BABE STUDIES

1. Chapter 14
DISPERSE SYSTEM

2. Suspensions
Is a two-phase system
consisting of a finely divided
solid dispersed in a liquid
vehicle. The finely divided
particles are also referred to
as ‘Suspensoids” .

3. In these preparations, the
substance distributed is referred to
as dispersed phase and the
vehicle is termed the dispersing
phase or dispersion medium.
Together, they produce a
dispersed system.
Suspensions

4. Dispersions containing coarse
particles, usually 10 to 50 um in
size, are referred to as coarse
dispersion.
Dispersions containing particles of
smaller size are termed fine
dispersions (0.5 to 10 um)
Suspensions

5. In general sense, Suspension
may include:
1. Gels
2. Lotions
3. Magmas and Milk
4. Mixtures
Suspensions

6. Characteristics of Oral
Suspension
 Particles should be small uniform
sizes that do not settle rapidly
 The particles that do settle to the
bottom of the container should
not pack in to a hard cake and
should be re-dispersed completely
and evenly with a minimum
amount of agitation

7. Should not be too viscous to
pour freely from the mouth of
the bottle
Should have an agreeable odor,
color and taste and must not
decomposed or support mold
growth during storage
Must have therapeutic efficacy
Characteristic of Suspensions

8. Characteristic of Suspensions
Suspensions for injections
must contain particles size
such that they can pass
freely through the syringe
needle called
“syringeability”.

9. Ophthalmic suspension
should be formulated such
that the particles do not
exceed 10 microns. Below
this size, the patient
experiences no pain when
instilled into the eyes.
Characteristic of Suspensions

10. For Topical use, fine
particles are desired to
avoid grittiness when applied
to the skin. The smaller the
size, the greater the covering
and protective power of the
preparation
Characteristic of Suspensions

11. Reasons for Suspensions
 Certain drugs are chemically
unstable when in solution but
stable when suspended.
 Suspension insures chemical
stability while permitting liquid
therapy.
 Many patients prefer liquid form
than solid forms for swallowing.

12. Convenience in administration of
usually large doses
Safety and convenience of liquid
doses for infants and children.
Disagreeable taste of certain drugs
when given in solution is
negligible when the drug is
administered as undissolved
particles of a suspension, e.g
chloramphenicol
Reasons for Suspensions

13. 1. A properly prepared suspension should
settle slowly and should be readily re-
dispersed upon gentle shaking of the
container.
2. The characteristics of the suspension
should be such that the particles size of
the suspensoid remains fairly constant
throughout long periods of undisturbed
standing.
3. The suspension should pour readily and
evenly from its container
Features Desired in a PharmaceuticalFeatures Desired in a Pharmaceutical
SuspensionsSuspensions

14. Good pharmaceutical suspensions, the particle
diameter is between 1 to 50.
Particle size reduction is generally accomplished
by dry-milling prior to the incorporation of the
dispersed phase into the dispersion medium.
One of the methods of producing fine drug
powders of about 10 to 50 um size is
micropulverization.
For still finer particles, under 10 um, the process
of fluid energy grinding, sometimes referred to as
jet-milling or micronizing.
Physical Features of the Dispersed PhasePhysical Features of the Dispersed Phase
of a Suspensionof a Suspension

15. Dispersion Medium
 Suspending agents are added to the
dispersion medium to lend its structure to
assist in the suspension of the dispersed
phase
 Examples:
Carboxymethylcelulose
Methylcellulose
Microcrystalline cellulose
Polyvinyl pyrolidone,
Xanthan gum
Bentonite

16. The amount of the
suspending agent must not be
such to render the suspension too
viscous to agitate (to distribute
the suspensoid) or to pour.
The study of the flow
characteristics is termed
rheology
Dispersion Medium

17. Sustained-Release Suspension
 In liquid preparations (suspensions) of the
coated particles, the drug remains adsorbed
onto resin, but slowly released by the ion-
exchange process when taken into
gastrointestinal tract. The use of a combination
of ion-exchange resins complex and particle
coating is called Pennkinetic system.
 Examples:
Hydrocodone polistirex =Tussionex
Pennkinetic Extended-Release Suspension

18. Packaging and Storage of
Suspensions
 All suspensions should be packaged in containers
having:
1. Adequate airspace above the liquid to permit
adequate shaking.
2. Should be provided in wide mouth containers to
permit the prompt and ease of removal of the
suspension.
3. Store in tight containers protected from freezing,
excessive heat and light.
4. Suspensions should be shaken before use.

19. Example of Preparation
Aluminum Hydroxide Compressed
Gel 326.8 g
Sorbitol Solution 282.0 mL
Syrup 93.0 mL
Glycerin 25.0 m
Methylparaben 0.9 g
Propylparaben 0.3 g
Flavor q.s
Purified water, to make
1000.0 mL
USE: ANTACID

20.  methylparaben and propylparaben -
preservatives; syrup and sorbitol - viscosity
and sweetness.
 In the preparation, the parabens are dissolved
in a heated mixture of the sorbitol solution,
glycerin, syrup and a portion of the water.
The mixture then cooled and the aluminum
hydroxide added with stirring. The flavor is
added and sufficient purified water to
volume. The suspension is then homogenized,
using hand homogenizer, homomixer, or
colloid mill
Preparation…

21. Examples of Oral Suspensions by Category
Antacids Alumina, Magnesia and Simethicone - Mylanta liquid
Magaldrate Oral Suspension - Riopan Oral Suspension
Magnesia and Alumina Oral - Maalox Suspension
Aluminum Hydroxide and Magnesium Carbonate - Gaviscon
liquid
Anthelminitics Pyrantel Pamoate - Antiminth Oral Suspension
Thiabenzadole Oral Suspension - Mintezol Oral Suspension
Antibacterial
(Antibiotics)
Chloramphenicol Palmitate - Chloromycetin Palmitae Oral
Suspen.
Ertythromycin Estolate - Ilosone Oral Suspension
Antibacterial (non-
antibiotic Anti-
infectives)
Methenamine Mandelate - Mandelamine Suspension/Forte
Sulfamethoxazole and Trimethoprim - Bactrim, Septra
Suspension
Sulfamethoxazole - Gantanol Suspension
Sulfisoxazole Acetyl Oral Suspension- Gantrisin Syrup/Pedia
Anticonvulsants Pimidone Oral Suspension - Mysoline Suspension
Antidiarrheal Bismuth Subsalicylate - Pepto-Bismol liquid

