Semisolids

1. Introduction to Solid & Semisolid
preparation
By: Alemayehu L. Duga
(SCU 2016 )

2. Outline:
• Introduction to Solid & Semisolid preparation
• Types and uses of solid and semi solid dosage forms
• Methods for Preparations of various solid and semi-solid df

3. Introduction Semisolids Preparations
 Definition: products of semisolid consistency and applied to skin for:
 therapeutic
 cosmetic function
 Protection against a harmful environment
 have the property to cling to the skin or mucous membrane for a protracted period of time
 exert their therapeutic effect through protection and occlusion
 E.g. Sun screen/SPF15,30,50

4. Introduction cont…
 Semisolid dosage forms usually are intended for localized drug delivery.
 They can be applied topically to the skin, cornea, rectal tissue, nasal mucosa,
vagina, buccal tissue, external ear lining etc
 Topical preparations are used for both local and systemic effects. Systemic
drug absorption should always be considered when using topical products if
the patient is pregnant or nursing, because drugs can enter the fetal blood
supply and breast milk and be transferred to the fetus or nursing infant.

5. Cont..
Ideal Properties Of Semisolid Dosage Forms
Physical Properties: -
a) Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non staining
f) Non hygroscopic/absorbing moisture

6. Cont…
• Physiological Properties: -
g) Non irritating
h) Do not alter membrane / skin functioning
i) Miscible with skin secretion
j) Have low sensitization index

7. Classification of Semisolid dosage forms
Semisolid dosage forms include
ointments
creams
Pastes
gels…
• Ointments: semisolid preparations intended for external application to the
skin or mucous membranes
• Ointments are 80% oil and 20% water
• The semisolid vehicle into which drug substances may be incorporated in
preparing medicated ointments.

8. Cont..
 There are four types of Ointment bases :
the hydrocarbon bases/ oleaginous
the absorption bases,
the water-removable bases,
the water-soluble bases.
 Each therapeutic ointments possesses as its base a
representative of one of these four general classes

9. Cont..
Cream: dosage forms containing one or more drug substances dissolved or
dispersed in a suitable base.
 Are products consisting of oil-in-water emulsions
 aqueous microcrystalline dispersions of long-chain fatty acids or alcohols that are water
washable and more cosmetically acceptable
 spread easily, absorb quickly and wash off with water

10. Cont…
Gels: – are transparent or translucent, non-greasy, semisolid
systems generally applied externally for their medication,
lubrication and miscellaneous purposes.
Pastes: – semisolid dispersion system, where a solid
particles (> 25%, e.g. ZnO) are dispersed in ointment
bases - mostly oleaginous (Petrolatum

11. NOTE:
 Ointments promote medication absorption over all other formulations.
 If an ingredient is in an ointment, it is always more potent than the exact same
ingredient packaged in a cream or lotion.
Cream Ointment
Good for oily skin moisturizing, and good for dry skin
Couse immunological sensitization due to
preservatives
low risk of sensitization
Liked by patients disliked by patients due to greasiness
Less potent More potent
Absorbed into skin faster Takes long
Lighter consistencies, cover large area Greasier and they have thicker consistencies.

12. Uses of topical preparations
 Topical antibiotics help a damaged barrier to ward off infection
 Sunscreen agents protect the viable tissues from ultraviolet radiation;
 Emollient preparations restore pliability to a desiccated horny layer
 Directing drugs to the viable skin tissues
 Delivering drugs skin for systemic treatment
Eg., transdermal therapeutic systems provide systemic therapy for
conditions such as motion sickness, angina and pain.

13. Skin structure
Skin also known as cutaneous membrane or integument
 external membranous covering of an animal body
 The largest organ of the body, it is thin at some places (eye lids thickness =0.5
mm) where as thick at other places (sole of foot, palm of hand
thickness=5mm).
 Average thickness of skin is 1-2mm (0.04-0.08in).

