1. SEMISOLID DOSAGE FORMS

2. SEMISOLID DOSAGE FORMS
Include drug delivery systems and dosage forms intended to be applied to the skin.
Ointments
Pastes
Creams
Gels

3. Preparations are applied to the skin for: Physical effects
skin protection, lubricants, emollients, drying agents
Medical effects
Treatment of skin conditions (non-systemic topical effect)
as skin infections, itching, burns, diaper rash, insect stings and bites, corns, calluses, warts, dandruff, acne, psoriasis, and eczema.
Systemic effect

4. The Skin The skin has a wide variety of functions:
Protect the organism from water loss and
mechanical, chemical, microbial, and physical
influences.

5. Structure of the Skin
The skin is the largest human organ and is composed of:
A film of emulsified material present upon the surface of
the skin composed of a complex mixture of sebum, sweat
Blood capillaries and
nerve fibers
Sweat glands
Hair follicles
Three functional layers:
Epidermis,
Dermis (true skin)
Hypodermis
(Subcutaneous fat layer).

6. The epidermis is the outermost layer of the skin
0.02 to 5 mm thickness
It has five layers,
Horny layer
(stratum corneum)
The uppermost layer
Composed of dead epidermal cells forms the permeability barrier
Barrier layer (stratum germinativum)
Beneath the hornylayer
Composed of living epidermal cells

7. The stratum corneum consists of:
Horny skin cells (corneocytes) which are connected via protein-rich attachments of the cell membrane
The corneocytes are embedded in a lipid matrix in “Brick and mortar” structure.
The corneocytes of hydrated keratin comprise the bricks and the epidermal lipids fill the space between the dead cells like mortar

8. Routes of skin Penetration
There are two diffusional routes to penetrate intact skin:
The Transappendageal route: 1 2
Include transport via:
1- Hair follicles and sebaceous
glands
2- Sweat glands
These routes avoid penetration through the stratum corneum and therefore known as shunt routes.

9. Although these routes offer high permeability, they are of
minor importance because of their relatively small area,
0.1% of the total skin area.
The transappendageal route seems to be most important for ions and large polar molecules which hardly permeate through the stratum corneum. 1 2

10. The transepidermal route :
Transepidermal transport means that molecules cross the intact horny layer

11. *The intercellular pathways
Two potential micro-routes are existing
*The transcellular (intracellular) rout
*The intercellular pathways
The principal pathway taken by drugs is decided by its partition coefficient
Hydrophilic drugs partition into the intracellular pathways, whereas lipophilic drugs traverse the stratum corneum via the intercellular route.

12. Factors Affecting Percutaneous Absorption
Percutaneous absorption is the absorption of substances from outside the skin to positions beneath the skin, including entrance into the blood stream.
Factors concerning the nature of the drug
Factors concerning the nature of the vehicle
Factors concerning the condition of the skin

13. 1. Drug concentration Percutaneous absorption
Drug partition coefficient (greater attraction to the skin
than to the vehicle) Percutaneous absorption
Molecular weight below 800
Percutaneous absorption
Particle Size
Solubility in mineral oil and water
Factors concerning the nature of the drug

14. Factors concerning the nature of the vehicle
1. Spreadability of the vehicle
Percutaneous absorption
2. Mixing with the sebum
3. Hydration of the skin Percutaneous absorption
Oleaginous vehicles act as moisture barriers through which the sweat from the skin cannot pass, thus increased hydration of the skin beneath the vehicle and increase Percutaneous absorption.

15. Factors concerning the condition of the skin
Transdermal absorption follow Fick’s First Law of Diffusion
Js = Km D Cs E
Js = Flux of solute through the skin
Km = Distribution coefficient of drug between vehicle and
stratum corneum
Cs = Concentration difference of solute across the
membrane
D = Membrane Diffusion coefficient for drug in stratum
corneum
E = Thickness of stratum corneum

16. 1. The thickness stratum corneum
Percutaneous absorption
Multiple application dosing
Percutaneous absorption than single Application
Time of contact with the skin
Broken skin permit (remove of the stratum corneum)

17. Percutaneous Absorption Enhancers
Mechanisms of action by which Materials enhance absorption through stratum corneum is either by
Enhancing drug release from the formulation to the skin
Reduction of the resistance of the stratum corneum by
altering it physicochemical properties

18. Alteration of the hydration of the stratum
This can be achieved by the following mechanisms:
Alteration of the hydration of the stratum
corneum using occlusive formulations
Carrier mechanisms in the transport of ionisable
drugs
Enhance absorption by directly influencing
the stratum corneum
(CHEMICALLY or PHYSICALLY)