22. Examples of Oral Suspensions by Category
Antiflatulent Simethicone Oral Suspension - Mylicone
Drop
Antifungals Nystatin Oral Suspension - Nystatin Oral
Suspension
Griseofulvin Oral Suspension -Grifulvin
Oral Suspension
Antihypertensive Methyldopa Oral Suspension - Aldomet
Oral Suspension
Antipsychotics, Sedatives, Antiemetic Hydroxyzine Pamoate Oral Suspension -
Vistaril Oral Suspension
Thioridazine Oral Suspension - Mellaril-
S Oral Suspension
Diuretic Chlorothiazide Oral Suspension - Diuril
Oral Suspension
Nonsteroidal Anti-inflammatory Indomethacin Oral Suspension - Indocin
Oral Suspension

23. Antacid Oral Suspension
Are intended to counteract the
effects of gastric hyperacidity
and such are employed by
persons, as peptic ulcer
patients, who must reduce the
level of acidity in the stomach.
Also referred to as “acid
indigestion”, “heartburn”, and
“sour stomach”

24. Examples:
Sodium Bicarbonate,
Aluminum hydroxide,
Aluminum phosphate,
Dihydroxyaluminum aminoacetate,
Calcium carbonate,
Calcium phosphate,
Magaldrate,
Magnesium carbonate,
Magnesium oxide
and Magnesium hydroxide.
Antacid Oral Suspension

25. Antibacterial Oral Suspension
 The antibacterial oral suspensions include
preparations of antibiotic substances
Examples:
 Antibiotics ( Chloramphenicol palmitate,
Erythromycin derivatives, and tetracycline and
its derivatives),
 Sulfonamides (Sulfamethoxazole, sulfisoxazole
acetyl),
 other chemotherapeutic agents( methanamine
mandelate and nitrofurantoin),
 combination of these ( sulfamethoxazole -
trimethoprim)

26. Otic Suspension
 Examples:
 Polymixin B sulfate,
 Neomycin sulfate,
 Hydrocortisone - pH 3.0 to 3.5;
 Cortisporin Otic Suspension - pH 4.8 to 5.1;
 PediOtic - pH of 4.1
 Note: Pharmacist must be aware that there
may be subtle differences in the formulation of
some otic suspensions that could be
potentially bothersome to the patient

27. Rectal Suspensions
Examples:
Barium sulfate for Suspension, USP may
be employed orally or rectally for the
diagnostic visualization of the GIT.
Mesalamine (5-aminosalicylic acid) - for
treatment of Crohn’s disease, distal
ulcerative colitis, proctosigmoiditis, and
proctitis.

28. Dry Powders for Oral Suspension
 Preparations consist of dry powder mixtures or granules, which are
intended to be suspended in water or some other vehicle prior to
administration.
The dry products contain
1. Antibiotic
2. Colorant (FD and C dyes)
3. Flavorants
4. Sweeteners - sucrose or sodium saccharin
5. Stabilizing agents - citric acid and sodium citrate
6. Suspending agents - guar gum, xanthan gum,
methylcellulose
7. Preserving agents - methylparaben, sodium benzoate
 NOTE: When called on to “RECONSTITUTE” and dispense, the
pharmacist loosens the powder at the bottom of the container by
lightly tapping it against a hard surface, and then adds label
designated amount of purified water, usually in portions, and shakes
well until all of the powder has been suspended.

29. Examples of Antibiotic Drugs for Oral Suspension
(Reconstitute)
Amoxicillin for Oral Suspension
AMOXIL
FOR ORAL SUSPENSION
Ampicillin for Oral Suspension
OMNIPEN
FOR ORAL SUSPENSION
Bacampicillin for Oral Suspension
SPECTROBID
FOR ORAL SUSPENSION
Cefaclor for Oral Suspension
CECLOR
FOR ORAL SUSPENSION
Cefixime for Oral Suspension
SUPRAX POWDER
FOR ORAL SUSPENSION

30. Examples of Antibiotic Drugs for Oral Suspension
(Reconstitute)
Cephadrine for Oral Suspension
KEFLEX
FOR ORAL SUSPENSION
Dicloxacillin Sodium for Oral
Suspension (PATHOCIL)
FOR ORAL SUSPENSION
Doxycycline for Oral Suspension
VIBRAMYCIN MONOHYDRATE
FOR ORAL SUSPENSION
Erythromycin Ethylsuccinate for Oral
Suspension
E.E.S. GRANULES
FOR ORAL SUSPENSION
Penicillin V for Oral Suspension

31. Other Examples (Combination)
1. Erythromycin ethylsuccinate/acetylsulfisoxazole
granules
- treatment for acute middle ear infection -
Hemophilus influenzae
2. Probenecid/ampicillin for reconstitution
- treatment for uncomplicated infections (urethral,
endocervical or rectal) - Neisseria
gonorrhoeae

32. Sample Products
TERGECEF GRANULES
FOR SUSPENSION
CEFIXIME
BIOGESIC SUSPENSION
PARACETAMOL
SOLMUX FORTE SUSPENSION
CARBOCISTEIN
E

33. EMULSIONS
The word emulsion, came from emulgio,
“meaning to milk out”.
Is a dispersion in which the dispersed
phase is composed of small globules of
a liquid distributed throughout a vehicle
in which it is immiscible.

34. Emulsion terminology
 The dispersed phase is referred to as the
Internal phase
 The dispersion medium as the External or
Continuous phase
 Emulsions having an oleaginous internal
phase and aqueous external phase are
referred to as oil-in-water (o/w) emulsions
 Emulsions having an aqueous internal phase
and an oleaginous external phase are termed
water-in- oil (w/o) emulsions.

35.  Unless a third component - the
emulsifying agent - is present the
dispersion is unstable, and the
globules undergo coalescence to form
two separate layers of water and oil
 Because the external phase of an
emulsion is continuous, an O/W
emulsion may be diluted with water or an
aqueous preparation, and W/O
emulsion with an oleaginous or oil miscible
liquid
Emulsion terminology

36. Emulsion terminology
 The aqueous phase may contain water-soluble
drugs, preservatives, coloring and flavoring agents
 The oil phase frequently consists of fixed oil or volatile
and drugs that exist as oil, such as oil-soluble vitamins
and antiseptic
 It is necessary to add antioxidant to prevent
autoxidation of the oil and rancidity/and or destruction
of any vitamin present.

