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456 | Page International Standard Serial Number (ISSN): 2319-8141 Full Text Available On www.ijupbs.com International Journal of Universal Pharmacy and Bio Sciences 3(2): March-April 2014 INTERNATIONAL JOURNAL OF UNIVERSAL PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89*** ICV 5.13*** Pharmaceutical Sciences RESEARCH ARTICLE……!!! FORMULATION AND IN-VITRO EVALUATION OF FAST DISSOLVING TABLET OF OLMESARTAN MEDOXOMIL Zinkal K Patel*, Rahul R. Patel, Dr K. R. Patel, Dr M. R. Patel. Department of Pharmaceutics, Shri B. M. Shah College of Pharmaceutical Education and Research Dhansura Road College campus Modasa, Dist:- Arvali. Pin code:- 383315 Gujarat, (India). KEYWORDS: Olmesartan medoxomil; solid-dispersion; FDT; Solubility; dissolution; superdisintegrants. For Correspondence: Zinkal K Patel* Address: Shri B. M. Shah College of pharmaceutical education and research Modasa-383315, Dist: Arvali. Gujarat, India E-Mail id:- [email protected] om ABSTRACT The aim of this investigation was to formulation and in-vitro evaluation of fast dissolving tablet of olmesartan medoxomil by direct compression method. Oral bioavailability of olmesartan medoxomil is very low (26%), due to its poor water solubility. For this purpose, initially solubility of olmesartan medoxomil was improved by using PEG 6000 and PVP K30 as a carriers by solid dispersion techniques. The prepared solid dispersion powder were evaluated for flow properties, solubility and in-vitro drug release, FTIR analysis, DSC. Then optimized batch of solid dispersion(P4) was used in formulation of fast dissolving tablet using different superdisintegrants. Various batches of tablets were evaluated for pre-compression and post-compression parameter of tablet. Optimized batch contain 93.91CPR, 100.0% drug content, 17sec.disintegration time. optimized batch compared with marketed formulation.

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  • 456 | P a g e International Standard Serial Number (ISSN): 2319-8141

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    International Journal of Universal Pharmacy and Bio Sciences 3(2): March-April 2014

    INTERNATIONAL JOURNAL OF UNIVERSAL

    PHARMACY AND BIO SCIENCES IMPACT FACTOR 1.89***

    ICV 5.13*** Pharmaceutical Sciences RESEARCH ARTICLE!!!

    FORMULATION AND IN-VITRO EVALUATION OF FAST DISSOLVING

    TABLET OF OLMESARTAN MEDOXOMIL

    Zinkal K Patel*, Rahul R. Patel, Dr K. R. Patel, Dr M. R. Patel.

    Department of Pharmaceutics, Shri B. M. Shah College of Pharmaceutical Education and

    Research Dhansura Road College campus Modasa, Dist:- Arvali. Pin code:- 383315 Gujarat,

    (India).

    KEYWORDS:

    Olmesartan medoxomil;

    solid-dispersion; FDT;

    Solubility; dissolution;

    superdisintegrants.

    For Correspondence:

    Zinkal K Patel*

    Address:

    Shri B. M. Shah College

    of pharmaceutical

    education and research

    Modasa-383315, Dist:

    Arvali. Gujarat, India

    E-Mail id:-

    [email protected]

    om

    ABSTRACT

    The aim of this investigation was to formulation and in-vitro

    evaluation of fast dissolving tablet of olmesartan medoxomil by

    direct compression method. Oral bioavailability of olmesartan

    medoxomil is very low (26%), due to its poor water solubility. For

    this purpose, initially solubility of olmesartan medoxomil was

    improved by using PEG 6000 and PVP K30 as a carriers by solid

    dispersion techniques. The prepared solid dispersion powder were

    evaluated for flow properties, solubility and in-vitro drug release,

    FTIR analysis, DSC. Then optimized batch of solid dispersion(P4)

    was used in formulation of fast dissolving tablet using different

    superdisintegrants. Various batches of tablets were evaluated for

    pre-compression and post-compression parameter of tablet.

    Optimized batch contain 93.91CPR, 100.0% drug content,

    17sec.disintegration time. optimized batch compared with

    marketed formulation.

