Formulation and Evaluation of Glipizide

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    Review of Literature

    Drug profile

    Diltiazem Hydrochloride

    Synonym : Cardizem

    CAS No : 33286-22-5

    Chemical Name : (2S-Cis)3- (Acetyloxy)-5-[2-(Dimethylamino)ethyl]-

    2,3-dihydro-2-(4-Methoxyphenyl) -1,5-benzo thiazepin

    4(5H)-One HydrochlorideMolecular Structure :

    Molecular Formulae : C22H26N2O4S.Hcl

    Molecular Weight : 450.98 gm

    Category : Calcium Channel Blocker, Anti Hypertensive

    Solubility : Soluble in Water, Methanol, Formic Acid

    Appearance : White to Off White Powder

    Long Term Storage : +20C

    Purity : 99% (HPLC)

    Log P Value : 4.53

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    Brand Names

    Cardizem

    CardizemCD

    CardizemLA

    CardizemSR

    Cartia XT

    Dilacor XR

    Dilt-CD

    Mechanism:

    Diltiazem is a potent vasodilator, increasing blood flow and variably decreasing the

    heart rate via strong depression of A-V node conduction. Its pharmacological activity is

    somewhat similar to verapamil. Potent vasodilator of coronary vessels. Vasodilator of

    peripheral vessels. This reduces peripheral resistance and afterload.

    Negative inotropic effect : Diltiazem causes a modest decrease in heart muscle contractility

    and reduces myocardium oxygen consumption.

    Negative chronotropic effect: Diltiazem causes a modest lowering of heart rate. This effect

    is due to slowing of the SA (sinoatrial) node. It results in reduced myocardium oxygen

    consumption.

    Negative dromotropic effect : By slowing conduction through the AV (atrioventricular)

    node, diltiazem increases the time needed for each beat. This results in reduced

    myocardium oxygen consumption by the body.

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    Contra-Indications And Precautions:

    CHF Patients with reduced ventricular function may not be able to counteract the

    inotropic and chronotropic effects of diltiazem, the result being an even higher

    compromise of function.

    SA node or AV conduction disturbances : Use of diltiazem should be avoided in patients

    with SA or AV nodal abnormalities, because of its negative chronotropic and

    dromotropic effects

    Low blood pressure : Patients with systolic blood pressures below 90 mm Hgshould not be treated with diltiazem.

    Wolff-Parkinson-White syndrome : Diltiazem may paradoxically increase ventricular

    rate in patients with WPW syndrome because of accessory conduction pathways.

    Drug Interactions :

    Beta-blockers : Intravenous diltiazem should be used with caution with beta-

    blockers because, while this combination is most therapeutically beneficial, there are rare

    instances of dysrhythmia and AV node block.

    Quinidine : Quinidine should not be used concurrently with calcium

    channel blockers because of reduced clearance of both drugs and potential

    pharmacodynamic effects at the SA and AV nodes.

    Miscellaneous : Diltiazem and verapamil inhibit hepatic cytochromes

    CYP3A4, CYP2C9 andCYP2D6,possibly resulting in drug interactions.

    http://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Congestive_heart_failurehttp://en.wikipedia.org/wiki/Heart_blockhttp://en.wikipedia.org/wiki/Hypotensionhttp://en.wikipedia.org/wiki/Wolff-Parkinson-White_syndromehttp://en.wikipedia.org/wiki/Quinidinehttp://en.wikipedia.org/wiki/CYP3A4http://en.wikipedia.org/wiki/CYP2C9http://en.wikipedia.org/wiki/CYP2D6http://en.wikipedia.org/wiki/CYP2D6http://en.wikipedia.org/wiki/CYP2C9http://en.wikipedia.org/wiki/CYP3A4http://en.wikipedia.org/wiki/Quinidinehttp://en.wikipedia.org/wiki/Wolff-Parkinson-White_syndromehttp://en.wikipedia.org/wiki/Hypotensionhttp://en.wikipedia.org/wiki/Heart_blockhttp://en.wikipedia.org/wiki/Congestive_heart_failure
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    Side Effects:

    A red, blistering skin rash, swelling in your hands or feet

    trouble in breathing, slow heartbeats, fast or pounding heartbeat

    dizziness, fainting, itching,

    upper stomach pain, loss of appetite, dark urine, clay-colored stools,

    jaundice

    severe skin reaction -- fever, sore throat, swelling in your face or tongue,

    burning in your eyes, skin pain, followed by a red or purple skin rash that

    spreads) and causes blistering and peeling.

