Best Slides of all excipient standardization

1. By :
Shubham Wakde

2. CONTENTS :
 NEED
 EVALUATION CRITERIA
 IMPURITY PROFILE
 PRECLINICAL TESTING OF EXCIPIENTS
 GUIDELINES
 ARRANGEMENT DURING STANDARDIZATION
 SIGNIFICANCE
 REFERENCES
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3. NEED:-
 After invention of any new component to be used as
an Excipient.
 To verify the particular use of an Excipient.
 To establish the standards for newly invented Excipient.
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4. STANDARDIZATION OF EXCIPIENTS:
IPEC (International Pharmaceutical Excipient
Council) Significant Change Guidance:
 Two areas of concern to excipient makers and users
have been those of significant change and
certificates of analyses.
 Any change by the manufacturer of an excipient
that alters excipient’s physical or chemical property
from the norm or that is likely to alter the
excipient’s performance in dosage form is
considered significant.
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5. The types of changes that might be considered
include:
 Site
 Scale
 Equipment
 Process
 Packaging
 Specifications
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6. EVALUATION CRITERIA:-
The evaluation criteria in the guideline include:
 Changes in the chemical properties of excipients owing
to the change.
 Changes in the physical properties of excipients.
 Changes in the impurity profile of excipients.
 Changes in the functionality of excipients
 Changes in the moisture level of excipients.
 Changes in the bioburden of excipients.
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7. IMPURITY PROFILE:-
The IPEA-Americas profile addresses the following
guide:-
 All specific organic impurities.
 Undefined organic impurities at or above 0.1% whether
specified or not.
 Residual solvents.
 Inorganic impurities.
 Toxic impurities.
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8. PRECLINICAL TESTING OF EXIPIENTS:
 Essentially, a new (novel) excipient is a material that
has not been previously used in a pharmaceutical
formulation.
 New proposed excipients cover a range of functions
from conventional use to active roles of enhanced
drug uptake and specific drug delivery.
 Indeed, the ‘‘activating’’ of older drug formulations
by inclusion of new excipients for a range of
pharmaceutical classes is an ongoing process.
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9.  The preclinical safety evaluation of a new excipient
commences after initial in vitro pharmacy work to
demonstrate the material’s proposed role.
 Additionally, some in vivo investigations may occur,
for example, comparing the new proposed material
in a drug formulation versus a marketed drug
formulation.
 Enhanced drug exposure and/or a reduced toxicity
profile may be a study end point.
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10. GUIDELINES:-
 As mentioned earlier, the testing strategies
proposed by IPEC and the FDA offer a useful
starting point for preclinical excipient testing.
 Proposed study types are given for a range of
dose routes, including oral, topical, parenteral
and inhalational.
 The FDA has divided testing requirements into
those needed to support maximum clinical
duration of up to 14 consecutive days (short-
term use), more than two weeks but three
months or less (intermediate use), and more
than three months of use (long-term use).
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11.  The latter level of testing is unnecessary because
very high doses of materials by oral gavages.
 Additional considerations for inhalation/intranasal
route: acute inhalation, application site, and
pulmonary sensitization studies.
 For parenteral route: acute parenteral toxicity and
application site studies.
 For mucosal use: application site evaluation.
 For transdermal and topical drugs: application site
and photo toxicity/photoallergy evaluation.
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12. ARRANGEMENT DURING
STANDARDIZATION:-
 Although it was originally intended that each
monograph contain only information about a single
excipient, it rapidly became clear that some
substances or groups of substances should be
discussed together.
 This gave rise to such monographs as ‘Coloring
Agents’ and ‘Hydrocarbons’. In addition, some
materials have more than one monograph depending
on the physical characteristics of the material, e.g.
Starch versus Pregelatinized Starch.
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13. Regardless of the complexity of the monograph
they are all divided into 22 sections as follows:
1. Nonproprietary Names
2. Synonyms
3. Chemical Name and CAS Registry Number
4. Empirical Formula and Molecular Weight
5. Structural Formula
6. Functional Category
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14. 7. Applications in Pharmaceutical Formulation or
Technology
8. Description
9. Pharmacopoeial Specifications
10. Typical Properties
11. Stability and Storage Conditions
12. Incompatibilities
13. Method of Manufacture
14. Safety
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15. 15. Handling Precautions
16. Regulatory Status
17. Related Substances
18. Comments
19. Specific References
20. General References
21. Authors
22. Date of Revision
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16. Section 1: Nonproprietary Names :
Lists the excipient names used in the current British
Pharmacopoeia, European Pharmacopeia, Japanese
Pharmacopeia, and the United States
Pharmacopeia/National Formulary.
Section 2: Synonyms :
Lists of other names for the excipient, including trade
names used by suppliers (shown in italics).
Section 3: Chemical Name and CAS
Registry Number :
Indicates the unique Chemical Abstract Services number
for an excipient along with the chemical name.
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17. Sections 4 and 5: Empirical Formula and
Molecular Weight and Structural Formula:
Are self-explanatory.
Section 6: Functional Category
Lists the function(s) that an excipient is generally thought to
perform, e.g., diluent, emulsifying agent, etc.
Section 7: Applications in Pharmaceutical
Formulation or Technology
Section 8: Description
Includes details of the physical appearance of the excipient ,
e.g., white or yellow flakes, etc. 17