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    INTRODUCTION1, 2, 3, 4

    Oral delivery is currently the gold standard in the pharmaceutical industry where it is regarded as the safest,

    most convenient and most economical method of drug delivery. Oral route of drug administration become

    popular route for systemic effects due to ease of ingestion, accurate dosage, self-medication, pain

    avoidance. Also solid oral delivery systems do not require sterile conditions Fast dissolving drug delivery

    system are Novel Drug Delivery techniques aim for designing dosage forms, convenient to be manufacture

    and administer without water, free of side effects, offering immediate release and enhanced bioavailability,

    so as to achieve better patient compliance.1 This segment of formulation is especially designed for

    pediatric, geriatric, bedridden, psychotic patients who are unable to swallow or refuse to swallow

    conventional oral formulation and also for active patients who are busy and traveling and may not have

    access to water. United states Food And Drug Administration (FDA) defined fast dissolving tablet (FDT)

    as a solid dosage form containing medicinal substance or active ingredient which disintegrate or dissolve

    rapidly within seconds when placed upon the tongue. Fast dissolving tablets are also known as mouth-

    dissolving tablets, rapid dissolving, melt-in mouth tablets, Orodispersible tablets, rapimelts, porous tablets,

    quick dissolving, quick melt, quick disintegrating tablets.2

    FDT prepared by various techniques like direct

    compression, lyophilization, spray drying, sublimation, test masking etc. But commonly used method to

    prepare FDT is direct compression. It is easiest way to manufacture tablets. Conventional equipments,

    commonly available excipients and a limited number of processing steps are involved in direct

    compression.

    Hypertension is fast becoming a major public health problem in world. Olmesartan medoxomil (OLM) is

    currently used as an alternative therapeutic antihypertensive agent for patient intolerant of angiotensin

    converting enzyme inhibitor. It is known that diabetic patient are at increased risk of cardiovascular disease

    and reduce vascular resistance and oxidative stress, addition to significant reducing BP in type -2 diabetic

    patients.5, 6

    OLM is a poorly aqueous soluble drug. Its solubility is reported to be 0.0077mg/ml. Rapid onset of action

    is desirable to provide fast relief in treatment of heart failure. Therefore, it is necessary to enhance the

    aqueous solubility and dissolution rate of OLM to obtain faster on set of action and improve its overall oral

    bioavailability102

    . Solubility of OLM is improve by solid dispersion because it cause reduction in particle

    size, improve drug porosity, increase wettability and convert crystalline drug in to amorphous state. OLM

    is a selective AT1 subtype angiotensinII receptor antagonist that has been approved by US Food and Drug

    Administration (FDA) for treatment of hypertension. OLM dose dependently reduces blood pressure

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    through arterial vasodilatation and reduce sodium retention. It is a prodrug that is rapidly de-esterified

    during absorption from GIT to produce an active metabolite olmesartan.OLM is BCS class-II drug. i.e. low

    solubility and high permeability. Oral bioavailability is very low (26%) due to its poor aqueous solubility.

    OLM given orally in single daily doses of 20mg-40mg. Having log p value 5.9 i.e. drug is lipophilic in

    nature. Elimination half life of OLM is 13hrs and 99%plasma protein binding. Pka value is 4.37, 8, 9

    MATERIALS AND METHOD

    Olmesartan Medoxomil was obtained from Sun Pharma Ltd. Baroda. Kyron T-314 was obtained from

    Corel Pharma Chem., Ahmadabad. Cross Carmellose Sodium, Crosspovidone, Avicel pH101, Aerosil was

    obtained from Orbicular Pharma. Tech. Pvt Ltd. PEG 6000 was obtained from Modern chemical corp.,

    Mumbai. PVP K30 was obtained from Oxford lab. Mumbai. Mannitol was obtained from Finar chemicals

    ltd, Mumbai.Aspartame was obtained from Lesar Chemicals, Ahmedabad.

    METHOD :

    Preparation of the Solid Dispersions10, 11

    Solid dispersion of olmesartan medoxomil (OLM) were prepared by solvent evaporation and fusion

    method using PEG 6000 and PVP K30 as a carrier.