    Less serious diltiazem side effects may include:

    headache, dizziness, weakness, tired feeling, nausea

    upset stomach, sore throat, cough, stuffy nose, flushing

    Dosage:

    The dose of Diltiazem in Supraventricular tachycardias is 0.25 mg/kg slow IV

    push. Most commonly, a 20 mg IV dose is given to the average size patient

    Dosing Information :

    Usual Adult Diltiazem Dose for Hypertension:

    Initial dose: 30 to 60 mg orally 3 to 4 times a day.

    Maintenance dose: 180 to 360 mg orally/day in divided doses.

    Initial bolus doses : 0.25 mg/kg as a bolus administered over 2 minutes.

    A second bolus of 0.35 mg/kg may be used if necessary.

    Initial infusion dose : 5 mg/hr.

    Maintenance infusion dose : The infusion rate may be increased in 5 mg/hr increments up

    to 15 mg/hr.

    http://en.wikipedia.org/wiki/Supraventricular_tachycardiahttp://en.wikipedia.org/wiki/Supraventricular_tachycardia
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    Usual Adult Diltiazem Dose for Atrial Fibrillation:

    Initial dose (oral): 30 to 60 mg orally 3 to 4 times a day.

    Maintenance dose: 180 to 360 mg orally/day in divided doses.

    Initial dose (IV): 0.25 mg/kg actual body weight bolus over 2 minutes. If necessary, a second

    bolus of 0.35 mg/kg ABW may be given. In some cases, an infusion of diltiazem 5 mg/hour

    may be started, and advanced in 5 mg/hour increments to 15 mg/hour for up to 24 hours.

    Usual Adult Diltiazem Dose for Atrial Flutter:

    Initial dose (oral): 30 to 60 mg orally 3 to 4 times a day.

    Maintenance dose: 180 to 360 mg orally/day in divided doses.

    Initial dose (IV) : 0.25 mg/kg actual body weight bolus over 2 minutes. If necessary, a second

    bolus of 0.35 mg/kg ABW may be given. In some cases, an infusion of diltiazem 5

    mg/hour may be started, and advanced in 5 mg/hour increments to 15 mg/hour for up to

    24 hours.

    Usual Adult Diltiazem Dose for Supraventricular Tachycardia:

    Initial dose (oral): 30 to 60 mg orally 3 to 4 times a day.

    Maintenance dose: 180 to 360 mg orally/day in divided doses.

    Initial dose (IV) : 0.25 mg/kg actual body weight bolus over 2 minutes. If necessary, a second

    bolus of 0.35 mg/kg ABW may be given. In some cases, an infusion of diltiazem 5

    mg/hour may be started, and advanced in 5 mg/hour increments to 15 mg/hour for up to

    24 hours.

    Usual Adult Diltiazem Dose for Angina Pectoris Prophylaxis:

    Initial dose: 30 to 60 mg orally 3 to 4 times a day.

    Maintenance dose: 180 to 360 mg orally/day in divided doses.

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    Excipients profile

    Mannitol:

    Mannitol occurs as a white, odourless, crystalline powder, or free-flowing granules. It

    has a sweet taste, approximately as sweet as glucose and half as sweet as sucrose, and imparts a

    cooling sensation in the mouth.

