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Drug Excipient Interaction.pptx
1. Drug Excipient Interaction
H R Patel Institute of Pharmaceutical
Education and Research
Presented By : Bagate Kuldip
Roll No. MPH-01
Mpharm (Pharmaceutics)
Guided By : Dr. Zawar Sir
2. Table of Content
Sr. No. Topics
1 Introduction
2 Drug Excipients
3 Drug Excipients Interaction
4 Types of Drug Excipients Interaction
5 Analytical Techniques used to detect Drug-Excipient Interaction
6 Conclusion
7 References
3. Introduction
Excipients play an Important role in formulating a dosage form
These are ingredients which along with active pharmaceutical ingredients
make up the dosage forms
Excipients act as protective agents, bulking agents and can also be used
to improve bioavailability of drug
Excipients as like other active pharmaceutical ingridients need to be
stabilized and standardized
5. Drug Excipient Interaction :-
● Drug Substance are usually in intimate
contact with excipient Although these are
pharmacologically inert, They can undergo
chemical and physical interaction with
drug substance under favorable condition.
These interaction can lead to instability
resulting in the formulation new entities.
7. Physical Interaction
01.
Physical interactions alter the rate of dissolution, dosage uniformity, etc.
Physical interactions do not involve chemical changes thus permitting the
components in the formulation to retain their molecular structure.
Physical interaction are difficult to detect.
8. 02. Chemical Interaction :-
Active pharmaceutical ingredients and excipients react with each other to form
unstable compounds.
Chemical interaction involves chemical reaction between drugs and excipients or
drugs and impurities/ residues present in the excipients to from different molecules.
Chemicals interactions are almost detrimental to the product because they produce
degradation products. They are as follows-
1. Chemical reaction between drug and excipients-
The ‘Maillard reaction’ is a classic example of a chemical incompatibility.
Primary amines
+ reducing sugar
Form imine
Which finally break into
amadori compounds
9. Release of Diclofenac sodium from matrix table was inhibited by polymer chitosan at
low pH, due to formation of ionic complex between diclofenac sodium and ionized
cationic polymer.
Sodium alginate dissolve in water to form large negatively charged anions co-
formulation in aqueous system with drugs such as neomycin and polymyxin
(positively charged) result precipitation.
2. Interaction of drug with excipient residues/impurities-
Excipients are not exquisitely pure. They have some residues which affect the drug
action.
Impurities found in common excipients-
10. Excipient Residue
Povidone, Polysorbate Peroxide
Magnesium stearate Antioxidants
Lactose Aldehydes, reducing sugars
Benzyl alcohol Benzaldehyde
Sterilization by autoclaving of parenteral preparations containing dextrose can cause
isomerization of dextrose in fructose and formation of aldehyde which react with
primary amino group to cause colour change.
Peroxide residues in povidone responsible for the enhanced formation of N-oxide
degradation product of the oestrogen receptor modulator, Raloxifene.
11. 03. Biopharmaceutical Interaction :-
These are the interaction which are observed after administration of medicine.
These interactions occurs in the form of-
The interaction is between the medicine (drug substance and excipients) and the
body fluids.
The interactions have the tendency to influence the rate of absorption of the drug.
Various examples of these interactions are as follows-
12. a) Premature breakdown of enteric coat-
Enteric coating polymers e.g., Cellulose acetate phthalate and hydroxyl propyl cellulose
acetate phthalate,
Dissolve prematurely in the stomach in the presence of antacid or drugs
Cause increase in the pH of stomach
Cause premature release of API in stomach itself, which results in degradation of drug in
stomach
13. b) Increase in Gastrointestinal motility-
Many excipients such as sorbitol and xylitol have the tendency to increase
gastrointestinal motility, thus reducing the available time for absorption of drug like
Metoprolol.
c) Effect on P-Glycoprotein efflux transporter-
P-glycoprotein thus interferes in the bioavailability of different anticancer and other
drug substance. Thus several excipients eg., Span 20, Tween 20, Tween 80, Pluronic ,
Poloxamer etc. are incorporated in the formulation which help in inhibition of P-
glycoprotein to enhance availability of drug into the cell , to produce the desired
action.
14. 4) Excipient-Excipient Interaction:-
This type of interaction occurs between two or more excipients in a drug molecule.
Example:- 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.
16. 1) Thermal Method
Thermal method of analysis comprise a group of techniques in
which the physiochemical properties of drug substance are
measured as a function of temperature. In this method, the
test samples are subjected to a controlled temperature over a
given period of time. This method of analysis plays a vital role
in drug-excipient compatibility studies and has been
frequently used quick identification of physiochemical
interaction between drugs and excipients.