    Solvent evaporation method

    In this method, 1 : 1 ratio of PEG 6000 : drug (SE1) and PVP K30 : drug (SE2) were carefully transferred

    into two beaker seperately and dissolved in methanol. The solution was transferred to a petridish and

    solvent was allow to evaporate at room temperature for 1 hr and then dried at 600c for 6 hr in a hot air

    oven. The mass obtained in each case was crushed, pulverized and sifted the 80#. All the solid dispersion

    was preserved in well closed glass container till use.

    By fusion method

    In this method, 1 : 1 ratio of drug : PEG 6000 (FM1) and drug : PVP K30 : (FM2) was heated in two

    different china dish to a temperature just above its melting point. The melt is solidified on an ice bath

    under vigorous stirring. The mass obtained in each case was crushed, pulverized and sifted the 80#. All the

    solid dispersion was preserved in well closed glass container till use. Solid dispersion prepared by PEG

    6000 by fusion method give good solubility. So, it used in different ration like 1: 1(P1), 1: 2(P2), 1 : 3(P3),

    1: 4(P4), 1: 5(P5), 1 : 6(P6).

    Evaluation of solid dispersion12, 13

    A. Saturation solubility studies

    Saturation solubility was performed according to method reported by higuchi and cannors. Excess quantity

    of solid dispersion, equivalent to 20 mg of drug was added to 100 ml conical flask containing 20ml 0.1N

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    Hcl and mixtures were shaken for 24 hour at 100rpm at room temperature in orbital shaker and filter

    through whatman filter paper No.41. The filtrate was suitably diluted and analyzed spectrophotometrically

    at 257nm against blank using UV visible spectrophotometer. The studies were carried out in triplicate and

    average value (SD) was noted

    B. Dissolution study of solid dispersion

    It was performed as described in Indian Pharmacopoeia 2010 using USP apparatus II (paddle). Quantity of

    solid dispersion equivalent to 20 mg of drug was kept in a flask of the dissolution apparatus containing

    900ml of 0.1N HCl as a dissolution media maintaining the temperature at 370.50C and at a speed of 50

    rpm. Aliquot of dissolution medium (5ml) was withdrawn at a specific time intervals and the samples were

    replaced with fresh dissolution medium. Sample was filter through whatman filter paper No.41. The filtrate

    was suitably diluted and analyzed spectrophotometrically at 257nm against blank using UV visible

    spectrophotometer.

    C. Differential scanning calorimetry

    Calorimetric measurements were performed with DSC instrument, over the temperature range from 30 to

    300oC at heating and cooling rates of 50

    oC/min. The temperature scale was calibrated with high purity

    standards. The glass transition was reported as the point of inflection of specific heat increment. Samples of

    OLM and solid dispersion powder were analysed in the aluminium pan and their DSC spectra were

    recorded.

    D. Fourier transform infrared (FTIR)

    Drug - carrier interaction play a vital role in the release of drug from formulation. FTIR has been used to

    study the physical and chemical interaction between drug and carriers. FTIR spectra of OLM and carrier

    were recorded using KBR mixing method on FTIR instrument.

    FORMULATION OF FAST DISSOLVING TABLET14

    Fast Dissolving Tablet of OLM were prepared by direct compression method according to the formula

    given in below table using optimized batch of solid dispersion(P4). Various superdisintigrants like CCS,

    Crosspovidone, Kyrone T-314 are use in the range of 2%, 4%, 6% to select the optimum concentration of

    superdisintigrants. All the required material were passed through sieve no.60# and mixed homogeneously

    for 15 min. Finally magnesium stearate and aerosil were added and mixed for 1 min. This blend was

    compressed using 8 mm size flat faced punch on rotary compression machine.

    Mannitol act as diluent. Microcrystalline cellulose act as binder. Aspartame was used as a sweetener.

    Aerosil was used as glidant and Magnesium stearate was used as lubricant.