14. Skin consists of three layers

15. Cont…
A. Epidermis
 The superficial, thinner portion composed of keratinized stratified squamous
epithelial tissue
 it is nourished by diffusion of nutrients from a vascular network of dermis
 Composed of four type of cells
keratinocytes Langerhans cell
Melanocyets Merkel cell

16. Cont..
Keratinocytes : keratino= horny like, cytes=cell
• 90 % of epidermal cells are keratinocytes.
• Responsible for production of keratin…a tough fibrous protein
protect the skin and underlying tissues from heat, microbes and chemical.
Melanocytes: Melano=black, cytes=cell
• 8% of epidermal cells are melanocytes.
• Produces a pigment melanin (a yellow red or black brown pigment) contribute:
in skin color
 absorbs damaging u-v light

17. Cont…
Langerhans cells
• Participate in immune responses against microbes that invade the skin
• Helps other cells of immune system to recognize an invading microbe and
destroy it.
Merkel cell
• Participate in detection of touch sensation.

18. Cont…
 Epidermis consists of different layers
a) Stratum corneum (Horney layer)
Barrier to Percutaneous absorption
b) Stratum lucidum (Barrier zone)
 Barrier to transfer of water across skin,
 damage resulted in increased permeability.
c) Stratum granulosum (Granular layer)
 Participate in keratinisation
d) Stratum spinosum
e) Stratum basale (Stratum germinativum)
 Melanocytes the pigment-producing cells of the epidermis,

19. Dermis :
 The sensitive connective tissue layer of the skin located below the epidermis,
containing nerve endings, sweat and sebaceous glands, and blood, hair
follicles, fibroblast, histocytes and lymph vessels.
• Composed of strong connective tissue containing collagen (for strength) and
elastin (for stretch )
• Play major role in temperature regulation.

20. Cont..
Hypodermis :
• Below the dermis is hypodermis also called subcutaneous layer
Sub mean under and cutaneous mean skin.
• Loose layer of connective tissue which is anchored to the underlined tissue (
muscle and bones).
• Most fat cells are present in hypodermis (adipose tissues)
 acts as insulator to protect the body from excessive heat and cold
environment

21. Cont..
Skin appendages
1.Sweat glands
 The sweat glands are coiled tubules in the dermis which open on to the skin surface; they can
be sub-divided in to two classes;
 Eccrine glands:
 The sweat glands which are involved in the regulation of body temperature by water
elimination.
 About two million eccrine sweat glands on the average human body.

22. Cont..
• Apocrine sweat glands:
 Are larger than eccrine sweat but few in number.
They are mainly located in the hairier regions of the maxillae
and around the nipples.
Apocrine sweat differs in composition from eccrine and may be
cloudy and colored

23. Cont..
2.Hair follicles
 Hair follicles are sebum-filled openings from which keratinous hair filaments
protrude.
 Follicles occupy about 0.1% of the skin surface area;
 absent from plantar and palmar surfaces, the red areas of the lips, and parts of the
genitalia.

24. Functions of skin
Containment of body fluid and tissue
Protection from external stimuli
 Microbial barrier
 Chemical barrier
 radiation barrier
Thermal barrier

25. Percutaneous absorption (Transdermal drug
delivery)
 Percutaneous absorption : the absorption of substances from outside the skin
to positions beneath the skin, including entrance into the blood stream
 Drugs may penetrate intact skin after topical application through
 the walls of the hair follicles,
 the sweat glands
 the sebaceous glands,
 Trough the cells of the horny layer

26. Cont….
 The main route for the penetration of drug is generally through the epidermal
layers ( b/c of surface area )
 The stratum corneum is the outermost ‘horny’ layer of skin, comprising about
partially desiccated, dead, keratinized epidermal cells.
 It is the rate-limiting barrier to percutaneous drug transport

27. Cont…
 Transport of lipophilic drug molecules is facilitated
 by their dissolution into intercellular lipids
 Absorption of hydrophilic molecules into skin can occur through ‘pores’ or
openings of the hair follicles and sebaceous glands
 But, the relative surface area of these openings is barely 1% of the total skin
surface.
limits the amount of drug absorption

