COMPATIBILITY STUDIES OF DRUG EXCIPIENT INTERACTION

1. DRUG-EXCIPIENT INTERACTION
SUBMITTED BY,
SRIPRIYA S
1st year M.Pharmacy

2. EXCIPIENT
■ An excipient is a substance formulated alongside the active ingredient of a
medication, included for the purpose of long- term stabilization, bulking up
solid formulations that contain potent active ingredients in small amounts.
 Consistency of drug release and bioavailability.
 Stability including protection from degradation.
 Ease of administration to the target patient population (s) by the intended route.

3. IDEAL PROPERTIES OF EXCIPIENT
 Feasible
 Pharmacologically inert
 No interaction with drug
 Cost effective
 Stable for handling
Excipient are inactive ingredients used as carriers for the active ingredients in a
pharmaceutical product.

4. Drug excipient interaction
■ In pharmaceutical dosage forms the active pharmaceutical ingredients are in intimate
contact with the excipient which are greater quantity excipient and drugs may have
certain incompatibility which lead to drug excipient interaction.
Importance of Drug – Excipient compatibility studies
 It maximizes the stability of a dosage form
 It bridges drug discovery and development.
 It is essential investigational new drug submission ( IND)

5. Methods / modes of drug decomposition
■ Hydrolysis - esters, amides, lactones etc.
■ Oxidation - aldehydes, alcohols, phenols etc
■ Isomerization - activity of L- adrenaline is 15 – 20 times higher than D – adrenaline ,
vitamin A.
■ Photolysis – Riboflavin, folic acid, nifedipine
■ Polymerization – Ampicillin, Ceftazidine

6. Types of drug excipient interactions
a. Physical interactions
b. Chemical interactions
c. Biopharmaceutical interactions
d. Excipient – excipient interactions.

7. PHYSICAL INTERACTION
■ Breaking or formation of new bonds
■ Alter their physical properties.
■ Changes in dosage uniformity, colour, odour, flow properties, solubility,
sedimentation rate, dissolution rate etc.
■ Physical interactions do not involve chemical changes thus permitting the
components in the formulation to retain their molecular structure.
■ Physical interactions are difficult to detect.

8. Interaction
■ Complexation:
1. Usually binds reversibly with drugs to form complex.
2. Insoluble complexes are formed which lead to slower dissolution
3. Decreased absorption of drug.
 BENEFICIAL EFFECT EXAMPLES
 Cyclodextrin is often used to improve bioavailability of poorly water soluble drugs.
 This increases bioavailability and increases rate.
 DETRIMENTAL EFFECT EXAMPLES
 Tetracycline formed insoluble complex with calcium carbonate leading to slower dissolution
and decreased absorption.

9. Chemical interactions
■ Chemical drug – excipient interactions
 Chemical degradation pathway.
 Bond breakage and bond formation.
unstable chemical entity
 Hydrolysis, oxidation, racemization, polymerization, Maillard reactions, photolysis
etc.
E.g.: Inhibition of diclofenac sodium release matrix tablet by polymer chitosan at low
pH

10. Types of chemical interaction
■ Chemical interaction between drug & excipients.
Primary amine group of chlorpromazine undergoes maillard
reaction with glycosidic hydroxyl group of reducing sugar dextrose.
 Interaction of drugs with excipients / impurities
Sterilizations by autoclaving of such parenteral preparations
containing dextrose cause isomerization of dextrose & formation of aldehyde
which react with primary amino group to form stiff base.

11. Biopharmaceutical interactions
■ Between the medicine ( drug substance and excipients) and the body fluids.
■ Influence the rate of absorption of the drug .
■ Premature breakdown of enteric coat -Enteric coating polymers E.g: cellulose
acetate phthalate and hydroxyl propyl cellulose acetate phthalate
■ Interactions due to adjust therapy – interaction between tetracycline
antibiotics and antacids containing aluminium, calcium, magnesium , bismuth
and zinc ions.

12. Excipient- Excipient Interaction
■ This type of interaction occurs between two or more excipients in a drug
molecule.
■ Examples : in proper addition of electrolyte such as Ca++ or Mg ++ ion
in suspension containing sodium carboxymethyl cellulose ( Na CMC )
which will cause formation of Calcium/ Magnesium CMC.
■ The suspending agent will be destroyed and cannot perform its function.

13. Analytical techniques used to detect Drug – Excipient
compatibility
 Thermal method of analysis
DSC – Differential Scanning Calorimetry
DTA - Differential Thermal Analysis
 Accelerated Stability Study
 FT- IR Spectroscopy
 DRS – Diffuse Reflectance Spectroscopy
 Chromatography
SIC – Self Interactive Chromatography
TLC- Thin Layer Chromatography
HPLC – High Pressure Liquid Chromatography
 Miscellaneous
Radiolabelled Techniques
Vapour Pressure Osmometry
Flourescence Spectroscopy