37. 1. Pharmaceutically
a. The pharmacist can prepare
relatively stable and homogenous
mixture of 2 immiscible liquids
b. Emulsification can permit the
administration of liquid drug in
the form of minute globules rather
than in bulk
Purpose of EmulsificationPurpose of Emulsification

38. 2. Therapeutically
A. Beneficial to the rate and degree of
absorption of the drug after administration by any
of the usual route
B. O/W emulsions may also be useful as
vehicle to develop the bioavailability of poorly
absorbed drugs
C. For orally administered emulsion the O/W
type permits the palatable administration of an
otherwise distasteful oil by dispersing it in a
sweetened, flavored vehicle.
Purpose of EmulsificationPurpose of Emulsification

39. D. The reduced particle size of the oil globules may
render the oil more digestible and more readily absorbed and
therefore more effective
E. Emulsion to be applied externally can be made
such that the medicinal agent that are irritating to the skin
surface may be incorporated in the internal phase than in the
external phase since the latter is in direct contact with the
skin
F. On the unbroken skin, a W/O emulsion can usually
be applied more evenly since the skin is covered with a thin
film sebum, and this surface is more readily wetted by oil
than by water. On the other hand, if it is easily removed from
the skin, O/W is preferred.
Purpose of EmulsificationPurpose of Emulsification

40. Theories of Emulsification
1. Surface Tension Theory
2. Oriented-Wedge Theory
3. Plastic or Internal Film Theory
4. Viscosity Theory

41. Surface Tension Theory
Surface tension
A property of liquids in which the
exposed surface tends to contract to the
smallest possible are. In a spherical drop
of liquid there are internal forces that
tend to promote the association of the
molecule of the substance to resist the
distortion of the drop into a less
spherical form.

42. The use of substances as emulsifiers
and stabilizers
Results in the lowering of the
interfacial tension of the 2 immiscible
liquids, reducing the repellant force
between the liquids and diminishing each
liquids attraction for its own molecules.
These tension lowering substances are
referred to as surface active
(surfactants) or wetting agents.
Surface Tension Theory

43. Oriented-wedge Theory
 Assumes monomolecular layers of emulsifying agent
curved around a droplet of the internal phase of the
emulsion.
 It is based on the presumption that certain emulsifying
agents orient themselves about and within a liquid in a
manner reflective of their solubility in that particular
liquid.
 An emulsifying agent having a greater hydrophilic
character than hydrophobic character will promote an
O/w emulsion and a W/O emulsion results through use
of more hydrophobic than hydrophilic emulsifiers.

44. Plastic or Interfacial-Film Theory
 Places the emulsifying agent at the interface
between the oil and water, surrounding the
droplets of the internal phase as a thin layer of
film adsorbed on the surface of the drops.
 The film prevents the contact and the
coalescence of the dispersed phase, the
tougher and more pliable the film, the greater
the stability of the emulsion.

45. Viscosity Theory
States that the viscosity of an emulsion
aids emulsification by the mechanical
hindrance to coalescence of the globules
although it is not the cause of
emulsification.

46. Emulsifying Agents
Natural
Emulsifying
Agents
• These materials form hydrophilic
colloids when added to water and
generally produced O/W emulsions.
Acacia is most frequently use.
Tragacanth and Agar - thickening
agents in Acacia emulsified products.
• These substances produce O/W
emulsions. The disadvantage of
gelatin is that the emulsion prepared
from it are too fluid.
Carbohydrates:
• acacia,
• tragacanth
• agar,
• chondrus,
• pectin
Proteins
• gelatin,
• egg yolk,
• casein
High
Molecular
Weight
alcohols
• These materials employed primarily as
thickening and stabilizing agents for O/W
emulsions such as lotion and ointments
• Cholesterol may also be employed in
externally used emulsion and promote W/O
emulsions.
• stearyl alcohol,
• cetyl alcohol,
• glyceryl
monostearate

47. Emulsifying Agents
Finely
Divided
Solids
•These materials generally form
O/W emulsions when the
insoluble material is added to the
aqueous phase if there is greater
volume of the aqueous phase
than of the oleaginous phase
Colloidal clays including
•Bentonite,
•Magnesium hydroxide
•Aluminum hydroxide
Synthetic •(wetting agents), which may be
Anionic, Cationic, Nonionic
•Anionic:
triethanolamine oleate and
sodium lauryl sulfate
•Cationic:
benzalkonium chloride
•Nonionic:
sorbitan esters (span);
polyethylene glycol 400
monostearate; polyoxyethylene
sorbitan esters (Tweens)

48. Qualities Required for
Emulsifiers
 Must be compatible with other ingredients in the
formula
 Must not interfere with the stability and efficacy of
the therapeutic agent
 Must be stable to microorganisms
 Must be non-toxic
 Must possess little or no odor, taste or color
 Must promote emulsification and maintain stability
of the emulsion for intended shelf-life

49. The HLB or Hydrophilic-
Lipophile Balance
 Each emulsifying agents has a hydrophilic portion
(water-loving) and a lipophilic portion (oil-loving) with
one or other being more or less predominant and
influencing
 A method indicative of the substances polarity devised
and lead to the assigning of an HLB value for each
agent. The usual range is between 1 to 20.
 Materials that are highly polar or hydrophilic have
assigned higher numbers than materials that are less
polar and were lipophilic.

50. The HLB System or Hydrophilic-
Lipophile Balance
 Surfactants having an assigned HLB value from 3 to 6 are
greatly lipophilic and produce W/O emulsions and those
HLB values of from about 8 to 18 produce O/W emulsions.
 In selecting an Emulsifier for an emulsion, choose one
having the same or nearly the same HLB value as the
oleaginous phase
 Example: Mineral oil has assigned HLB of 4 if a W/O
emulsion is desired and a value of 10.5 if O/W emulsion is
prepared
 Therefore, use surfactant SPAN 80 (Sorbitan monoleate)
with HLB 4.3 for W/O emulsion and methylcellulose with
HLB of 10.5 for O/W.