28. Cont…
Permeation of the substances in SC can occur by diffusion
via:
1.Transcellular penetration: the transportation of solutes
through a cell
2. Intercellular penetration: the transportation of solutes
between cells

29. Cont…

30. Cont…

31. Factors influencing Percutaneous absorption
I. Skin conditions
II. Physicochemical characteristics of the drug
III. Vehicles
IV. Miscellaneous Factors

32. 1. Skin conditions
a) Damage and disease
• Intact skin presents a barrier to absorption that can be reduced considerably
when the skin is damaged or is in a diseased state
• Skin can be damaged by dryness, irritation, allergic reactions or by abrasion
• Certain acids and alkalis may injure barrier cells
• In heavy industry, workers' skins may lose their reactivity or 'harden' because
of frequent contact with irritant chemicals.
• Many solvents open up the complex dense structure of the horny layer

34. Cont..
b. Age
 The skin of the young and the elderly is more permeable than adult tissue (but
little evidence for any dramatic difference).
 Children are more susceptible to the toxic effects of drugs and chemicals
partly because of their greater surface area per unit body weight
 Potent topical steroids, boric acid and hexachlorophane have produced severe
side-effects and death.
 Premature infants may be born with no stratum corneum.
 Advantageous to treat breathing difficulties with caffeine or pain with
buprenorphine, via simple topical application

35. Cont..
C. Blood flow
 Changes in the peripheral circulation could affect transdermal absorption
 An increased blood flow could raise the conc. gradient across the skin.
 Potent vasoconstricting agents, such as topical steroids, could reduce their own
clearance rate or that of another drug.
 The high blood flow the greater absorption will be

36. d. Skin metabolism
 The skin metabolizes steroid hormones, chemical carcinogens and some drugs.
 Such metabolism may determine the therapeutic efficacy of topically applied
compounds
• (particularly prodrugs)
• It has been estimated that the skin can metabolize some 5% of candidate
topical drug

37. Cont…
e. Skin hydration
 When water saturates the skin the tissue swells, softens and wrinkles
permeability increases markedly.
 The keratinized cells of the stratum corneum have the ability to hold water.
 Hydration may result from water diffusing from underlying epidermal layers
that accumulates after the application of an occlusive vehicle or dressing.
Eg. use of occlusive plastic films in topical steroid treatment (penetration
increases ten fold)

38. f. Temperature
 Absorption is influenced by environmental factors such as skin temperature
and surface humidity.
Diffusion can be accelerated by raising surface temperature.
Occlusive vehicles increase skin temperature by a few degrees, but any
consequent increased permeability is small compared to the effect of hydration.

39. g. Sex and race
 No evidence to suggest that the permeability characteristics of male and
female skin differ.
 But one study demonstrated that skin penetration may be influenced by race;
e.g Propranolol was found to be absorbed by Negroid skin at a rate that was
forty times slower than that demonstrated by Caucasian skin in vitro.
• Negroid stratum corneum has more layers
But, there is no difference in actual thickness

40. II. Physicochemical characteristics of the
drug
1. The permeability constant
 Is the product of stratum corneum / vehicle partition
coefficient and degree of diffusion of the compound in the
skin.
KmD = Permeability constant
E
 A substances that are very soluble in a particular vehicle will
tend to have a low permeability constant and will therefore be
poorly absorbed.
 Low permeability constant ~poorly absorbed

41. Cont…
2. The thermodynamic activity (Chemical potential)
 Describes the potential of substance to be absorbed; compounds diffuse from regions of high
activity to area of low activity.
 Both the permeability constant and the thermodynamic activity of an active substances are influenced by:
 Its ionization constant
 The pH of the skin
• Generally, drugs penetrate the skin better in their unionized form. Nonpolar
drugs tend to cross the cell barrier through the lipid-rich regions
(transcellular route), whereas the polar drugs favor transport between cells
(intercellular route)

42. 3. Molecular modification
 Molecular modification of active substances can have marked
effects on their activity.
 Changes in functional groups that alter the solubility and
partition coefficient of substance b/n the vehicle and skin barrier.

