DILUENTS AND DISINTEGRANTS

about diluents and disintegrants in pharmaceutical solid dosage form

1. DILUENTS AND DISINTEGRANTS 1

2. 2 CONTENTS Introduction to diluents Classification Advantages and disadvantages Introduction to disintegrants Classification Advantages and disadvantages Conclusion References

3. INTRODUCTION TO DILUENTS In addition to the active or therapeutic ingredients, tablets contain a number of inert materials. The latter are known as additives or excipients. They may be classified according to the part they play in the dosage form.They are binders, diluents, disintegrants, lubricants, sorbents, coating agents, preservatives, colours, flavours and sweetners. DILUENTS Diluents are the fillers used to increased the bulk content in the dosage form this is done in a situation where the active constituent to be incorporated in the formulation is of less quantity. PURPOSE OF SELECTION To enhance bulkiness To provide improved cohesion To enhance flow To allow direct compression manufacturing 3

4. IDEAL PROPERTIES OF DILUENTS They must be non toxic They must be commercially available in acceptable grade There cost must be low They must be physiologically inert They must be physically & chemically stable They must be free from all microbial contamination They do not alter the bioavailability of drug They must be color compatible. CLASSIFICATION Diluents are classified into 3 types. Based on natural source Based on chemical nature Based on solubility 4

5. CLASSIFICATION OF DILUENTS A) BASED ON SOURCE 1)SUGARS Dextrose, Lactose, Sorbitol, Mannitol. Sucrose. 2)POLYSACHCHARIDES Starch, Micro crystalline cellulose, Modified-starch. B) BASED ON CHEMICAL NATURE 1)ORGANIC MATERIALS Dextrose, lactose, mannitol, sorbitol, starch, sucrose . 2)INORGANIC MATERIALS Dibasic calcium phosphate, Tribasic calcium phosphate, Calcium carbonate, C) BASED ON SOLUBILITY 1)SOLUBLE DILUENTS Dextrose, lactose, Mannitol, Sorbitol, Sucrose. 2)INSOLUBLE DILUENTS Starch, Dibasic calcium phosphate, Tribasic calcium phosphate, Calcium carbonate, 5

6. STARCH   Starch may be obtained from corn, wheat or potatoes. It is occasionally used as a tablet diluent ·        USP grade of starch is usually possesses poor compression and flowability moisture content between 11 to 14%. ·        Specially dried types of starch that have a standard moisture level of 2-4% are available, but are costly. DIRECTLY COMPRESSIBLE STARCHES Sta–Rx 1500     – free flowing, directly compressible starch                         – if drug content lies between 5-10%, it require other lubricating agent. Emdex and cellutab - due to sweet taste and cool feeling ,used in place of mannitol. DEXTROSE (D–Glucose )        Available in two forms: as hydrates and anhydrous forms. Dextrose turns brown in the presence of alkaline compounds and undergo reaction with amines, lactose and sucrose resulting in its discoloration. Available under brand name- CERELOSE 6

7. LACTOSE (MILK SUGAR) Lactose is the  most widely used diluent for tablet formulation.   It is obtained in hydrous and anhydrous form. The anhydrous form, picks up moisture when exposed to elevated humidity. Such tablets should be packed in moisture proof packets or containers. When a wet granulation method is employed, the hydrous form of lactose should generally be used.   3 grades of lactose are commercially available: 60 to 80 mesh        – coarse 80 to 100 mesh      – regular grade 200 to 450 mesh -- impalpable Lactose is a reducing sugar and undergoes Maillard reaction. Available in different forms : hydrous lactose, unhydrous lactose, spray dried lactose and fast flo lactose. Brand names : PHARMATOSE, RESPITOSE, TABBLETOSE. 7

8. MANNITOL It is an odourless, white, crystalline powder with slight sweet taste. It dissolves slowly and imparts a cool sensation in the mouth due to its negative heat of solution, hence used in chewable tablet diluent. Mannitol being inert and non – hygroscopic is used in vitamin formulations which are moisture sensitive. Formulations containing mannitol require large amount of lubricants due to its less flowability. Available under brand name : MANNOGEN 2080. SORBITOL It is white, granular powder which is water soluble. Sorbitol and mannitol are optical isomers. Sorbitol when used in combination with mannitol reduces the cost of diluent. Available brand names : NEOSORB 6O, SORBOGEN AND SORBIDEX P. 8

9. SUCROSE It is a white odourless, sweet tasting substance available in different particle sizes like granular, fine granular, fine, super fine and confectioners sugar. Confectioner sugar with 3% corn starch is used for wet granulation to avoid caking of tablets. Sucrose is hygroscopic, soluble in water and alcohol , it has good compactibility and stability. Tablets containing sucrose possess long disintegration time. Brand names of sucrose based diluents BRAND NAMES COMPOSITION DiPac Nu Tab Sugartab 97% sucrose + 3% Modified dextrin. 95% sucrose + 4% invert sugar + small quantities of corn and magnesium stearate. 90 – 93% sucrose + 7 – 10% invert sugar. 9

