POLYPHASIC SYSTEM

1. a. Acacia Mucilage USP

• Formula:
Acacia, in small fragments 350g
Benzoic Acid 2g Purified Water, qs
To make 1000ml
Procedure: Place the acacia in a wide mouth graduated bottle with a capacity not exceeding
1000ml, wash the drug with cold purified water, drain and add sufficient quantity of purified
water in which the benzoic acid has been dissolved to make 1000ml. Stopper and lay the
bottle on its side, rotate occasionally, and when acacia has been dissolved strain the mucilage.
It may be also prepared as follows: Dissolve the benzoic acid in 400ml of purified water with
the aid of heat. Add the solution to 350g of acacia in a mortar, triturating until the acacia is
dissolved. Add sufficient quantity of purified water to make 1000ml. Strain if necessary.

b. Calamine Lotion USP

• Formula:
Calamine 80 g
Zinc Oxide 80 g
Glycerin 20 mL
Bentonite Magma 250 mL
Calcium Hydroxide Topical Solution,
A sufficient quantity to make 1000 mL
Procedure: Dilute Bentonite Magma with an equal volume of Calcium Hydroxide Topical
Solution. Mix the powders intimately with the glycerin and about 100 mL of the diluted
magma, triturating until a smooth, uniform paste is formed. Gradually incorporate the
remainder of the diluted magma. Finally add enough Calcium Hydroxide Topical Solution to
make 1000 mL, and shake.
If a more viscous consistency in the Lotion is desired, the quantity of Bentonite Magma may
be increased to not more than 400 mL.
Note - Shake Calamine Lotion before dispensing.

c. Calamine Ointment USP

• Formula:
Calamine 80 g
Zinc Oxide 80 g
Glycerine 20 mL
Bentonite Magma 250 mL
Calcium Hydroxide Topical Solution,
A sufficient quantity to make 1000 mL
Procedure: Dilute the Bentonite Magma with an equal volume of Calcium Hydroxide
Topical Solution. Mix the powders intimately with the Glycerin and about 100 mL of the
diluted magma, triturating until a smooth, uniform paste is formed. Gradually incorporate
the reminder of the diluted magma. Finally add enough Calcium Hydroxide Topical Solution
to make 1000 mL, and shake.
If a more viscous consistency in the lotion is desired, the quantity of bentonite magma may
be increased to not more than 400 mL.
NOTE----Shake the calamine topical suspension before dispensing.
d. Rose Water Ointment USP
• Formula:
Cetyl Esters Wax 125 g
White Wax 120 g
Almond Oil 560 g
Sodium Borate 5g
Stronger Rose Water 25 mL
Purified water 165 mL
Rose Oil 200 mcg
To make about 1000 g
Procedure: Reduce the cetyl esters wax and the white wax to small pieces, melt them
in a steam bath, add the almond oil, and continue heating until the temperature of the
mixture reaches 70 degrees. Dissolve the sodium borate in the purified water and the
stronger rose water, warmed to 70 duress, and gradually add the warm aqueous phase to the
melted oil phase, stirring rapidly and continuously until it has cooled about 45 degrees. Then
incorporate the rose oil.
Note- Rose Water Ointment is free from rancidity. If the ointment has been chilled, warm it
slightly before attempting to incorporate other ingredients.

e. Bentonite Magma
• Formula:
Bentonite 50 g
Purified Water, a sufficient quantity,
To make 1000 g
Procedure: Sprinkle the bentonite, in portions, upon 800 g of hot purified water, allowing
each portion to become thoroughly wetted without stirring. Allow it to stand with occasional
stirring for 24 hours. Stir until a uniform magma is obtained, add purified water to make 100
g, and mix.
The Magma may be prepared also by mechanical means such as by use of a blender, as
follows. Place about 500 g of purified water in the blender, and while the machine is
running, add the bentonite. Add the purified water to make up to about 1000 g or up to the
operating capacity of the blender. Blend the mixture for 5 to 10 minutes, add purified water
to make 100 g, and make

