Transcript definition - nubacad.com

Definition
Pharmaceutical excipients are agents
which are used other than active
ingredients
-to increase stability of the products,
-to enhance patients acceptance
-to ease manufacturing process
For the liquid preparation the
following additives are used:
1. Preservative: e.g. Phenol, Boric acid &
its salts, Benzoic acid & its salts, Sorbic
acid & its salts, Alkyl ester of
parahydroxy benzoic acid (PARABEN),
2. Antioxidant: e.g. Sodium Sulphite,
Sodium metabisulfite, Ascorbic acid.
3. Sweetening agent: e.g. Sucrose, Liquid
glucose, Saccharine, Sorbitol, Glycerin
4.Flavoring agent: e.g Vanilla
5. Coloring agent: e.g. FD&C Red# 3, D&C
Red# 8
6. Solvent: Water.
7. Co solvent: e.g. Poly ethylene glycol
8. Viscosity imparting agent: e.g. Poly vinyl
pyrrolidone (Povidone), Methyl cellulose
9. Surface active agents: e.g. Tween, Span
10. Chelating agent: e.g. EDTA (Ethylene
Diamine Tetra acetic acid)
11. Buffering agent: Phosphate buffer
12. Humectants: e.g. Polyethylene glycol,
sorbitol
For solid preparation the following
additives are used:
1. Binding agent:
e.g. Acacia, Tragacanth, Starch, cellulose(HPMC),
Povidone (Poly vinyl pyrrolidone)
2. Diluents/ Fillers:
e.g. Starch, Lactose, Sucrose, Mannitol,
CMC(Carboxymethylcellulose)
3. Lubricant:--A lubricant is a substance (often a liquid)
introduced between two moving surfaces to reduce the
friction between them, improving efficiency and
reducing wear e.g. Mg-Stearate, Talc
4. Glidant:--A glidant is a substance that is added to a
powder to improve its flowability e.g. colloidal silica
5. Disintegrating agent: e.g. sodium starch glycolate ,
Microcrystalline cellulose
Antioxidant:
The oxidative decomposition of Pharmaceuticals is
responsible for the instability of products. These
reactions are mediated by Free radical or by
molecular oxygen. The most common form of
oxidative decomposition is auto oxidation. Auto
oxidation may be defined as the reaction of any
material with molecular oxygen. Free radicals are
produced by reactions involving homolytic bond
fission of a covalent bond. Free radical is odd
number electron containing compound.
 Free radical are highly unstable compound and
readily takes electron from other substance
Free radical reaction mechanism
The auto oxidation of an organic substance RH by a
free radical chain process can be simply described as
following three steps:
1. Initiation:
RH → R. + H.
2. Propagation:
R. + O2 → ROO.
ROO. + RH → ROOH + R.
ROOH → RO. + .OH
3. Termination:
ROO. + X → inactive products
ROO. + ROO. → 2ROO inactive products
R. + R. → R-R
Where X can be free radical inhibitor.
Classification of antioxidant:
Depending on mode of action Antioxidant can divided
into four types:
1. Reducing agent:
e.g. Sodium Sulfite, Sodium metabiosulfite, Ascorbic
acid.
- Reducing agents acts by being prefentially
oxidized.
2. Blocking agent:
- Blocking agents acts by blocking the free radical
reaction mechanism.
e.g. BHT. BHA, Tocopherol
3. Synergists: (Combine effect)
- They help the reducing agent.
e.g. Ascorbic acid, Citric acid, Tartaric acid.
4. Chelating agent (Complexing agent):
- Acts by formation of complex with metals.
So metals are not available for initiation
step of free radical reaction.
e.g.
EDTA ( Ethylene Diamine Tetra acetic acid)
Concentration range used for
antioxidant:
Ascorbic acid
- 0.02-0.1%
- Sodium bisulfite
- 0.1-0.15%
- Sodium metabisulfite - 0.1-0.15%
 Blocking agent: Butylated hydroxy
toluene (BHT)- 0.005-0.02%
 Chelating agent: EDTA salt - 0.010.075%
Preservative:
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Antimicrobial preservatives are agents which are used
to prevent the presence/growth of microorganism.