10. MICROCRYSTALLINE CELLULOSE ( MCC ) It is white odourless, tasteless inert crystalline powder with good flowability and contains porous microfibres of cellulose. As length of cellulose polymer increases, the tensile strength of the tablet also increases. It is used in both direct compression and wet granulation methods of tabletting. When used in wet granulation MCC promotes faster and uniform distribution of granulating agent. Available brand names : AVICEL PH, VIVACEL. DIBASIC CALCIUM PHOSPHATE It consist of small micro crystals of (dibasic) calcium phosphate in the form of free flowing aggregates. It is a fine white powder, insoluble in water. Directly compressible dibasic calcium phosphate occurs in dihydrate form, and loses its water of hydration at temperature above 60 degree Celsius. It does not require lubricants. Available brand names : DITAB 10

11. TRIBASIC CALCIUM PHOSPHATE It has properties similar to dibasic calcium phosphate. It is a fine, white powder, insoluble in water, slightly alkaline in nature and non – hygroscopic. It is less used in wet granulation. It should not be used with : Salts of strong acids, Acetate salts, Palmitate or acetate esters of vitamin E or vitamin A. Available brand names : TRITAB CALCIUM CARBONATE It is dense, fine white powder which is usually insoluble whose solubility depends on pH. It is obtained from grounded oyster shells and mined limestone. It is directly compressible diluent which exert significant pharmacological action as an antacid and also as nutritional supplement. 11

12. 12 ADVANTAGES Provide mechanical strength to the tablet. Non – toxicity. Enhance compression and bulkiness. Good organoleptic properties. DISADVANTAGES Some large amount of diluents causes hardness of tablet. Forms caking of tablet. It should not be used with salts of strong acids and acetate salts .

13. INTRODUCTION TO DISINTEGRENTS DISINTEGRANTS Disintegrants induce breakup of dosage form when it comes in contact with aqueous fluid in the GIT and this process of desegregation of constituent particles occurs, before the drug dissolution is known as disintegration process and excipients which induce this process are known as disintegrants. PURPOSE OF SELECTION The objectives behind addition of disintegrants are to increase surface area of the tablet fragments and to overcome cohesive forces that keep particles together in a tablet. IDEAL PROPERTIES The ideal properties of disintegrants include, good hydration, poor solubility and poor gel formation capacity. 13

14. CLASSIFICATION OF DISINTEGRANTS A) STARCH AND CELLUSE BASED EXCIPIENT Starch, Pregelatinisied starch, Microcrystalline cellulose, B) SOME CLAYS Veegum HV, Bentonite. C) SOME GUMS Agar, Guar gum, Tragacanth, Alginates. D) SOME RESINS Polacrilin potassium E) FINELY DIVIDED SOLIDS Colloidal silicon dioxide, Magnesium aluminum silicate. 14

15. STARCH Starch was the first disintegrating agent widely used in tablet manufacturing, among which potato, maize and corn starches are the most common types used. The typical concentration range of starch is 5-20% of tablet weight. Cost is very low. PREGELATINISED STARCH (STA-1500) Pregelatinized starch is widely used and produced by the hydrolyzing and rupturing of the starch grain. It is a directly compressible disintegrants and its optimum concentration is 10%. The main mechanism of action of Pregelatinized starch is through swelling. MICROCRYSTALLINE CELLULOSE (AVICEL)    Like pregelatinized starch, microcrystalline cellulose is widely used in formulations because of its excellent flow and binding properties. It is also an effective tablet disintegrant when used in a concentration of between 10-20%. 15

16. ALGINATES Alginates are alginic acid and salts of alginic acid. Alginic acid is insoluble in water, slightly acidic in reaction. Hence, it should be used in only acidic or neutral granulation. It can be successfully used with ascorbic acid, multivitamin formulations and acid salts of organic bases. Alginic acid at a concentration of between 5-10% is an effective, but very expensive disintegrant. ION-EXCHANGE RESIN (AMBERLITE 88) It  has disintegrant properties at a concentration of between 1-5%. But this type of disintegrant is rarely used. It has highest water uptake capacity than other disintegrating agents like starch . It has tendency to adsorb certain drugs. 16

17. 17 ADVANTAGES Faster therapeutic effect They have good compressability and flow property with poor gel formation. Used in oral disintegrating dosage forms and mouth dissolving tablets. DISADVANTAGES Some are more hygroscopic in nature. Some are anionic and may cause in – vitro binding.

18. CONCLUSION Diluents are used for better compressability and flowability for obtaining better dosage form with no toxicity. hence diluents should have ideal properties for selection. these are also used in vaccine preparation for long storage. therefore, plays an important role in pharmaceutical formulations. Disintegrants are an essential component to tablet formulations. The ability to interact strongly with water is essential to disintegrant function. Disintegration by capillary action or by swelling is the major mechanism for disintegrants. Disintegrant can be added intragranular or extragranular.   18

19. REFERENCES The Theory And Practice Of Industrial Pharmacy By Leon Lachman,a.Lieberman. Wikipedia.Org/Wiki/Diluent Wikipedia.Org/Wiki/Disintegrants Carterpharmaceuticalconsulting.Com/Articles/The-role-of-disintergrants.Html Pharmainfo.Net/Tablet-disintegrants http://formulation.vinensia.com/2011/11/diluents-fillers-for-tablet-formulation.html 19

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