Formulation Excipients of Tablets

Hello pharma bloggers, in this present blog we shall have an over look on the formulation ingredients of tablets.

This is blog is aimed to cater the needs of those pharma fresher graduates who have just completed their graduation and looking to find their future in the phrama industry rather than higher education. If you seem to have interest in the production department or quality control department you need to have a keen knowledge of tablets and capsules.

Tablet is an solid dosage form which consist of one or more active ingredient with excipients, excipients are very important part of the tablet formulation,

Excipients are pharmacologically inactive substances included in the formulation which is used as a carrier of active ingredient.

In a conventional tablet the excipients used in the tablet formulation include

1.Diluents/fillers

2Binders

3.Disintegrants

4.Lubricants

5.Glidants

6.Miscellaneous

ODiluents:

Diluents are used to increase the bulk content of the dosage form, this is done in a situation where the active constituent to be incorporated in the formulation is of less quantity. For ex if the active ingredient is just 5 mg, is such a case a tablet of just 5 mg is very difficult to manufacture and handle too, thus the bulk content is increased by addition of inactive excipient.

Round tablets of weight 120mg to 700mg and for oval tablets 800mg are easy to handle

Examples of excipients:

lactose, lactose anhydrous, lactose spray dried, directly compressible starch, hydrolyzed starch, MCC, other cellulose derivatives, dibasic calcium phosphate dihydrate, mannitol, sorbitol, sucrose, calcium sulfate dehydrate, dextrose.

*Most of the excipients are dehydrates, i.e. contain certain amount of bound water, this bound water is important during granulation process, it reduces the hygroscopic nature of the formulation. Making the formulation stable.

*For the active ingredients which are sensitive to water anhydrous excipients are used like anhydrous lactose or anhydrous, dibasic calcium phosphate.

* Spray dried lactose, direct compressible starch and MCC (avicel) are the diluents that can be used when the formulation is prepared by direct compression.

*Mannitol is one of the costliest diluents but it is still used due to the refreshing sensation given by it when it is used in the chewable tablets.

*Sucrose or sugar based diluents are used for direct compression formulations. Sucrose based diluents include: Sugartab( 90-93% sucrose+ 7 to 10%invert sugar), Dipac (97% sucrose + 3% modified dextrin) and Nutab( 95%sucrose+4%invertr sugar with small amount of corm starch and magnesium stearate)

OBinders:

*These are the dry powders or liquid which are added during wet granulation to promote granules or to promote cohesive compact during direct compression.

*It provides mechanical strength to the tablet.

*Binders can be in powder form and liquid form example of binders are

Powder binders: cellulose, methyl cellulose, polyvinyl pyrrolidine, PEG

Solution binders: gelatin, PVP, HPMC, PEG, sucrose, starch

*Binders can be added in the following ways to the formulation

oAdded as powder before wet agglomerisation so that the binder is evenly distributed.

oAs solution form it is used as agglomerisation liquid in the wet granulation. It is called as liquid binder

oAs a dry powder, which is mixed with other ingredients before compaction (slugging or tabletting). It is called as dry binder.

*Natural binders like acacia and tragacanth are used in solution form in the concentration of 10-25%, alone or in combination for wet granulation and they can be added as powder for the direct compression process.

*Gelatin is used along with acacia or alone this form a better binding agent than the above two natural polymers.

*Polymers like MC, HPMC are used as dry powders in case of direct compaction, they act as good binding agents, in the solution form they act as good adhesives.

*Ethyl cellulose and HPMC can be used in alcoholic solutions. they act as anhydrous adhesives.

ODisintegrant:

*Disintegrant are added to the formulation as it breaks the dosage form into smaller particles when it comes in contact with the liquid, these smaller fragments have greater surface area which will increase the dissolution of the drug.

*Various mechanism of disintegrations are proposed:

oBy breaking into fragments: When the tablet comes in contact with the liquid, the liquid penetrates into the pores of the tablets and breaks it into fragments. To improve the water uptake into the pores certain hydrophilic polymers are added to the formulation

oBy swelling: when the tablet comes in contact with the water it swells and ruptures the tablet into small particles.

*Examples of disintegrants are: starch, starch derivatives, clay, cellulose, alginates, PVP, cross linked Na CMC

*Starch is used for in the concentration range of 5 to 20% of the tablet weight

*Modified starch are also used which like Primogel, Explotab. These are used in the low concentration like 1 to 8%, Pregelatinised starch is also employed in the formulation with 5% concentration.

*Clay like Veegum HV and Betonite are used in 10% level,

*Polymers like cross linked PVP, CMC are also used as disintegrants.

OLubricants:

*Lubricants are used to reduce the friction between the tablet and die cavity when the tablet die cavity is getting ejected from the die.

*Lack of lubricant can lead to problems like capping, scratch on the sides of the tablet, fragmentation of the tablet, shape out etc...