17. DSC represents a leading thermal screening techniques that has been increasingly used
for excipient compatibility studies for over decades. In this techniques the DSC curves
of pure samples are compared to that obtained from 50% mixture of the drug excipient
(usually 5mg of drug in a ratio of 1:1 with excipient) It is assumed that the sum of the
individual components if the components are compatible with each other . An absence,
a significant shift in the melting of the components or appearance of a new
exo/endothermic peak shape height and width are expected due to possible difference
in the mixture geometry.
A) Differential scanning Calorimetry (DSC)
18.
19.
20. DSC’s
Limitations
Conclusion based on DSC results
alone may be misleading and have to
be interpreted carefuly.
DSC cannot be used if thermal
changes are very small. Therefore, it
should always be supported by some
non thermal method like TLC or FT-
IR.
Advantages
Requires of short time of analysis.
Low sample consumption.
Provide usefule indication of any
potential incompatibility
21. B) Differential Thermal Analysis
This technique is useful in the investigation of solid-state interactions and detection of
eutectics.
In this change in temperature between test sample and reference material is measured
under controlled and identical condition.
This differential temperature is plotted against time or temperature.
Interaction can be identified by comparing DTA curve obtained from the test sample
with those of reference material.
22. If any
interaction
occur
If no
interaction
occur
Thermogram (DTA curve) of a
mixture show appearance or
disappearance of one or more
peaks corresponding to those of
the components.
The thermogram of mixtures
show same patterns
corresponding to those of the
individual components
23. Chromatographic Techniques:
Compared to other available analytical techniques used in drug excipient compatibility
studies, chromatography is known for its characteristics of high resolution and detection
power, making it suitable for detecting multiple components in a complex mixture with high
accuracy, precision, specificity, and sensitivity.
a) Thin Layer Chromatography :
In TLC, solution of the test sample are prepared and spotted on the same baseline at the
end of the plate. The plate is then placed upright in a closed chamber containing mixture
of organic solvents which serves as the mobile phase. The analyte moves up the plate,
under the under the influence of the mobile phase which moves through stationary
phase by capillary action.
The distance moved by the analyte is dependent relative affinity for the stationary or the
mobile phase. Incompatibilities are indicated by formation of a spot with Rf value
(retardation factor) different from that of the controls after the plate has been
developed with solvent.
24. An excipient on the other hand is considered to be potentially compatible with the drug
substance if the spots produced have identical Rf value with those Of the controls. Because
some samples undergo negligible thermal changes which might be difficult to detect by
thermal methods Of analysis, TLC is widely used in drug-excipient compatibility study as
confirmative test Of compatibility after performing DSC
Advantages:
The technique is robust and cheap.
The compound formed as result of incompatibilities between the drug and the excipient can
be detected if suitable detection reagent is used.
Batch chromatography can be used to analyze many samples at time, thus increasing the
speed of analysis.
25. Spectroscopy:
Spectroscopic analytical methods include all techniques which probe certain features
of given sample by measuring the amount of radiation emitted or absorbed by the
molecular or atomic species of interest.
This method of analysis uses electromagnetic radiation to interact with matter and
thus investigate certain features of a sample as a function of wavelength.
a) Vibrational spectroscopy:
Vibrational spectroscopy are not only used to investigate solid state properties of
drug substance and their formulations, but also used as compatibility study tool as
the vibrational changes serve as probe of potential intermolecular interaction among
the components .
Thus drug excipient interaction that occur during processing can easily be detected
with the aid of these spectroscopic techniques.
26. Using this method ,information on the molecular structure and environment of organic
compounds are generated by measuring the vibrations of chemical bonds that results from
exposure to electromagnetic energy at various frequencies. These vibrations are commonly
studied by infrared.
27. Conclusion
Drug Excipient compatibility study is a necessary prerequisite to the
development of drug products that are safe and stable for use. Proper
selection and assessment of possible incompatibilities between the drug &
excipient during preformulation studies is of paramount importance the
target product profile and critical quality attributes.
In order to avoid stability problems encountered during drug development
and post commercialization, there is need for proper assessment of possible
incompatibilities between the drug and excipient using appropriate
analytical techniques.
These analytical techniques are needed not only to generate useful
information with regards to each excipients is compatible with a drug
substance, but also for troubleshooting unexpected problems which might
arise during formulation processes.
28. REFERENCES
Lachman & Lieberman, The Theory and Practice of Industrial Pharmacy
N. Fathima, Kajal Ahir, Vandana Patel, Lata Manani, Chirag Patel Drug excipient
interaction and its importance in dosage form development, Journal of applied
Pharmaceutical Science 2011
Priyanka Patel, Kajal Ahir, Vandana Patel, Lata Manani, Chirag Patel Drug-
Excipient compatibility studies: First step for dosage form development, The
Pharma Innovation Journal 2015
Bapi Gorain, Hira Choudhury, Manisha Pandey, Thiagarajan Madheswaran,
Prashant Kesharwani and Rakesh K. Tekade Drug- Excipient Interaction and
Incompatibilities 2018