43. 4. Concentration
An increase in the concentration of an active substance in vehicle usually
produces an increase in the thermodynamic activity of the system and
subsequent increase in the quantity of the material absorbed.
5. Molecular size
 Molecules of small size in high concentration tend to penetrate more readily
than large molecules

44. 6. Particle size
 Particle size reduction has been used to enhance the
percutaneous absorption of poorly soluble drugs such as
hydrocortisone or hydrocortisone acetate

45. III VEHICLE
 Nature of vehicle affect release of drugs
 For most drugs the rate limiting factor for penetration of skin is diffusion
through skin
 Certain steroids(very low solubility), rate limiting is release of the drug from vesicles
Nature of vehicle affect:
- diffusion coefficient
- partition coefficient
 Substances that have high affinity for vehicle exhibit low thermodynamic
activity…released slowly

46. IV. Miscellaneous Factors
Site of application
Time of contact
 Amount of preparation employed
 State of ionization
 pH of applied preparation
 pH of Skin
Molecular structure etc

47. Maximizing the bioavailability of drug to
skin
 Drug or prodrug selection
 Hydration
 Ultrasounds(phonophoresis)
 Ionophoresis
 Stratum corneum removal
 Chemical penetration enhancers

48. Chemical penetration enhancers
Materials used to enhance absorption:
 surfactants, azone, dimethylsulfoxide (DMSO), dimethylacetamide,
dimethylformamide, alcohol, acetone, propylene glycol, and polyethylene
glycol.
 Surfactants/surface-active agents/amphiphiles: are compounds with two
distinict regions in their chemical structure termed hydrophilic(water-liking)
and hydrophobic(water-hating) which have the tendency to accumulate at the
boundary between two phases. Examples: poly(oxyethylene)-
poly(oxypropylene)-poly(oxyethylene)

49. Mechanism of action for percutaneous
absorption enhancers
 Reduction of the resistance of the stratum corneum
 Alteration of the hydration of the stratum corneum
 Effecting a change in the structure of the lipids and lipoproteins in the cellular
channels, through denaturation
 Carrier mechanism in the transport of ionizable drugs

50. Iontophoresis and Sonophoresis
 Iontophoresis: the delivery of charged chemical compounds across the skin
membrane using an applied electrical field.
Eg: lidocaine, amino acids/peptides/insulin, verapamil, and propanolol
 Sonophoresis occurs because ultrasound waves stimulate micro-vibrations
within the skin epidermis and increase the overall kinetic energy of molecules
making up topical agents. Eg.: hydrocortisone, lidocaine, and salicylic acid
in such formulations as gels, creams and lotions

53. Transdermal Drug Delivery(TDD)
 TDD is the passage of therapeutic quantities of drug substances through the skin and into the
general circulation for their systemic effects.
 Examples: clonidine- Transdermal therapeutic system to deliver therapeutic dose of
antihypertensive drug at constant rate for 7 days.
 TDDS generally applied to hairless or shaven area of upper arm or torso
 Nicotine-Transdermal therapeutic systems providing continuous release, systemic delivery of
nicotine to aid smoking cessation.
 Patches vary somewhat in nicotine content and dosing schedules
 Scopolamine-Continuous release of drug over 3 days to prevent nausea and vomiting of
motion sickness. Patch is placed behind the ear. For repeated administration, first patch is
removed and second placed behind the other ear. Also approved to prevent nausea of certain
anesthetics and analgesics used in surgery

54. Advantage of TDD
 Avoids gastrointestinal drug absorption difficulties
 Substitutes for oral administration of medication when that routes is unsuitable
 Avoids first-pass effect,
 Provides the capacity for multiday therapy with a single application,
 Provides sustained and controlled administration(for chronic diseases
 Provides capacity to terminate drug effect rapidly.
 Permit self administration
 Extends the activity of drugs having short half-life through the reservoir of drug present in the
therapeutic delivery system

