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Presented By Guided By Nitesh V. Punde Prof. Santosh KumbharT.Y.B.Pharm. M.Pharm . Dept. :- Pharmaceutics

A REVIEW ON MOUTH DISSOLVING TABLET

SINHGAD TECHNICAL EDUCATION SOCIETIES SINHGAD INSTITUTE OF PHARMACY

NARHE PUNE-411041

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CONTENT’S

INTRODUCTION

DEFINITION & IDEAL PROPERTIES

MAIN INGREDIENTS USED IN MDT

CRITERIA FOR DRUG SELECTION

APPROACHES FOR PREPARATION OF MDT

PATENTED TECHNOLOGIES FOR PREPARATION OF MDT

PREFORMULATION STUDIES

EVALUATION OF MDT

MARKETED PRODUCTS OF MDT

REFERENCES

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INTRODUCTION

Tablets and capsules are the most popular dosage forms.

But one important drawback of such dosage forms is ‘Dysphagia’ or difficulty in swallowing.

This is seen to nearly about 35% of the general population.

This disorder is also associated with a number of conditions like :-

1. Parkinsonism

2. Motion sickness

3. Unconsciousness

5. Children

6. Mentally disabled persons

To overcome such problems MDT’s are developed.

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Definition“A solid dosage form containing medicinal substances or active ingredients which disintegrates rapidly within a few seconds when placed up on tongue”

Ideal properties of MDT Mouth Dissolving Tablet should Not require water or other liquid to swallow. Easily dissolve or disintegrate in saliva within a few seconds. Have a pleasing taste. Leave negligible or no residue in the mouth when administered. Be portable and easy to transport. Be able to be manufactured in a simple conventional manner within low cost. Be less sensitive to environmental conditions like temperature, humidity etc.

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Main ingredients used in preparation of MDTSuperdisintegrants:Disintegrants play a major role in the disintegration and dissolution of MDT.Criteria :- Should have rapid disintegration rate when tablet comes in contact with saliva in mouth.Produce good mouthfeel to patient.Should be non toxic.Should compatible with API.

Mechanism of action of Super disintegrants

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Mechanism of action of disintegrants The tablet breaks to primary particles by one or more of the mechanisms listed below:‐ •By capillary action :- Replaces the air adsorbed on the particles, which weakens and breaks the tablet into fine particles•By swelling :- Perhaps the most widely accepted general mechanism of action for tablet disintegration is swelling which creates pressure leads to disintegration.•Due to release of gases :- The tablet disintegrates due to generation of pressure within the tablet. (CO2 RELEASE)•Due to repulsion :-The electric repulsive forces between particles are the mechanism of disintegration and water is required for it.

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No bitter taste.

Dose lower than 20mg.

Good stability in water and saliva.

Partially non-ionized at the oral cavities pH.

Ability to diffuse and partition into the epithelium of the

upper GIT.

Criteria for Drug Selection

EXAMPLES OF SUPERDISINTEGRANTS1. NATURAL :- GUMS, MUCILAGE, PLANTAGOOVATA

MUCILAGE.2. SYNTHETIC :- CROSS POVIDONE,CROSS

CARMELLOSE,Ac-Di-Sol.

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Approaches for preparation of MDT Various technologies used in the manufacture of

Mouth Dissolving Tablets include:

1. Freeze‐drying or lyophilization

2. Sublimation

3. Moulding

4. Mass extrusion

5. Direct compression

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1.Freezedrying

First of all, the material is frozen to bring it below its eutectic point.Then primary drying is carried out to reduce the moisture to around 4% w/w of dry product. Finally, secondary drying is done to reduce the bound moisture to the required volume.2. Sublimation

This process involves addition of some inert volatile substances like urea, urethane, naphthalene, camphor,etc..Removal of volatile material by sublimation creates pores in tablet structure, due to which tablet dissolves when comes in contact with saliva.

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Sublimation Technique for Preparation of MDT

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3. Moulding

Tablets prepared by this method are solid dispersions.The drug can exist as discrete particles or micro particles in the matrix. It can dissolve totally to form a solid solution or dissolve partially in the molten carrier and remaining, if any, stays undissolved and dispersed in the matrix.

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4. Mass extrusionIn this technique, a blend of active drug and other ingredients is

softened using solvent mixture of water soluble polyethylene glycol,

using methanol .

Then the softened mass is extruded through the extruder or

syringe to get a cylinder of product, which is finally cut into even

segments with the help of heated blades to get tablets.

The dried cylinder can be used to coat the granules of bitter

tasting drugs and thereby masking their bitter taste.

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5. Direct compression

The disintegrant addition technology (direct compression) is the most preferred technique to manufacture the tablets due to certain advantages: -

High doses can be accommodated and final weight of the tablet can exceed that of other methods. Easiest way to manufacture the tablets. Conventional equipment and commonly available excipients are used. A limited no. of processing steps are involved. Cost‐effectiveness.

