F5 196±1.5 29±2.7 4.26±0.5 0.61±0.05 3.21±0.1 98.12±1.0

F6 201±3.0 24±2.5 4.31±0.2 0.78±0.07 3.27±0.7 96.55±2.5

F7 198±2.5 40±2.0 4.08±0.3 0.84±0.08 3.31±0.5 95.16±1.0

F8 205±2.8 16±2.6 3.99±0.4 0.96±0.02 3.18±0.03 98.36±1.2

F9 202±3.5 10±1.0 4.12±0.6 0.74±0.04 3.22±0.2 96.66±0.5

Values are intimate as design ± SD (n = 3) Discussion all parameter of tablets:-

The prepared tablets were evaluated for physical parameters hardness; friability, weight variation, thickness and drug content result are given in (table 5.3). Hardness of tablets were found to be in range of 3.80±0.4 to 4.54±0.7kg/cm2. The friability of all prepared tablets was found to be range 0.56±0.04 to

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0.96±0.02%. The thickness of prepared tablets were found range 3.18±0.1 to 3.34±0.4mm. The weight variations of all tablets were established to be 196±1.5-206±2.5mg. The Floating time 10±1.0 to42±2.0 and highest % drug content 98.60±1.6.

Fig:-8 Graphical representations of hardness and thickness found in different batches of formulation

Fig:-9 Graphical representations of weight variation and drug content found in different batches of

formulation

In-Vitro Drug Release Studies:-

Table:-6 In vitro drug release studies F1 to F5

Time % Release drug

Formulation F1 F2 F3 F4 F5

1 10.14±0.18 9.11±0.008 11.66±0.04 9.52±0.9 10.18±0.11

2 16.36±0.05 16.45±0.010 18.17±0.12 14.90±0.10 20.85±0.16

3 23.45±0.08 23.30±0.06 24.70±0.16 20.76±0.03 26.16±0.10

4 30.62±0.09 32.30±0.14 31.11±0.19 26.38±0.06 34.40±0.012

5 36.65±0.12 39.35±018 38.41±0.20 31.03±0.17 42.70±0.052

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Table:-7 In vitro drug release F6 to F9 Point are communicate as mean ±standard deviation (n = 3)

Discussion:-

The percentage of drug released from the formulation F1, F2 and F3 was found to be 95.46±0.016%, 95.46±0.016% and 92.46±0.028% respectively. The percentage of drug released from the formulations F4, F5 and F6 was found to be 96.28±0.010%, 95.70±0.02% and 90.11±0.032%. The formulation F7, F8 and F9 percentage drug release was found to be 93.22±0.024%, 95.35±0.016% and 92.30±0.018%

respectively. The best % drug released of formulation F4. It was also observed that the amount of polymer increase in the formulation then it was decrease in drug release rate, may be due to drug entrapped in hydro gel by forming hydrophilic polymer. The minimum combination of HPMC, HPMC K 15 M and Ethyl Cellulose of various ratios in the different formulation.

6 45.81±0.091 45.76±0.31 45.34±0.23 35.19±0.02 50.58±0.125

7 54.19±0.060 51.56±0.21 51.50±0.014 41.81±0.16 60.30±0.019

8 64.74±0.044 58.85±0.05 58.49±0.05 52.34±0.007 68.34±0.065

9 71.49±0.025 65.45±0.12 66.56±0.026 62.79±0.036 76.78±0.017

10 80.36±0.010 74.18±0.014 74.26±0.012 72.26±0.016 82.15±0.015

11 89.51±0.036 83.36±0.022 82.51±0.018 82.62±0.024 90.54±0.06

12 95.46±0.016 92.58±0.014 92.46±0.028 96.28±0.010 95.70±0.02

Time % Release drug

Formulation F6 F7 F8 F9

1 11.06±0.13 10.70±0.15 9.52±0.09 8.62±0.05

2 16.82±0.17 19.88±0.03 15.90±0.21 15.41±0.11

3 24.40±0.02 24.07±0.03 21.76±0.09 21.25±0.04

4 32.45±0.36 29.33±0.05 28.38±0.11 27.50±0.25

5 39.63±0.21 38.75±0.22 35.03±0.01 35.48±0.31

6 48.16±0.023 43.72±0.018 42.12±0.005 46.77±0.13

7 56.06±0.046 50.70±0.003 50.19±0.61 51.35±0.25

8 64.21±0.08 59.79±0.036 59.81±0.012 60.56±0.33

9 69.42±0.058 67.43±0.032 68.56±0.09 68.49±0.29

10 76.51±0.015 75.14±0.012 75.43±0.014 74.14±0.08

11 83.12±0.020 84.62±0.021 82.48±0.010 80.10±0.017

12 90.11±0.032 93.22±0.024 95.35±0.016 92.30±0.018

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Kinetics Parameter of all Formulation:-