51. Examples of HLB Values for
Selected Emulsifiers
 Ethylene glycol distearate 1.5
 Sorbitan tristearate (Span 65) 2.1
 Propylene glycol monostearate 3.4
 Triton X-15 3.6
 Sorbitan monooleate (Span 80) 4.3
 Sorbitan monostearate (Span 60) 4.7
 Diethylene glycol monolaurate 6.1
Examples of HLB Values for Selected Emulsifiers
 Sorbitan monopalmitate (Span 40) 6.7
 Sucrose dioleate 7.1
 Acacia 8.0

52. Examples of HLB Values for
Selected Emulsifiers
 Amercol L-101 8.0
 Polyoxyethylene lauryl ether (Brij 30) 9.7
 Gelatin 9.8
 Triton X-45 10.4
 Methylcellulose 10.5
 Polyoxyethylene monostearate (Myrj 45) 11.1
 Triethanolamine oleate 12.0
 Tragacanth 13.2
 Triton X-100 13.5
 Polyoxyethylene sorbitan monostearate (Tween 60) 14.9
 Polyoxyethylene sorbitan monooleate (Tween 80) 15.0

53. Examples of HLB Values for
Selected Emulsifiers
 PSM (Tween 20) 16.7
 Pluronic F 68 17.0
 Sodium oleate 18.0
 Potassium oleate 20.0
 Sodium lauryl sulfate 40.0

54. Activity and HLB Value of
Surfactants
Activity Assigned HLB
1. Antifoaming 1 to 3
2. Emulsifiers (W/O) 3 to 6
3. Wetting agents 7 to 9
4. Emulsifiers (O/W) 8 to 18
5. Solubilizers 15 to 20
6. Detergents 13 to 15

55. Methods of Preparation
1. Continental or Dry gum method
2. English or wet gum method
3. Bottle or Forbes bottle method
4. Auxiliary method
5. In SITU soap method
6. Microemulsions

56. Continental or Dry gum method
( G + O + W )
 The method is also referred to as the “4:2:1”
method because for every 4 parts (volumes)
of oil, 2 parts of water and 1 part of gum are
added in preparing the initial or primary
emulsion.
 For instance, if 40 mL of oil are to be
emulsified, 20 mL of water and 10 g of gum
would be employed, with additional water or
other formulation ingredients being added
afterward to the primary emulsion

57. Preparation of Continental or Dry
Gum Method
1. The acacia or other O/W emulsifier is
triturated with the oil in a perfectly dry
Wedgewood or porcelain mortar until
thoroughly mixed.
2. After the oil and gum have been mixed, the
two parts of water are then added all at once,
and the mixture is triturated immediately,
rapidly, and continuously until the primary
emulsion that forms is creamy white and
produces a crackling sound to the movement
of the pestle
3. Generally, about 3 minutes of mixing are
required to produce such a primary emulsion.

58. 4. Other liquid formulative ingredients that are soluble
in or miscible with the external phase may then be
added to the primary emulsion with mixing.
5. Solid substances such as preservatives, stabilizers,
colorants, and any flavoring material are usually
dissolved in a suitable volume of water and added
as a solution to the primary emulsion
NOTE: A mortar with a rough rather than smooth
inner surface must be used to ensure proper
grinding action and the reduction of the globule size
during the preparation of the emulsion. A glass
mortar has too smooth a surface to produce the
proper size reduction of the internal phase.
Preparation of Continental or Dry
Gum Method

59. Bottle or Forbes Bottle Method
(G+O+W)
 For the extemporaneous
preparation of emulsions from
volatile oils or oleaginous
substances of low viscosities, the
bottle method is used. (2:2:1)

60. Preparation:
1. The powdered acacia is placed in a dry bottle
2. Two parts of oil is then added, and the mixture is
thoroughly shaken in the capped container.
3. A volume of water approximately equal to the oil is then
added in portions
4. The mixture being thoroughly shaken after each addition
5. When all of the water has been added, the primary
emulsion thus formed may be diluted to the proper
volume with water or other an aqueous solution of other
formulative agents
NOTE: This method is not suited for viscous oils, because
they cannot thoroughly agitated in the bottle.
Bottle or Forbes Bottle Method
(G+O+W)

61. Auxiliary Methods
An emulsion by either the wet gum or dry
gum methods can generally be increased in
quality by passing it through a hand
homogenizer.
In this apparatus, the pumping action of
the handle forces the emulsion through a very
small orifices which reduces the globules of
the internal phase to about 5 um and
sometime less

62. In SITU Soap Method
Two types of soap developed by this
method are Calcium soaps and Soft
soaps.
Calcium soaps
water - in - oil emulsions which
contain certain vegetable oil (e.g. Oleic
acid) in combination with lime water
( Syn: Calcium Hydroxide Solution USP)
and prepared by mixing equal volumes
of the oil and lime water

63.  Example: Calamine Liniment (itchy, dry
skin, sunburn)
Calamine………………………
Zinc Oxide ……………………. 80.0 g
Olive oil …………………………
Calcium Hydroxide Sol’n aa q.s ad
1000.0 mL
In SITU Soap Method

64. Microemulsions
 Thermodynamically stable, optically
transparent, isotropic mixtures of a biphasic
oil-water system stabilized with surfactants.
 The diameter of droplets in a microemulsion
may be in the range of 100 A (10 microns) to
1000 A whereas in a microemulsion the
droplets may be 5000 angstroms in
diameter.
 Both O/W and W/O microemulsions may be
formed spontaneously by agitating the oil
and water phases with carefully selected
surfactant.

65. Advantages:
More rapid and efficient oral absorption of
drugs than through solid dosage forms
Enhance transdermal drug delivery through
increased drug diffusion into the skin
The technique potential application of
microemulsion in the development of artificial
red blood cells and in the argeting of
cytotoxic drugs to cancer cells
Microemulsions

66. Examples of Emulsions
1. Turpentine Oil Emulsion
Rectified Turpentine oil 150 mL
Acacia powder 50 g
Purified water, q.s to make 1000 mL
2. Liquid Petrolatum Emulsion - Mineral oil Emulsion; Liquid Paraffin
Mineral oil………………………………… 500 mL
Acacia …………………………………….. 125 g
Syrup ……………………………………… 100 mL
Vanilla …………………………………….. 40 mg
Alcohol ……………………………………. 60 mL
Purified water, q.s to make 1000 mL
3. Cod liver Oil Emulsion - laxative with empty stomach
Cod liver oil …………………………….. 500 mL
Acacia ……………………………………. 125 g
Syrup …………………………………….. 100 mL
Methyl salicylate ……………………….. 4 mL
Purified water, q.s to make 1000 mL

