QUIZ 3 ADDITIVES (Midterms)

9. Emulsifying agent

Added to emulsions to prevent the coalescence or the globules of the dispersed phase and can
reduce the interfacial tension to form stable interfacial film so the formulation which involves oil
and water will be fully dispensed depending whose the disperse phase oil or water. used to
break down the oil into small globules so that it can associate with the aqueous solution.

Anionic - dissociate to form a negatively charge anion widely used emulsifying agents. it is only
used externally.

Alkali metals - Most efficient in an alkaline medium but it is incompatible with polyvalent.
Ammonium soaps - cation usually used for oil in water
Soaps of divalent - Calcium salts are used in calamine
Trivalent metals - Lotions and water in oil emulsion
Amine soap - Triethanolamine use in pharmaceutical and cosmetic in oil and water emulsion.
PH is neutral incompatible with acids high concentration of electrolytes.

Sulphonated compounds - Sodium dioctysulphosuccinate less widely used as emulsifying

used and more used as wetting agents or detergency.
Cationic - Quaternary ammonium compounds.
-Oil in water emulsifier
-used with non- ionic soluble emulsifying agent.
-Used as disinfectant and preservative property.
-Highly toxic and incompatible with anionic surfactant polyrate anions.
- Unstable at high ph

Non-Ionic - low toxicity and and initacy they can be used for oral and parenteral emulsion.
- Greater degree of compatibility with other material.
- Less sensitivity to change of ph and addition of electrolytes
- More expensive
- Used either in oil to water soluble components
example : Glycol and Glycerol enters , sorbitan esters, Polysorbates, Fatty alcohol polyglycol
ethers.

Glycol and Glycerol esters - self emulsifying with anionic emulsifying agents
- used in oil and water
Sorbitan - lypophilic in nature.
- used enter in oil and together with polysorbates.
Polysorbates - used together with sorbitan esters.
- compatible with cationic, amionic and some non ionic
 - Stable with ph neutral, heat low toxicity but ph change with high concentration of
electrolytes
- Unpleasant taste
- Can become inactive preservative through complexation.

Fatty alcohol polyglycol ethers- water soluble can be used in oil and water emulsion. They
maybe salted out by addition of high concentration of electrocytes. Stable over a wide ph range.

Amphoteric - Cationic at low ph and anionic at high ph

ex. lecithin

Naturally occuring - can have batch to batch variation because of different source and different
characteristics.
- Susceptible to microbial or mold growth
Polysaccharide : Acacia
Semi synthetic polysaccharides: Methyl celluslose and carmellose Na
Sterol containing subs- Beesmax and wool fat
Finely divided solids - can be absorbed at the oil in water interphase.
Clay and colloidal silicon dioxide - used externally
Aluminum and magnesium hydroxides- used orally

10. Density modifiers - used to have same densities so sedimentation will not occur
- used in injection and emulsion
ex. Dextrose, sucrose, glucerol, propylene glycol

11.Isotonicity modifiers - used for solutions for injections, solutions to be applied in mucous
membranes and opthalmic.
- To avoid destroying the cells.
ex. Dextrose, sodium chloride and boric

Tablet Excipients
A. Filler - also know “diluent” They add volume or mass to a drug substance. Requirement
dor minimum weight tablet is 50mg
Criteria
chemically inert- it should not change immediately or cause harm or change its chemical
composition when mixed with other excipients.

-Non hygroscopic
- Biocompatiblw
-Passes good biopharmaceutical properties
- Acceptable taste
-Inexpensive

1. Lactose - filler because iy disolves readily in water and pleasant tasting.

-Non hygroscopic
-Non reactive
- Good compatibility with other ingredients.
-Not essilu softened by frictional forces of compression due to its high melting point. 202 degree
cel.
- Not for patients with lactose intolerant

Crystalline - prepared by prescription

Amorphous - Sprayed by lactose more advantage their dissolution and compatibility is better.
-Produce spherical shape
-used at 40-50% tablet weight
-Direct composition but it is hygroscopic.

