1. OINTMENTS, CREAMS, PASTES, GELS, Poulice and PLaster
Semi solid dosage
form
OINTMENTS, CREAMS, PASTES, GELS, Poulice and PLaster

2. Definition
Definition: Semi solid pharmaceutical system comprise a body of product ,which when applied to skin or accessible mucous membranes tends to alleviate or treat a pathological condition or other protection against harmful environment.
Gels/
Jelly
Creams
Ointments
Pastes
Plaster
Poultices

3. Physiological properties
Ideal properties of
Semi solid dosage form
Physical properties
Physiological properties
Non irritating
Do not alter membrane function
Miscible with skin secretion
Smooth texture
Elegant in appearence
Non dehydrating
Non gritty
Non greasy and non staining
Non hygroscopic
Application properties
Easy applicable with efficient drug release
High aqueous washibility

4. composition
They contain one or more active ingredients dissolved or uniformly dispersed in a suitable base and any suitable excipients such as emulsifiers, viscosity increasing agents, anti microbial agents, antioxidents, or stabilizing agents.

5. Advantage of semi-solid dosage form:
It is used externally
Probability of side effect can be reduce
Local action
First pass gut and hepatic metabolism is avoided.
Patient compliance is increased, the drug termination is problematic cases is facilitated as compared with other routes of drug administration.

6. Disadvantages of semi-solid dosage form:
There is no dosage accuracy in this type of dosage form
The base which is used in the semi-solid dosage form can be easily oxidized.
If we go out after using semi-solid dosage form problems can occur.

7. Classification (types)
Ointment
Creams
Pastes
Gels
Poultices
Plaster

8. Ointments
Ointments are homogenous, translucent, viscous, semi solid preparation intended for external application to skin or mucous membranes. Ointment may be medicated or not..
Applied to mucous membrane or skin
Uses
Emollient
Application for active ingredients to the skin
Occlusive

9. OINTMENTS (cont.)
Ointment Bases are classified based on their composition and physical Characteristics.
are classified based on their water solubility
Hydrophobic ointment
Hydophilic ointment
Water-emulsifying ointment
Oleaginous Bases
Absorption Bases
Water-Removable Bases
Water-Soluble Bases
are classified based on their therapeutic activity and penetration to skin
Epidermic ointment
Endodermic ointment
Diadermic ointment

10. CLASSIFICATION OF BASES
WATER SOLUBLE BASE
EMULSION base
ABSORPTION BASE
Oleaginous base
CLASSIFICATION OF BASES

11. I. OLEAGINOUS BASES (a) Petrolatum (Soft paraffin)
These bases consists of oils and fats (hydrophobic). The most important are the Hydrocarbons i.e. petrolatum, paraffins and mineral oils.
The combination of these materials can produce a product of desired melting point and viscosity.
They ae highly compatible, occlusive and good emollients
(a) Petrolatum (Soft paraffin)
This is a purified mixture of semi-solid hydrocarbons obtained from petroleum or heavy lubricating oil.
Yellow soft paraffin (Petrolatum; Petroleum jelly)
This a purified mixture of semisolid hydrocarbons obtained from petroleum.
It may contain suitable stabilizers like, antioxidants e.g. a-tocopherol (Vitamin E), butylated hydroxy toluene (BHT) etc. Melting range : 38 to 560C.
White soft paraffin (White petroleum jelly, White petrolatum)
This a purified mixture of semisolid hydrocarbons obtained from petroleum, and wholly or partially decolorized by percolating the yellow soft paraffin through freshly burned bone black or adsorptive clays. Melting range : 38 to 560C.

12. (b) Hard paraffin (Paraffin)
This is a mixture of solid hydrocarbons obtained from petroleum.
It is colorless or white, odorless, translucent, wax-like substance. It solidifies between 50 and 570C and is used to stiffen ointment bases.
(c) Liquid paraffin (Liquid petrolatum,; White mineral oil)
It is a mixture of liquid , hydrocarbons obtained from petroleum. It is transparent, colourless, odourless, viscous liquid.
On long storage it may oxidize to produce peroxides and therefore, it may contain tocopherol as antioxidants.
It is used along with hard paraffin and soft paraffin to get a desired consistency of the ointment. Tubes for eye, rectal and nasal ointments have nozzles with narrow orifices through which it is difficult to expel very viscous ointments without the risk of bursting the tube. To facilitate the extrusion upto 25% of the base may be replaced by liquid paraffins.