55. Disadvantage of TDD
 unsuitable for drugs that irritate or sensitize the skin.
 Only relative potent drugs are suitable candidates
 Technical difficulties are associated with the adhesion of the systems to
different skin types and under various environment conditions
 Poor diffusion of large molecules

58. Ointments

59. Ointments
Classification of ointments
According to their therapeutic properties based on penetration
Epidermic ointments
 Act on epidermis & produce local effect.
 Used as protectives, antiseptic,local anti-infectives & parasiticides.
Endodermic ointments
 Act on deeper layers of cutaneous tissues.
 Partially absorbed & act as a emollients, stimulants &
local irritants.
Diadermic ointments
 Meant for deep penetration and release the medicaments and produce systemic
effects.

60. Advantages
 Ointments retained at the site of application as an occlusive layer thereby
preventing moisture loss from the skin.
 useful in restoration of the physical characteristics of the skin (e.g. due to
inflammation)
 Ointments are associated with lubricating properties that may be employed to
reduce trauma of an affected site upon spreading

61. Disadvantage
 Ointments are generally greasy and difficult to remove (cosmetically
unacceptable).
 Staining of clothes is the problem
 Problematic in ensuring spreading of the dosage form
 Pharmaceutical ointments may not be applied to exuding sites
 Problems concerning drug release from pharmaceutical ointments may occur
if the drug has limited solubility in the ointment base

62. Cont..
 The formulation of ointments involves the dispersal or dissolution of the
selected therapeutic agent into an ointment base
 The physicochemical properties of the ointment base are fundamental to:
the clinical
 non-clinical performance of this type of dosage form.

63. The choice of ointment base is dependent on several factors, including:
1.Dermatological factors
Absorption and penetration
Effect on the skin
Miscibility with skin secretion
Compatibility with skin secretion
Non-irritant
Emollient property
Patient skin condition (old, baby and young)
 the site of application;

64. 2. Pharmaceutical factors
1. the required rate of drug release;
2. Chemical stability
3. the effect of the therapeutic agent on formulation
viscosity
4. Solvent properties

65. Ointment Bases
Bases play an important role in the proper formulation of
semisolid preparations,
there is no single base universally suitable as a carrier of
all drug substances or for all therapeutic indications
Semisolid vehicle for medicated ointments

66. Types of base for ointments and pastes
• There are four types of base that are used to formulate
pharmaceutical ointments and pastes:
(1) hydrocarbon;
(2) absorption;
(3) water-miscible/removable; and
(4) water-soluble.

67. Cont..
1. Hydrocarbon bases
 Oleaginous bases
 Hydrophobic
 non-aqueous formulations, emollient
 restrict water loss from the site of application
 Due to the formation of an occlusive film
 Excellent retention on the skin
 Predominantly hydrophobic
 Difficult to remove from the skin by washing
 difficult to apply to (spread over) wet surfaces (e.g. mucous membranes, wet skin)

68. Cont.…
 Small amount of water (5%) can be incorporated into it with difficulty
 Can be protective to water labile drugs such as tetracycline and bacitracin.
 Greasy and can stain clothing.
 Chemically inert

69. Cont..
Eg. of hydrocarbon bases:
1. Petrolatum, USP
 Yellow petrolatum/petrolatum jelly /Vaseline
 Melts at 38-60oC
2. White petrolatum, USP
 Decolored petrolatum,
 White petroleum jelly/white vaseline

70. Cont…
3. Yellow ointment, USP
Yellow beeswax (5% w/w) + petrolatum (95% w/w )
4. White ointment, USP
White beeswax + white petrolatum
 Hydrocarbon bases frequently contain the following components:
(1) hard paraffin;
(2) white/yellow soft paraffin; and
(3) liquid paraffin (mineral oil)

71. Cont…
Hard paraffin
• A mixture of solid saturated hydrocarbons that are derived from petroleum or
shale oil.
• a colourless or white wax-like material that is physically composed of a
mixture of microcrystal.
• The melting temperature of hard paraffin is between 47 and 65oc and,
used to enhance the rheological(The study of flow characteristics)
properties of ointment bases.