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    (Table 1.1 - preliminary formulation of fast dissolving tablet)

    INGREDIENTS

    (mg)

    PRELIMINARY FORMULATION BATCH CODE

    F1 F2 F3 F4 F5 F6 F7 F8 F9

    Solid dispersion

    (1:4)

    100 100 100 100 100 100 100 100 100

    CCS 4 8 12 - - - - - -

    Kyron T-314 - - - 4 8 12 - - -

    Crosspovidone - - - - - - 4 8 12

    Avicel pH-101 60 60 60 60 60 60 60 60 60

    Mannitol 22 18 14 22 18 14 22 18 14

    Aspartame 10 10 10 10 10 10 10 10 10

    Mg.stearate 2 2 2 2 2 2 2 2 2

    Aerosil 2 2 2 2 2 2 2 2 2

    Total wt. 200 200 200 200 200 200 200 200 200

    FORMULATION USING 32 FULL FACTORIAL DESIGN

    15, 16

    It is desirable to develop an acceptable pharmaceutical formulation in shortest possible time using

    minimum number of man-hours and raw materials. The technique of factorial design is an effective method

    of indicating the relative significance of a number of variables and their interactions. On the basis of

    preliminary study to evaluate that whether in combination, superdisintegrants can give far better result or

    not, A 32 randomized full factorial design was adopted to optimize the variables. It is suitable for

    investigating the quadratic response surfaces and for constructing a second order polynomial model.

    In this design two factors were evaluated, each at 3 levels, and experimental trials were performed at all 9

    possible combinations.

    Y= b0 + b1X1 + b2X2 + b12X1X2 + b11X11 + b22X22

    To demonstrate graphically the influence of each factor on response, the response surface plots was

    generated using statistical software 10.0 (stat soft. Inc, USA). Response Surface Methods are designs and

    models for working with continuous treatment.

    (Table 1.2 - Selection of independent and dependent variables)

    Independent variables Dependent variables

    X1 X2 Y1 Y2 Y3

    Conc. of

    crospovidone

    Conc. of

    kyrone T-314

    Disintigration

    time (Sec.)

    Wetting time

    (Sec.)

    Drug release

    at 5min.

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    (Table 1.3 - Actual and coded value for factorial design)

    Batches Coded value Actual value(%)

    X1 X2 X1 X2

    E1 -1 -1 2 2

    E2 -1 0 2 4

    E3 -1 1 2 6

    E4 0 -1 4 2

    E5 0 0 4 4

    E6 0 1 4 6

    E7 1 -1 6 2

    E8 1 0 6 4

    E9 1 1 6 6

    (Table 1.4 - Formulation of 32 Factorial Designs batches)

    INGREDIENTS

    (mg)

    FORMULATION BATCH CODE

    E1 E2 E3 E4 E5 E6 E7 E8 E9

    Solid dispersion

    (1:4)

    100 100 100 100 100 100 100 100 100

    Crosspovidone 4 4 4 8 8 8 12 12 12

    Kyron T-314 4 8 12 4 8 12 4 8 12

    Avicel pH-101 60 60 60 60 60 60 60 60 60

    Mannitol 18 14 10 14 10 6 10 6 2

    Aspartame 10 10 10 10 10 10 10 10 10

    Mg.stearate 2 2 2 2 2 2 2 2 2

    Aerosil 2 2 2 2 2 2 2 2 2

    Total wt. 200 200 200 200 200 200 200 200 200

    EVALUATION PARAMETERS OF TABLETS 18, 19, 20, 21

    Weight variation was performed using 20Tablets and weighted individually to check for weight variation.

    Hardness for FDT is usually kept in lower range to facilitate early disintegration in the mouth. It is

    measured by hardness tester (Monsanto hardness tester). It measured in kg/cm2

    or pound. Friability of each

    batch was measure in Electro lab friabilator. Ten pre-weighed tablets were rotated at 25 rpm for 4 min or

    total 100 times dropping a tablet at height of 6 inches in each revolutions, the tablets were then reweighed

    and the percentage of weight loss was calculated by the following equation. Limit of friability is 0.1-.9%.

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    Disintegration time was carried out on 6 tablets using the apparatus specified in I.P. Distilled water at 37C

    2C was used as a disintegration media and time requied for complete disintegration of tablet with no

    palatable mass remaining in the apparatus was measured .

