Selection of excipients must be done with an utmost care to avoid physical and chemical interactions that ultimately lead to the degradation of the quality of the product.
1. Drug-excipient interaction and its
importance in dosage form
development
Neeraj Ojha
7th sem Bpharm
CIST COLLEGE KATHMANDU NEPAL
2. Introduction:
• Excipient is a pharmacologically inactive substance formulated
along side the active pharmaceutical ingredient of a
medication.
• Excipients although inert can initiate, propagate or participate
in chemical or physical interactions with drug compounds,
which may compromise the effectiveness of a medicine.
• In other words, they might enhance the effect of the drug,
inhibit or change nothing.
• Excipients also provide bulk to the formulations, facilitate
drug absorption or solubility, aid in handling of API during
manufacturing , and provide stability and prevent from
denaturation.
3. Contd.
• For the development of proposed pharmaceutical
dosage form, three components which should be
considered are:
1. Properties and limitations of API;
2. Properties and limitations of excipients;
3. Advantage and limitation of methods used;
Excipients are classified according to their functions as:
Binders; disintegrants; fillers; Lubricants; Glidants;
Compression aids; Colors; sweeteners; preservatives;
flavors; film formers/coatings; suspending/dispersing
agents/surfactants.
4. Advantages/Limitations of Excipients:
• Excipients are included in the dosage forms for the :
1. Improvement of the stability of API in the dosage form;
2. Modulation of bioavailability of active pharmaceutical
ingredients;
3. Maintain the pH of liquid formulations;
4. Maintain the rheology of semisolid dosage form;
5. Act as tablet binders, tablet disintegrants;
6. Act as antioxidant and emulsifying agents;
7. To allow the adequate administration etc.
Limitations of the excipients are that they may cause chemical
interaction or affect the quality of packaging materials.
5. Contd.
• Benefits of Active Pharmaceutical Ingredients (APIs):
• Lower risk of drug interaction.
• Increased understanding of the drug and its action.
• Increased compliance from the patient.
• Better acceptance of the drug's side effects and symptoms.
• Better choice of brand.
Limitations:
APIs can exist in different polymorphic forms as well as in
amorphous state. Polymorphic and amorphous forms of APIs can
differ in physicochemical properties which in turn can
significantly influence their therapeutic safety and effectiveness
of the treatment.
6. Definition:
• Excipients according to IPEC, “These are substances other
than the API which has been appropriately evaluated for
safety and is included in a drug delivery system to either aid
processing of the system during manufacturing or protect,
support or enhance stability, bioavailability or patients
compliances or assist in product identification and enhance
any other attributes of overall safety and effectiveness of drug
product during storage or use.”
7. Mode of drug degradation
Common modes of degradation are:
1. Hydrolysis: It means the break down of the substance in
the presence of water. Drugs with functional groups
such as esters, amides, lactones, or lactams are the
most susceptible. Water also has great potential of
causing microbial contamination that leads to easy
degradation eg. Methyldopa, Procaine, Penicillins.
2. Oxidation: It involves the removal of electropositive
atom, radical or electron or, conversely , addition of an
electronegative moiety. Aldehydes, alcohols, ph-
8. Contd.
enols, alkaloids and unsaturated fats and oils are all
susceptible to oxidation eg. Calcitonin, Ascorbic acid,
Isoprenaline.
3. Isomerization: Isomers may be of several types.
Different isomers of the same compound might possess
different pharmacological and toxicological properties eg.
Tetracycline, Vitamin A, Adrenaline.
4. Photolysis: Several reactions take place in the presence
of light like redox reactions, ring alterations and
polymerizations eg. Riboflavin, Folic acid, Nifedipine.
5. Polymerization: Intermolecular reactions lead to the
formation of macromolecules eg. Ceftazidime, Ampicillin.
9. Mechanism of Interactions:
• Physical interactions:
A general example of a physical interaction is
interactive mixing. In this smaller particles interact
with the surface of the larger carrier particles
through physical forces.
In other words, physical interaction involves no
change in the integrity of the substance.
An example of a physical interaction between an
API and an excipient is that between primary amine
drugs and microcrystalline cellulose.
10. Chemical interactions:
• These are chemical reactions between drug and
impurities/residues to form different molecules.
• One of the best example of chemical interactions
between drugs and excipients is: Primary amine
group of chlorpromazine undergoes Maillard
reaction with glycosidic hydroxyl group of
reducing sugar dextrose to form imine, which
finally breakdown to form Amidori compounds.
• Chemical interactions bring about the change in
the integrity of the substance itself.
11. Conclusion:
• There is a paucity of information in compendia or
other publications on potentially damaging
residues in even the most common excipients.
• Proper knowledge and understanding of drug-
excipient interactions is a necessary prerequisite
to the development of dosage forms that are
stable and of good quality.
• It is clear from the above facts that excipient
selection should be done with a great care and
consideration to produce quality drugs.