FORMULFORMULATION ASPECTS OF SPECIAL TABLET LIKE -BUCCAL,CHEWABLE,SUBLINGUAL TABLETS & LOZENGES (Medicated Lozenges) Presented By…Nisargrx@hotmail.co.uk

CONTENTS:-

Introduction Definition Types of Formulation

Factors Formulation

Techniques Processing

Problems & Remedies

Recent Review Conclusion Reference

INTRODUCTION:-

Conventional Oral Dosage Form:- It is related to Oral Solid Dosage Form, Oral Liquid Dosage Form.

Special Solid Oral Dosage Form:- i.e. Special Tablets like Buccal Tablet, Sublingual Tablet, Chewable Tablet, Lozenges & Medicated Lozenges.

Also there another forms special tablets like:- Tablet Triturate, Floating Tablets, Single layered, Double Layered, Multi layered Tablets,& Tablet In Tablet.

DEFINITION & RELATED TERMS:-

Chewable Tablet:-It is defined as oral solid dosage form which is intended to be chewed in the mouth prior to swallowing & not intended to be swallowed intact.

Buccal Tablet, Sublingual Tablet:- These two classes of tablets are intended to be held in the mouth, where they release the medicaments for absorption directly through the oral mucosa. Buccal (Tablets are placed bet. The cheek &teeth/ in cheek pouch) Sublingual (Tablets are placed beneath the tongue).

Lozenges/ Medicated lozenges:- Originally termed as PASTILLEES. These types of tablets are used in oral cavity where they are intended to exert a effect in mouth (local)/ at distant site (systemic) by absorption (sucked) of drug through gastric mucosa

lozenges are prepared by incorporation of drug in FLAVORED HARD CANDY BASE.

Another form of Lozenge is compressed lozenges i.e. TROCHES are manufactured by compression process.

LOZENGES/ MEDICATED LOZENGES:-

TYPES:- Lozenges are classified by two way's i.e.

According to effect of drug at the site According to manufacturing techniques.1) According to effect of drug at the site.

I. Local Effect:- ex: Antiseptics, Antibiotics.II. Systemic Effect:- ex: Vitamins

2) According to manufacturing techniques.I. Hard candy Lozenges (boiled) II. Compressed Tablet Lozenges.

HARD CANDY LOZENGES:-

Are Discoid-shaped solid dosage form containing mixture of sugar & other carbohydrate with medicament in an amorphous/ glassy condition.

This form can be considered as solid syrup of sugars, gelatin (glycerinated) which contains 0.5-1.5 % moisture content.

ASPECTS:-

CONTENTS FORMULATION FACTORS PROCESSING FORMULATION

CONTENTS OF LOZENGES:-

Raw material:- Sugars (Sucrose)

Corn syrup:- Production by:-

I. Acid Hydrolysis

II. Enzyme Hydrolysis

III. Acid/Enzyme Hydrolysis

Invert Sugars:- levulose & dextrose

Reducing Sugars:- maltose, lactose etc

Acidulents:- citric acid, tartaric acid

Colors:- Flavors:- Medicaments:-

• Dextrose Equivalent (DE):- is a measure of the reducing sugar content of a product calculated as dextrose & expressed as a % of total dry substances/• DE is the % of pure dextrose that gives the same analytical effect as is given by the corn syrup.• Applications of Corn Syrup.

Dextrose Equivalent (DE):-

PROPERTIS & FUNCTIONAL USES OF CORN SYRUP:-

Cooking. Base Candy Mfg.

Principle. Mixing. Batch Forming. Rope sizing. Lozenge Forming. Cooling. Lozenge Sizing. Lozenge storage. Packaging.

COOKING:-

Types of cookers.• Fire Cookers• High Speed Atmospheric Cookers.• vacuum Cookers:

a) Pure-Sugar cookersb) Standard Vacuum CookersI. Continuous Batch Process Cookers Pre Cookers Cooking MachinesII. Continuous Process Cookers

COMPRESSED TABLET LOZENGES:-

Material used in the preparation of C.T.L:-

1) Tablet Base/ Vehicles:-

- sugar &sugar base vehicles:-

e.g. Dextrose & its trend names (Emdex, Mor- rex, Nu-tab etc…)

-sugar free base vehicles:-

e.g. Mannitol, Sorbitol ….