2. a. Colloids - a colloid is a substance microscopically dispersed throughout another

substance.
b. Emulsions - is a two phase system consisting of two incompletely miscible liquids, one
of which is dispersed as finite globules in the other.
c. Suspensions - is a coarse dispersion in which the internal phase (therapeutically active
ingredient) is dispersed uniformly throughout the external phase.
d. Micelles - A micelle is an electrically charged particle formed by an aggregate of
molecules, above a critical concentration and occurring in certain colloidal electrolyte
solutions, especially those of soaps and detergents
e. Magma - Magmas are aqueous suspensions of insoluble inorganic drugs. They differ
from gels in that the suspended particles are larger.
3. Suspensions:
a. Provide 2 routes of administration
• Taken by mouth (orally)
• Placed under the tongue (sublingually) or between the gums and cheek (buccally)
b. Give 2 commercially available examples of each route
• Orally: Paracetamol (Biogesic) Tablet and Phenylephrine HCl (Neozep)
• Sublingually: Loratadine (Claritin) and Nitroglycerin (Nitrostat)
c. Purpose of adding suspending agents
• Suspending or thickening agents are added to suspensions to thicken the suspending
medium, thereby reducing the movement (sedimentation) of suspended particles and
physically stabilizing the product.
d. 5 examples of suspending agents
• methylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose,
hydroxypropylmethylcellulose and gum tragacanth

4. Explain the following:

a. Caking - is when the particles in suspension settle to a dense sediment before bonds can
be established between the closely-packed particles.
b. Flocculation - is a process by which a chemical coagulant added to the water acts to
facilitate bonding between particles, creating larger aggregates which are easier to separate.
The method is widely used in water treatment plants and can also be applied to sample
processing for monitoring applications.

5. Advantage of a synthetic dispersing agent

The advantages of synthetic dispersing agents are renewability, sustainability,
biocompatibility, and cost efficiency have shifted attention towards natural homologues, in
particular, cellulose-based ones. Within the past decade, cellulose derivatives, obtained via
chemical and mechanical treatments of cellulose fibrils, have successfully been used for these
purposes.

6. Emulsion:
a. Purpose of emulsifying agents
• An emulsifying agent (emulsifier) is a surface-active ingredient which adsorbs at the newly
formed oil–water interface during emulsion preparation, and it protects the newly formed
droplets against immediate coalescence.
b. 5 examples of emulsifying agents
• Commonly used emulsifiers in modern food production include mustard, soy and egg
lecithin, mono- and diglycerides, polysorbates and carrageenan.
c. Discuss the 2 types of emulsion
Emulsions can be classified on the basis of the properties of the dispersed phase and the
dispersion medium.
1) Oil in water (O/W):
In this type of emulsion, the oil will be the dispersed phase and water will be the
dispersion medium. The best example for o/w emulsion is milk. In milk, the fat globules
(which act as the dispersed phase) are suspended in water (which acts as the dispersion
medium).
 2) Water in oil (w/o):
In this type, water will be the dispersed phase and oil will be the dispersion medium.
Margarine (a spread used for flavouring, baking and working) is an example of water in oil
emulsion.
d. Methods of preparing emulsions
There are two methods of preparing a primary emulsion:
1. Dry gum method:
• Emulsifiers (acacia) are mixed with oil before water is added.
• The quantities of oil, water and gum for primary emulsion are calculated. The acacia
and the oil are placed in a dry porcelain mortar. When the acacia is thoroughly
distributed throughout the oil, Water is added, all at once. The mixture is triturated
continuously but lightly in one direction until the mixture thickens under the pestle.
• The primary emulsion is triturated for at least 5 minutes. Finally, the emulsion is
transferred to a graduated cylinder and brought to volume with water. The emulsion
should be Labeled "Shake well before use.
2. Wet gum method:
• Emulsifier is added to water to form a mucilage then oil is slowly added to emulsion.
• Thequantitiesofoil,waterandgumforprimaryemulsionarecalculated.Acaciaandwateraret
rituratedtoformmucilageinaporcelainmortar.TheoilisaddedinSmallamountswithconsta
nt,rapidandlighttrituration.Whenalltheoilhasbeenadded,themixtureistrituratedvigorou
slyforafewminutes.Finally,theemulsionistransferredtograduatedcylinderandbroughtto
volumewithwater.
 CHARACTERISTICS OF PARTICLES

