Diwakar chudalB.Pharmacy , Institute of Medicine (IOM)

Definition Drug absorption is defined as the process of

movement of unchanged drug from the site of administration to systemic circulation.

Excipients.

Nature and type of dosage form.

Storage conditions.

Non-drug components which are added during formulation of drug are called excipients.

Excipients are added during drug formulation because:

Ensures physico-chemical stability.

Gives uniformity to composition.

Gives optimum bioavailability.

Gives suitable colouration and taste.

Despite their importance in the drug formulation, excipients can highly influence the absorption of drugs.

More the number of excipients in a dosage form, more complex the drug becomes and more likely to show problems in drug absorption and bio-availability.

Most commonly used excipients during formulation of dosage form are:Vehicle, diluents, binders or granulating agents, disintegrants, lubricants, coatings, suspending agents, surfactants, buffers, complexing agents, colorants, sweetningagents, precipitation inhibitors, etc

Vehicle or solvent system is the major component of liquid oral and parenteraldosage form.

Basically, 3 types of vehicles are used▪ Aqueous vehicles (water, syrup, etc)

▪ Non-aqueous water-miscible vehicles (propylene, glycol, glycerol, etc)

▪ Non-aqueous water-immiscible vehicles (vegetable oils)

Aqueous and water miscible vehicles are miscible with the body fluids so the drugs from them are rapidly absorbed.

Absorption of drugs in different vehicles follows the order :

water-miscible vehicles > aqueous vehicles >water-immiscible vehicles.

Absorption of a drug from a viscous vehicle is slower in comparison to non-viscous vehicle.

Thus, nature of vehicles and viscosity of vehicles is also one of the factor affecting the drug absorption.

Diluents are commonly added to tablets and capsule formulations if the required dose is inadequate to produce necessary bulk.

Inorganic Organic

Organic diluents: Starch, lactose, microcrystalline cellulose, etc

Inorganic diluents: Dicalcium phosphate (DCP) is most common.

Sometimes Drug-diluent interactions alters the absorption of drug.

Example:Tetracycline and DCP when interacts, divalent calcium-tetracycline complex is formed which is poorly soluble and thus unabsorbable.

Granulating agents are the substance which are used to hold powders together to form granules.

It ensures that the tablet remains intact after compression.

Starch, cellulose derivatives, gelatin, sugar solutions,etc are most common granulating agents.

Large amount of such granulating agents increases hardness and decreases dissolution rates of tablets and hence decreases the rate of absorption.

Example:PEG 6000 when binds with phenobarbital, it forms complex compound with very low solubility.

Disintegrants are the substance which increases the dissolution of tablets in water.

When drug comes in contact with water, disintegrantshelps to overcome the cohesive force between drug molecules and dissolution of tablets takes place in aqueous medium.

However, adsorbing disintegrants like bentonite and vegum should be avoided with low dose drugs like digoxin, alkaloids and steroids since a large amount of dose is adsorbed and only a small fraction is available for absorption.

Lubricants are added to tablets to reduce interparticle friction and sticking.

Also called as anti-frictional agents. Lubricants are mostly hydrophobic in nature

and thus inhibits the penetration of water into the tablets.

Lubricants are applied by coating it over the surface of tablets.

Coating:

The process of applying one substance on the surface of another.

Deleterious effects of various coatings on drug dissolution from a tablet follows the order:

▪ Enteric coat > suger coat > non-enteric film coat

Suspending agents are the substance which stabilize the solid drug particles by reducing their rate of settling through an increase in the viscosity of the medium.

Also called as viscosity imparters.

Mostly used suspending agents are hydrophilic polymers like:

▪ Vegetable gums (eg. Acacia)

▪ Semi-synthetic gums(eg. CMC, MC)

An increase in viscosity by some suspending agents acts as a mechanical barrier to the diffusion of drug from the dosage form into the bulk of GI fluid and from GI fluid to the mucosal lining.

Example:

CMC forms unabsorbable complexes with amphetamine.

Surfactants are used in drug formulations as wetting agents, solubilizers,etc

Surfactants may either increase or retard the drug absorption interacting with drug molecules.

Surfactants usually increases drug absorption by increasing membrane permeability of the drug.

Decrease in absorption of drug in the presence of surfactant is due to formation of unabsorbable drug-surfactant complex at surfactant concentrations above the critical concentration.

Thus, higher surfactants concentration always decreases the rate of drug absorption.

Buffers are the solutions whose PH value remains almost constant after addition of small amounts of acids or alkali.

Buffers are sometimes useful in increasing the rate of dissolution of drug. Eg.bufferedaspirin tablets.

But, certain buffer systems containing potassium cations inhibits drug absorption as seen in vit B2 and sulphanilamide.

Inhibitory effect of the various buffer cationson the drug absorption follows the order:

K+ > NH4+ > Li+ > Na+ >TRIS+

In some drugs, complexing agents are added to alter the physico-chemical and bio-pharmaceutical properties of a drug.

A complexed drug may have different stability, solubility, molecular size, diffusion rate, etc

Examples of complexation which increases the drug absorption are:

Ergotamine tartarate – caffeine complex. (increases dissolution)

Caffiene-PABA complex. (increases membrane permeability)

• However, complexation can sometime decrease the drug absorption due to formation of poorly absorbable complex

Eg. Complexation of tetracycline with divalent and trivalent cations like calcium, iron, magnesium, aluminium,etcdecreases absorption.

Colorants are added in drug formulations to mask the unattractive original colour of a drug.

But, colourants can also largly affect the drug absorption.

Very low concentrations of water soluble dye can have an inhibitory effect on dissolution rate of several crystalline drugsEg. Brilliant blue dye retards dissolution of

sulpathiazole.

When concentration of free drug increases above the saturation, it results in supersaturation which leads to drug precipitation or crystallization.

PVP, HPMC, PEG, PVA, etc are some polymers which prevents drug precipitation by: Increasing the viscosity of vehicle

Adsorbing on the faces of crystals thus reducing crystal growth.

The rate of absorption and bio-availability of certain drug largely depends on the proper selection of dosage form of that drug.This is due to the relative rate at which a particular

dosage form releases the drug to the biological fluids and membrane.

As a general rule, bio-availability of a drug from various dosage forms decreases in the following order:

Solutions > emulsions > suspensions > powders > capsules > coated tablets > enteric-coated tablets > sustained-release tablets.

Thus, absorption of a drug from solution is fastest with least potential for bioavailability problems whereas absorption from sustained-release product is slowest with greatest bioavailability risk.

A number of changes in the physico-chemical properties of a drug can result due to storage conditions which can adversely affect absorption and thus bio-availability.

When shelf-life of the solutions becomes long, solubility of drug changes and precipitation can occur.

Similarly, decrease in rate of dissolution occurs in suspension dosage form

High temperature and humidity results in increase in hardness of tablets which decreases the rate of absorption.

Therefore, storage conditions and product age has significant role in the absorption of drug from different dosage forms.

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