2) Other Fillers:- e.g. compress, Teera-allba,

avicel

3) Binders:-4) Flavors:-5) Colors:-6) Lubricants:-

e.g. Cab-o-cil,

7) Medicaments:-

MANUFACTURING STPES INVOLVED IN C.T.L:-

DIE FILLING WEIGHT ADJUSTEMENT. COMPRESSION HARDNESS TABLET EJECTION

SUBLINGUAL DOSAGE FORM:-

Factors Relating To Sublingual Tablets.

Molded Sublingual Tablets. Formulation Of M.S.T. Hand Molding Of Tablets. Machine Molding Of Tablets.

FORMULATION FACTORS:-

SITE RELEATED:- PARTITION COEFFECIENT:- DOSING OF DRUG:- IONIC NATURE:- TASTE:-

MOLDED SUBLINGUAL TABLETS:-

Originally Introduced By FULLER In 1878. Also referred as TABLET TRITURATE.

FORMULATION OF M.T:-1) DRUG2) An EXIPENT/BASE3) ANTIOXIDANT4) SOLVENT

HAND MOLDING & MACHINE MOLDING:-

HAND MOLDING

Powder Mix. Blended by mortar. Then solvent mix. Is added to form damp mass. This mass is pressed in molding plates

&molded tablets are formed.

Same pri. Is involved in machine molding tablets . Here the machines are used.

MOLDING PROBLEMS

1) Solvents:- Aqueous

solvent2) Drying :-

MOLDING PLATE:-

COMPRESSED SUBLINGUAL TABLET:-

Generally Molded S.T get easily absorbed &give better effect but Compressed S.T. also disintegrate rapidly & allow the ingredients to dissolved in saliva &to available for absorption without requiring the complete solution of all ingredients of the formulation.

E.g.:- Compressed nitroglycerin tablet. This type have less weight variation &better

content uniformity. Also are harder & less fragile than Molded tablets.

According to USP the disintegration time should be 3-7 sec.

Formulation aspects are same as that of Compressed Tablet Lozenges.

BUCCAL TABLETS:-

Developed by H.S.Russel. Basic principle behind this is same that of

Sublingual Tablet. Buccal tablets are most often used when

replacement hormonal therapy is goal. Flat, ellipitcal/ capsule shaped tablets are used. Circular &concave depression in each side of

major surfaces. Flexible in nature. Compressed Buccal Tablets are prepared either

by Wet granulation/ Direct compressed method. Main factor relating to B.T is that swallowing of

drug is not allowed as the drugs are not allowed to absorbed from G.I.T. /they get destroyed by G.I.T./liver enzymes.

CHEWABLE TABLETS:-

Chewable Tablet:-It is defined as oral solid dosage form which is intended to be chewed in the mouth prior to swallowing & not intended to be swallowed intact.

Formulation factors1. Organoleptic properties

Taste Flavor

Mouth feel After effect

2.Physical propertiesAmount of Drug

FlowCompressibilityCompatibility

Desired product attributeGood taste& mouth feelAcceptable bioavailability

Acceptable stability&Quality

Economical formula&Process.

Formulation TechniquesMicro encapsulation

AdsorptionIon exchange

Spray congealing& coatingGranulation& coating

Amino acids& protein hydrolysatesFormation of salts

Formulation approaches Artificial sweeteners

Flavoringcoloring

FORMULATION TECHNIQUES:-

MICROENCAPSULATION ADSORPTION ION EXCHANGES SPRAY CONGEALING &SPRAY COATING FORMATION OF DIFFERENT

SALTS/DERIVATIVES COATING BY GRANULATION USE OF AMINO ACID &PROTINE

HYDROLYSATES

MICROENCAPSULATION:-

Coating of drug particles/ liquid droplets with edible polymeric materials there by masking the taste &forming of free flowing microcapsules of 5-5000 µm size.