67. Emulsion Stability
A stable emulsion is characterized by the
following:
1. Absence of flocculation and creaming
2. Absence of coalescence of globules and
separation of the layers
3. Absence of deterioration due to
microorganisms
4. Maintenance of elegance with respect to
appearance, odor, color and consistency

68. Emulsion is considered physically unstable if:
The internal or dispersed phase upon standing tends
to form aggregates of globules.
Large globules or aggregates of globules rise to the
top or fall to the bottom of the emulsion to form
concentrated layer of the internal phase.
If all or part of the liquid of the internal phase becomes
“unemulsified” and forms a distinct layer on the
top or bottom of the emulsion as result of the
coalescing of the globules of the internal phase
Emulsion Stability

69. Terminology
Flocculation - is the joining together of globules to form large clumps or floccules which
rise or settle in the emulsion more rapidly than do the individual
particles
Creaming is the rising (upward creaming) or settling (downward creaming) of
globules or floccules to form a concentrated layer at the surface or to
the bottom of the emulsion
Coalescence and
breaking
unlike creaming, the coalescence of globules and the subsequent
breaking of an emulsion are irreversible processes. In creaming, the
globules are still surrounded by a protective coating or sheath of
emulsifying agent and may redispersed simply by agitating the
product.
Deterioration by
Microorganism
Molds, yeast and bacteria may bring about decomposition and
contamination of the emulsion. Preservatives should be more
fungistatics than bacteriostatic
Miscellaneous
Physical and
Chemical
Change
Light and rancidity affect the color and the odor of oils and may destroy
their vitamin content. Freezing and thawing and high temperature
result in the coarseness and breaking of an emulsion.

70. Terminology Related To Gels
Imbibition is taking up of a certain amount of liquid without a measurable
increase by a gel with an increase volume.
Swelling is the taking up of a liquid by a gel with an increase in volume. Only
those liquid that solvate a gel can cause swelling. The swelling
of protein gels is influenced by pH and thepresence of
electrolytes.
Syneresis is when the interaction between particles of the dispersed phase
becomes so great than on standing, the dispersing medium is
squeezed out in droplets and the gel shrinks. Syneresis is a form
of instability in aqueous and nonaqueous gels
Thixotrophy is a reversible gel-sol formation with no change in volume or
temperature-a type of non-Newtonian flow.
Xerogel is formed when the liquid is removed from a gel and only the
framewok remains. Examples: gelatin sheet, tragacanth ribbons
and acacia tears

71. Classification and Types of Gels
Two general classification
1. Inorganic hydrogels
are usually two phase systems such as Aluminum
Hydroxide Gel and Bentonite Magma
2. Organic Gels
are usually single phase systems and may include such as
gelling agents as Carbomer and Tragacanth and those that
contain an organic liquid, such Plastibase.

72. Classification and Types of Gels
Second classification Scheme
1. Hydrogels
include ingredients that are dispersible as colloidals or
soluble in water and include organic hydrogels, natural and
sythetic gums and inorganic hydrogels
Examples: silica, bentonite, tragacanth, pectin, sodium alginate,
methylcellulose, sodium carboxymethylcellulose and alumina
2. Organogels
include the hydrocarbons, animal and vegetable fats, soap
base greases and the hydrophilic organogels.
Examples: Hydrocarbon - Jelene, or Plastibase

73. Preparation of Magmas and Gels
1. By freshly precipitating the disperse
phase
2. By direct hydration in water

74. Examples of Gelling Agents
1. Acacia 11. Alginic acid
2. Bentonite 12. Carbomer
3. Carbocymethylcellulose sodium 13. Cetostearyl Alcohol
4. Colloidal silicon dioxide14. Ethylcellulose
5. Gelatin 15. Guar gum
6. Hydroxyethylcellulose 16. Hydroxypropryl cellulose
7. Hydroxypropryl methylcellulose 17. Magnesium aluminum silicate
8. Maltodextrin 18. Methylcellulose
9. Polyvinyl alcohol 19. Povidone
10. Propylene carbonate 20. Sodium alginate
21. Sodium starch glycolate 22. Starch
23. Tragacanth 24. Xanthan gum

75. Examples of Gelling Agents
1. Alginic acid
obtained from seaweed, prepared products is tasteless, odorless,
yellowish-white colored fibrous powder
used as thickening agent in concentrations of 1 to 5%
swells in water to about 200 to 300 times its own weight without
dissolving
2. Carbomer (Carbopol)
resins with high molecular weight allylpentaerythritol-cross-linked
acrylic acid-based polymers modified with C10 to C30alkyl acrylates
fluffy white powders with large bulk density (0.5 and 1% aqueous
dispersion)
Example: Carbomers 910,934,934P,940 and 1342

76. Examples of Gelling Agents
3. Carboxymethylcellulose
concentrations of 4 to 6% of medium viscosity can be used to
produce gel; glycerin may be added to prevent drying;
incompatible with alcohol
4. CMC sodium
soluble in water at all temperature
5. Colloidal silicone dioxide
can be used with other ingredients of similar refractive index to
prepare transparent gels
6. Gelatin
dispersed in hot water and cooled to form gels

77. Examples of Gelling Agents
7. Magnesium aluminum silicate (Veegum)
concentrations of about 105 forms a firm thixotropic gel
material is inert and has few incompatibilities but is less used
above pH 3.5
8. Plastibase (Jelene)
mixture of 5% low molecular weight polyethylene and 95% mineral
oil
9. Poloxamer (Pluronic)
concentrations ranging from 15 to 50% to form gel
poloxamers 124 (L-44 grade), 188 (F-68 grade), 237 (F-87 grade),
338 (F-108 grade) and 407 (F-127 grade) types are freely soluble
in water F = refers to flake form L = refers to liquid form

78. Examples of Gelling Agents
10. Polyvinyl alcohol (PVA)
used at concentrations of about 2.5% in the preparartion of
various jellies that dry rapidly when applied to the skin
borax is a good agent that will gel PVA solutions
for best result, dispersed PVA in cold water, followed by hot
water. It is less soluble in cold.
11. Povidone
about 10% in concentrations to prepare gels
also increase solubility of poorly soluble drugs

79. Examples of Gelling Agents
12. Sodium alginate
10 % to produce gels
aqueous preparations are most stable at pH 4 to 10; below pH 3,
alginic acid is precipitated
13. Tragacanth gum
used to prepare gels that are most stable at pH 4 to 8
must be preserved with 0.1% benzoic acid or .17% methylparaben
and 0.03% propyl paraben
14. Methylcellulose
5% to form gels; dispersed with high shear in about 1/3 of water

80. MAGMAS and MILK
Are aqueous suspensions of
insoluble, inorganic drugs and differ
from gels mainly in that the
suspended particles are larger.
When prepared, they are thick and
viscous, so need of a suspending
agent.