    Dissolution test was performed in 0.1N HCl using USP apparatus-II (paddle). Tablet was kept in a flask of

    the dissolution apparatus containing 900ml of 0.1N HCl maintaining at 370.50C and 50 rpm. Aliquot of

    dissolution medium (5ml) was withdrawn at a specific time intervals and the samples were replaced with

    fresh dissolution medium. Sample was filter through whatman filter paper No.41. The filtrate was suitably

    diluted and analyzed spectrophotometrically at 257nm against blank using UV visible spectrophotometer.

    In Drug content test ten tablets were weighed and powdered in a glass mortar. Quantity of powder

    equivalent to 20mg was transferred in a 100 ml volumetric flask. Make final volume in volumetric flask up

    to 100ml using 0.1N HCl and filter through whatman filter. The filtrate was suitably diluted and analyzed

    spectrophotometrically at 257nm against blank using UV visible spectrophotometer.

    Wetting time was closely related to the inner structure of the tablets and to the hydrophilicity of the

    excipients. To measure wetting time, five circular tissue papers of 10cm diameter are placed in a petridish

    with a 10cm diameter. 10ml of water containing eosin, a water soluble dye, is added to petridish. A tablet is

    carefully placed on the surface of the tissue paper. The time required for water to reach upper surface of the

    tablet is noted as a wetting time.

    The stability studies were carried out on the most satisfactory formulations as per ICH guidelines Q1C. The

    samples of optimized batch were kept at 40C 5C and 75% relative humidity for one month in vial

    which is sealed with rubber cap. At the end of study the tablet were withdrawn and analyzed for physical

    characterization such as Hardness, Drug content, Wetting time, Disintegrations, and Dissolution etc.

    RESULT AND DISCUSSION

    Phase Solubility Study of Preliminary Batches of Solid Dispersion

    (Table 1.5 - phase solubility of preliminary batches of solid dispersion)

    BATCH SOLUBILITY (mg/ml)

    Pure drug 0.526 0.002 SE1 0.94 0.002 SE2 0.86 0.002 FM1 1.19 0.001 FM2 0.91 0.002

    From above evaluation it was concluded that solid dispersion by fusion method with PEG 6000 give good

    solubility. So, OLM : PEG 6000 in different ratio like 1:1, 1:2, 1:3, 1:4, 1:5, 1:6 were used in further study

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    to enhance solubility of drug. This all batches are evaluated for in-vitro dissolution, flow properties and

    phase solubility study.

    Phase solubility study of solid dispersion

    (Table 1.6-phase solubility of solid dispersion batches)

    BATCH SOLUBILITY (mg/ml)

    P1 1.19 0.001 P2 1.26 0.002

    P3 1.73 0.002

    P4 2.01 0.001

    P5 1.910.002

    P6 1.77 0.002

    The improved solubilization of OLM is depend on hydrophilic nature of PEG 6000 and to reduction of

    particle aggregation of the drug, increased wettability, dispersibility and alteration of surface properties of

    drug particles.

    Dissolution of Solid Dispersion

    (Table 1.7 % cumulative drug release of solid dispersion batches)

    The rate of dissolution increases as concentration of PEG 6000 increases in solid dispersion upto 1:4 drug:

    carrier ratio. Further improvement in concentration of PEG 6000 did not enhance the dissolution rate. This

    might be due to viscous boundary layer formed by PEG 6000 in higher amount surround drug particles

    which retard the drug release. So, 1:4 ratio of drug : carrier used in preparation of tablets

    SR.NO. TIME

    (min.)

    Cumulative percentage drug release

    P1 P2 P3 P4 P5 P6

    1 0 0 0 0 0 0 0

    2 5 29.57 34.57 38.71 41.85 37.15 33.05

    3 10 40.21 48.21 51.33 56.42 49.28 42.79

    4 15 51.64 57.64 63.29 68.35 61.87 54.25

    5 20 60.15 69.15 72.45 79.29 73.46 63.96

    6 25 69.44 77.44 83.61 88.78 80.11 72.35

    7 30 78.83 83.93 89.25 95.61 87.65 82.43

    Results are the mean of three observations. SD are less than 0.5

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    Differential scening calorimetry (DSC)

    (Figure 1.1 - DSC spectra of OLM )

    (Figure 1.2 - DSC spectra of solid dispersion)

    The DSC thermograms (fig 5.8), shows endothermic peak of OLM at 182 0C, which corresponds to its

    melting point, indicating its crystalline nature. Thermograms of solid dispersion observed the absence of a

    peak, suggesting that OLM meight be in dissolved state in PEG 6000. The disappearance of endothermic or

    exothermic peaks of drug is mostly an indication of formation of solid dispersion which is observed in

    thermogram of solid dispersion(fig. 5.9) .

