This document discusses drug-excipient interactions, including the types (drug-excipient, drug-drug, excipient-excipient, drug-container), mechanisms (physical, chemical, physiological), and methods of evaluation such as differential scanning calorimetry (DSC), X-ray powder diffraction (XRPD), and Fourier transform infrared spectroscopy (FTIR). DSC is used to study thermal transitions like melting points and glass transition temperatures to detect interactions. XRPD provides information on crystalline structure and changes from interactions. FTIR detects changes in molecular vibrations from interactions. Together these methods help evaluate excipient compatibility and identify interactions.

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Department of Pharmacy (Pharmaceutics) | Sagar savale

2. CONTENTS
 INTRODUCTION
 TYPES OF INTERACTION
 MECHANISM OF INTERACTION
PHYSICAL INTERACTION
CHEMICAL INTERACTION
PHYSIOLOGICAL INTERACTION
 METHOD OF EVALUATION FOR EXCIPIENTS
DSC
XRD
FTIR
 DRUG-CONTAINER INTERACTION
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3. INTRODUCTION
 Excipients are one of the three components that in combination produce the medicine that the patient will
take.
 In therapeutic terms, the API is of primary importance because without it there is no treatment and no
product.
 In term of drug manufacturing all three of them are equally important so we cannot neglect anyone of them.
 The interactions between excipients and the other two components (the API and the manufacturing process),
and/or between two or more excipients, are fundamental to the transformation of an API into a medicinal
product.

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4. TYPES OF INTERACTION
 DRUG - EXCIPIENT INTERACTION
 DRUG – DRUG INTERACTION
 EXCIPIENT – EXCIPIENT INTERACTION
 DRUG – CONTAINER INTERACTION
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5. MECHANISM OF INTERACTION
 PHYSICAL INTERACTION
 CHEMICAL INTERACTION
 PHYSIOLOGICAL/BIOPHARMACEUTICAL
INTERACTION
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6. PHYSICAL INTERACTION
Physical interactions do not involve chemical change. The
components retain their molecular structure.
For example, silicified microcrystalline cellulose after processing
cannot be separated entirely into its two separate components. But by
investigation they shows different spectra.
Physical interaction evaluated by using DSC,TGA,HPTLC,XRD
and TLC method
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7. CHEMICAL INTERACTION
Chemical interactions involve chemical reactions; i.e., a different
molecule (or molecules) is (are) created.
Some example of chemical interaction are;
Maillard reaction.
Lactone formation.
Oxidation.
Hydrolysis
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8. PHYSIOLOGICAL INTERACTION
Physiological interactions are the interactions between the
excipient(s) and the body fluids.
One physiological interaction that can potentially cause serious
problems for the patient is the interaction between enteric coatings
and antacids.
A classic biopharmaceutical incompatibility is the interaction
between tetracycline antibiotics and calcium and magnesium ions.
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9. METHOD OF EVALUATION FOR
EXCIPIENTS
Thermal Analysis
DSC, DTA, DTG & Isothermal calorimetry
Chromatography
HPLC, TLC
IR, XRD
LC-MS/MS,NMR
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10. DIFFERENTIAL SCANNING
CALORIMETRY
Calorimeter
Measures the heat into or out of the sample
Differential Calorimeter
Measures the heat of the sample relative to the
reference
Differential Scanning Calorimeter
Dose all the above and heat the sample and
reference with linear temperature range. 10

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 Differential Scanning Calorimetry (DSC) measures the
temperatures and heat flow associated with the transitions in the
material as a function of time and temperature in a controlled
atmosphere
These measurements provides qualitative and quantitative
information about the physical and chemical changes that involve
endothermic and exothermic processes or changes in the heat capacity
Cover the temperature range from -60°to 1600°C with variable
atmospheres
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12. WORKING PRINCIPLE OF DSC
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13. DSC INSTRUMENTATION
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Power Compensated DSC Heat Flux DSC

14. THE DSC THERMOGRAPH
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IBUPROFEN-Mg OXIDE INTERACTION BY
DSC
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16. APPLICATION OF DSC
Accurate determination of melting point
Determination of the purity without knowing type of impurity
For quantifying the crystallinity of lyophilized or spray dried
product
For identification of polymorphism in formulation
For stability determination
To study the decomposition and degradation kinetics
For determination of the glass transition temperature
To check the drug excipient compatibility
Determination of the molecular environment of water in crystals
and hydrates
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18. PRINCIPLE OF XRD
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X-ray of known wavelength is focused onto a crystal that can be
aligned until a diffraction pattern is created.