13. Advantages of hydrocarbons bases:
(i)     They are not absorbed by the skin. They remain on the surface as an occlusive layer that restricts the loss of moisture hence, keeps the skin soft.
(ii)   They are sticky hence ensures prolonged contact between skin and medicament.
(iii) They are almost inert. They consist largely of saturated hydrocarbons, therefore, very few incompatibilities and little tendency of rancidity are there.
(iv)  They can withstand heat sterilization, hence, sterile ophthalmic ointments can be prepared with it.
(v)   They are readily available and cheap.

14. Disadvantages of hydrocarbon bases;
(i)     It may lead to water logging followed by maceration of the skin if applied for a prolonged period.
(ii)   It retains body heat, which may produce an uncomfortable feeling of warmth.
(iii) They are immiscible with water; as a result rubbing onto the surface and removal after treatment both are difficult.
(iv)  they are sticky, hence makes application unpleasant and leads to contamination of clothes.
(v)   Water absorption capacity is very low, hence, these bases are poor in absorbing exudate from moist lesions.

15. II. ABSORPTION BASE
The term absorption base is used to denote the water absorbing or emulsifying property of these bases and not to describe their action on the skin.
These bases (some times called emulsifiable ointment bases) are generally anhydrous water insoluble and water unwashable.
        Preparations of this type do not contain water as a component of their basic formula but if water is incorporated a W/O emulsion results.
Wool Fat (anhydrous lanolin)
It is the purified anhydrous fat like substance obtained from the wool of sheep.
·      

16.   It is practically insoluble in water but can absorb water upto 50% of its own weight. Therefore it is used in ointments the proportion of water or aqueous liquids to be incorporated in hydrocarbon base is too large.
·        Due to its sticky nature it is not used alone but is used along with other bases in the preparation of a number of ointments.
e.g. Simple ointment B.P. contains 5% and the B.P. eye ointment base contains 10% woolfat.
Hydrous Wool Fat (Lanolin)
·        It is a mixture of 70 % w/w wool fat and 30 % w/w purified water. It is a w/o emulsion. Aqueous liquids can be emulsified with it.
·        It is used alone as an emollient.
·        Example:- Hydrous Wool Fat Ointment B.P.C
Beeswax
It is purified wax, obtained from honey comb of bees.
It contains small amount of cholesterol. It is of two types: (a) yellow beeswax and (b) white beeswax.

17. Advantages of absorption bases:
(i)      They are less occlusive nevertheless, are good emollient.
(ii)   They assist oil soluble medicaments to penetrate the skin.
(iii) They are easier to spread.
(iv)  They are compatible with majority of the medicaments.
(v)   They are relatively heat stable.
(vi)  The base may be used in their anhydrous form or in emulsified form.
(vii)They can absorb a large quantity of water or aqueous substances.
Disadvantages: 
Inspite of their hydrophilic nature, absorption bases are difficult to wash.

18. III. Water removable base A-WATER MISCIBLE BASES Emulsion Base)
1-They are miscible with an excess of water. 2-Ointments made from water-miscible bases are easily removed after use. 3-O/w emulsion 4- can be diluted with water 5- can be used to absorbed exudate (discharge) from skin lesion. There are three official anhydrous water-miscible ointment bases:-
Example:-           
Emulsifying ointment B.P.   - contains anionic emulsifier.
Cetrimide emulsifying ointment B.P.      - contains cationic emulsifier
Cetomacrogol emulsifying ointment B.P.      - contains non-ionic emulsifier
W/O EMULSION BASE
O/W EMULSION BASE
Hydrous
Will absorb water
Insoluble in water
Not washable
washable

19. Advantages of water miscible bases:
e.g. Hydrophilic ointment
sodium lauryl sulfate 1% emulsifying agent
steryl alcohol 25% emulsifying ointment
while petrolatum 25% oleaginous base
PEG 12% aqueous phase water 37% aqueous phase
Advantages of water miscible bases:
(i)     Readily miscible with the exudates from lesions.
(ii)   Reduced interference with normal skin function.
(iii) Good contact with the skin, because of their surfactant content.
(iv)  High cosmetic acceptability, hence there is less likelihood of the patients discontinuing treatment.
(v)   Easy removal from the hair.