    Description of mannitol

    a) Synonyms

    Cordycepic acid; E421; manna sugar; D-mannite; Mannite; Mannogem; Pearlitol.

    b) Chemical name and CAS registry number

    D-Mannitol [69-65-8]

    c) Empirical formula and molecular weight

    Empirical Formula : C6H14O6

    Molecular weight : 182.17

    d) Structural Formula

    e) Functional Category

    Diluent; diluent for lyophilized preparations; Sweetening agent; Tablet and Capsule

    diluents; Tonicity agent.

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    Applications in pharmaceutical formulation or technology

    In pharmaceutical preparations it is primarily used as a diluent (1090% w/w) in

    tablet formulations, due to its non hygroscopic nature and may thus be used with moisture-

    sensitive active ingredients. Mannitol may be used in direct-compression tablet applications, for

    which the granular and spray-dried forms are available. Specific tablet applications include

    antacid preparations, and Vitamin preparations. Mannitol is commonly used as an excipient in

    the manufacture of chewable tablet formulations because of its negative heat of solution,

    sweetness, and mouth feel.

    Solubility of mannitol

    Freely soluble in water. Practically insoluble in ether.

    Incompatibilities of mannitol

    Mannitol solutions, 20% w/v or stronger, may be salted out by potassium chloride or

    sodium chloride. Mannitol is incompatible with Xylitol infusion and may form complexes with

    some metals such as Aluminum, Copper, and Iron. Reducing sugar impurities in mannitol have

    been implicated in the oxidative degradation of a peptide in a lyophilized formation. Mannitol

    was found to reduce the oral bioavailability of Cimetidine compared to sucrose.

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    Microcrystalline cellulose (MCC)

    Microcrystalline cellulose occurs as a white, odourless, tasteless, crystalline

    powder composed of porous particles.

    Description of microcrystalline cellulose (MCC)

    a) Synonyms

    Avicel PH; Celex; Cellulose gel; Celphere; Ceolus KG; Crystalline cellulose; E460; Emcocel;

    Ethispheres; Fibrocel; Pharmacel; Tabulose; Vivapur.

    b) Chemical name and CAS Registry Number

    Cellulose [9004-34-6]

    c) Empirical formula and molecular weight

    (C6H10O5) n 36 000, Where n 220.

    d) Structural formula

    e) Functional Category

    Adsorbent, Suspending agent, Tablet and Capsule diluents, Tablet disintegrant.

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    Applications in pharmaceutical formulation or technology

    Microcrystalline cellulose is widely used in pharmaceuticals, primarily as a

    binder/diluent in Oral tablet and capsule formulations where it is used in both wetgranulation and

    direct compression processes. In addition to its use as a binder/diluent, microcrystalline cellulose

    also has some lubricant and disintegrant properties that make it useful in tableting.

    Solubility of microcrystalline cellulose

    Slightly soluble in 5% w/v sodium hydroxide solution; practically insoluble in water, dilute

    acids, and most organic solvents.

    Incompatibilities of MCC

    Microcrystalline cellulose is incompatible with strong oxidizing agents.

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    Sodium starch glycolate

    Sodium starch glycolate is a white to off-white, odourless, tasteless, freeflowing powder.

    The Ph Eur 2005 states that it consists of oval or spherical granules, 30-100 m in diameter, with

    some less-spherical granules ranging from 10-35 m in diameter.

    Description of sodium starch glycolate

    a) Synonyms

    Carboxymethyl starch, Sodium salt; Explosol; Explotab; Glycolys; Primojel; Starch

    carboxymethyl ether, Sodium salt; Tablo; Vivastar P.

    b) Chemical name and CAS registry number

    Sodium carboxymethyl starch [9063-38-1]

    c) Empirical formula and molecular weight

    The PhEur 2005 describes three types of material: Types A and B occurs as the sodium

    salt of a cross-linked partly O-carboxymethylated potato starch, containing 2.8-4.2% and 2.0-

    3.4% of sodium respectively. Type C is the sodium salt of a cross-linked by physical

    dehydration, partly Ocarboxymethylated starch containing 2.8-5.0% sodium. Sodium starch

    glycolate may be characterized by the degree of substitution and cross linking. The molecular

    weight is typically 5 105-1 10

    6.

    d) Structural formula

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    e) Functional category

    Tablet and capsule disintegrant.