2. Sugar alcohols - Pleasant tasting 72% sweet. Requires more lubricant than the others 3-6
times

Sorbitol and mannitol - chewable tablets and lozenges

Mannitol - Optical isomer is hygroscopic and more water soluble and can be combined with the
equivalent amount of dicalcium phosphate as direct compression carrier.

3. Celluloses - Can be used as dry binders and disintegrants. Biocompatible chemically inert,
good tablet forming and disintegrating properties. Hygroscopic

Microcrystalline Cellulose - obtained by strong acid hydrolysis if formed the powdery

microcrystalline cellulose by spray drying. 5-15% conc.

4. Inorganic substance

Dicalcium phosphate

Water insoluble but hydrophilic non hygroscopic. Available in fine and aggregated form (good
florability than fine)

B. Binder

Also known as "adhesive" to ensure that granules and tablets can be formed with the required
mechanical strength. It holds the ingredients. Give volume to low active dose tablet.

Ways of addition:

1. As dry powder before wet agglomeration

2. As solution during wet agglomeration
 3. As dry powder before completion (Dry binder, MLL, PVP)

Polymers
PVP (Polyvinylpyridine) 3-15 %

Cellulose derivatives
HMPC (Hydroxypropylmethyl cellulose), LMC (Sodium carboxymethyl cellulose, methyl
cellulose and ethyl cellulose 5-15%

Glucose
25-50%

Acacia
Mannitol binder (10-25%)

Gelatin
10-20% Good binder and easier to handle they can approve disintegration and dissolution.

Sucrose
Used for dry or wet granulation, hygroscopic changes color into brown with acidic and basic
substances. Tablets are brittle and hard.

Starch paste
10-20% tables are soft and brittle

C. Disintegrant
- Ensures that the tablet when in the contact with liquid breaks down into small fragments.
Promote rapid drug dissolution.

Addition of disintegrants:
Intragranular - commonly used method. Disintegrant is to be mixed with granules before
compression.
Extragranular - disintegrants can be mixed with other ingredients prior to granulation.
Or both

2 types of mechanism
1. Facilitated water uptake - exothermic wetting reaction. Heat generation to break down
the powder compacts or facilitate transport fluids into tablet, then break into fragments.
2. Rapture the tablet - works by swelling of particles, particle repulsion, particle
deformation. Disintegrant will induce tablet rapturing following the swelling of particles
and because of electrical repulsive focus induced, when comes in contact with water will
revert the original shape.
Types:
a. Starch - undergoes swelling and repulsion.
Potato, corn (10%), modified starch (1-5%)
b. Starch derivatives: Na starch glycolate ( explotab 1-5%-) also known as
“superdisintegrant”.
c. Clays - veegum, bentonite
d. Cellulose - MCC,Na, CML, MLC
e. Gums - tragacanth, Karaya, guar
f. Bicarbonate salts - easily decompose with acidic water.
Function is by producing a gas. Ex. effervescent tablet.

D. Glidant
- Improve flowability of powder by reducing the interparticle friction.
a. Talc - 1-2%
b. Colloidal silica
c. Magnesium stearate - (0.2%)
d. Cornstarch - (<1%)
e. Syloid
f. Aerosil - add to granulation before tableting

E. Lubricants
- Ensures that tablet formation and ejection can occur with low friction between solid and
di-wall. Prevents ingredients from clamping together or form sticking.

2 mechanisms:
1. Fluid lubrication - layer of fluid is located between and separates the moving surfaces
from each other .
Ex. liquid paraffin

2. Boundary lubrication - sliding surfaces are separated only by a very thin film of
lubricant.
Ex. stearic acid and salt at less than 1%.
- Affected by the amount of lubricants, manner of addition and mixing time and
intensity affects lubrication. Combine surfactant and PEG

To prevent hydrophobic and decrease disintegration and dissolution rate, add lubricant at last
prior to compression. Mix time 2-5% minutes only.