20. B. WATER SOLUBLE BASES
Water soluble bases contain only the water soluble ingredients and not the fats or other greasy substances, hence, they are known as grease-less bases.
Water soluble bases consists of water  soluble ingredients such as polyethylene glycol polymers (PEG) which are popularly known as “carbowaxes” and commercially known as “macrogols”. Unlike water miscible ointment contain no olegenous baase Like water miscible ointment are washable Water soluble, water washable non greasable
The PEGs are mixtures of polycondensation products of ethylene and water and they are described by numbers representing their average molecular weights. Like the paraffin hydrocarbons they vary in consistency from viscous liquids to waxy solids.
Example:-
               Macrogols 200, 300, 400              - viscous liquids
               Macrogols 1500                            - greasy semi-solids
               Macrogols 1540, 3000, 4000, 6000  - waxy solids.
Different PEGs are mixed to get an ointment of desired consistency.

21. Advantages of PEGs as ointment base:
(a)    They are water soluble; hence, very easily can be removed from the skin and readily miscible with tissue exudates.
(b)   Helps in good absorption by the skin.
(c)    Good solvent properties. Some water-soluble dermatological drugs,
such as salicylic acid, sulfonamides, sulfur etc. are soluble in this bases.
(d)   Non-greasy.
(e)    They do not hydrolyze, rancidify or support microbial growth.
(f)    Compatibility with many dermatological medicaments.
Disadvantages:
(a)    Limited uptake of water. Macrogols dissolve when the proportion of water
reaches about 5%.
(b)   Reduction in activity of certain antibacterial agents, e.g. phenols,
hydroxybenzoates and quaternary compounds.
(c)    Solvent action on polyethylene and bakelite containers and closures.

22. EXAMPLES of bases Oleaginous Bases Absorption Bases Emulsion Bases
Hydrocarbons (mineral oils, petrolatums, paraffins, waxes)
Animal fats/vegetable oils (castor oil, cottonseed oil, olive oil)
Synthetic esters (glyceryl monostearate, butyl stearate,
isopropyl lanolate, stearyl alcohol)
Hydrophilic petrolatum
Aquaphor
Aquabase
Water-in-oil:
Cold Cream (Petrolatum-Rose Water Ointment)
Lanolin
Oil-in-water:
Hydrophilic Ointment
Velvachol
Polyethylene Glycol Ointment
Biozyme Ointment, Desenex Ointment, Whitfields Ointment
Veegum 10% Dermatological base
Veegum 5% Thixotropic lotion
Oleaginous Bases
Absorption Bases
Emulsion Bases
Water Soluble Bases

23. Ointment Bases are classified based on their composition and physical Characteristics.
Oleaginous Bases
Absorption Bases
Water-Removable Bases
Water-Soluble Bases
are classified based on their water solubility
Hydrophobic ointment
Hydophilic ointment
Water-emulsifying ointment
are classified based on their therapeutic activity and penetration to skin
Epidermic ointment
Endodermic ointment
Diadermic ointment