72. Cont..
White/yellow soft paraffin
• A purified mixture of semisolid hydrocarbons that are derived from petroleum.
• Consists of microcrystals embedded in a gel composed of liquid and
amorphous hydrocarbons
• White soft paraffin and yellow soft paraffin (the former being a bleached form
of yellow soft paraffin)
 used as an ointment base without the need for additional components, although it may
be combined with liquid paraffin

73. Cont..
Liquid paraffin (mineral oil, Liquid petrolatum)
 mixture of refined liquid saturated hydrocarbons obtained from petroleum
 Levigating agent to incorporate lipophilic solids
 An excipient in topical formulations where its emollient properties are
exploited
 Usually formulated with white/yellow soft paraffin
 Formulations containing liquid paraffin require the incorporation of an
antioxidant
 due to the ability of this material to undergo oxidation

74. Advantages of hydrocarbons bases
• They remain on the surface as an occlusive layer that restricts the loss of
moisture hence, keeps the skin soft.
• ensures prolonged contact between skin and medicament
• They are almost inert
• They consist largely of saturated hydrocarbons
• They can withstand heat sterilization(sterile ophthalmic ointments )
• They are readily available and cheap.

75. Disadvantages of hydrocarbon bases:
• It retains body heat, which may produce an uncomfortable
feeling of warmth.
• Rubbing onto the surface and removal after treatment are
difficult.
• Makes application unpleasant and leads to contamination
of clothes.
• Poor in absorbing exudate from moist lesion

76. 2. Absorption bases
 Absorption bases, unlike the hydrocarbon types, are hydrophilic-
absorb considerable amounts of water or aqueous solutions.
I. Non-emulsified bases
 These bases absorb water and aqueous solutions to produce water-
in- oil ( W/O ) emulsions.
Compared with the hydrocarbon bases:-
• They are less occlusive, nevertheless, are good emollients
• They assist oil-insoluble medicaments to penetrate the skin
• They are easier to spread.

77.  Typically non-emulsified bases are commonly composed of:
(1) one/more paraffins, and
(2) a sterol-based emulsifying agent.
 Examples: (1) lanolin (wool fat);
(2) wool alcohols; and
(3) beeswax (white or yellow).

78. Lanolin (wool fat)
 Lanolin is a wax-like material that is derived from sheep’s wool.
 It is available in two forms, termed
Anhydrous lanolin (wool fat) and hydrous lanolin.
Anhydrous lanolin:
called wool wax, wool fat, or wool grease,
 a greasy yellow substance
 contains < 0.25% of water

79.  Typically mixed with paraffins to produce an ointment base
 Can absorb approximately twice its own weight of water to produce water
in oil emulsions.
 The usual concentrations of lanolin used in ointments (e.g. Simple
Ointment BP) range from 5 to 10% w/w.

80. • Wool fat is a major constituent of Simple Ointment B.P and Eye Ointment
B.P
Simple ointment B.P
• Hard paraffin ………50g
• Cetosteryl alcohol….50g
• Wool fat……………..50g
• Soft paraffin……….850g
Eye Ointment B.P
Liquid paraffin…..100g
Wool fat…………100g
Yellow soft paraffin……850g

81. Wool alcohols
 A crude mixture of sterols and triterpene alcohols
 Added to mixtures of paraffins (hard, white/yellow soft or liquid) to produce the required
consistency.
 The inclusion of wool alcohols (5% w/w) results in a 300% increase in the concentration of
water
eg. wool alcohol ointment B.P contains 6% wool alcohol and hard, liquid and soft paraffin.

82. Beeswax (white or yellow)
• A wax that consists of esters of aliphatic alcohols (C24–C36) and linear
aliphatic fatty acids (up to C36) that is combined with paraffins to produce
non-emulsified bases.
 White beeswax is the bleached form of yellow beeswax.
 included in some ointment bases to increase water-absorbing power.
Eg. Paraffin ointment B.P. contains beeswax

83. II. Water in oil emulsions
These are similar in properties to the previous group and are
capable of absorbing water.
Absorption bases are less occlusive than the hydrocarbon bases
and easier to spread.
They are good emollients.
 Eg. hydrous lanolin, which is a mixture of lanolin and 25–30% water.

