AKD Class notes -semi solid dosage forms.ppt

semi solid dosage form notes for B.pharm 1st year

1. Semi-solid
dosage forms

2. Semi-solid dosage forms
Semisolid dosage forms: are products which are
applied to skin or mucous membranes for a
therapeutic or protective action or cosmetic
function.
They may be medicated (containing therapeutic
agents) or non-medicated (used for their physical
effects as protectants , lubricants and emollients).

3. External
Internal
Classification of semisolid dosage forms

4. TYPES OF CONVENTIONAL SEMISOLID DOSAGE FORMS
Ointments:
Creams
Gels
Paste
Suppositories
An ointment is usually applied to a dry scaly skin.
A cream is applied to weeping or oozing surfaces

5. Semi-solid dosage forms
Site of application: they are intended for topical
application (non-invasive delivery), being applied as
follows:
oTo the skin
oPlaced on the eye surface
oUsed nasally
oIntroduced into body
cavities, eg. rectally.
Mucous
membranes

6. Ideal properties of semi-solid dosage
forms
Physical properties:
a)Smooth texture
b)Elegant in appearance
c)Non dehydrating
d)Non greasy and non
staining
e)Non hygroscopic
Application properties:
a)Easily applicable with
efficient drug release
b)High aqueous wash-ability
c) Non irritating
d) Miscible with skin secretion
e) Have low sensitization
effect

7. • It can be used externally
• Probability of side effect is less.
• Local action of the drug on affected area.
• Convenient for unconscious patient
or patient having difficulty on oral administration.
• Suitable dosage form for bitter drugs.
ADVANTAGES OF SEMI SOLID DOSAGE FORMS

8. DISADVANTAGES OF SEMI SOLID DOSAGE FORMS
• There is no dosage accuracy in this type
of dosage form
• May cause staining.
• They are bulky to handle.
• Application with finger may cause
contamination.
•Physico-chemically less stable than solid
dosage form.
• May cause irritation or allergy to some
patients

9. 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 glands ,
 sweat glands Three functional layers:
 Epidermis,
 Dermis (true skin)
 Hypodermis
(Subcutaneous fat layer).
 Blood capillaries and
nerve fibers
 Sweat glands
 Hair follicles

11. Drug permeability through skin
Possible routes of skin penetration:
Drugs can penetrate skin barrier by three routes:
- Transcellular (across cells)
- Intercellular (between cells)
- Transappendageal (via hair follicles, sweat and sebum glands).
Mechanism of drug penetration through Skin

12. Mechanism of drug penetration through Skin

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

14. 1 2
 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 The transappendageal route
seems to be most important for seems to be most important for ions ions
and large and large polar molecules which polar molecules which
hardly permeate through the hardly permeate through the
stratum corneum.stratum corneum.

15. Transepidermal transport means that molecules cross
the intact horny layer stratum corneum
The The transepidermal route :transepidermal route :

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

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

18. 1. Drug concentration Percutaneous absorption
3. Molecular weight below 800
Percutaneous absorption
4. Particle Size
Percutaneous absorption
5. Solubility in mineral oil and water
Percutaneous absorption
 Factors concerning the nature of the drug

19. 1.1. Spreadability of the vehicle
Percutaneous absorption
2. Mixing with the sebum
Percutaneous absorption
3. Hydration of the skin Percutaneous absorption

Factors concerning the nature of the vehicle

20. 1.1. The thickness stratum corneum
Percutaneous absorption
2. Multiple application dosing
Percutaneous absorption than single Application
3. Time of contact with the skin
Percutaneous absorption
4. Broken skin permit (remove of the stratum corneum)

Percutaneous absorption
 Factors concerning the condition of the skin

21. Excipients used for formulating semisolids dosage
forms
1. Active pharmaceutical ingredient API
2. Vehicle (i.e a Bases)
3. Antimicrobial preservative
4. Humectants
5. Fragrances
6. Buffers
7. Permeation enhancer

22. 1. APIs used in semi-solid formulations
2. Bases (vehicle)

23. Bases
Semisolid bases do not only act as the carriers of
the medicaments, but they also control the extent of
absorption of medicaments incorporated therin .
An ointment base should be compatible with skin,
stable, smooth, non-irritating, non-sensitizing, inert,
capable of absorbing water or other liquid
preparations, and of releasing the incorporated
medicament, readily .
A base for ophthalmic semisolids must be non-
irritating to the eye, and it should also be
sterilizable conveniently .

24. Bases
Bases may be classified in several ways but the
following classification based on composition is
generally used which are as follow:
A)Oleaginous (hydrocarbon) bases .
B)Absorption bases.
C)Emulsion bases (water-removable bases).
D)Water soluble bases .