Questions:
1. Define the following:
a. Micromeritics
• Micromeritics refers to a discipline of science and technology that deals with studies
related to the fundamental as well derived properties of particles. A precise
knowledge of the particle's size is of supreme importance in pharmaceutical and
materials science. It is related directly to the physical, chemical, as well as
pharmacological characteristics of an active pharmaceutical ingredient (API).
• Micromeritics in the area of tablet and capsule manufacture, control of the particle
size is essential in achieving the necessary flow properties and proper mixing of
granules and powders.
b. Porosity
• Porosity is defined as the ratio of the volume of pores to the volume of bulk rock
and is usually expressed as a percentage.
• Porosity, or the void portion in a substance, can be a critical physical property of
particles. In pharmaceutics, porosity can help to predict deformation properties
during compression, shelf life, moisture penetration, and bioavailability.
c. Bulk volume
• A term used relative to the density and volume of a porous solid, such as a refractory
brick. It is defined as the volume of the solid material plus the volume of the sealed
and open pores present.
d. Void
• opening, gap, empty space: emptiness, vacuum: the quality or state of being without
something : lack, absence: a feeling of want or hollowness.
• Void (astronomy), the spaces between galaxy filaments that contain no galaxies. Void
(composites), a pore that remains unoccupied in a composite material. Void,
synonym for vacuum, a space containing no matter. Void, a bubble within a
mechanical part that causes cavitation when it collapses
e. True volume
• bulk volume = true volume + volume of spaces between particles.
• Defined as the volume of the pores and voids within the sample.
f. Apparent density
• Apparent density is the bulk density of the powder. It provides the mass per unit
volume of loose packed powders. This value is a first, low-cost evaluation of a
powder to determine consistency from lot to lot. A low apparent density can be an
indication of fine particles and a high apparent density can be an indication of large
particles. A change in apparent density can also indicate a change in the surface
roughness of the powder; for example, atomization satellites may reduce apparent
density. Also, if a powder is heavily agglomerated, this may appear as an increase in
apparent density.
g. True density
• True density is the measure of the solid particles in a powder or granule. Pycnometer
uses helium gas to fill the voids in the powder bed to measure the volume taken up
by the powder. True density is the density of a material at 0% porosity.
• Defined as the volume of the pores and voids within the sample
2. Explain how a drug's powder particle size influences the pharmaceutical dosage form that will be
used to administer it.
• In the pharmaceutical industry, particle characterization of powder materials has become one
of the crucial aspects in drug product development and quality control of solid oral dosage
forms. The particle size distribution (PSD) of the drug substance may have significant effects
on final drug product performance (e.g., dissolution, bioavailability, content uniformity,
stability, etc.). Furthermore, the PSDs of both drug substance and excipients can affect drug
product manufacturability (e.g., flowability, blend uniformity, compactibility, etc.), which,
ultimately, can impact safety, efficacy, and quality of the drug product. Therefore, the impact
of particle sizes of pharmaceutical powders on drug product manufacturability and
performance should be evaluated at different pharmaceutical development phases for each
specific drug application. Once these particle size effects have been determined in the final
development phase, the target PSDs of pharmaceutical powders can be selected and the
appropriate particle size specifications should be established for control of drug product
quality and ensuring manufacturing consistency.

3. What is the importance of particle size determination?

• Particle size is a critical factor in determining the efficiency of manufacturing processes and
performance of the final product.
• Particle size analysis is a very important test and is used for quality control in many different
industries. In just about every industry where milling or grinding is used, particle size is a
critical factor in determining the efficiency of manufacturing processes and performance of
the final product.

4. Discuss in detail. Andreason pipette method.

• The particle size distribution of fine powder can be determined by examining a sedimenting
suspension of the powder The pipette method: e.g. the Andreasen pipette (fixed position
pipette): Allow a homogeneous suspension to settle in a cylinder, take samples from the
settling suspension at a fixed horizontal level at intervals of time. Each sample will contain a
representative sample of the suspension, with the exception of particles greater than a critical
size, all of which will have settled below the level of the sampling point.
• Another discussion of the Andreason pipette method.
Andreasen pipette is a glass laboratory device used in physical chemistry . It is used
to determine the grain size distribution of particles up to a size of approx. 1 μm and is
named after Alfred Andreasen .
The method is part of sedimentation analysis and is used in process engineering,
including in the pharmaceutical industry.
The particles to be examined (e.g. a powder ) are first suspended in a suitable liquid
and distributed evenly.
At first it can be assumed that the suspended particles are equally concentrated in all
transverse layers of the suspension. With the passage of time, however, the particles
sediment, with the larger particles sedimenting more quickly than the smaller ones according
to Stokes' equation . By modifying the above equation, the sinking speed equivalent diameter
can be determined for any given sedimentation time.
The Andreasen pipette has a device for withdrawing the liquid and a scale that
provides information about the filling level of the liquid, so the height of the liquid level
after each sample withdrawal and the withdrawal time result in a rate of descent that can be
equated with the rate of descent in Stokes' equation is
 The size d is called the sinking velocity equivalent diameter and, during the
measurement, depends on the height of fall (or liquid level) h and the time t of the sampling
- thus each h and t has a certain particle diameter that represents the maximum particle size
in the sample volume.
The sample volumes are then evaporated and the mass of the respective residue is
determined in order to create a run sum curve for further evaluation.
The decisive factor for evaluable data is the validity of Stokes' equation, which must
be ensured with a Reynolds number Re <0.2 (area of creeping flow).
Furthermore, the substance to be examined must neither swell, dissolve nor
chemically change in the dispersing liquid.