84. It is used alone as an emollient and is an ingredient of several
B.P ointment bases, i,e
Hydrous wool fat ointment
Calamine and coal tar ointment
Methylsalicylate ointment

85. Properties of absorption bases
• Non-emulsified absorption bases (anhydrous)
• Emollient
• Occlusive
• Absorbs water
• Greasy
• W/O emulsion
• Emollient
• Occlusive
• Contains water, absorbs additional water
• Greasy

86. 3. Water-washable/removable bases
 Water-miscible bases that are used to form O/W emulsions.
• They can be applied to scalp and other hairy regions.
• There are 3 official anhydrous water-miscible
bases.
• Emulsifying ointment B.P – anionic
• Cetrimide emulsifying ointment B.P – cationic
• Cetomacrogol emulsifying B.P- non-ionic
E.g. Compound Benzoic Acid Ointment (Whitfield’s Ointment) - used as antifungal ointment.

87. Water-washable/removable bases
• Advantages of water-miscible bases
 able to accommodate large volumes of water
 able to accommodate excess moisture
e.g. exudate from abrasions & wounds.
 Reduced interference with skin function
 easily washed from the skin and from clothing.
 readily applied to (and removed from) hair, skin. Hence High cosmetic
acceptability

88. Characteristics of water removable bases
a. Resemble creams in their appearance
b. May be diluted with water or with aqueous solution
d. Certain medicinal agents may be better absorbed in the skin
f. Water washable
h. Can absorb water
i. Non-occlusive
j. Non-greasy

89. 4.Water-soluble bases
• Completely water-soluble bases have been developed from
the Macrogols (Polyethylene glycols), a range of
compounds with the general formula:-
CH2OH.(CH2OCH2)n.CH2OH
• PEG is also known as polyethylene oxide (PEO) or
polyoxyethylene (POE)

90. • Polyethylene glycols are polymers of ethylene oxide and water
Polycondensation
C2H4O + H2O Poyethylene glycol (Macrogol )
 The chain length may be varied to achieve polymers having desired viscosity
and physical form.
 Macrogols 200,300 ,400 - Viscous liquid
 Macrogol 600- 1500 - Semi-solid
 Macrogols >1000 - waxy solids

91. Example:
• PEG ointment, NF
- PEG 3350 ………400 g
-PEG 400 ………. 600 g

92. Advantages of water- soluble bases
 Water solubility
– Easily removal from the skin
– Readily miscible with tissue exudates
 Good absorption by the skin
 valuable when drugs are required to penetrate the skin
 Good solvent properties
– For some water soluble dermatological e.g. Hydrocortisone

93. Freedom from greasiness
 Satisfactory ageing properties
• They don’t hydrolyze, rancidity or support microbial growth.
Compatibility with many dermatological medicaments
e.g. - Ammoniated mercury
- Yellow mercuric oxide

94. Disadvantages of water-soluble bases
• Less bland than paraffins/lacking strong features or characteristics
– Reduction in activity of certain antimicrobial agents, due to hydrolysis by (phenols,
hydroxybenzoates and quaternary compounds).
• Solvent action on polythene and bakelite;
– these plastics should not be used in containers or closures for macrogol ointments

95. • Inability to incorporate large volumes of aqueous solutions b/c
 Ointments will soften or
 dissolve the ointment base if the concentration of water is large enough (
5% w/w).
Its use is usually reserved for the incorporation of solid therapeutic agents.
• It may incorporate up to 25% of an aqueous solution if a portion of the lower-
molecular-weight polyethylene glycol is replaced with stearyl alcohol.
– This enhance the mechanical properties of the ointment.

96. Properties of water-soluble bases
Water soluble and washable
Non-greasy
Non/less occlusive
Lipid free
Synthetic base
Relatively inert
Does not support mold growth
Little hydrolysis, stable

97. Summary of ointment bases