18. Section 9: Pharmacopeial Specifications :
Briefly presents the compendial standards for the
excipient . Information included is obtained from BP, USP,
IP, PhEup , JP,etc .
Section 10: Typical Properties:
Describes the physical properties of the excipient which
are not shown in Section 9.
All data are for measurements made at 20°C unless
otherwise indicated. Where the solubility of the excipient
is described in words, the following terms describe the
solubility ranges:
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19. Very soluble 1 part in less than 1
Freely soluble 1 part in 1–10
Soluble 1 part in 10–30
Sparingly soluble 1 part in 30–100
Slightly soluble 1 part in 100–1000
Very slightly soluble 1 part in 1000–10 000
Practically insoluble or
insoluble
1 part in more than 10 000
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20. Section 11: Stability and Storage Conditions :
Describes the conditions under which the bulk material as
received from the supplier should be stored. In addition
some monographs report on storage and stability of the
dosage forms that contain the excipient.
Section 12: Incompatibilities :
Describes the reported incompatibilities for the excipient
either with other excipients or with active ingredients.
Section 13: Method of Manufacture :
Describes the common methods of manufacture and
additional processes that are used to give the excipient its
physical characteristics.
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21. Section 14: Safety :
Describes briefly the types of formulations in which the
excipient has been used and presents relevant data
concerning possible hazards and adverse reactions that have
been reported.
Section 15: Handling Precautions:
Indicates possible hazards associated with handling the
excipient and makes recommendations for suitable
containment and protection methods.
Section 16: Regulatory Status :
Describes the accepted uses in foods and licensed
pharmaceuticals where known.
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22. Section 17: Related Substances:
Lists excipients similar to the excipient discussed in the
monograph.
Section 18: Comments :
Includes additional information and observations relevant to
the excipient.
Section 19: Specific References
Is a list of references cited within the monograph.
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23. Section 20: General References
Lists references which have general information about this
type of excipient or the types of dosage forms made with
these excipients.
Section 21: Authors:
Lists the current authors of the monograph in alphabetical
order.
Section 22: Date of Revision :
Indicates the date on which changes were last made to the
text of the monograph.
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24. SIGNIFICANCE:
 For reproducibilty of excipient lot to lot & vendor to
vendor is a necessity for the production of finished
product batches having consistent quality.
 The customer remains obligated to assure excipient
quality in terms of meeting compedial and mutually
agreed-upon specified requirements.
 The benefit to the excipient supplier is a reduction in
their resources to host frequent customer audits and
assurance that the excipient GMP audit is conducted
against appropriate GMP conformance expectations.
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25. REFERENCES:-
1. Baldrick P. Pharmaceutical excipient testing—
a regulatory and preclinical perspective. In:
Swarbrick J, Boylan JC, eds. Encyclopedia of
Pharmaceutical Technology. 2nd ed. NewYork:
Marcel Dekker, Inc., 2002:2141.
2. European Agency for the Evaluation of Medicinal
Products (EMEA), www.emea.eu.int/
index/indexh1.htm
3. United States Food and Drug Administration,
Center for Drug Evaluation and Research (FDA,
CDER). www.fda.gov/cder/drug/default.htm
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26. 4. Japanese Pharmaceutical Excipient Directory,
Japanese Pharmaceutical Excipient Council
(JPEC), ed. Tokyo: Yakuji Nippon Ltd, 1996.
5. Rowe RC, Sheskey PJ, Weller PJ, Handbook of
Pharmaceutical Excipients, 4th ed, American
Pharmaceutical Association and The
Pharmaceutical Press, 2003.
6. International Pharmaceutical Excipients Council
(IPEC), The proposed guidelines for the safety
evaluation of new excipients, The IPEC Europe
Safety Committee, Eur Pharm Rev 1997.
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27. 7. European Commission, Rules relating to
marketing authorisation of medicinal products
for human use, Council Directive 75/318/EEC,
Luxembourg: Office for Official Publications of
the European Communities, 1998.
8. Committee for Proprietary Medicinal Products
(CPMP), Note for guidance on repeat dose
toxicity, Final guidance issued by EMEA CPMP,
October 2000, www.emea.eu.
9. Center for Drug Evaluation and Research
(CDER), Guidance for Industry: Nonclinical
Studies for Development of Pharmaceutical
Excipients, Final guidance issued by FDA, CDER,
May 2005, www.fda.gov/cder/guidance
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