19. Chemicals used to enhance absorption by directly influencing the stratum corneum
Chemicals interact with the keratin structure in the stratum
corneum and open the tight protein structure, this leads
increase the diffusion coefficient D for substances which use
the transcellular route:
Surfactants, Dimethylsulfoxide (DMSO) and Urea
Solvents extract lipids and making the stratum corneum more
permeable: Dimethylsulfoxide (DMSO) and Ethanol

20. Chemical enhancers which intercalate into the structured
lipids of the horny layer and disrupt the packing. Thus
make the regular structure more fluid and increases the
diffusion coefficient of drugs:
Azone, Oleic acid, and isopropyl myristate
Solvents increase solubility and improve partitioning:
Alcohol, acetone, polyethylene and propylene glycol

21. Ointments
Ointments are semisolid preparations intended for external application.
Ointments may be medicated or non-medicated
Non-medicated ointment bases used for their emollient, lubricating effect or as vehicles in the preparation of medicated ointments

22. Ointment Bases Ointment bases are classified into 4 groups:
Hydrocarbon bases (Oleaginous Base)
Absorption bases
Water-removable bases
Water ­soluble bases

23. Hydrocarbon bases (oleaginous bases)
Water-free
Difficult to wash off
Aqueous preparations are difficult to be
incorporated into them
Used as occlusive dressings for their emollient effect
(helps the skin retain moisture)
It can treat diaper rash (protect skin from
urine) and dry skin (retain moisture)
Stable, don’t dry upon aging

24. Petrolatum (Soft Paraffin) Yellow Petrolatum (Vaseline)
Mixture of semisolid hydrocarbons obtained from petroleum.
Melts at temperatures between 38° and 60°C
Form an ointment-like gel with Polyethylene (PLASTIBASE) which is compatible with most medicaments.
White Petrolatum (White Vaseline)
Decolorized petrolatum
More esthetically acceptable to patients than petrolatum.

25. Yellow Ointment (Simple Ointment)
Contains 5% of yellow wax and 95 % of petrolatum.
Yellow Wax, is the purified wax obtained from the honey
White Ointment (Simple Ointment)
Contains 5% of White wax and 95 % of White petrolatum

26. Absorption Bases
An absorption base is an oleaginous base that permit the
incorporation of aqueous solutions, and can be used as
emollients
Like the oleaginous bases,
Absorption bases are not water washable
They can incorporate 50% of their volume water,
where aqueous solution first incorporated into the
absorption base, then added into the oleaginous base

27. There are two types of absorption bases:
1) Contains a w/o emulsifying agent:
When water is taken up into the base, it will form a w/o
emulsion
(e.g. Hydrophilic Petrolatum and Anhydrous Lanolin)
2) Water-in-oil emulsions (emulsion bases) that permit the
incorporation of small, additional quantities of aqueous
solutions
(e.g. Lanolin and Cold cream)

28. Hydrophilic Petrolatum (Aquaphor)
Hydrophilic Petrolatum is composed of 3% cholesterol, 3% stearyl alcohol, 8% white wax, and 86% white petrolatum.
It has the ability to absorb water (upto 3 times its weight), with formation of water-in-oil emulsion W/O

29. Anhydrous Lanolin (Wool Fat)
It is insoluble in water, but mixes without separation with water twice its weight of water with the formation of a water­in-oil emulsion
Lanolin (Hydrous Wool Fat)
Obtained from the wool of sheep
It is a water-in-oil emulsion W/O that contains between 25 and 30% water Additional water may be incorporated into lanolin by mixing

30. Water-Removable Bases
oil-in-water emulsions
Oil in Water emulsions
Have the general formula: 30 % Emulsifying wax
50 % White soft Paraffin
20 % Liquid Paraffin
Water washable
They can be diluted with water or with aqueous
solutions. “water-loving “
They have the ability to absorb serous discharges
in dermatologic conditions

31. Hydrophilic Ointment Have the general formula: emulsifying agent 1 %
1 %
Sodium Lauryl Sulfate
emulsifying agent
25 %
Stearyl Alcohol
  oleaginous phase
White Petrolatum
  aqueous phase
12 %
Propylene Glycol
aqueous phase
37 %
Purified Water
Methyl and propyl parabens are used as preservatives

32. Water-Soluble Bases (greaseless bases)
Unlike water-removable bases,
which contain both water-soluble and water-insoluble
components, water-soluble bases contain only water­soluble
components with the absence of any oleaginous materials
Like water-removable bases,
They are water washable
Because they soften greatly with the addition of water, aqueous solutions are not preferred to be incorporated into these bases. They are better used for the incorporation of nonaqueous or solid substances

33. Polyethylene Glycol Ointments
Polyethylene glycols are polymers of ethylene oxide and water represented by the formula
HOCH2(CH2OCH2)nCH2OH
The chain length varied to achieve polymers with different physical form (liquid, semisolid, or solid).