    Fourier transform infrared (FTIR)

    (Figure 1.3 - FTIR spectra of OLM)

    IR spectra of olmesartan showed characteristic peaks at 2829 cm-1

    (Aliphatic CH strech), 2956 cm-1

    (Aromatic CH strech), 3290 cm-1

    (Broad, intermolecular hydrogen bonded, O-H strech), 1832 cm-1

    (C=O

    of carboxylic group), 1600 cm-1

    (ring C=C stretch), 1481 cm-1

    (CN strech), 1388 cm-1

    (in plane O-H

    bend), 1136 cm-1

    (ring C-O-C stretch).

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    (Figure 1.4 - FTIR spectra of solid dispersion)

    It was found that there were no considerable changes in the IR peaks of the solid dispersion when

    compared to pure olmesartan. In the FTIR study, the breakdown of the intermolecular hydrogen bond

    between the crystalline drug molecule and formation of hydrogen bond between the drug and the polymers

    might be related to the slight shift of the absorption band

    EVALUATION OF TABLET

    Disintegration time of preliminary batches of tablets

    BATCH F1 F2 F3 F4 F5 F6 F7 F8 F9

    DT

    (sec.)

    97

    1.7

    91

    1.24

    88

    1.63

    79

    1.24

    67

    2.05

    65

    0.94

    61

    1.69

    56

    1.25

    59

    1.69

    From the above data, it was concluded that the disintegration time of three superdisintigrant in three

    different concentrations are CCS> Kyrone T-314 > Crosspovidone. Different nine formulation are

    obtained using 32 factorial design. These all formulation are evaluated for pre-compression and post-

    compression parameter

    Flow Properties of Factorial Design Batches of Tablet

    (Table 1.8 - Flow Property of factorial design batches of tablet)

    Batch Angle of

    repose()

    Bulk density

    (g/ml)

    Tapped density

    (g/ml)

    Carrs

    index (%)

    Hausner

    ratio

    E1 31.29

    0 0.494 0.564 12.41 1.14

    E2 31.71 0 0.482 0.559 13.77 1.15

    E3 33.37 0 0.482 0.560 14.28 1.16

    E4 26.41 0 0.496 0.558 11.11 1.12

    E5 25.15 0 0.495 0.557 11.13 1.12

    E6 26.92 0 0.487 0.553 11.93 1.13

    E7 31.76 0 0.479 0.550 12.90 1.14

    E8 32.03 0 0.478 0.549 12.93 1.14

    E9 32.74 0 0.485 0.564 14.00 1.16

    Results are the mean of three observations. SD are less than 0.5

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    (Table 1.9 - post compression parameter of factorial design batches)

    Batch E1 E2 E3 E4 E5 E6 E7 E8 E9

    Hardness*

    (kg/cm2)

    3.1

    0.23

    3.0

    0.4

    3.2

    0.23

    2.8

    0.23

    3.0

    0.40

    3.0

    0.40

    2.8

    0.23

    3.3

    0.23

    3.0

    0.40

    Thickness*

    (mm)

    3.9

    0.04

    4.06

    0.04

    4.0

    0.08

    4.0

    0.00

    4.03

    0.04

    4.03

    0.09

    4.03

    0.12

    4.06

    0.04

    3.9

    0.09

    Friability*

    (%)

    0.66

    0.04

    0.60

    0.05

    0.65

    0.05

    0.47

    0.02

    0.41

    0.02

    0.47

    0.04

    0.76

    0.03

    0.82

    0.04

    0.88

    0.04

    Wt.

    variation#

    (%)

    199

    3.6

    200

    5.3

    199

    5.3

    200

    5.2

    200

    3.7

    199

    5.1

    201

    4.4

    201

    4.9

    199

    5.7

    Drug*

    content(%)

    97

    2.1

    99

    1.2

    96

    3.0

    98

    1.6

    100

    0.9

    100

    4.0

    99

    3.6

    98

    2.0

    96

    3.7

    DT

    (sec.)