Steps involved in micro encapsulation:-

1) Formation of three immiscible phases:- vehicle (liquid) phase, core (drug) phase, coating material phase.

2) Depositing the liquid polymer coating by sorption around the core material by mixing three phases.

3) Rigidizing the coating by chemical cross-linking/ desolvation techniques to form a microcapsules.

phase-separation& co-acervation technique is used for Microencapsulation.

ADSORPTION:-

The drug is going to be adsorbed on a suitable substrates which is capable of keeping drug adsorbed while in the mouth but releasing them eventually in the stomach/G.I.T.

e.g. Dextromethorphan HBr on Mg.trisilicate

adsorbate Adsorbent

impart undesirable taste

ION EXCHANGE:-

VitaminsVitamins Coating Coating agentagent

%W/W%W/W

Thiamine Thiamine mononitratmononitratee

Mono& Mono& diglycerdiglycerides-ides-

33.333.3

RiboflavinRiboflavin -Of -Of Fatty-Fatty-

33.333.3

PyridoximPyridoximee

-acid-acid 33.333.3

NiacinamiNiacinamidede

Stearic Stearic acidacid

33.333.3

Substrate Resin (Cationic/ Anionic) possesses affinity for oppositely charged drug molecule, this form a complex which is stable in mouth for longer time.

e.g. resin bound form of Vit.B12. in presence of Vit.C (Ascorbic acid)

Amberlite (cation exchange resin)

SPRAY CONGEALING &SPRAY DRYING:-

Cooling (congealing) of melted substances in the form of fine particles during their travel from a spray nozzle to the distant vicinity of a spraying chamber held at temp. below the melting point.

SPRAY DRYING:-

THIS Process Involves Evaporation of solvent from a solution of coating material leaving a film of the coating material on the particle of substance being coated.

e.g. Coating of ANTIBIOTICS (sod. Dicloxacillin) by means of ethyl cellulose.

FORMATION OF DIFFERENT SALTS:- The modification of chemical composition of the

drug substance is done to form a salt/ derivative which it self render it less soluble in saliva & there by less stimulating for taste buds.

COATING BY CONVENTIONAL GRANULATING METHOD:-

Direct granulation method. Dry granulation method. Wet granulation method.

USE OF AMINO ACIDS & PROTEIN HYDOLYSATE:-

By combining Amino acids /its salts it is possible to substantially reduce the bitter taste of the drug (PENICILLIN).

Some used Amino acids:- Sarcosine, Alanine, Taurine, Glutamic acid, & Glycine.

MATERIAL USED IN FORMULATION OF CH.TAB.:-

1) Direct compression vehicle.

2) Flavor.

3) Colors.

4) Active in gradients.

1) DIRECT COMPRESION VEHICLE :-

Characteristics required for D.C.V. Moisture uptake characteristic Loading potential Hardness of tablets with vehicles Relative sweetness of the vehicle & Auxillary sweetness

MOISTURE UPTAKE CHARACTERISTICS:-

EQUILIBRIUM MOISTURE CONTENT(E.M.C):-

E.M.C. By given vehicle is defined as its ability of vehicle remain in equilibrium under the presence of moisture.

e.g. Graphic representation of Mannitol, Sucrose, Lactose, Xylitol, Sorbitol, Fructose, at 50, 65, 75, &85% RH.

Mannitol remain unchanged under any %RH while Fructose & lactose having high tendency to absorbed more moisture under %RH.

Mannitol/ Lactose< Sucrose< Dextrose/Xylitol < fructose/Sorbitol

HARDNESS OF TABLET WITH DEXTROSE, MANNITOL, SUCROSE….

For chewable tablets the hardness should be greater than regular tablet. In above e.g. it is indicated that Hardness of the given tablet upon storage going to decrease even at low humidity.

In such cases an Auxillary dry binder (M.C.C) is added in gran. Process to avoid softening.