81. Preparations
1. By Hydration –
Example: Hydration of Magnesium oxide
MgO + H2O Mg(OH)2
2. Chemical Reaction
Milk of Bismuth is made by reacting Bismuth
subnitrate with Nitric acid and Ammonium carbonate
with Ammonium solution and then mixing the
resulting two solutions
2NaOH + MgSO4 Mg(OH)2 + Na2SO4
(direct hydration)
MAGMAS and MILK

82. Examples of Magmas and Gels
Bentonite Magma NF suspending agent
Sodium Fluoride and Phosphoric Acid
Gel
USP dental care prophylactic
Fluocinonide Gel USP Anti-inflammatory corticosteroid
Tretinoin Gel USP treatment for acne
Erythromycin and Benzoyl peroxide Gel
Clindamycin Topical Gel
Hydroquinone Gel Hyperpigmented skin
Salicylic acid Gel keratolytic
Desoximethasone Gel anti-inflammatory and antipruritic agent
Aluminum Phosphate Gel (Amphogel) USP antacid
Aluminum hydroxide Gel USP antacid
Dihydroxyaluminum Aminoacetate
Magma
USP antacid
Milk of Magnesia (Magnesia Magma) USP Antacid; laxative

83. Sample Product
ALAXAN GEL
METHYL SALICYLATE +
MENTHOL

84. AEROSOLS
 Are pressured dosage forms containing one or
more active ingredients which upon actuation
emit a fine dispersion of liquid and/or solid
materials in gaseous medium
 The term Pressurized package is commonly
used when referring to the aerosol container or
completed product. Pressure is applied to the
aerosol system through the use of one or more
liquefied or gaseous propellants.

85. Aerosols used to provide an airborne mist are termed
space sprays. Examples: room disinfectants,
room deodorizers, and space insecticides.
Aerosols intended to carry the active ingredient to a
surface are termed Surface sprays or surface
coatings.
Examples: dermatologic aerosols, pharmaceutical
aerosols, as personal deodorant sprays,
cosmetic hair lacquers and sprays, perfumes and
cologne sprays, shaving lathers, toothpaste, surface
pesticide sprays, paint sprays and others.
AEROSOLS

86. Advantages of the Aerosol
Dosage Forms
1. A portion of medication may be easily withdrawn from the
package without contamination or exposure to the remaining
material.
2. Hermetic character, the aerosol container protects medicinal
agents from atmospheric oxygen, moisture and even from
light.
3. Topical medication may be applied in a uniform, thin layer to
the skin, without touching the affected area thus, reducing
irritation.
4. By proper formulation and valve control, the physical form
and the particles size of the emitted product may be
controlled which may contribute to the efficacy of a drug.
Example: the fine controlled mist of an inhalant aerosol.
Through the use of metered valves, dosage may be
controlled.
5. Aerosol application is “clean” process, requiring little or no
“wash-up” by the user.

87. The Aerosol Principle
As aerosol formulation consists of 2 components:
1. The product concentrate
is the active ingredient of the aerosol combined
with the required adjuncts, such as antioxidants,
surface-active agents, and solvents, to prepare a
stable and efficacious product.
2. The propellant
when the propellant is a liquefied gas or a mixture
of liquefied gases, it frequently serves the dual role of
propellant and solvent or vehicle for the product
concentrate

88. Examples of Propellants
1. Carbon dioxide
2. Nitrogen
3. Nitrous oxide
4. Fluorinated Hydrocarbons:
Trichloromonofluoromethane;
Dichlorodifluoromethane;
Dichlorotetrafluoroethane;
Chlorpentafluoroethane;
Monochlorodifluoroethane;
Octafluorocyclobutane

89. Aerosol Container and Valve
Assembly
 The effectiveness of the aerosol depends on:
1. proper combination of formulation,
2. container
3. valve assembly.
 The formulation must not chemically interact with the
container or valve components to avoid unstability of
the formulation.
 The container and the valve must be capable of
withstanding the pressure required by the product
 It must be corrosive resistant
 Valve must contribute to the form of the product to be
emitted.

90. AEROSOL SYSTEMS
SPACE AEROSOLS usually operate at pressures
between 30 to 40 psig (pounds per square inch
gauge) at 700
F and may contain as much as 85%
propellant
SURFACE AEROLSOLS commonly contain 30 to
70% propellant with pressures between 25 to 55
psig at 700
F
FOAM AEROSOLS usually operate between 35
and 55 psig at 700
F and may contain only 6 to 10%
propellant

91. AEROSOL SYSTEMS
TWO PHASE SYSTEM = comprised (1) the liquid phase –
propellant and product concentrate (2) the vapor phase
THREE PHASE SYSTEM = comprised (1) layer of water
immiscible liquid propellant, (2) layer of highly aqueous
product concentrate, and (3) vapor pressure
COMPRESSED GAS SYSTEM = compressed rather
liquefied, gases may be used to pressure aerosols. The
pressure of the compressed gas contained in the headspace
of the aerosol container forces the product concentrate up
the dip tube and out of the valve
Examples: Nitrogen; carbon dioxide; nitrous oxide

92. Containers
1. Glass, uncoated or plastic coated
2. Metal, including tinplated steel, aluminum, and
stainless steel
3. Plastics
The selection of containers for an aerosol product is
based on
1. Its adaptability to production methods
2. Compatibility with formulation components
3. Ability to sustain the pressure intended for the product
4. The interest in design and aesthetic appeal on the
part of the manufacturer, and
5. Cost

93. VALVE ASSEMBLY
 The function of the valve assembly is to permit
the expulsion of the contents of the can in the
desired form, at the desired rate, and, in the
case of metered valve, in the proper amount or
dose.
 The materials used in the manufacture of
valves must be inert and approved by BFAD.
 Among the materials used in making valve
parts are plastic, rubber, aluminum, and
stainless steel.