    Applications in pharmaceutical formulation or technology

    Sodium starch glycolate is widely used in oral pharmaceuticals as a disintegrant in

    Capsule and Tablet formulations. It is commonly used in tablets prepared by either direct

    compression or wet-granulation processes. The usual concentration employed in a formulation is

    between 2% and 8%. Disintegration occurs by rapid uptake of water followed by rapid and

    enormous swelling. Although the effectiveness of many disintegrants is affected by the presence

    of hydrophobic

    excipients such as lubricants, the disintegrant efficiency of sodium starch glycolate is

    unimpaired. Increasing the tablet compression pressure also appears to have no effect on

    disintegration time.

    Solubility of sodium starch glycolate

    Sparingly soluble in ethanol (95%); practically insoluble in water.

    Incompatibilities sodium starch glycolate

    Sodium starch glycolate is incompatible with ascorbic acid.

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    Literature review

    Koizumi K et al., presented an invention, which related to rapidly dissolving tablets using

    sublimation technique. Compressed tablets of Mannitol did not dissolve in water due to

    the low porosity. To increase the porosity of tablets sublimation was done. Tablets were

    prepared by direct compression containing mannitol and camphor. A high porosity was

    achieved due to formation of many pores due to camphor sublimation. The compressed

    tablets have high porosity (approximately 30%) rapidly dissolved within 15 seconds in

    saliva.

    Remon JP et al., prepared the rapidly disintegrating tablets by lyophilization. Tablets

    contained hydrochlorothiazide, Maltrodextrin, hydroxyethylcellulose and gelatine. The

    solutions were poured into blisters and freeze dried. Maltrodextrin could be a filler of

    choice for the production of lyophilized tablets as freeze-drying due to amorphous

    network, which dissolved in the water with seconds. They evaluated gelatine, xanthan

    gum and hydroxyethylcellulose a binding agents in the formulation of freeze dried tablets

    with Maltrodextrin as filling agents.

    Nayak SM et al., prepared fast dissolving tablets of Promethazine theoclate using

    effervescent melt, super disintegration addition and melt technologies.Tablets from

    effervescent melt and super disintegration addition technique released 92 % and 89 % of

    the drug at the end of 10 min.

    Shirwaiker AA et al., prepared fast disintegrating tablets of Atenolol. The preparation

    contained an active ingredient, sugar (mannitol), superdisintegrant and dicalciumphosphate. Required quantities of each ingredient were weighed, mixed and prepared the

    tablets by dry granulation. All the formulation had disintegration time of less than 70

    seconds. Among the three superdisintegrant Ac-Di-Sol showed the highest efficacy.

    Formulation containing 10 % Ac-Di-Sol showed the least disintegration time of 30 2

    seconds compare to Explotab and Polyplasdone X.

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    Amin PD et al., presented an invention, which relates to fast disintegration tablets for oral

    administration. Taste masked adsorbents of Ofloxacin were prepared using cationic

    exchange resins. Taste evaluation of tablets showed complete masking of the bitterness of

    Ofloxacin. The taste-masked complex of the Ofloxacin was further incorporated into

    mouth dissolve tablets in combination with Metronidazole benzoate. All the formulation

    exhibited an in vitro dispersion time less than 50 seconds.

    Chaudhari PD et al., prepared fast dissolving tablets of Famotidine. In this study the

    bitter taste of Famotidine was masked using drug: Eudragit E 100 in different ratios (1:1

    to 1:10). For taste masking the ratio was optimized to 1:4 by time intensity. The different

    superdisintegrant (Ac-Di-Sol, Polyplasdone) with their varying concentration were used

    for disintegration of tablets in mouth. The formulation containing 2 % of Ac-Di-Sol and

    Polyplasdone showed 91.89 % and 101.07 % release respectively in 12 min

    Halakatti PK et al., formulated rapidly disintegrating tablets of Domperidone by applying

    two methods. Sodium starch glycolate and treated agar used as superdisintegrants in mass

    extrusion technique and treated agar method respectively.