Vehicles Vehicles Initial Initial hardness hardness (Sc)(Sc)

Hardness (sc unit) after 12 days Hardness (sc unit) after 12 days

43%RH 65.%RH 75%RH 43%RH 65.%RH 75%RH 100%RH100%RH

Lactose (Ah)Lactose (Ah) 14.014.0 12.0 11.2 10.8 7.912.0 11.2 10.8 7.9

MannitolMannitol 9.99.9 7.5 4.9 3.6 1.77.5 4.9 3.6 1.7

SorbitolSorbitol 14.714.7 12.2 8.1 6.4 4.212.2 8.1 6.4 4.2

DextroseDextrose 15.615.6 11.4 6.2 4.0 1.811.4 6.2 4.0 1.8

SucroseSucrose 15.115.1 7.2 2.3 1.2 0.27.2 2.3 1.2 0.2

LOADING POTENTIAL:-

LOADING POTENTIAL:- It is defined as the ability of D.C.V. to accept other materials in the formulation including active drug & other agents.

It is expressed as % w/w of the vehicle weight. Greater the L.P. The more economical

formula. For given vehicle the L.P should be dependent

on each specific formulation E.g. VIT.C. formulation. Sorbitol having L.P. of

45% & that of Dextrose having 33%. The L.P. is also dependent on inherent compr.

Character of drug. E.g. acetaminophen.

RELATIVE SWEETNESS OF VEHICLE /AUXILLARY SWEETENER:-

Acceptance of D.C.V. mainly depend upon their ability to mask the bad taste of drug

The D.C.V should require the property of sweetness.

Auxillary sweeteners :- necessary in order to supplement the natural sweetness of vehicle.

E.g. neo hesperdin diHcl, Saccharin etc.

2). FLAVORING AGENTS:-

Natural flavors Spray dried flavors Adsorbed flavors Microencapsulated

flavors

The selection of flavors depends upon

1) Therapeutic agents2) Active drug

formulation 3) Formulation4) Dose/ tablet &

frequency of administration

5) Intended patient population

6) Marketing preference.

RECENT DEVELOPMENT & ASPECTSCHEWING GUMS (chewable tablets):- AIM:-Data from medicines monitoring

unit (MEMO) at university of DUNDEE finds that 1/3rd of patients:-fully compliance with drug prescription

1/3rd of patients:- non compliance Remaining patients:-fully non

compliance FLARER SA based company

developed a system of chewing gum(3 TAB GUM)

Advantages:- 1) Dissolved in saliva:- compliance,

bioavailability, readily available for absorption.

2) Use to act locally:- oral cavity disease treatment.

3) Administration of lower dosage:- side effects.

4) Gastric mucosa will not suffer:- risk of intolerance/erosion.

5) If gum is swallowed :-mechanism of release of drug is negated.

6) Separate process of formulation technique:- prevent gum base heating, avoid destruction of API.

7) Useful for combination of two/more API:-i.e.imcompatible / immediate, slow releasing drugs.

FORMULATION ASPECT:-

NATURE OF CHEWING GUMS

Chewing gum(3TAB GUM) is divided into 3 layers:- upper & lower external layer & core layer (Drug).

Upper & lower layer mainly composed of anti adhesive excipients.

External layersExternal layers %% Core layerCore layer %%

Antiadherant Antiadherant layerlayer

70-9070-90 ActiveActive 0.1-80.1-8

Compression Compression adj.adj.

1-101-10 Gum baseGum base 70-8070-80

SweetenerSweetener 1-101-10 Compr. adj.Compr. adj. 1-101-10

FlavorsFlavors 1-101-10 SweetenerSweetener 1-101-10

FlavorsFlavors 2-202-20

MELT-IN-MOUTH TABLETS BY SUBLIMATION TECHNIQUE:-

Melt-in-mouth tablets:-Novel slid dosage form. Disintegrate & dissolved rapidly in saliva, No need of water for administration. Melt-in-mouth tablets overcome the feeling of rough texture (Side effect of compressed tablets,

disintegrating agent).