34. AVERAGE MOLECULAR WEIGHT Clear viscous colorless liquid
MOISTURE CONTENT MAX.
HYDROXYL VALUE
MELTING POINT
AVERAGE MOLECULAR WEIGHT PH
APPEARANCE AT 25° C
PEG
1.0%
<65°C
Clear viscous colorless liquid
PEG-200
<15°C
PEG-300
4-8°C
PEG-400
15-17°C
PEG-600
37-38°C
White waxy solid
PEG-1000
70-90
44-45°C
PEG-1500
50-70
45-46°C
White flakes
PEG-2000
30-36
53-56 °C
PEG-4000
16-20
55-63 °C
PEG-6000

35. Preparation of polyethylene glycol ointment base:
Combine polyethylene glycol 3350 (solid) %
and polyethylene glycol 400 (liquid) %
If an aqueous solution is to be incorporated into the base, substitution some of polyethylene glycol 3350 with an equal amount of stearyl alcohol would be advantageous to render the final product more firm.

36. ABSORPTION OINTMENT BASES Drug Incorporation Potential
WATER-SOLUBLE
OINTMENT BASES
WATER-REMOVABLE
ABSORPTION OINTMENT BASES
OLEAINOUS G
Polyethylene Glycols (PEGs)
Oleaginous base + Water (> 45%) + O/W surfac. (HLB >9)
Oleaginous bases +
w/o surfactant
Oleaginous compounds
Composition
anhydrous, hydrous
hydrous
anhydrous
Anhydrous
Water Content
hydrophilic
Hydrophobic
Affinity for Water
moderate to easy
easy
difficult
Spreadability
washable
non-washable
Washability
stable
unstable
oils poor; hydrocarbons better
Stability
Solid
Aqueous solutions
Non-aqueous solutions
Aqueous solutions (small amounts)
Solids
Oils
Oils (oil soluble drugs)
Drug Incorporation Potential

37. ABSORPTION OINTMENT BASES
WATER-SOLUBLE
OINTMENT BASES
WATER-REMOVABLE
ABSORPTION OINTMENT BASES
OLEAGINOUS
Continue 
good
fair to good
poor
but > oleaginous
Drug Release no
yes
Occlusiveness
Drug vehicles
Emollients
Vehicles for solid, liquid, or non-hydrolyzable drugs
Protectants
Vehicles for
aqueous
solutions, solids,
and non
hydrolyzable
drugs
Vehicles for hydrolysable drugs
Uses
PEG Ointment
Hydrophilic Ointment
Hydrophilic
Petrolatum
(Aquaphor®),
Anhydrous
Lanolin
Yellow
White
Ointment
Examples

38. Selection of the Appropriate Base
The selection of the base of an ointment depends on many factors:
Patient Factors
The condition of the patient's skin, e.g. oozing or dry
The rule in dermatology that
if a patient's skin is dry-wet it, If it is wet-dry it
if a patient's skin is dry, occlusive ointment base that retain moisture is preferable

39. Physicochemical Factors1
The desired release rate of the drug from the ointment base
The desired enhancement of the percutaneous absorption
of the drug
The desired occlusion of moisture from the skin by the base
The stability of the drug in the ointment base, for a drug that
hydrolyzes rapidly as antibiotics, a hydrocarbon base would
provide the greatest stability
The influence of the drug on the consistency of the ointment
base 2 3 4 5

40. 6 7 8 The influence of the drug on the consistency of the ointment
base
The desired washability of the base as for application to
hairy regions, a Polyethylene Glycol base is preferred
For ophthalmic ointments, non-irritant bases are desired.
Absorption O/W emulsion bases and water soluble bases
are irritants due to the effect of the surfactants in the base
It is preferred to use yellow paraffin but not white due to the
irritation effect of the bleaching agents 6 7 8

41. Preparation of Ointments
depending on the nature of the ingredients ointments are prepared by two methods:
Incorporation method
Fusion method.