25. Mainly ointment bases are of following types:
A. Oleaginous (hydrocarbon base).
B. Absorption bases.
C. Water removable bases.
D. Water soluble base

28. A) Oleaginous base or hydrocarbon base
These bases have following properties
a) Small amount of aqueous component can be incorporated
into these bases.
b) These bases have emollient effect.
c) These bases are difficult to wash off as these are w/o type of
bases.
d) These base do not dry out.
e) These base keep the medicament in prolonged contact with
skin.
f) These bases act as occlusive dressing.
Examples: white petrolatum
yellow petrolatum

29. White Wax 5% ________ g
White Petrolatum 95% ________ g
BASE NO. I: Oleaginous Base (White Ointment)
Procedure for Preparation:
• Melt the white wax on a hot plate. No need to heat beyond 70 - 75°C
• When the wax has completely melted, add the petrolatum and allow the entire
mixture to remain on the hot plate until liquefied.
• Following liquefication, remove from heat and allow the mixture to congeal. Stir the
mixture until it begins to congeal.

30. B) Absorption ointment 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

Eg:
1) Hydrophilic Petrolatum
2) Lanolin
These bases have following properties:
a) Useful as emollients
b) Difficult to remove from skin

31. Cholesterol 3% ________ g
Stearyl Alcohol 3% ________ g
White Wax 8% ________ g
White Petrolatum 86% ________ g
BASE NO. II: Absorption Base
Procedure for Preparation:
• Melt the stearyl alcohol, white wax, and petrolatum together on a hot plate.
• Add the cholesterol to the mixture; stir until completely dissolved.
• Remove the mixture from the hot plate and stir until congealed.

32. C) Water washable base (O/W Emulsion Base )
These bases are also called as oil in water type of
emulsion bases.
• These are water washable bases.
• Mostly these bases are preferred for cosmetic purpose.
Advantages of these base are:
a) Some medicament are more effective in these bases.
b) These bases may be diluted with water.
Example: Vanishing cream

33. Sodium Lauryl Sulfate 1.0% ________ g
Propylene Glycol (SP Gr = 1.035) 12.0% ________ g
Stearyl Alcohol 25.0% ________ g
White Petrolatum 25.0% ________ g
Purified Water 37.0% ________ g
BASE NO. III: O/W Emulsion Base (Hydrophilic Ointment)
Procedure for Preparation:
• Melt the stearyl alcohol and white petrolatum on a hot plate.
• Heat this mixture to 70°C.
• Dissolve remaining ingredients in water and heat the solution to 70° C.
• Add the oleaginous phase slowly to the aqueous phase, stirring constantly.
•Remove from heat and stir the mixture until it congeals.

34. D) Water soluble base
These bases are greaseless bases containing water soluble
constituents
Advantages of these bases are:
a) These are completely water washable.
Example: PEG
Polyethylene glycols are polymers of ethylene oxide and water represented
by the formula
HOCH
2(CH
2OCH
2)
nCH
2OH

35. Polyethylene Glycol 400 (SP Gr = 1.12) 60% ________ g
Polyethylene Glycol 3350 40% ________ g
BASE NO. IV: Water Soluble Base
Procedure for Preparation:
• Melt the PEG 400 and Carbowax 3350 on a hot plate.
• Warm the mixture to about 65°C and add polyethylene glycol.
• Remove from the hot plate and stir until congealed.

36. CLASSIFICATION OF BASESCLASSIFICATION OF BASES

37. 3. Antimicrobial preservative
Some base, although, resist microbial attack
but because of their high water content, it
require an antimicrobial preservative.
Example: Methyl hydroxyl benzoate,
Propyl- hydroxybenzoate,
Chlorocresol, metacresol
Benzoic acid.

38. 4. Humectants
They are used in semisolids to increase
solubility, skin penetration of active
ingredients and to elevate the hydration of
the skin.
Example: Poly Ethylene Glycol, Glycerol
or Sorbitol is added as humectants

39. 5. Fragrances
They are added for the patient compliance.
Examples :Lavender oil,
Rose oil,
Lemon oil,
Almond oil
6. Gelling agent
Example: Sodium alginate
7. BUFFERS: They are added to make semisolids
preparation compatible with skin, for drug stability and
drug solubility.
Example: Sodium acetate

40. Penetration enhancer works by reversibly disordering the
lamellar packing of stratum corneum, increasing the
thermodynamic activity of the drug and increasing the
amount of drug in solubilized form at the skin surface.
Example: Limonene, Geraniol
8. Permeation enhancer

41. METHOD OF PREPARATION OF OINTMENT
Preparation of ointment mainly depend on nature of
ingredients.
Ointments are mainly prepared by two general method:
• Incorporation/ Trituration/ Spatulation
• Fusion

44. Examples of medicated ointments:
•Ophthalmic ointments
•Rectal Ointment: it is used for the symptomatic
relief
Medicated ointments primarily consist of a drug
and a vehicle ( a carrier) called a base.

46. *Penetration-A weighed quantity of ointment is rubbed over
skin for a given period of time and unabsorbed ointment is collected
and weighed. The differences in weights represent the amount
absorbed.
*Rate of release of medicament-To assess rate of
release of medicament, small amount of the ointment can be placed
on the surface of nutrient agar contained in a Petri dish or alternately
in a small cup cut in the agar surface.
If the medicament is bactericidal the agar plate is previously seeded
with a suitable organism like S.aureus. After a suitable period of
incubation, the zone of inhibition is measured and correlated with the
rate of release.