24. Ointment further classified based on their water solubility
Hydrophobic ointments: oleaginous base (hydrocarbon)
Hydrophobic (lipophilic) ointments are usually anhydrous and can absorb only small amounts of water. Typical bases used for their formulation are water-insoluble hydrocarbons such as hard, soft and liquid paraffin, vegetable oil, animal fats, waxes, synthetic glycerides and polyalkylsiloxanes.
Water-emulsifying ointments: w/o emulsion – water absorption base
o/w emulsion- water miscible base
Water-emulsifying ointments can absorb large amounts of water. They typically consist of a hydrophobic fatty base in which a w/o agent, such as wool fat, wool alcohols, sorbitan esters, mono glycerides, or fatty alcohols can be incorporated to render them hydrophilic. They may also be w/o emulsions that allow additional quantities of aqueous solutions to be incorporated. Such ointments are used especially when formulating aqueous liquids or solutions.
Hydrophilic ointments: water soluble base (PEG-macrogol)
Hydrophilic ointment bases are miscible with water. The bases are usually mixture of liquid and solid polyethylene glycols (macrogols)

25. Classification of ointments According to their therapeutic properties
based on penetration of skin.
(a) Epidermic, (b) Endodermic, (c) Diadermic
(a) Epidermic ointments
These ointments are intended to produce their action on the surface of the skin and produce local effect.
They are not absorbed.
They acts as protectives, antiseptics and parasiticides.
(b) Endodermic ointments
These ointments are intended to release the medicaments that penetrate into the skin. They are partially absorbed and acts as emollients, stimulants and local irritants.
(c) Diadermic ointments
These ointments are intended to release the medicaments that pass through the skin and produce systemic effects.

26. anhydrous hydrophobic
Oleaginous Ointment Bases
Absorption Oint. Bases
Water-absorption
Oil/Water Emulsion Oint.Bases
Water-misicble
Water-miscible Ointment Bases
Water soluble
Composition
oleaginous compounds
oleaginous base + w/o surfactant
oleaginous base + water (> 45% w/w) + o/w surfactant (HLB >9)
Polyethylene Glycols (PEGs)
Water Content
anhydrous
hydrous
anhydrous, hydrous
Affinity for Water
hydrophobic
hydrophilic
Spreadability
difficult
easy
moderate to easy
Washability
nonwashable
washable

27. oils poor; hydrocarbons better
Stability
oils poor; hydrocarbons better
unstable, especially alkali soaps and natural colloids; nonionics better
stable
Drug Incorporation Potential
solids or oils (oil solubles only)
solids, oils, and aqueous solutions (small amounts)
solid and aqueous solutions (small amounts)
solid and aqueous solutions
Drug Release Potential*
poor
poor, but > oleaginous
fair to good
good
Occlusiveness
yes no

28. protectants, emollients (+/-), vehicles for hydrolyzable drugs
Uses
protectants, emollients (+/-), vehicles for hydrolyzable drugs
protectants, emollients (+/-), vehicles for aqueous solutions, solids, and non-hydrolyzable drugs
emollients, vehicles for solid, liquid, or non-hydrolyzable drugs
drug vehicles
Examples
White Petrolatum, White Ointment
Hydrophilic Petrolatum, Anhydrous Lanolin, Aquabase™, Aquaphor®, Polysorb®
Hydrophilic Ointment, Dermabase™, Velvachol®, Unibase®
PEG Ointment, Polybase™

29. 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

30. 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

32. 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.

33. 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

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

35. *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 (Transcellular) pathways, whereas lipophilic drugs traverse the stratum corneum via the intercellular route.

36. 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

37. 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

38. 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.

39. 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.
D = Membrane Diffusion coefficient for drug in stratum
corneum.
Cs = Concentration difference of solute across the
membrane.
E = Thickness of stratum corneum.

40. 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)

41. creams
Creams are homogeneous, semi-solid preparations consisting of opaque emulsion systems.
Consistency depends on the type of emulsion whether the cream is W/O or O/W, and on the nature of the solids in the internal phase. Creams are intended for the application to the skin or certain mucous membranes for protective, therapeutic, or prophylactic purposes, especially where an occlusive effect is not necessary.
W/O Creams
O/W Creams
Contain lipophyllic emulsifying agent
Contains O/W emulsifying agent
Used as emollient or as cleansing agent
O/W creams are elegant drug delivery system

43. Pastes
are homogeneous, semi-solid preparations containing high concentrations of insoluble powdered substances (usually not less than 20%) dispersed in a suitable base.
The pastes are usually less greasy, more absorptive, and stiffer in consistency than ointments because of the large quantity of powdered ingredients present. Some pastes consist of a single phase, such as hydrated pectin, and others consist of a thick, rigid material that does not flow at body temperature
They have good adhesion on skin and less greasy. .
Thus when protective, rather than therapeutic action is desired, the formulation pharmacists will favor a paste, but when therapeutic action is required, he will prefer ointments and creams..

