Interaction between drug API and various excipients used in formulation.Different methods of Interaction between them.Mechanism of interaction between them. Excipient Compatibility Studies. Analytical Techniques for Drug Excipents Compatibility Studies.

1. Presented by:
Atul Adhikari
M.Pharm(Pharmaceutics)
1st semester,
Assam downtown university, Guwahati
Guided by:
Ananta Chaudhary,
Department of Pharmacy,
Assoiate Professor, ADTU, Guwahati

2. Dosage
form=API+excipients
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3.  Colour/appearance changed
 Mechanical properties changes(e.g.:tablet hardness)
 Physical form conversion
 Loss through sublimation
 Decrease in potency
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4. 1. Hydrolysis-esters, amides, lactones, etc
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5. 2. Oxidation: aldehydes, alcohols, phenols, etc.
Epinephrine into quinones
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6. 3. Isomerization: Activity of L-adrenaline is 15-20 times higher
than D-adrenaline, Vitamin-A.
Pilocarpine is polymerized by base catalysis.
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7. 4. Photolysis: Riboflavin, folic acid, nifedipine
5. Polymerization: Ampicillin, Ceftazidine
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8. 1. Physical interactions
 Quite common but difficult to detect
 MDA(methylenedioxyamphetamine) and CMC( microcrystalline
cellulose)- adsorption of API cause lower dissolution.
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9. 2. Chemical interactions
A) chemical interaction between excipients and drugs
 Sodium alginate dissolve in water to form large negatively
charged anions. Co-formulation with drugs like neomycin and
polymixin( API are positively charged) in aqueous system result
in precipitation.
 Chloramphenicol sterate and colloidal silica during grinding
cause polymorphic transformation of chloramphenicol.
 Silicon dioxide catalyze oxidation of methyl lenolate,
diethylstibestrol which cause decomposition of API( aldehydes)
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10. B) interactions between drug and excipient residue/impurities
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Excipients Residues
Povidone. Peroxides
Magnesium sterate. Antioxidants
Lactose. Aldehydes
Benzyl alcohol. Benzaldehyde
Starch. Water

11.  Autoclaving of dextrose cause isomerisation into fructose and
formation of aldehyde which will react with primary amino
group to cause colour change.
 Oxazolam degrades in presence of CMC may be due to
carboxylic acid present on cellulose surface.
 High moisture content of polyvinyl pyrrolidine enhance aspirin
hydrolysis.
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12.  Observed after administration in the body.
 Influences the rate of absorption.
 Premature breakdown of enteric coating like cellulose acetate
phthalate or hydroxyl cellulose acetate phthalate due to acidic
pH of stomach cause release of API in stomach.
 Tetracycline form complex with calcium and magnesium ions
which are common excipients used in formulations when
coadministered with tetracycline therapy.
 Sorbitol increase gastrointestinal motility which will lower the
absorption for drugs like metoprolol.
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17. Objectives:
 To select dosage form components
 Delineate stability profile of drug
 Identify degradation products
 Understand mechanisms of reactions.
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18. 1. Thermal method of analysis
 DSC- differential scanning calorimetry
2. Accelerated stability studies
3. FT-IR spectroscopy
4. Chromatography
5. Others
 Fluorescence spectroscopy
 Vapour pressure osmometry
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19.  Measurement of rate of heat evolved or absorbed by the
sample during a temperature programme.
METHOD: Prepare drug excipient(1:1) ratio mixture
 To detect interactions:
A. Onset of peak
B. Change in peak shape
C. Appearance of new peak
D. Area of peak/enthalpy
E. Elimination of endothermic peak
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25.  40ºC/75% RH
 Different formulations of same drug.
 Drug content at regular intervals are monitored.
 Drug decomposed Vs time(month) is plotted.
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27.  Presence of peak at a specific wave number indicates presence
of specific bonds
 Matching the peaks of spectra.
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29.  Experimental technique for determination of a polymer’s
number average molecular weight.
 Decrease in vapour pressure that occurs when solutes are
added to pure solvent.
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31.  Stability of dosage form is maximized
 Avoid surprise problems.
 DECS data is required for IND(investigational new drug)
submission.
 Determine list of excipients that can be used in final dosage
form.
 To reduce side effects associated with DECS.
 To overcome problems associated with incorporating multiple
excipients in any dosage forms.
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32.  P J Crowley and L.G. Martini, “excipients in Pharmaceutical
products” Encyclopedia of Pharmaceutical Technology(Marcel
Dekker Inc. New York, USA
 N.Fathima, Et. Al, (2011), Drug excipient interaction and its
importance in dosage form development, journal of applied
pharmaceutical Science, vol 01, pg: 66-71
 Qui Y. et.al : Developing solid oral dosage forms; Elsevier
Academic Press, 2011; page: 125-143
 Lachman and liberman; Pharmaceutical dosage form, 2010
 Banker and Rhodes, Modern Pharmaceutics, Marcel Dekker
Inc, 2002
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