48. * Absorption of medicament into blood stream
The ointment should be evaluated for the rate of absorption of drug
into the blood stream. This test can be run in-vivo only.
Definite amount of ointments should be rubbed through the skin.
Under standard conditions and medicaments are estimated in the blood
plasma or urine.
*Irritant Effect
The irritant effect can be judged to a certain extent by injecting the
ointment into thigh muscles and under the abdominal skin of rats.
Reaction are noted at intervals of 24,48,72 and 96 hours. Lesions on
cornea, iris, conjunctiva are used for judging the irritancy to the eyes.
Presence of patches on the skin within 2 weeks indicate irritancy.

49. Creams
Semisolid preparations containing one or more
medicinal agents dissolved in either an o/w or w/o
emulsion or in another type of water-washable
base.
Typically of low viscosity.
Appears “creamy white” due to the scattering of
light.
Traditionally, it is the w/o cold cream.
Currently and most commonly, it is the o/w
emulsion.

50. Oil in Water (O/W) Cream
Water in Oil (W/O) Cream

51. oil-in-water(O/W)creamswhicharecomposedof
small droplets of oil dispersed in a continuous phase.
More comfortable and cosmetically acceptable as they are
less greasy and more easily washed off using water.
Emulsifyingagentsof natural origins
(beeswax,wool alcohols, wool fat).
Emollient and creamy, white or translucent and stiff.
E.g. Vanishing Cream

52. 
water-in-oil (W/O) creams which are composed of small
droplets of water dispersed in a continuous oily phase.


More difficult to handle but many drugs which are
incorporated into creams are hydrophobic and will be
released more readily from a W/O cream than an O/W
cream.


More moisturizing as they provide an oily barrier which
reduces water loss from the stratum corneum, the
outermost layer of the skin.
e.g. Cold Cream

53. 
They gives prolong contact in their site of application
than any other pharmaceutical semi- solid dosage
forms.
Injured area can be dried quickly by creams than
other semi-solid preparations.
Non-irritating when applied to the skin.
Easily water washable. Easy to wipe away.
Less greasy compared to ointment.
Easy to spread on the skin's surface (i.e. easy to
apply).

54. Stability is not as good as ointment.
They are less hydrophobic than other semi- solid
preparation, so risk of contamination is high than
the others.

55. It should liquefy at body temperature.
Itshouldpenetratetheepidermis
Itsviscosityshouldbelowenoughtopermit
easy spreading.
It should be non-toxic.
It should be non-irritant.
It should be non-inflammatory.

56. •
pH of the cream
•
Viscosity

57. 
The pH of various formulations was determined by
using digital pH meter.


About 1gm of the cream was weighed and dissolved
in 100 ml of distilled water and stored for two hours.


The measurement of pH of each formulation was
done in triplicate and average values were
calculated.

58. 
Viscosity of the formulation was determined by
Brookfield Viscometer.


At 20 rpm at a temperature of 25
o C and the
determinations were carried out in triplicate and the
average of three readings was recorded.
Viscosity is measured in centipoises

59. Globule size
Phase separation
Moisture absorption studies
Spreadability

60. 1mlofcream wasdilutedto10ml
with glycerin.
Afewdrops ofthis were
transferredontoa glass slide and was
focused in a microscope.
By using eyepiece micrometer, the diameters of
200 particles were determined randomly.

61. The formulated cream was kept intact in a closed
container at 25 - 30
0C not exposed to light.
Phase separation was observed carefully every
24 hrs for 30 days.
Any change in phase separation was checked.

62. About 50 mg of cream was taken on a watch glass.
Abeakerwastakenwithfullofwaterand
was kept in a desiccator without adsorbents.
Watch glass with cream was introducedinto the
desiccator.
It was left for 24 hrs.

63. TheSpreadabilitywasexpressedintermsof
time in seconds.
Taketwo slides to slip offfrom the cream, placed in
between the slides, under certain load.
Lesser the time taken for separation of the two slides,
better the Spreadability.

64. Gels (jellies)
•A semisolid dispersion systems containing a gelling
agent in sufficient quantities to impart a 3-
dimensional polymeric matrix
•Provides a cooling sensation when applied to the skin
•Usually translucent and non-greasy.
•They are used for medication and lubrication.
•They are based on the use of gelling agents and such
agents may include:

65. Pastes
Pastes are basically ointments into which a high percentage of
insoluble solid (granular material in a background fluid) dispersed
in an aqueous or fatty vehicle.
They are usually prepared by incorporating solids (i.e 25-50%)
directly into a congealed system by levigation with a portion of the
base to form a paste like mass. The remainders of the base are
added with continued levigation until the solids are uniformly
dispersed in the vehicle.
Pastes are less greasy and less penetrating than ointments and do
not flow at body temperature.
Like ointments, pastes forms an unbroken, relatively water–
impermeable film, but unlike ointments the film is opaque and
therefore, an effective sun block accordingly. Skiers apply pastes
around the nose and lips to gain a dual protection.
Examples:
-Fatty pastes: e.g, zinc oxide paste
-toothpaste, mustard.