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Patented Technologies for preparation of MDT

1 Zydis technology:

‘Zydis’ is the first mouth dissolving dosage form in the market.Dissolves in less than 3 seconds.It is a unique freeze‐dried tablet in which the active drug is incorporated in a water‐soluble matrix, then transformed into blister pockets and freeze dried to remove water by sublimation.

Drawbacks

A water insoluble drug can be incorporated only upto 400 mg per tablet or less .On the other hand water soluble drug can be incorporated only upto 60 mg

2 Orasolv technologyThis technology involves taste masking of active drug.Effervescent disintegrating agent is also used.Less force of compaction is used for manufacturing so as to obtain soft and quickly disintegrating tablets.

 

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3.Durasolv technologyDeveloped by Ciba, second-generation technology .This is one of the suitable technologies to prepare products requiring low amounts of active drug. Due to higher force of compaction used, tablets prepared are rigid.

4.Wowtab technology

Yamanauchi pharmaceutical company patented this technology.‘wow’ means ‘without water’. The active ingredients may constitute upto 50% w/w of the tablet.Highly mouldable substance has high compressibility and thus shows slow dissolution.The combination of high and low mouldable(lactose,glucose) is used to produce tablets of adequate hardness.

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Preformulation Studies 1. Bulk Density

Formula :- ρb = M / V Where : -ρb - Bulk density, M- Weight of powder, and V- Volume of powder.

2. Tapped Density

ρt = M / Vt

Where : ρt - Tapped density, M- Weight of powder, and Vt- Minimum volume occupied after tapping.

Formula :-

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3. Compressibility Index

Simplest way for measurement of flow of powder.

% C.I. = ρt – ρb/ρt x100 Formula :-

4. Hausner ratio Hausner ratio is an indirect index of ease of powder flow.

Lower the value of Housner ratio better is the flow property.

Hausner ratio = ρt/ ρbFormula :-

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Flow property

% C.I. Hosner ratio

Excellent ≤10 1.00-1.11Good 11-15 1.12-1.18Fair 16-20 1.19-1.25

Passable 21-25 1.26-1.34Poor 26-31 1.35-1.45

Very poor 32-37 1.46-1.59Very, very

poor>38 >1.6

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5.Angle of repose

ϴ = Tan-1 ( h / r ) Formula :- Where,ϴ- Angle of repose, h- Hight of the heap, and r- Radius of the heap.

Flow property Angle of repose (degrees)Excellent 25-30

Good 31-35Fair- aid not needed 36-40

Passable- must agitate, vibrate

41-45

Poor 46-55Very poor 56-65

Very, very poor >66

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Evaluation of Mouth dissolving tablets 1. Thickness Measured using Vernier calipers

2. Hardness Force required to break a tablet by compression in the radial direction.

Pfizer hardness testers Monsanto hardness tester

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3. Friability test

Determined using Roche friability.

Subjected to 100 revolutions (25rpm/minute).

f = (1- W0 / W) × 100Formula :-

Where,f- Friability, W0- Weight of the tablets before, and W- Weight of the tablet after the test.

4.Dissolution test Dissolution study performed using USP II apparatus (paddal speed 50rpm).USP monographs dissolutions conditions should be followed in addition 0.1N HCl, pH 4.5 & 6.8 buffers should be evaluated.

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5. Stability study

As per ICH Q1A guidelines for accelerated studies.

Tablets stored at 40±1ºC/75% ± 5% RH for 4 weeks.

6. In-vitro dispersion time test

Drop a tablet in a beaker containing 50ml of sorrenson’s buffer pH 6.8 & time required for complete dispersion was determined.

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Marketd products of MDT

Brand name Active ingredient

Application company

Claritin® RediTabs®

Loratadine Antihistamine Scherig corporation

Feldene Melt® Piroxicam NSAIDs Pfizer Maxalt® -MLT® Rizatritpan

benzoate Migrane Merck

Pepeid® ODT Femotidene Anti-ulcer Merck Zyperxa® Olazepine Psychotropic Eli Lilly Zofran® ODT Olandansetron Antiemetic Galaxo Smith

kline Resperdal® M-TabTM

Resperidone Schizophrenia Janssen

ZubrinTM (Pet drug)

Tepoxelin Canine NSAIDs Scherig corporation

ZelaparTM Selegiline Parkinsons disease

Elanl Amarin corporation

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REFERENCES1. Biradar, S. S., Bhagavati, S. T., Kuppasad I. J., Fast

Dissolving Drug Delivery Systems: A Brief Overview, Internet J. Pharmacology, 2006, 4(2).

2. Kuccherkar B.S., Badhan A.C., Mahajan H.S., Mouth dissolving tablets: A novel drug delivery system, Phrma Times, 2003, 35, 3- 10.

3. Amin, A.F., Shah, T.J., Bhadani, M.N., Patel, M.M., Emerging trends in orally disintegrating tablets, www.pharminfo.net, 2005.

4. Lailla, J.K., Sharma, A.H., Freeze-drying and its applications, Indian Drugs, 1993, 31, 503- 513.

5. Seager, H., Drug delivery products and zydis fast dissolving dosage form, J. Pharm. Phamacol., 1998, 50, 375-382.

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