Pharmaceutical excipients are inactive substances included in drug formulations to enhance stability, bioavailability, or patient acceptability. They must be safe, commercially available, cost-effective, and physiologically inert while providing necessary functions like binding, disintegrating, or lubricating in various forms of medications. The document also discusses the medicinal uses of willow bark, highlighting its historical significance and potential benefits for conditions such as pain and inflammation, alongside considerations for safety and interactions with other medications.

1. IF YOU DON’T WANT TO GIVE UP ON SOMETHING, LOVE IT
SO BADLY
GROUP
1V

2.  Pharmaceutical excipients are substances that are included in a
pharmaceutical dosage form not for their direct therapeutic action
but to aid the manufacturing processes, to protect, support or
enhance stability, or for bioavailability or patient acceptibility. The
term comes from a latin word "excipiens" to receive or to take out.
According to International pharmaceutical excipient council
(IPEC), excipients are the process aids or any substances other
than the Active Pharmaceutical ingredients (API) that is included
in Pharmaceutical dosage forms. API are bulk drugs that are
pharmaceutically active and generate a desired pharmacological
effect whereas excipients are pharmacologically inactive
substances that are generally used as a carrier of the API in the
drug.
1) EXCIPIENTS

3. 1. They must be nontoxic and acceptable to the regulatory agencies in all
countries where the product is to be marketed.
2. They must be commercially available in an acceptable grade in all countries
where the product is to be manufactured.
3. Their cost must be acceptably low.
4. They must not be contraindicated by themselves (e.g., sucrose) or because
of a component (e.g., sodium) in any segment of the population.
5. They must be physiologically inert.
CHARACTERISTICS OF EXCIPIENTS

4. 6. They must be physically and chemically stable by themselves and in
combination with the drug(s) and other tablet components.
7. They must be free of any unacceptable microbiologic load.
8. They must be color-compatible (not produce any off-color appearance).
9. If the drug product is also classified as a food, (certain vitamin products),
the diluent and excipients must be approved direct food additives.
10. They must have no deleterious effect on the bioavailability of the drug(s)
in the product.
CONT…..

5. 1. Excipients for use in oral Medicines.
a. Excipients used in solid dosages form.
b. Excipients used in liquid dosage forms.
c. Excipients used in semi-solid forms.
2. Excipients used for parenteral (injection).
3. Excipients used in topical (application to the skin) drug delivery systems.
4. Excipients used in intranasal delivery systems
CLASSIFICATION OF EXCIPIENTS

6. 1) Diluents (filler)
PRIMARY EXCIPIENTS

7.  They act as bulking agents to make the tablet weight
practical (minimum weight 50mg) for the patient. The
dosage can be as low as 20 micrograms for oral steroids.
They aid compression that is deforms and fragments
readily to facilitate robust bonding in tablet compacts.
They also function to enhance flow by reducing viscosity,
to archive targeted content uniformity, and to facilitate
tablet handling during manufacture. Examples of diluents
include sugar compounds (lactose, dextrin, glucose,
sucrose, sorbitol), inorganic compounds (silicates,
calcium and magnesium salts, sodium chloride).

8.  Binder are used to hold active pharmaceutical ingredient and inactive
ingredients together, ensuring mechanical strength and exhibiting cohesive
and adhesive force. Binders can be soluble (HPMC) or insoluble (starch) in
water or in both water and ethanol such as providone. They can be
classified according to their application, for example dry binders find use
in direct powder compression and dry granulating and as a solution or
paste in wet granulation. Most binders are either polysaccharide,
disaccharides, protein, natural gums or synthetic polymers. Examples of
binders include starches, modified cellulose, sugar alcohols, etc.
2) BINDERS (ADHESIVES)

9.  They disintegrate and cause rapid breakup of the tablet compact upon exposure
to moisture. They aid dispersion of the tablet in the GIT releasing the active
ingredients and increasing the surface area for dissolution.
 Modes of action and examples:
 Swelling (cellulose and its derivatives)
 Porosity and capillary action (microcrystalline cellulose)
 Deformation by enzymatic reaction: enzymes destroy the binding action of the
binder. For example amylase acts on starch binder and protease acts on gelatin.
3) DISINTEGRANTS AND SUPER-
DISINTEGRANTS

10.  They are used in formulations to smooth ejection of the tablet from cavity,
reduce friction between particles during compression, improve flow of
powder blend and granules into the die cavity, and prevent sticking of the
powder on punch faces.
4) LUBRICANTS