Lubricants:

Water soluble Water insoluble

 Boric acid Stearates ( Mg, Ca, Na)

Sodium benzoate and Sodium acetate Stearic acid

Sodium chloride Sterotex

DL - Leucine Talc

Carbowax 4000 -6000 Waxes

Sodium oleate, benzoate, acetate Stearowet

SLS or Mg lauryl sulfate

- To reduce adhesion between powder and punch phases . Prevent adhesion of tablet
surface to di-walls, same as lubricants.
- If too much, it prevents sticking of tablet.
Ex. talc, cornstarch, syloid, DL- leucine, SLS, metallic stearates.

G. Sorbents
- Soak up oil from the water for oil or oil drug solution to be compacted into tablets.
Ex. Microcrystalline cellulose, silica.

H. Plasticizers
- Used to promote flexibility and elasticity of the coating to provide durability. (20-30%)
cone.
Ex. Glycerol, Sorbitol, PEG, Propylene glycol, diethyl phthalate, dibutyl subacetate , castor oil.

Purpose of coating tablet because it adds protection, mask the unpleasant taste of the tablet,
show elegance, ease of swallowing and identification.

I. Opacifiers
- To make the tablet or dosage from opaque. Used in cosmetics,
EX. titanium dioxide, water gelatin.

J. Film former
- Produce smooth thin films reproducible under a conventional coating conditions.
Ex. Cellulose acetate phthalate, HPMC, hydroxypropyl cellulose, methyl cellulose.

K. Glossant
- Provide shiny texture
EX. beeswax, carnauba wax
Additives in Semi-Solid dosage

Ointment bases

A. Hydrocarbon bases

Also known as "deagenous bases". It has emulgent effect and effective as dressing in open
rounds. Difficult to wash off and limited amount that may be incorporated

Examples: Petrolatum, white petrolatum, white ointment, yellow ointment.

B. Absorption bases

Example: Hydrophilic petrolatum and lanolin. Less occlusive property not easily removed by
water. Used as pharmaceutical adjunct

Hydrophilic petrolatum - used for absorption bases that permit incorporation of aqueous
solutions resulting in the formation of water in oil emulsions.

Lanolin - absorption bases that are in water in oil emulsion and permit of incorporation of
additional quantities of aqueous solutions.

C. Water - removable bases

Used for oil in water resenable as cream.

Example: Hydrophilic ointment - easily washed, diluted with water or aqueous solutions and
absorbs serous dischargers.

D. Water soluble bases

Completely water, washable bases do not have oil greaseless. Not used to incorporate aqueous
solutions.
Example: Polyethylene glycol ointment.

Suppository bases

A. Fatty or Oleaginous bases

Hydrogenated fatty acids of vegetable oils, glyceryl monostearate.

1. Cocoa butter

Usually melts between 30-36°C. Polymorphism. Alpha form or Beta form but B form is stable.

2. Fatti base

Triglycerides from palm, palm kernel and coconut oils with self - emulsifying glyceryl
monostearate and polyxyl stearate.

3. Wecobee bases

Triglycerides from coconut oil

4. Witepsol bases

Triglycerides Of saturated fatty acids C12-C18 with varied portions of the corresponding partial
glycerides

B. Water soluble and water miscible

1. Glycerinated gelatin

Mixture of gelatin and glycerin used for vaginal and provide more prolony release but they
absorb moisture. For urethral conc is 60%

2. Polyethylene Glycol

Do not melt at body temperature but dissolves with body fluids slower release storage do not
require refrigeration.

C. Miscellaneous bases

Performed emulsion water in oil. Have the ability to hold water and aqueous solution and
hydrophilic bases.
 1. Polyoxyl - 40 stearate

Mixture of monostearate and distearate esthers of polyxoxy ethylene diols and glycols. Melting
point 39-45°C