An ideal preservative should meet the following
characteristics:
It must be effective against a broad spectrum of
microorganism.
It must be physically, chemically and microbiologically
stable for the lifetime of the product.
It must be non-toxic, non-sensitizing, adequately soluble,
compatible both with other formulation components
acceptable with suspect to taste and odor at the
concentration use.
Classification of antimicrobial agents
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Antimicrobial agents are classified into four categories:
a. Acidic:
 e.g. Phenol, Boric acid & its salts, Benzoic acid & its
salts, Sorbic acid & its salts, Alkyl ester of parahydroxy
benzoic acid (PARABEN), Methyl-PARABEN, PropylPARABEN, Butyl-PARABEN
N.B.- Combination of parabens give synergistic effect.
b. Neutral:
- Chlorobutanol, Benzyl alcohol
c. Mercurials:
- Phenyl mercuric acetate, Phenyl mercuric nitrate,
Thimerosal
d. Quartanary amonium compound:
e.g. Benzal Konium chloride.
Sweetening agent:
Sweetening agents are agents, which are used to,
sweetened the preparation & make it palatable.
1. Sucrose: (Not for diabetes patient)
- It is soluble in aqueous media (85%)
- It is available in highly purified form at
reasonable cost.
2. Liquid glucose: (For diabetes patient)
- Extremely viscid substance that imparts both
body and sweetness to liquid formulations.
- It is prepared by the partial hydrolysis of starch
with strong acid.
3. Saccharine:
- It is used to supplement sugars.
- It is approximately 250-500 times as sweet
as sugar.
4. Aspartame:
- It is synthetic sweetener.
- It is 200 times sweeter that sucrose but it
has no after taste of saccharine.
5. Sorbitol: (For diabetes patient)
6. Glycerine: (For diabetes patient)
Viscosity imparting agent:
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Sometime it is desirable to increase the
viscosity of a liquid either to serve as adjacent
for palatability or to improve pour ability.
Example:
Poly vinyl pyrrolidone (Povidone)
Methyl cellulose(Methocel)
Sodium carboxy methyl cellulose
Acacia, Tragacanth, Sodium-Alginate.
Veegum (Mg-Al-silicate)
Carbomer (Carboxy poly methylene)
Flavoring agent:
Flavoring agents add flavor to the
pharmaceutical formulation & make it
palatable
 It has aesthetic value.
 There are four basic taste sensations:
 1. salty, 2. Bitter, 3. Sweet, 4. Sour
 A combination of flavoring agent is
usually required to mask these taste
sensation.
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Menthol & Chloroform are used as flavor
adjunct. They impact a flavor & odor of
their own to the product. And have a mild
anesthetic effect on the sensory receptor
organ.
 Example of flavoring agent:
 Sweet flavor: Fruit, Berry, and Vanilla.
 Sour flavor: Citrus flavor, Raspberry
 Salty flavor: Wintergreen, Mint
 Bitter flavor: Wild cherry, Chocolate.
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Coloring agent:
Purpose of using coloring agent
 Produces aesthetic value
 Helps in Differentiation
 Helps in Identification
1.Pigment: Mineral color are frequently
termed as pigment and used to color, lotion,
cosmetic, external preparation. Eg, red
Fe2O3, yellow Fe2O3, Tio2, Carbon black
2. Dye:
- Nitrogenous compound used in Textile
- Water soluble used in liquid preparation
Certain structural element in organic molecule called
chromospheres group give color to the molecules.
Chromophore group:
 Azo group (-N=N-)
 Nitroso group (-N=O)
 Nitro group (-NO2)
 Azoxy group (-N=NO-)
 Carboxyl group ( C=O)
 Ethylene group ( C=C )
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Dyes dissolve in water, but are not
soluble in oil. Dyes are manufactured as
powders, granules, liquids or other
special purpose forms. They can be
used in beverages, dry mixes, baked
goods, confections, dairy products, pet
foods, and a variety of other products.