11. They enhance flow property of powder blend by overcoming powder
cohesiveness
5) GLIDANT

12.  : prevent sticking to the punch
6) ANTIADHERENT

13. 1) Flavours
SECONDARY EXCIPIENTS

14.  They are used to impart a pleasant flavour and odour
to pharmaceutical formulations. They ensure patient
compliance especially in pediatric formulations.
They can be natural (pepper mint, and lemon oil) or
artificial (butterscotch).
 Bitter product-mint, cherry may be used
 Salty product-peach, apricot may be used
 Sour product-raspberry or liquorice may be used
 Excessively weet product-vanilla may be used

15.  They are incorporated in tablets to impart sweetness to the product and
hence the acceptability of tablets. They are of particular importance if the
tablet has a bitter drug substance. Can be artificial such as saccharine and
its salt, aspartame, and acesulfame-K or natural such as sorbitol and
sucrose
2) SWEETENERS

16.  These excipients are added to tablets to help make large, difficult to
swallow pill easier to swallow. They prevent deterioration from water and
moisture. Enteric coating allow for breakdown in the small intestine,
preventing breakdown in the acidic environment of the stomach. A
Hydroxypropyl methylcellulose (HPMC) film coating is used in most
coated tablets because it is sugar free and free of potential allergens. Other
coating materials include synthetic polymers, Cellulose acetate, phthalate,
ethlycellulose, and methlycellulose
3) COATING AGENTS

17.  They are substances that are added to drugs to make them softer and more
flexible and to decrease their viscosity. They are used for physical
modification of coating polymer. Examples, Glycerin monosterate,
Polysobate80, Triethyl citrate, Triacetin
4) PLASTICIZERS

18.  They are chemical substance that increase the spreading and penetrating
properties of a liquid by lowering its surface tension. Not all are suitable
for oral administration. Examples include polysorbates and sodium louryl
sulphate but these can cause excessive foaming if levels are too high
5) WETTING AGENTS (SURFACTANT)

19.  They are generally employed in tablet manufacture either for
aesthetics or to uniquely identify finished tablets. They minimize
the possibility of mix ups. A distinction should be made between
excipients which have inherent colour and those that are used as
colorants. Colorants can either be water soluble dyes or water
insoluble pigments. Each country has its own list of approved
colorants. Any of the approved, certified, water soluble FD&C
dyes, mixtures of the same, or their corresponding lakes may be
used to colour tablets. The colour should be uniformly distributed
throughout the tablets. Examples include iron oxides, titanium
dioxide, and aluminium lakes
6) COLOURANTS

20. 1) Buffers
MISCELLANEOUS EXCIPIENTS

21.  Buffers can be necessary to maintain pH of
the formulation in order to ensure physical
compatibility, and optimize solubility.
Sodium phosphate, citric acid and acetic
acid and tromethamine.

22.  They are agents that will either allow substances to stick or adhere
to them. Adsorbents are used whenever they is need to include a
liquid or semi-solid drug substance or excipient within the tablet
formulation. They adsorb moisture that may attack tablets or
cause cohesiveness of tablet power/granules from these liquid or
semi-solid components thus allow proper tablet compression
during tablet formulation. The liquid or semi-solid constituents is
adsorbed onto a solid component which in many cases may be
one of the other components in the tablet formulation (eg diluents
during mixing). If this approach is not possible then an adsorbent
is specifically included in the formulation. Examples Silicon
dioxide, bentonite, caolin, magnesium silicate, tricalcium
phosphate, magnesium carbonate and magnesium .
2) ADSORBENTS

23.  Willow bark is the common name for the dried bark of variouse species of the plant salix. The
willow family includes a number of different species of trees and shrubs native to Europe,
Asia, and some parts of North America. Some of the more commonly known species are white
willow/European willow (Salix alba), black willow/pussy willow (Salix nigra), crack willow
(Salix fragilis), purple willow (Salix purpurea), and weeping willow (Salix babylonica). The
willow bark sold in Europe and the United States usually includes a combination of the bark
from white, purple, and crack willows. Willow bark preparations are obtained by comminuting
(reducing into tiny pieces) or powdering the bark and as dry or liquid extracts. Extracts are
obtained by putting the plant material in a solvent (such as ethanol or water) to dissolve
compounds and form a liquid extract. The solvent is then evaporated to obtain a dry extract.
Herbal medicines containing these willow bark preparations are usually available as herbal tea
to be drunk and in solid or liquid forms to be taken by mouth.
 Willow bark preparations may also be found in combination with other herbal substances in
some herbal medicines.
2) WILLOW BARK