42. Incorporation method A- INCORPORATION OF SOLIDS:
Using the geometric dilution method
The powdered components reduced to fine powders to
prevent grittiness
Fine powdered drugs are blended
Then powder are levigated with agent that is compatible
with the base, e.g., mineral oil or glycerin
The amount of levigating agent equal to the material to be
levigated

43. Solid materials soluble in a solvent that is compatible
with the product may first be dissolved
e.g., dissolve salicylic acid crystals in alcohol
Mix with a portion of the base until the product is smooth
and uniform
Another portion of the base is added to the
mixture
The process being repeated until all of the ointment base has been incorporated

44. Ointment roller mills resulting in a products
that are smooth and uniform in composition
and texture

45. INCORPORATION OF LIQUIDS
For aqueous solutions:
Water-absorbable or hydrophilic ointment bases are suitable
In oleaginous ointment base, a portion of the base must
be replaced with a hydrophilic base,
Incorporates the solution in it, and mixes the product
with the original base

46. For Alcoholic solutions
Oleaginous vehicles or emulsion bases are suitable
Other liquid materials as natural balsams
(Peru balsam)
It is difficult to be incorporated into ointment bases
Mix balsam with an equal portion of castor oil before
incorporating it into the base
This procedure reduces the surface tension of the balsam
and aid in distribution of the balsam through the vehicle

47. Ointment bases containing components as:
Fusion method
Ointment bases containing components as:
beeswax, paraffin, stearyl alcohol, and high molecular weight polyethylene glycols, which do not mix well by incorporation, are prepared by fusion

48. The components of an ointment are combined by being
melted together and cooled with constant stirring until
congealed
Components not melted are added to the congealing
mixture during cooling and stirring
Heat-labile and volatile substances are added when the
temperature of the mixture is low enough

49. Many substances are added to the congealing
mixture in solution, others are added as insoluble
powders levigated with a portion of the base
Once congealed, the ointment may be passed
through an ointment mill to ensure a uniform
texture

50. If the item having the highest melting point is
melted first and the other components are added to
this hot liquid, all the components will be subjected
to this high temperature, irrespective of their own
individual melting points

51. By melting the component having the lowest
melting point first and adding the components of
higher melting points in order of their individual
melting points a lower temperature is usually
sufficient to achieve fusion
*This is due to the solvent action exerted by the first
melted component on the other components

52. In the preparation of ointments having an emulsion type:
Melting process and emulsification process are used
The water­ immiscible components such as oil and
waxes are melted together in a steam bath to about
70 to 75°C
Aqueous solution of all of the heat-stable, water-soluble
components is prepared in the amount of water in the
formula and heated to the same temperature as the
oleaginous components
The aqueous solution is slowly added to the melted
oleaginous mixture, with constant stirring

53. The temperature is maintained for 5 to 10 minutes
to prevent crystallization of waxes.
Then the mixture is slowly cooled with the stirring
until congealing

54. Preservation of Ointments
Semisolid preparations as ointments especially
those utilizing bases which contain water require
the addition of antimicrobial preservatives to
inhibit the contamination
Using preservatives as p­hydroxybenzoates,
phenols, benzoic acid, sorbic acid, quaternary
ammonium salts
Ultra filtration of the vehicle and using aseptic
manufacturing processes

55. Packaging and Storage of Ointments
Semisolid preparations must be protected through proper packaging and storage from the destructive influences of air, light, moisture, and heat, and the possible chemical interactions between the preparation and the container

56. The jars Ointments are usually packaged either in jars or in tubes
May be made of Plastic or glass,
uncolored, colored green, amber, or
blue, or opaque and porcelain-white.
The jars
Opaque and colored-glass containers are useful for
ointments containing drugs that are light sensitive
Jars for ointments may vary in size from as little as 1/2 oz
to 1lb or more

57. The jars Ointment jars are filled by forcing the ointment down and
along the sides of the jar to avoid the entrapment of air
Ointments prepared by fusion may be poured directly into
the ointment jars for congealing within the jar
Most ointments must be stored at temperatures below
30°C to avoid the softening and liquefying of the base,
to prevent settling of insoluble medicaments to the bottom
of the containers
to prevent separation of emulsion
bases into two phases
The jars

58. Tubes The collapsible tubes are made of tin or plastic
Some tubes co-packaged with special tips when the
ointment is to be used for rectal, ophthalmic, vaginal or
nasal application
Tubes of ointments for topical use are of 5 g to 30 g size
Tubes of ointments for ophthalmic use are
most commonly packaged in small, tin or
plastic collapsible tubes holding about 3.5 g
of ointment

59. Tubes are filled by pressure fillers from the open back end
which is then closed and sealed
Ointments in tubes are less exposed to air and
contaminants and are more stable
than ointments packaged in jars 1 3 2