94. Metered Dose Inhalers (MDIs)Metered Dose Inhalers (MDIs)
Example: Allupent. Each metered dose is
delivered through the mouthpiece upon actuation
of the aerosol unit’s valve
Nitrolingual spray - permits a patient to
spray droplets onto or under the tongue for acute
relief of an attack, or prophylaxis, of angina
pectoris due to coronary artery disease. The
product contains 200 doses of nitroglycerin in a
propellant mixture of dichlorofluoromethane and
dichlorotetrafluoroethane

95. Filling OperationsFilling Operations
Fluorinated hydrocarbon gases may be liquefied by cooling
below their boiling points or by compressing the gas at room
temperature. These 2 features are utilized in the filling of aerosol
containers with propellant.
Cold FillingCold Filling
Both the product concentrate and the propellant must be
cooled to temperatures of -300
to -40 0
F. This temperature is
necessary to liquefy the propellant gas. The cooling system may be a
mixture of dry ice and acetone.
Pressure FillingPressure Filling
The product concentrate is quantitatively placed in the
aerosol container, the valve assembly is inserted and crimped into
place, and liquefied gas, under pressure, is metered into the valve
stem from a pressure burette.

96. Parts of Aerosol Valve
Actuator The actuator is the button which the user presses to activate the valve assembly
for the emission of the product.
Stem The stem supports the actuator and delivers the formulation in the proper form to
the chamber of the actuat
Gasket The gasket, placed snugly with the stem, serves to prevent leakage of the
formulation when the valve is in closed position
Spring The spring holds the gasket in place and also is the mechanism by which the
actuator retracts when pressure is released, thereby returning the valve to the
closed position
Mounting
cup
The mounting cup, which is attached to the aerosol can or container, serves to
hold the valve in place.
Housing The housing, located directly below the mounting cup, serves as the link between
the dip tube and the stem and actuator. With the stem, its orifice helps to
determine the delivery rate and the form in which the product is emitted.
Dip tube The dip tube, which extends from the housing down into the product, serves to
bring the formulation from the container to the valve.

97. Testing the Filled Containers
Container is tested under various environmental
conditions
1. Leaks
2. Weakness in the valve assembly or container
3. Proper function s of the valve
4. The valve discharge rate - determine by discharging a
portion of the contents of a previously weighed
aerosol during a given period of time, and calculating,
by the difference in weight, the grams of contents
discharged per unit of time.
5. Particle size distribution of the spray
5. For accuracy and reproducibility of dosage when
using metered valves

98. Aerosols
Topical Aerosols
 Aerosols packages for topical use on the skin which include:
Antiinfectives: Povidone - iodine, Tolnaftate and Thimerosal
Adrenocortical steroids: Betamethasone and Triamcinolone
Acetonide
Local anesthetic: Dibucaine hydrochloride
Vaginal and Rectal Aerosols
• Aerosols foams are commercially available containing estrogenic
substances and contraceptives agents.
Example:
ProctoFoam - contains pramoxine hydrochloride
- use to relieve inflammatory anorectal disorder

99. Examples of Inhalation Aerosols
Albuterol Inhalation Proventil Inhalation
Aerosol
Beta-adrenergic
Beclomethasone
Dipropionate
Beclovent Inhaltion Adrenocortical Beconace
steroid
Cromolyn Sodium Intal Inhaler Atiasthmatic, Antiallergic
Ipratropium Bromide Atrovent Anticholinergic
Isoetharine Mesylate Bronkometer Sympathomimetic - brochial
asthma
Metaproterenol Sulfate Alupent Sympathomimetic
Salmeterol Xinafoate Serevent Beta-adrenergic agonist
Terbutaline Sulfate Brethaire Beta-adrenergic agonist
Triamcinolone Acetonide Azmacort Corticosteroids for asthma

100. NASAL PREPARATIONS
aqueous preparations, rendered
isotonic to nasal fluids (approximately
equivalent to 0.9% sodium chloride)
buffered to maintain drug stability while
approximating the normal pH range of
the nasal fluids (pH 5.5 to 6.5), and
stabilized and preserved as required.

101. Examples of Some Commercial
Nasal Preparations
Afrin Nasal Spray/ drops Oxymetazole nasal decongestant/adrenergic
Beconase AQ Nasal Spray Bechlomethasone
diproprionate
synthetic corticosteroid
Diapid Nasal Spray Lopressin antidiuretic; prevention of
diabetes
Nasalcrom Spray Cromolyn - allergic rhinitis
Ocean Mist Isotonic sodium chloride restore moisture/relieve dry
Privine HCl Solution Naphazoline HCl nasal adrenergic/decongestant
Syntocinon Spray Tetrahydrozoline HCl adrenergic/decongestant
Neo-Synephrine Oxymetazoline HCl nasal adrenergic/decongestant
Nasalide Nasal Solution Flunisolide perennial/seasonal rhinitis

102. OTIC SOLUTIONS
 sometimes referred to as ear or aural
preparations.
 Preparations frequently used in the ear, with
suspensions or ointments also finding some
application.
 Usually placed in the ear canal by drops or
small amounts for the removal of excessive
cerumen (ear wax), or treatment of ear
infections, inflammation, or pain.

103. Examples of Some Commercial
Otic Preparations
AMERICAINE Benzocaine local anesthetic
AURALGAN Antipyrine, Benzocaine Acute otitis media
CERUMENEX DROPS Triethanolamine Cerumenolytic agent
CHLOROMYCETIN Chloramphenicol Anti-infective
CORTISPORIN SOLUTION Polymyxin B sulfate,
neomycin sulfate
antibacterial
DEBROX DROPS Carbamide Peroxide Ear wax remova
PEDIOTIC Polymyxin B sulfate
neomycin sulfate
- Antibacterial
METRETON Prednisolone sodium
phosphate
Antiinflammatory
OTOBIOTIC SOLUTION Polymyxin B Sulfate,
hydrocortisone
Antibacterial
VOSOL SOLUTION Acetic acid Antibacterial/Antifungal

104. MUCILAGES
The official mucilages are thick, viscid,
adhesive liquids, produced by dispersing
gum in water or by extracting with water
mucilagenous principle from vegetable
substances.
Mucilages are used primarily to aid in
suspending insoluble substances in
liquids due to their (1) colloidal character
and (2) viscosity which prevents the
immediate sedimentation