19. X-RAY POWDER DIFFRACTION (XRPD)
One of the most powerful techniques for analyzing the crystalline
nature of solids.
The sample is usually in a powdery form
In this method the crystal is reduced to a fine powder and is placed in
a beam of monochromatic x-rays.
Powder methods - λ fixed, θ vari
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20. XRPD PROVIDES FOLLOWING
INFORMATION
Type and nature of crystalline phase present
Degree of crystallnity
Degree of amorphous content
Microstrain & size and preferred orientation of crystallites
Also used for studying particles in liquid Suspensions or
polycrystalline solids (bulk or thin film materials).
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21. X-RAY DIFFRACTION PATTERN
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23. PRINCIPLE
When sample comes to exposure of IR radiation it shows
vibrations (either stretching or bending) depending on
characteristic of the sample. When the frequencies of these
vibrations becomes same as that of IR radiation it shows
characteristic peak on IR spectrum.
Vibrations
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Stretching Bending

24. IR SAMPLING METHODS
Salt disks (NaCl): for liquids (a drop) and small amounts of solids. Sample
is held between two plates or is squeezed onto a single plate.
KBr/CsI pellet: a dilute (~1%) amount of sample in the halide matrix is
pressed at >10000 psi to form a transparent disk.
 Disadvantages: dilution required, can cause changes in sample
Mulls: Solid dispersion of sample in a heavy oil (Nujol)
 Disadvantages: big interferences
Cells: For liquids or dissolved samples. Includes internal reflectance cells
(CIRCLE cells)
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25. INTERPRETATION OF IR SPECTRA
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26. DRUG-CONTAINER INTERACTION
Most probably the pharmaceutical container are:
Glass
Plastic
Rubber
Metal
The main interaction between drug-container are:
Leaching
Sorption
Permeation
Flaking
Chemical reactivity
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27. REFERENCES
1. Blecher L. The formation of the International Pharmaceutical Excipients Council.
Pharm Technol 1991; 15(6):54, 56.
2. Blecher L. Excipients–the important components. Pharm Process 1995; 12(1):6–7.
3. Chrzanowski FA, Ulissi LA, Fegely BJ, Newman AC. Preformulation excipient
compatibility testing: application of a differential scanning calorimetric method versus
a wet granulation simulating, isothermal stress method. Drug Devel Ind Pharm 1986;
12(6):783–800.
4. Botha SA, Lotter AP. Compatibility study between Naproxen and tablet excipients
using differential scanning calorimetry. Drug Dev Ind Pharm 1990; 16(4):673–683.
5. Foda NH. Compatibility study between Fluvoxamine Maleate, mebeverine
hydrochloride and tablet excipients using differential scanning calorimetry. Egypt J
Pharm Sci 1992; 33(1–2):73–81.
6. Wilson RJ, Beezer AE, Mitchell JC. Determination of thermodynamic and kinetic
parameters from isothermal heat conduction microcalorimetry: applications to long
term reaction studies. J Phys Chem 1996; 99:7108–7113.
7. Guillory JK, Soon CH, Lach JL. Interactions between pharmaceutical compounds by
thermal methods. J Pharm Sci 1969; 58(3):301–308.
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8. S. Class et al.; Differential Scanning Calorimetry: Applications in Drug
Development, PSTT Vol. 2, No.8, Aug 1999,1-10
9. J.Luypaert et al.; Near-infra red spectroscopy applications in pharmaceutical
analysis, Talanta, 72(2007), 865-883
10. J. Connolly et al.; Introduction to X ray powder diffraction, Spring 2007;1-9
11.Kratos; Analytical Applications Note "X-Ray Diffraction for Solid State
Pharaceutical Products", NY Office, August 1998
12.http://www.kratos.com/XRD/Apps/index.html
13.http://www.assainternational.com/workshops/iwpcps_1/exhibitors.cfm
14.http://www.ptli.com/testlopedia/tests/DSC- d3417.asp
15.http://www.psrc.usm.edu/macrog/dsc.htm