24.  The use of willow bark dates to the time of Hippocrates (400 BC) when
people were advised to chew on the bark to reduce fever and
inflammation. Hippocrates burned willow leaves to make smoke for
“fumigating” the uterus to get rid of a miscarried pregnancy. Willow bark
has been used throughout the centuries in China and Europe, and
continues to be used today for the treatment of pain (particularly low back
pain and osteoarthritis), headache, and inflammatory conditions, such as
bursitis and tendinitis.
HISTORY OF WILLOW BARK

25.  Willow bark is used to ease pain and reduce inflammation. Researchers
believe that the chemical salicin, found in willow bark, is responsible for
these effects. However, studies show several other components of willow
bark, including plant chemicals called polyphenols and flavonoids, have
antioxidant, fever-reducing, antiseptic, and immune-boosting properties.
Some studies show willow is as effective as aspirin for reducing pain and
inflammation (but not fever), and at a much lower dose. Scientists think
that may be due to other compounds in the herb. More research is needed.
MEDICINAL USES AND INDICATIONS

26.  Studies suggest that willow bark may be useful for the following
conditions:
 Headache
 Willow bark has been shown to relieve headaches. There is some evidence
that it is less likely to cause gastrointestinal side effects than other pain
relievers, such as ibuprofen (Advil) and other nonsteroidal anti-
inflammatory drugs, do. However, studies have not shown this beyond all
doubt, and people who are prone to stomach upset may want to avoid
willow bark. Large-scale studies are needed to fully determine how safe
and effective willow bark is for chronic or recurring headaches
TREATMENT

27.  Willow bark appears to be effective for back pain. In a well-designed study
of nearly 200 people with low back pain, those who received willow bark
experienced a significant improvement in pain compared to those who
received placebo. People who received higher doses of willow bark (240
mg salicin) had more significant pain relief than those who received low
doses (120 mg salicin).
LOW BACK PAIN

28.  Several studies show that willow is more effective at reducing pain from
osteoarthritis than placebo. In a small study of people with osteoarthritis
of the neck or lower back, those who received willow bark experienced
significant improvement in symptoms compared to those who received
placebo. A similar study of 78 people hospitalized with osteoarthritis of
the knee or hip joint found that people who received willow bark had
significant pain relief compared to those who received placebo.
OSTEOARTHRITIS

29. Professional herbalists may recommend willow bark for the following
conditions, however, more research is needed.
• Menstrual cramps
• Fever
• Flu
• Tendonitis
• Bursitis
• Cancer
OTHER USES

30.  Because of the danger of developing Reye syndrome (a rare but serious illness
associated with the use of aspirin in children), children under the age of 18
should not take willow bark.
 Adult
 Speak to your doctor to determine the appropriate dose for you.
 Precautions
 Because willow bark contains salicin, people who are allergic or sensitive to
salicylates (such as aspirin) should not use willow bark. Some researchers
suggest that people with asthma, diabetes, gout, gastritis, hemophilia, stomach
ulcers, or with kidney or liver issues should also avoid willow bark. If you have
any of these conditions, or if you take nonsteroidal anti-inflammatory drugs
(NSAIDs) or blood-thinning medication, ask your health care provider before
taking willow bark. Children under the age of 16 should not take willow bark.
DOSAGE AND ADMINISTRATION
PEDIATRIC

31.  Side effects tend to be mild. However, stomach upset, ulcers, nausea,
vomiting, and stomach bleeding are potential side effects of all
compounds containing salicylates. Overdoses of willow bark may cause
skin rash, stomach inflammation/irritation, nausea, vomiting, kidney
inflammation, and tinnitus (ringing in the ears).
SIDE EFFECTS

32.  Salicylates are not recommended during pregnancy, so pregnant and
breastfeeding women should not take willow bark.
PREGNANCY AND BREASTFEEDING

33.  Because willow bark contains salicylates, it might interact with a number of
drugs and herbs. Talk to your doctor before taking willow bark if you take
any other medications, herbs, or supplements.
INTERACTIONS AND DEPLETIONS