105. Example of Mucilage
 Method: Place acacia in wide mouth graduated bottle with capacity not
exceeding 1000 mL. Wash the drug with cold water, drain and add
sufficient quantity of purified water in which benzoic acid has been
dissolved to make 1000 mL, Stopper and lay the bottle, rotate
occasionally, and when acacia has been dissolved, strain the mucilage
 Uses: Demulcent, suspending agent, excipient in making pills and
troches,and as emulsifying agent for cod liver oil
Preparation: Acacia Mucilage NF
Synonym: Mucilago Acaciae; Mucilage of Gum Arabic
Formula : Acacia, in small fragments 350 g
Benzoic acid 2 g
Purified water, q.s to make 1000 mL

106. Example of Mucilage
Preparation: Tragacanth Mucilage NF
Synonym: Mucilago Tragacanthae
Formula : Tragacanth 6.0 g
Benzoic acid 0.2 g
Glycerin 18.0 g
Purified water, q.s to make 100 g
Method : Mix 75 mL of purified water with glycerin in a tared vessel, heat to
boiling, discontinue application of heat, add Tragacanth and the Benzoic
acid and macerate during 24 hours, stirring occasionally. Add sufficient
quantity of purified water to make the mucilage 100 g, stir actively until
uniform consistency and strain through muslin cloth
Uses: excipient for pills or troches, suspending agent for insoluble
substances for internal mixtures and as protective agent

107. INHALANTS
 Are drugs or combinations of drugs that by virtue of
their high vapor pressure can be carried by an air
current into the nasal passage where they exert their
effect.
 The device in which they are administered is termed
an inhaler.
 Examples:
1. Amyl Nitrite Inhalant - treatment of anginal pain
2. Propylhexedrine Inhalant - nasal decongestant

108. INHALATIONS
Inhalations are drugs or solutions of drugs
administered by the nasal or oral respiratory
route.
 A widely used instrument capable of producing
fine particles for inhalation therapy is the
NEBULIZERS.
 When volatile medication is added to the water
in the chamber, the medication is volatilizes
and also inhaled by the patient, HUMIDIFIERS
will be used.

109. INHALATIONS
The common household VAPORIZER,
produces a fine mist of steam that may
be used to humidify a room will be used
also.
ULTRASONIC HUMIDIFIERS are also
available.
Examples:
1. Isoetharine inhalation - bronchial asthma
2. Isoproterenol Inhalation - bronchial asthma

110. Sample Products
LIBRENTIN INHALER
SALBUTAMOL

111. LOTIONS
Also called “WASHES” or meaning
“LOTIO” or “LAVARE” to wash. Lotions
are liquid suspension or dispersion
intended for external application to the
skin, frequently containing suspended
particles or emulsified liquid droplets.
Depending therefore, whether they are
solid-liquid or liquid-liquid dispersions,
some lotions can also classified as
suspension or emulsion.

112. Characteristics:
 Since the finely powdered substances
are insoluble in the dispersion
medium, the use of suspending agents
and dispersion agent is made.
If the substance is immiscible, an
emusifying agent is used. Most
commonly, the vehicles of lotions are
aqueous.
LOTIONS

113. Characteristics Of GOOD Lotion
 Dries quickly and provides a protective film
that will not rub off easily. It should not run
off the surface of the skin.
 The particles settle or rise only slowly and
solid do not form a hard cake at the bottom
of the vessel.
 The lotion should pour freely from the bottle
and apply evenly over the affected area.
 Should have an acceptable color and odor.
 Must remain physically and chemically stable
 Free from contamination during storage

114. Methods Of Preparation
1. Trituration
Example: Calamine lotion
2. Chemical Reaction
Example: White lotion

115. Types Of Lotion According To
Use
1. Medical Lotions
A. Antiseptic and germicidal
B. As cooling and mildly anesthetic for skin irritations
Examples
Benzyl Benzoate Lotion
Benzyl Benzoate 250 mL; Triethanolamine 5 g; Oleic acid 20 g;
water 750 mL - emulsion type lotion
Use: for scabies
Calamine Lotion, USP
liquefied phenol 10 mL; Calamine lotion 990 mL to make 1000
mL
Uses: anesthetic and antiseptic
Lotio Alba; Lotio Sulfurata
Uses: for acne and antiseptic since it has sulfur

116. Example:
Calamine Lotion
Calamine 80 g
Zinc Oxide 80 g
Glycerin 20 mL
Bentonite Magma 250 mL
Calcium Hydroxide solution q.s.
to make 1000 mL
Uses: relieves itching and pain of sunburn,
insect bites
MEDICATED LOTION

117. Types Of Lotion According To
Use
2. Cosmetics Lotions - are applied to hair, scalp, face and
hands. They are common as sunscreen preparation.
Contain glycerin, perfume and preservatives.
Examples Of Medicated Lotions
1. Ammonium Lactate - Lac-Hydrin- Promotes hydration,
removal of excess keratin dry skin, hyperkeratolytic
conditions
2. Benzoyl Peroxide - Sulfoxyl Lotion - antibacterial
(Propionibacterium acnes)
3. Betamethasone Diproprionate - Diprolene - Anti-
inflammatory
4. Betamethasone Valerate- Betatrex - Anti-inflammatory
5. Calamine Lotion -Topical protectant
6. Clotrimazole - Lotrimin - dermal infections tinea pedis,
tinea cruris, and tinea corporus

118. Types Of Lotion According To
Use
7. Lindane - Kwell Lotion - Pediculicide; scabicide
(twice a week)
8. Hydrocortisone - Hytone - Adrenocortical steroid and
anti-inflammatory
9. Permethrin Rinse - Nix Crème Rinse - a synthetic
pyrethroid which is active against lice, i.e. pediculosis
10. Selenium Sulfide - Selsun and Selsun Blue - Anti-
fungal, antiseborrheic. Used principally in the
treatment of dandruff and seborrheic dermatitis
11. Urea Lotion - Ureacin 10 Lotion - Promotes
hydration and removal of excess keratin dry skin and
hyperkeratotic conditions.

119. Calamine Liniment/Lotion. Oily BPC
Calamine 50 g
Wool fat 10 g
Oleic acid 5 mL
Arachic oil 500 mL
Ca(OH)2 solution to make 1000 mL
Triturate the calamine with the wool fat, the arachis oil
and oleic acid, previously melted together. Transfer to
a suitable container, add the Ca(OH)2 solution and
shake vigorously.