    Shirwaikar A et al., formulated and evaluated fast dissolving tablets of Granisetron

    hydrochloride by direct compression method using superdisintegrants. A combination of

    mannitol and silicified microcrystalline cellulose (SMCC) in the ration 70:30 was used in

    the study. Study concluded that crospovidone and croscarmellose sodium are better

    disintegrant for formulation of fast dissolving tablets of Granisetron HCl.

    Vijaya KS et al., prepared Meloxicam rapidly disintegrating tablets by direct

    compression. The tablets were prepared with three superdisintegrant like SSG, Ac-Di-Sol

    and L-HPMC. The hardness of tablets was found to be less than 10% and disintegration

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    time of tablets was found to be less than 1 minute, except LHPMC.In-vitro drug release

    study showed enhance dissolution rate compared to pure Meloxicam.

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    Materials and equipments

    Analytical methods

    Formulation of fast dispersable Tablets Of Diltiazem Hydrochoride

    MATERIALS & EQUIPMENTS

    The following materials those were either AR/LR grade or the best possible

    pharmaceutical grade were used as supplied by the manufacturer.

    S.No Materials Category

    1

    2

    3

    4

    5

    6

    7

    Diltiazem

    Potato Strach

    Primogel

    Micro Crystalline Cellulose

    Mannitol

    Magnesium Stearate

    Talc

    Active Ingredient

    Disintegrant

    Super Disintegrant

    Directly Compressible Vehicle

    Directly Compressible Vehicle

    Lubricant

    Glidant

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    ANALYTICAL METHODS

    Determination of max of Diltiazem Hydrochloride by UV analysis

    25 mg of Diltiazem Hydrochloride was accurately weighed and dissolved in 25 ml

    of Distilled Water to get 1 mg/ml solution. This solution was further diluted to get 6g/ml. UV

    spectrum was recorded in the wavelength range of 200 - 400 nm. The l max of drug was

    determined by UV-Visible Spectrophotometer using Distilled Water as a blank.

    Construction Of Calibration Curve Of Diltiazem Hydrochloride

    25mg of Diltiazem Hydrochloride was accurately weighed and dissolved in 25ml of

    water to get 1mg/ml solution. From this Solution,1ml was taken and dissolved in 10ml Distilled

    Water. This solution was then serially diluted with Distilled water to give solutions of

    concentration ranging from 2 mg/ml to 10 mg/ml. The absorbances of these solutions were

    measured at 240 nm using Distilled Water as table blank and standard graph was plotted.

    S.No Equipment

    1

    2

    3

    4

    5

    6

    Monsanto Hardness Tester

    Friability Tester

    Tablet Dissolution Tester (USP)

    Tablet Disintegration Test Machine

    Tablet Punching Machine

    UV-Visible Spectrophotometer

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    Physical Properties

    Angle of Repose ()

    The frictional forces in a loose powder can be measured by the angle of repose (). It is an

    indicative of the flow properties of the powder. It is defined as the maximum angle possiblebetween the surface of a pile of powder and the horizontal plane. Angle of repose was

    determined by using funnel method. Powder was poured from funnel, which can be raised

    vertically until a maximum cone height, h, was obtained. Diameter of heap, D, was measured.

    The repose angle, , was calculated by formula,

    = Tan-1 (2h/D)

    Flow properties for different values of angle of repose are given below.

    S.No Angle Of Repose Flow

    1

    2

    3

    4

    40

    Excellent

    Good

    Moderate (addition of 0.2% glident is required)

    Poor

    Table : Relationship between Powder Flow and Angle of Repose

    Bulk Density (Db)

    It is the ratio of total mass of powder to the bulk volume of powder. It was measured by pouring

    the weighed amount of powder (passed through standard sieve #20) into a measuring cylinder

    and the initial volume was noted. From this, the bulk density is calculated according to the

    formula mentioned below. It is expressed in g/ml and is given by,

    Db = M / V0

    Where, M is the mass of powder

    V0 is the bulk volume of the powder.