    27

    1.7

    29

    1.24

    31

    1.63

    28

    1.24

    22

    2.05

    26

    0.94

    33

    1.69

    36

    1.25

    36

    1.69

    Wett. Time

    (sec.)*

    22

    1.24

    24

    3.74

    25

    0.74

    21

    1.7

    17

    1.69

    20

    0.47

    28

    1.24

    30

    0.81

    31

    1.25

    WAR

    (%)*

    71.6

    2.5

    63.7

    1.7

    54.6

    2.9

    75.3

    1.3

    83.6

    2.4

    79.7

    1.6

    44.3

    2.0

    39.4

    1.2

    35.6

    1.2

    * All values are mean SD, (n =3), All values are mean SD, (n =6), # All

    values are mean SD, (n =20).

    In-Vitro Dissolution of Factorial Design Batches of Tablet

    (Table 1.10 - % cumulative drug release of factorial design batches)

    TIME

    (Min.)

    Cumulative Percentage Drug Release

    E1 E2 E3 E4 E5 E6 E7 E8 E9

    0 0 0 0 0 0 0 0 0 0

    5 41.08 37.51 40.25 48.98 52.51 49.35 43.33 36.75 38.57

    10 52.61 46.86 53.44 60.03 64.77 57.19 52.13 47.48 46.85

    15 60.23 55.92 62.73 68.47 71.34 68.53 59.24 54.23 53.46

    20 68.53 65.44 70.69 76.11 79.82 76.27 66.97 61.94 60.87

    25 74.35 73.17 77.24 82.25 86.14 85.29 73.86 69.17 67.42

    30 81.03 85.25 84.18 89.09 93.91 91.05 80.74 76.02 73.93

    Results are the mean of three observations. SD are less than 0.5

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    ( Figure 1.5 - % cumulative drug release of factorial design batches)

    RESPONSE SURFACE PLOT:

    it was observed that crosspovidone with

    combination of kyrone T-314 is very

    effective to decease the disintegration

    timeThe high values of X12 Coefficient

    also suggest that the interaction between

    X1 and X2 has significant effect on

    disintegration time.

    it was observed that crosspovidone with

    combination of kyrone T-314 is very

    effective to decease the wetting time

    which is desirable. The high values of X12

    Coefficient also suggest that the

    interaction between X1 and X2 has

    significant effect on wetting time.

    0102030405060708090

    100

    0 5 10 15 20 25 30

    E1 E2 E3 E4 E5 E6 E7 E8 E9

    Time (Min.)

    % C

    PR

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    it was observed that crosspovidone with

    combination of kyrone T-314 is very

    effective to increase drug release at 5 min

    which is desirable. The high values of X12

    Coefficient also suggest that the

    interaction between X1 and X2 has

    significant effect on drug release at 5 min.

    CONCLUSION

    From the above work it was concluded that the release of drug from the E5 formulation was quick when

    compared to other formulation. It shows that the combined effect of crosspovidone and kyrone T-314

    gives synergistic effect. Undoubtedly the availability of various technologies and the manifold advantages

    of FDT will surely enhance the patient compliance, low dosing, rapid onset of action, increased

    bioavailability, low side effect, good stability and its popularity in near future

    ACKNOWLEDGEMENT

    We are thankful to Sun Pharma Ltd. Baroda, Corel Pharma Chem., Ahmadabad, Orbicular Pharma. Tech.

    Pvt Ltd. , Modern chemical corp., Mumbai. , Oxford lab. Mumbai. , Lesar Chemicals, Ahmedabad., Finar

    chemicals ltd, Mumbai for the gift samples of the drug and excipients, Department of Pharmaceutics,

    Nootan Pharmacy College, Visnagar for providing facilities to carry out DSC study. We are also thankful

    to Shri B. M. Shah College of Pharmaceutical Education and Research, modasa. for providing the

    opportunity to carry out our research work successfully. I heartly thanks to Patel, Dr k. r. patel, Dr m. r.

    patel for providing us Kind support all the time throughout the work.

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