Fig:- 10 Zero order release kinetics

Fig:- 11 First-order release kinetics of Zolmitriptan y = 7.4803x - 2.8909

R² = 0.973

-20 0 20 40 60 80 100 120

0 5 10 15

% drug release

Time (hr)

Zero Order Kinetics

F1 F2 F3 F4 F5 F6 F7 F8

y = -7.4803x + 102.89 R² = 0.973

0 20 40 60 80 100 120

0 5 10 15

Cummulative % drug release

Time (hr)

First Order Kinetics

F1 F2 F3 F4 F5 F6 F7 F8

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Fig:-12 Higuchi model release kinetics of Zolmitriptan

Fig:-13 Korsmeyer-Peppas model release kinetics of Zolmitriptan Release kinetics for all floating tablets of Zolmitriptan

Table:-8 Release kinetics for all floating tablets of Zolmitriptan Formulation

code

Zero order 1^st-order Higuchi Peppas

r² r² r² r²

F1 0.9976 0.9976 0.9974 0.8285

F2 0.9976 0.998 0.9984 0.8286

F3 0.997 0.997 0.9949 0.7916

F4 0.973 0.973 0.9826 0.8313

F5 0.9973 0.9973 0.9973 0.8092

F6 0.9982 0.998 0.998 0.8068

F7 0.9962 0.9953 0.9953 0.7996

y = 2.6603x - 0.0495 R² = 0.9826

-2 0 2 4 6 8 10 12

0 1 2 3 4

Square root of % drug release

Square root of time in (hr)

Higuchi Model

F1 F2 F3 F4 F7 F8 F9

y = 1.2869x + 0.5889 R² = 0.8313

0 0.5 1 1.5 2 2.5

0 0.2 0.4 0.6 0.8 1 1.2

Log of % drug result

log of time (hr)

Peppas Model

F1 F2 F3 F4 F5 F6 F7 F8 F9 Linear (F4)

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F8 0.9972 0.995 0.995 0.8341

F9 0.9973 0.9965 0.9976 0.8456

Discussion:-

According to this data the release kinetics were studied by fitting the data into various models. The r² values for each kinetic model as Zero order, 1^st-order, Higuchi and Korsmeyer Peppas in show (table 5.6).

The release kinetics of some formulation like F2, 3, 4, 5 and 9 followed Higuchi model, formulation F1, 5, 6, 7 and 8 followed the Zero order and formulation F1 and 5 followed 1^st-order.

Stability Studies:-

Table:- 9 Stability study for best formulation F4

S.No. Parameters Initial 1 Month 2 Month 3 Month

1 Colour No Change No Change No Change No Change

2 Hardness 4.18±0.4 4.16±0.2 4.12±0.6 4.11±0.3

3 Drug Content 98.60±1.6 98.40±0.4 97.20±3.0 96.08±0.9

4 In-Vitro Drug Release

96.28±0.010 96.16±0.013 95.95±0.070 94.90±1.05

Discussion:-

The duration of stability studies of the Formulation 4, there is no change in colour, but the variation of a Hardness, Drug Content and In vitro Drug Release.

Summary and Conclusion Summary:-

The main aim of this present study was investigation of floating tablet Zolmitriptan. By using wet granulation method.Various studies like Preformulation studies, UV spectroscopy,was done by using this.