3. Lake:
- are formed by the absorption of water soluble dye on a
hydrous oxide especially Al2O3 which result is in
insoluble form of the dye.
Dye + Al2O3 → Water insoluble dye (lake)
- Lakes are used to color powders, pharmaceuticals, foods,
candies.
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Lakes are made by combining dyes with
salts to make insoluble compounds.
Lakes are not oil soluble, but are oil
dispersible. Lakes are more stable than
dyes and are ideal for coloring products
containing fats and oils
Classification of coloring agent:
Coloring agents are classified into three types.
1.Food, Drug and Cosmetic color
2.Drug and Cosmetic color
3.External Cosmetic color
Permitted color: Approved by FDA (Food & Drug
Administration
Surfactants:
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Surfactants are wetting agents that lower the surface
tension of a liquid, allowing easier spreading, and
lower the interfacial tension between two liquids.
A shortened form of "surface-active agent", a
surfactant is a chemical that stabilizes mixtures of oil
and water by reducing the surface tension at the
interface between the oil and water molecules.
Because water and oil do not dissolve in each other, a
surfactant has to be added to the mixture to keep it
from separating into layers.
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1.
2.
3.
4.
5.
6.
Surfactants in cosmetics provide one or more of six
functions:
Detergents - for cleansing
Wetting agents - in perms
Foaming agents - for shampoos
Emulsifiers - in creams and lotions
Conditioning agents - in skin and hair-care products
Solubilizers - for perfumes and flavors
Surfactant (Surface active agent)
A molecule must fulfill specific structural
requirement to become a surfactant.
First requirement: A surface acting agent
must contain a lipophilic region.
Second requirement: A surfactant must
contain a hydrophilic region.
A balance of the hydrophilic & lipophilic
region of a surfactant is usually required.
Properties
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A micelle - the lipophilic tails of the surfactant
molecules remain on the inside of the micelle
due to unfavourable interactions. The polar
"heads" of the micelle, due to favourable
interactions with water, form a hydrophilic
outer layer that in effect protects the
hydrophobic core of the micelle..
Classification of Surfactant:
1. Anionic surfactant (Here hydrophilic region is anion)
 e.g. Sodium lauryl sulphate
2. Cationic surfactant (Here hydrophilic region is cation)
 e.g. Cetyl trimethyl ammonium bromide(Cetrimide)
3. Non-ionic surfactant:
e.g. Tween 80 (Polyoxyethylene sorbitan monooleate)
Span (Sorbitan ester of lauric acid, oleic acid).
4. Amphoteric surfactant
 e.g. Lecithin, N-dodecyl alanine
HLB
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The hydrophilicity and lipophilicity are different among
emulsifiers, and the balance between the two is called
HLB value. The value ranges from 0 to 20.
An emulsifier with higher lipophilicity shows a lower
HLB whereas higher hydrophilicity has high HLB, and
the behaviors and functions to water depend on this
HLB.
Characteristic
behaviors
related to
water
ratio
HLB
functions
hydrophilic
part
lipophilic part
0
100
0
not dispersing
2
slightly
dispersing
10
90
20
80
30
70
anti-foaming
agent
4
W/O
emulsifica
tion
6
milky
dispersion
wetting agent
8
40
60
O/W
emulsifica
tion
Wetting agent:
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Wetting is the displacement of either a liquid or
a gas from a surface by a second liquid.
Wetting agents are surfactants with HLB
values of 7-9. Wetting agents aid is attaining
intimate contact between solid particles and
liquids.
Contact angle
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The contact angle is a useful indicator of wetting. A low
contact angle indicate that adhesive forces between
the liquid and the solid predominate and wetting
occurs. While a high contact angle indicates the
cohesive forces of the liquid predominate. contact
angle may vary from 0° to 180°.
 If the drop of liquid/gas is completely insoluble,  =
180°
 If the drop of liquid/gas is completely soluble,  = 0°