*Thus to avoid this lubricants are to be used

*For a lubricant the time of addition, concentration in which it is to be added and the combination are the important parameters

oConcentration: as most of the lubricants are hydrophobic in nature thus the an increased concentration of lubricant would lead to problems like poor wettability, and dissolution and disintegration problem this they are added in the concentration less that 1%

oTime of mixing: it is important as over mixing may lead to reduction in tablet dissolution and disintegration

oCombination: if the lubricant is mixed with the disintegrant it will lead to formation of an film of lubricant on the tablet surface which will reduce the disintegration.

*Examples of lubricants are: stearic acid, stearic acid salt, stearic acid derivatives, talc, PEG, surfactants, waxes

*Calcium stearate and magnesium stearate (0.25-0.50% w/w) are the most commonly used lubricants followed by talc.

*Higher molecular weight poly ethylene glycol and certain polymeric surfactants are used as water soluble lubricants.

*Lubrication can be achieved by two ways

oFluid lubrication: it is achieved by the addition of liquid paraffin which forms an liquid film over the surface, but this is rarely followed

oBoundary lubrication: in this powder is mixed to the formulation which forms a film on the surface which reduces the friction.

*Lubricants can be of two types

oInsoluble lubricants: these are added to the formulation at the end before the compression of the tablet examples include: magnesium stearate, stearic acid, glyceryl behnate, glyceryl palmito stearate,

oSoluble lubricants: these are added to overcome the defects caused by the insoluble lubricants. Examples include: PEG, poly oxy ethylene stearate, lauryl sulphate salt

OGlidant:

*Glidants are used to improve the flow property of the formulation, it reduces the friction between the particles and between the hopper and particles and die cavity and partices

*Actually glidant, lubricant and antiadherent have a close relation to each other. They have some functions in common.

*Most of the glidants used are hydrophobic thus they are to be carefully added i.e. concentration regulated.

*Examples of glidants are talc, colloidal silicone dioxide, corn starch.

*Glidants should be of small size so that they can retain with in the small pores of the granules have a greater surface area.

OMiscellaneous:

*Above from the above mentioned principal ingredients following excipients also improve the dosage form characters they are adsorbents, colouring agents,

OAdsorbent:

*Adsorbents are used when there is an need to add a liquid or semisolid ingredient in the formulation, adsorbents are capable of sorbing the liquid component on to the dry powder.

*Thus oil or liquid component can be incorporated into the powder

*Examples of adsorbents include: magnesium oxide, kaolin/bentonite,

OFlavorants:

*These are incorporated into the formulation to improve the flavor or give a pleasant taste to the formulation.

*Flavoring agents are mostly restricted to the formulations in which are intended to be released in the mouth or chewable tablets.

*They are usually added in along with the granules.

OColourants:

*Colouranats are added to the formulation in order to increase the patent compliance or for identification of the formulation.

*Usually the colurants are added in the form of insoluble powder or in the form as liquid in the granulation liquid.

*Examples of colorants are: FD&C and D &C dyes and lakes.

All the above excipients described above can be seen in an conventional tablet.

Other type of tablets also contain the same formulation ingredients but with a few variation in composition.

Formulation variables in different types of tablets:

1.Enteric coated tablet:

*Enteric coated tablets are intended to be insoluble in the stomach ph and get solublized in the intestinal ph.

*Thus for this purpose in the formulation of enteric coated tablets polymers like cellulose acetate phthalate, polyvinyl acetyl phthalate, HPMC phthalate are used

*All the above polymers contain a dicarboxylic group and phthalic acid in the partly esterifies form. These acid esters remain insoluble in the acidic ph below 4 and they get hydrated in the ph range of 4 to 6 i.e. in duodenum, when the drug molecule enters into the intestines where the ph is in the range of 7 to 8 where these polymers get ionized, and the ester bonds between them is broken by the esterase present in the intestinal fluid.

2.Film coated :

*Film coating is applied to the tablets to give a smooth finish to the tablets and to protect the tablet from the external atmospheric conditions

*For film coating a material containing a plasticizer and a surfactant (for even spreading) is used.

*Examples of polymers used for enteric coating are hydroxyl propyl cellulose, HPMC.

3.Effervescent tablets:

*These tablets are intended to produce effervescence when they come in contact with the water or liquid.

*Thus the formulation of these tablets includes organic acid and bicarbonates.

*Water soluble lubricants are preferred here

*Binders are not included in the formulation or rather a very less concentration is employed.

*Effervescent tablets are prepared by the direct compression or by compaction of the granules; wet granulation method is very seldom used.

This blog is free from any plagiarized material

Reference:

1) The theory and practice of industrial pharmacy by Leon Lacman, Herbert A Lieberman, Joseph L.Kang third edition, Varghese publishing house page no - 321- 333

2) Pharmaceutics the science of dosage form design edited by M.E.Aulton Churchill Livingstone Second edition Page no- 405 -417

3) Pharmaceutical dosage form and design by david jones pharmaceutical press 2008 edition pg.no- 210 - 218