FTIR Spectroscopy, Evaluation of powders for matrix tablet, Formulation Development, Evaluation Parameter, Kinetic Release Parameters and Stability studies were performed. The formulations were prepared by wet granulation method using distinct drug as Viscosity grades of Hydroxy Propyl Methyl Cellulose (50;45;40;40;35;30;30;25;20), HPMC K 15 M (15;20;25), ethyl cellulose (15;15;15) in F9 various ratios designated. Zolmitriptan tablet undergo the Standardization of drug to find out absorbance 284nm and different concentration then produce different absorbance. The Preformulation studies note out FTIR spectrum of Zolmitriptan show design due to Nitrogen-Hydrogen extending at 3241.42/cm, Carbon=Oxygen extending at 1731.03/cm and C=Carbon stretching at 1551.0/cm. These assay were meeting the arrive values. The FTIR scope of optimised formulation F9 (Zolmitriptan+Material) reveal peak N-H stretching at 3244.70/cm, Carbon=Oxygen extending at 1734.05/cm and C=C stretching at 1546.09/cm. The physical mixtures for matrix tablet were evaluated with respect to Angle of repose was found between 20.60±0.08 to 25.20±0.10and Carr’s index values were found between 14.76±0.6 to 30.68±0.8% the powder of all batches indicating excellent to poor flow ability and compressibility.

Hausner ratio was found to be range 1.15±0.06 to 1.48±0.20. Bulk density ratio was found to be range 0.215±0.08 to 0.299±0.12 and tapped density ratio 0.275±0.02 to 0.375±0.06 for all the batches indicating

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that possible and poor flow properties. The prepared tablets were evaluated for physical parameters hardness; friability, weight variation, thickness and drug content result are given in (table 5.3). Hardness of tablets were found to be in range of 3.80±0.4 to 4.54±0.7kg/cm2. The friability of all prepared tablets was found to be range 0.56±0.04 to 0.96±0.02%. The Thickness of prepared tablets were found range 3.18±0.1 to 3.34±0.4mm. The weight variations of all tablets were established to be 196±1.5-206±2.5mg.

The Floating time 10±1.0 to42±2.0 and highest % drug content 98.60±1.6 (table 5.3). The percentage of drug released from the formulation F1, F2 and F3 was found to be 95.46±0.016%, 95.46±0.016% and 92.46±0.028% respectively. The percentage of drug released from the formulations F4, F5 and F6 was found to be 96.28±0.010%, 95.70±0.02% and 90.11±0.032%. The formulation F7, F8 and F9 percentage drug release was found to be 93.22±0.024%, 95.35±0.016% and 92.30±0.018% respectively. The best % drug released of formulation F4. It was also observed that the amount of polymer increase in the formulation then it was decrease in drug release rate, may be due to drug entrapped in hydro gel by forming hydrophilic polymer. The minimum combination of HPMC, HPMC K 15 M and Ethyl Cellulose of various ratios in the different formulation. According to this data the release kinetics were studied by fitting the data into various models. The r² values for each kinetic model as Zero order, 1^st-order, Higuchi and Korsmeyer Peppas in show (table 5.6). The release kinetics of some formulation like F2, 3, 4, 5 and 9 followed Higuchi model, formulation F1, 5, 6, 7 and 8 followed the Zero order and formulation F1 and 5 followed 1^st-order. The duration of stability studies of the Formulation 4, there is no change in colour, but the variation of a Hardness, Drug Content and In vitro Drug Release.

Conclusion:-

Floating Zolmitriptan tablet were prepared by using Hydroxy Propyl Methyl Cellulose, HPMC K 15 M &

Ethyl cellulose in different ratios. The Sodium bicarbonate was added in varying concentrations as a gas generating agent to improve floating capacity of tablet. The tablets were prepared by using wet granulation method. All tablets were evaluated for their parameters for Pre-compression Bulk density, Tapped density, Carr’s index, Hausner’s ratio and Angle of repose and Post-compression Hardness, Thickness, Friability, Weight variation and Content uniformity. FTIR studies proved that no chemical interaction in Zolmitriptan and polymers. In-vitro drug release study were conduct all formulation F1- F9 by apply 0.1N HCL homogeneous mixter at 37ºC. Formulation F4 containing minimum concentrations of polymers showed best in-vitro drug release range of (96.28%) for 12hrs. The highest % drug released of formulation F4 for another formulation. It was also observed that the amount of polymer increase in the formulation then it was decrease in drug release rate, may be due to drug entrapped in hydro gel by forming hydrophilic polymer. The stability studies of optimised formulation (F4) were carried out according to ICH guideline. The correct formulation was subjected to stability at 40±2°C/75±5% RH for 90 days. In-vitro floating studies were carried out which increased the gastric residence time and improved bioavailability of the drug. Hence in present work floating tablets have been synthesized to overcome drawbacks associated with Antimigraine tablet of Zolmitriptan.

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