5. State another method of determining particle size.

• A typical sieve analysis uses a column of sieves with wire mesh screens of graded mesh size.
After the shaking is complete the material on each sieve is weighed. The mass of the sample
of each sieve is then divided by the total mass to give a percentage retained on each sieve.

6. Explain the relationship between angle of repose and flowability of solid particles.
• The angle of repose is a relatively simple technique for estimating the flowability of a
powder. Such measurements give at least a qualitative assessment of the internal cohesive
and frictional effects under low levels of external loading, as might apply in powder mixing,
or in tablet die or capsule shell filling operations.
• The relationship between flow properties and angle of repose has been established. When
the angle of repose is less than 25 degrees, the flow is said to be excellent; on the other hand,
if the angle of repose is more than 40 degrees, the flow is considered to be poor.
• The effect of particle size on the angle of repose has been studied by a number of
investigators with a general conclusion that increasing particle size will decrease the angle of
repose ͓ 12–14.

PHYSICAL AND CHEMICAL CHANGES

Physical Changes

Physical change - occurs when a substance changes, but no new substance is formed. Physical
changes occur when the state of a substance changes (eg melting, evaporation, freezing, condensing)
or a substance is crushed, ground or cut into smaller pieces. Physical changes are often easy to
reverse.

Change of State

Remember
• The particles in a solid are close together and vibrate.
• The particles in a liquid are further apart and slide over each other.
• The particles in a gas are far apart and bump into each other as they move quickly.

The following are examples of physical change.

• A plate is dropped and shatters.
• Ice melts.
• Water boils.
• Wax melts.
• Iodine sublimes.

Chemical Changes

Chemical change - or chemical reaction occurs whenever a new substance forms.

Evidence that a new substance is formed are –
• a change in colour.
• a gas given off.
• a new solid forms.
• a change in temperature.

The following are examples of chemical change.

• Wood burns
• An egg is cooked to become a white and yellow solid.
• A metal panel on a car rusts.
• Fireworks explode.
• Concrete hardens.
• An egg cooks.
• Paper burns.

Matter is everywhere.
Matter is anything that takes up space and has mass.
Matter is constantly experiencing both chemical and physical changes.

A physical change alters the form of a substance, but does not change it to another substance.
• It changes shape or size
• It dissolves.
• It changes phase (freezes,
• boils, evaporates, condenses)
Example:
Making Orange Juice

Physical changes - occur when matter changes its property but not its chemical nature.
Physical property - changes could include a change in: texture, shape, size, color, odor, volume,
mass, weight, and density.

EXAMPLE OF PHYSICAL CHANGE

• Boiled egg
• Crushing an insulin
• Cutting paper
• Ice melting
• Sawing wood
• Disappearing puddle
• Dry ice
 Chemical Change

Chemical changes are changes matter undergoes when it becomes new or different matter.

• It burns
• Temperature changes without heating/cooling
• It bubbles (makes a gas)
• It changes color
• It forms a precipitate

• When a substance undergoes a chemical change, it isa changed into a different substance
with different properties.

• To identify a chemical change look for signs

such as color change, bubbling and fizzing,
light production, smoke, and presence of
heat.

Example: Baking a Cake

Signs of Chemical Change

1. Precipitation
2. Color change
3. Gas Production
4. Temperature change

A chemical change occurs when fireworks are used. Fireworks are made of metals such as
magnesium and copper. These change chemically as they light up the sky

EXAMPLE OF CHEMICAL CHANGE

• Lighter fluid burning
• Sugar dissolving in tea
• Logs burning
• Breaking water up by separating it into hydrogen and oxygen
• Toast burning
• Rocket fuel burning
• Metal Rusting
• Candle burning