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    a. Tapped Density (Dt)

    It is the ratio of total mass of powder to the tapped volume of powder. The volume was measured

    by tapping the powder for 500 times. Then the tapping was done for 750 times and the tapped

    volume was noted, if the difference between these two volumes is less than 2%. And if it is more

    than 2%, tapping is continued for 1250 times and tapped volume was noted. Tapping was

    continued until the difference between successive volumes is less than 2% (in a bulk density

    apparatus). It is expressed in g/ml and is given by,

    Dt = M / Vt

    Where, M is the mass of powder

    Vt is the tapped volume of the powder.

    b. Compressibility Index (Carrs Consolidation Index)

    One of the method of measurement of free flowing powder is compressibility as computed from

    density of a powder. It was calculated by using the formula,

    % Compressibility = [Tapped density-bulk density/tapped density] x 100

    Percentage Compressibility Flow Description

    5-15

    12-16

    18-21

    23-28

    28-35

    35-38

    >40

    Excellent (free flowing granules)

    Excellent (free flowing granules)

    Fair (powdered granules)

    Poor (very fluid powder)

    Poor (fluid cohesive powder)

    Very poor (fluid cohesive powder)

    Extremely poor (cohesive powder)

    Table : Relationship between Powder Flow and Percentage Compressibility

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    c. Hausner Ratio

    Hausner ratio is an indirect index of ease of powder flow. If the hausner ratio of powder is near

    to 1.25, indicates better powder flow. It is calculated by the formula,

    Hausner Ratio = Dt / DbWhere, Db = Bulk density of the powder

    Dt = Tapped density of the powder

    Table : Relationship between Powder Flow and Hausner Ratio

    Hausner Ratio Flow Description

    1-1.11

    1.12-1.18

    1.19-1.25

    1.26-1.34

    1.35-1.45

    1.46-1.56

    Excellent

    Good

    Fair

    Passable

    Poor

    Very Poor

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    Formulation And Development of Dispersible Tablet

    Of Diltiazem Hydrochloride

    Formulation development:

    Formulation of Diltiazem Hydrochloride Dispersible tablets by direct compression involve use of

    mannitol, and microcrystalline cellulose as diluent, mannitol also used as sweetener. Talc as

    glident and magnesium stearate as lubricant. Sodium starch glycolate (Primojel) was used as

    superdisintegrant. To select best formulation effective concentration various batches were taken

    at different concentration range from 4 to 8 % w/w for each superdisintegrant.

    Formulations:

    Formulation 1:

    S.No Ingridents

    Formulations

    F1 F2 F3

    1

    2

    3

    4

    5

    6

    7

    Diltiazem Hydrochloride

    Potato Strach

    Primogel

    Magnesium Stearate

    Talc

    Micro Crystalline Cellulose

    Mannitol

    30

    18

    3.8

    3.6

    3.6

    60.5

    60.5

    30

    18

    10.8

    3.6

    3.6

    57

    57

    30

    18

    14.4

    3.6

    3.6

    50.2

    50.2

    Table : Composition of formulations F1,F2 & F3

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    Procedure:

    Mix Diltiazem Hydrochloride, Potato Strach, Primogel, Micro Crystalline Cellulose,

    Mannitol And Sift Through # 80 Sieve

    Load sifted material of Step-1 into Mortar & Pestle and mix for 15 Mins.

    Lubricate the blend of Step-2 with # 80 passed Magnesium Stearate using Mortar &

    Pestle for 2 minutes.

    Add Talc as Glident to the Blend in Step-3 which was passed through # 80 Sieve

    Compress the blend of Step-4 into tablet using Cad-mach Punching Machine to a tablet

    of 180mg.