34.  Anticoagulants (blood-thinning medications): Willow bark may strengthen
the effects of drugs and herbs with blood-thinning properties, and increase
the risk of bleeding.
 Beta Inderal LA). Willow bark may make these drugs less effective.
 Diuretics (water pills): Willow bark may make these drugs less effective.
 Nonsteroidal anti-inflammatory drugs: including ibuprofen (Advil, Motrin)
and naproxen (Aleve). Taking willow bark with these drugs may increase risk
of stomach bleeding.
 Methotrexate and phenytoin (Dilantin): Willow bark may increase levels of
these drugs in the body, resulting in toxic levels.
 blockers: including Atenolol (Tenormin), Metoprolol (Lopressor, Toprol-
XL), Propranolol (Inderal,
WILLOW BARK MAY INTERACT WITH ANY OF
THE FOLLOWING:

35. CLINICAL TRIALS PHASE 3
֍unseen

36. Phase III trials are done to gather more information about a drug’s safety
and effectiveness by studying different populations and different dosages
and by using the drug in combination with other drugs. The purpose is to
determine efficacy and monitoring adverse reactions. These studies involve
more participates from 300-3000 who have the disease or conditions.
Length of study is 1-4 years. It is expensive (about 75-400 million dollars).
INTRODUCTION

37.  Confirm the efficacy i.e the ability to produce the desired outcome of
the therapy
 Monitor adverse events and side effects
 Compare effectiveness relative to current therapies
 Describe the benefit/risk ratio across different types of patients
OBJECTIVES

38.  The FDA provides general recommendations concerning risk
assessment in terms of quantity of data (ensuring that enough
patients were studied) and quality of data (the appropriateness of
assessment performed, the population studied, and how the data
were analysed).
 Data Monitoring Committees (DMC) are used in many studies to
monitor the clinical data collected to ensure the safety of
individuals participating in the trial and to make recommendations
concerning the appropriateness of continuing the trials or the need
to modify its scientific or procedural aspects
 DMC should be composed of independent experts from the field of
clinical medicine, biostatistics, epidemiology, pharmacology, ethics,
and patients advocacy groups.
PROCEDURE

39.  Safety is accessed by frequent follow up visits adverse events
assessment and clinical laboratory measurements
 According the rule of 3 described by Handley and Lippman-Hand in
1983, and applies to situations where a study has found no events or
alternatively everyone has had an event (that is, 0% and 100%
outcomes)
 This rule describes the 95% confidence interval for such a situation.
 It is calculated by 3/n , where n is the number of subjects studied( For
accuracy n should be > 30)
 The rule of 3 highlights the significance of phase IV trials in identifying
less common adverse drug reactions and is one reason why the FDA
usually requires more than one phase III trial to establish drug safety
and efficacy.
CONTI…..

40.  In Comparative efficacy trials (placebo-controlled trials) there is
comparing of the intervention of interest with either a standard
therapy or a placebo
 Even in the best designed placebo controlled studies it is not
uncommon to demonstrate a placebo effect
 This highlights the uniqueness of study participants and why a
trial may lack external validity
 Pharmaceuticals are also expected to asses and minimize the
potential for medication erros that might be caused by the
product’s name packaging, formulation/ labelling
 When randomization is done neither the doctor nor the patient
knows which of the treatments the patient is getting
CONTI…..

41.  This type of study is called a double blind study
 There is collection of larger amounts of high quality of data on all
subjects and answers can be provided concerning adverse effects
and efficacy
 Clinical trials are limited because they normally involve relatively
smaller number of highly selected subjects who take the drug for
a relatively short period of time
 Conversely a marketed drug is given to a relatively large number
of individuals for a longer period of time
 Many of these individuals have concurrent medical conditions and
are on concurrent therapies.
CONTI….

42. THANK YOU !!!
֍unseen

43. 1. Willow bark | University of Maryland Medical Center (archive.org)
2.
https://www.versusarthritis.org/about-arthritis/complementary-and-alternative-t
reatments/types-of-complementary-treatments/willow-bark/
3.
Hippocrates and Willow Bark? What You Know About the History of Aspirin is
Probably Wrong (greekreporter.com)
4. https://pharmaceutical-journal.com/article/infographics/a-history-of-aspirin
5. History of Aspirin- Willow Bark Extract - Good News! (goodnewsplanet.com)
6. Coating Systems Excipients | American Pharmaceutical Review
7.
https://www.pharmapproach.com/excipients-used-manufacture-tablets/2/#:~:te
xt=Examples%20of%20adsorbents%20used%20in%20the%20manufacture,of%2
0tablets%20include%20magnesium%20oxide%2Fcarbonate%2C%20kaolin%2Fb
REFERENCES