MECHANISM:-It involves sublimation of volatile oils/sublimating agent, which causes pre formation in the tablet saliva enter in this pores &causes the rapid disintegration of tablet in oral cavity.

Compressible Mannitol (PEARLITOL SD200):-used as diluent, sweetener

subliming

agent pores created on sublimation

Compressed tablet

sublimation at appropriate condition e.g. olanzapine tablet (Anti-psychotic)

Name of Name of IngredientsIngredients

FormlFormlnn

SO 1SO 1

SO 2SO 2 SO 3SO 3

OlanzapineOlanzapine 5.05.0 5.05.0 5.05.0

Pearlitol Pearlitol SD200SD200

113.1113.122

94.3794.3755

75.62575.625

Ammo. Ammo. bicarbonatebicarbonate

-- 18.7518.7500

37.50037.500

AspartameAspartame 3.1253.125 3.1253.125 3.1253.125

FlavourFlavour 1.8751.875 1.8751.875 1.8751.875

Aerosil 200Aerosil 200 0.6250.625 0.6250.625 0.6250.625

Magnesium Magnesium StearateStearate

1.2501.250 1.2501.250 1.2501.250

Formulation Formulation codecode

Disint. Disint. TimeTime

in sec.in sec.

In OralIn Oral

SO 1SO 1 8080+/-5+/-5 80+/-580+/-5

SO 2SO 2 75 75 +/-5+/-5 60+/-560+/-5

SO 3SO 3 80 80 +/-5+/-5 35+/-535+/-5

MOUTH DISSOLVING TABLETS:-

Mouth dissolving tablet (MDT)/ Orally disintegrating tablets (ODT) have emerged as Novel solid oral dosage form, which dissolve/ disintegrate/ disperse in saliva within few seconds. According to European Pharmacopoeia, the ODT disintegrate less than three minutes. MDT/ODT basically contains super disintegrating agent like Cross linked carboxymethylcellulose (Croscarmellose), Sodium starch glycolate (Primogel, explotab) ,Polyvinylpyrrolidone (Polyplasdone) etc.

TECHNOLOGIES FOR PREPARING MDT:-

1) FREEZ DRYING METHOH:-

2) MOULDING:-

3) SUBLIMATION:-

4) SPARY DRYING:-

5) DIRECT COMPRESSION:-

QUIT SMOKING LOZENGES:-

Quit smoking lozenges are a popular stop smoking aid. They are in the form of a small candy that are a) easy to carry with you, b) keep your mouth occupied and c) help you quit smoking of course.

Quit smoking lozenges are particularly good for people who light up their first cigarette in less than half an hour other they wake up in the morning. Most lozenges come in various forms depending on this time-factor.

well-know fact that the nicotine addiction and the cessation symptoms (nervousness, anxiety, sweating, headaches, depression, etc) are the two things making smoking cessation an impossible task for many smokers.

Q.M.L. will reduce the withdrawal symptoms thus leaving the person more stop-smoking-stress-free time to cope with yourself. Moreover the use of quit smoking lozenges will reduce the cravings.

Quit smoking lozenges are particularly preferred by women who often postpone smoking cessation because they are afraid of gaining weight one of the most popular brands quit smoking lozenges are the Commit stop smoking lozenges.

E.g. Bupropion Hydrochloride

www.google.com

REFERENCES:-

THE THEORY & PRACTICE OF INDUSTRIAL PHARMACY BY LEON LACHMAN 3RD EDITION.

PHARMACEUTICAL DOSAGE FORMS- TABLETS VOL-1 BY HERBERT, LIBERMAN, LACHMAN.

BIOPHARMACEUTICS & PHARMACOKINETICS BY BRAHMANKAR AMERICAN PHARMACY REMINGTON PHARMCEUTICAL SCIENCE 17TH EDITION. TABLET MANUFACTURING ndc. JOURNAL OF PHARMACEUTICAL RESEARCH VOL.4 NO.3 JULY

2005 & VOL.3 NO.2 APRIL 2004. MANUFACTURING CHEMIST MARCH 2005.

www.manufacturingchemist.com www.google.com

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