    Formulation 2:

    S.No Ingridents

    Formulations

    F4 F5 F6

    1

    2

    3

    4

    5

    6

    Diltiazem Hydrochloride

    Potato Strach

    Primogel

    Magnesium Stearate

    Talc

    Mannitol

    30

    18

    3.8

    3.6

    3.6

    121

    30

    18

    10.8

    3.6

    3.6

    114

    30

    18

    14.4

    3.6

    3.6

    110.4

    Table : Composition of formulations F4,F5 & F6

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    Procedure:

    Mix Diltiazem Hydrochloride, Potato Strach, Primogel, Mannitol And Sift Through # 80

    Sieve

    Load sifted material of Step-1 into Mortar & Pestle and mix for 15 Mins.

    Lubricate the blend of Step-2 with # 80 passed Magnesium Stearate using Mortar &

    Pestle for 2 minutes.

    Add Talc as Glident to the Blend in Step-3 which was passed through # 80 Sieve

    Compress the blend of Step-4 into tablet using Cad-mach Punching Machine to a tablet

    of 180mg.

    Evaluation of Dispersible Tablets Of Diltiazem

    Hydrochloride:

    General Appearance and Organoleptic PropertiesThe control of a general appearance of a tablet involves the measurement of

    a number of attributes such as a tablets size, shape, color, presence or absence of anodour, taste,

    surface texture, physical flaws and consistency, and legibility of any identifying markings.

    Shape, Thickness and Dimension

    Six tablets of each batch were selected and measured for thickness and diameter

    using digital vernier calipers. The extent to which the thickness of each tablet deviated from 5% of the standard value was determined. Hardness of the tablet was determined by Monsanto

    Hardness Tester. The tester consists of a barrel containing a compressible spring held between

    two plungers. The lower plunger is placed in contact with the tablet, and zero reading is taken.

    The upper plunger is then forced against a spring by turning a threaded bolt until the tablet

    fractures. As the spring is compressed, a pointer rides along a gauge in the barrel to indicate the

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    force. The force of fracture is recorded, and the zero force reading is deducted from it. Six tablets

    from each batch were selected and evaluated, and the average value with standard deviation was

    recorded.

    Friability Test

    It is the phenomenon whereby tablet surfaces are damaged and/or show evidence

    of lamination or breakage when subjected to mechanical shock or attrition. The friability of

    tablets was determined by using Roche Friabilator. It is expressed in percentage (%). Ten tablets

    were initially weighed (Winitial) and transferred into friabilator. The friabilator was operated at

    25 rpm for 4 minutes or run up to 100 revolutions. The tablets were weighed again (Wfinal). The

    percentage friability was then calculated by,

    F = WinitialWfinal x 100

    W initial

    % Friability of tablets less than 1% is considered acceptable. The friability is expressed as the

    loss of mass and it is calculated as a percentage of the initial mass.

    Weight Variation Test

    Weigh 20 tablets selected at random and calculate the average weight. Not

    more than two of the individual weights deviate from the average weight by more than the

    percentage shown in table 10 and none deviates by more than twice that percentage.

    Average weight of tablet Percentage deviation

    130 mg or less

    More than 130 mg but less than 324 mg

    324 mg or more

    10

    7.5

    5

    Table : IP Standards for percentage weight variation

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    Disintegration Time

    The disintegration time for all formulations was carried out using

    LABINDIA tablet disintegration test apparatus. Six tablets were placed individually in each tube

    of disintegration test apparatus. The water was maintained at a temperature of 372C and time

    taken for the entire tablet to disintegrate completely was noted.

    Drug Release Studies

    In vitro drug release studies were carried out by using LABINDIA

    Dissolution Test Apparatus DS8000 using paddle stirrer at rotation speed of 50 rpm. The drug

    release profile from tablets (n=3) of each formulation was studied in 900 ml of distilled water

    maintained at 37 0.5C. Aliquots of 5 ml of dissolution medium were withdrawn at specific

    time intervals (5, 10, 15, 20, 25,30,40,50 and 60 minutes), filtered and the amount of drug in the

    samples was estimated using UV-Visibile spectrophotometer at wave length of 240nm and

    results were reported.