44. Gels and Jellies
Gels are semi solid system in which liquid phase is constrained
With a 3-d polymeric matrix having a high degree of physical
Or chemical cross linking by means of gelling agent
Gels are aqueous colloidal system of hydrated forms of insoluble medicaments.
Jellies are transparent or translucent non greasy semisolid and contain more water than gels.
Used for medication, lubrication and carrier for spermicidal agents to be used intra vaginally with diaphragm.

45. Types of gel-PHASE Single Phase
Gels in which the macromolecules are uniformly distributed throughout a liquid with no apparent boundaries between the dispersed macromolecules and the liquid
Usually involve organics
Two Phase(Domain)
When the gel mass consists of floccules of small distinct particles
Usually involve inorganics

46. Hydrophobic gels: Hydrophobic gel (oleogel) bases usually consist of liquid paraffin with polyethylene or fatty oils gelled with colloidal silica or aluminium or zinc soaps.
Hydrophilic gels: Hydrophilic gels (hydrogel) bases usually consist of water, glycerol, or propylene glycol gelled with suitable agents such as tragacanth, starch, cellulose derivatives, carboxyvinyl polymers, and magnesium aluminium silicates.

47. With a reduction of kinetic energy or thermal agitation.
Gel Composition
Gelation
Gelling agent
Water
Cosolvents
Preservatives
Stabilizers
As a hot, colloidal dispersion of gelatin cools, the gelatin macromolecules lose kinetic energy.
With a reduction of kinetic energy or thermal agitation.
Gelatin, agar, pectin, Irish moss, pectin, tragacanth form gels by this mechanism.
Kinds of Gels
Hydrogels
Silica, bentonite, pectin, sodium alginate, methylcellulose, alumina
Organic Gels
Contain an organic liquid (e.g., Plastibase)
Carbomer Gels
Aqueous dispersion neutralized with sodium hydroxide or triethanolamine
Methylcellulose Gels
Starch Glycerite
Aluminum Hydroxide Gel

48. Poultices
(Cataplasma) It is a soft mass of vegetable constituents or clay, usually heated before application
They are solid masses of solid matter applied to skin in order to
Reduce inflammation and in some cases to act as a counter irritant.
Poultices must retain heat for a considerable time.
After heating the preparation is spread on dressing and applied to the affected area .
. Kaolin poultice BP is prepared by mixing and heating dried, heavy kaolin and boric acid with glycerin. After cooling, the aromatic substances are incorporated with stirring. The product is spread on a dressing and applied hot to the skin.

49. Plasters
Plasters are solid or semi solid masses made by incorporating medicaments in the resinous or waxy bases which are melted or spread on suitable baking material..
They are generally used to,
Afford protection and medicinal support.
Furnish on occlusive and mecerating action.
Bring medication in to close contact with the surface of skin.

51. tHird lecture

52. Formulation of semi solid dosage form
Ingredients used in preparation of semi solid dosage form:
Active pharmaceutical ingredients
Bases
Preservatives
Humectants
Anti oxidants
Emulsifier
Gelling agent
Permeation enhancer
Buffers

53. Bases
It is one of the most important ingredient used in the formulation of semisolid dosage form
Ointments and suppository base do not merely acts as the carrier of the medicaments, but they also control the extent of absorption of medicaments incorporated with them

54. Presevatives
Some bases , although, resist microbial attack but because of their high water content, it require an anti microbial preservative.
Commonly used preservative include:
Methyl hydroxy benzoate
Propyl hydroxy benzoate
Chlorocresol
Benzoic acid
Phenyl mercuric nitrate

55. Antioxidant
Oxygen is highly reactive atom that is capable of becoming of potentially damaging molecules commonly called “free radicals”.
Free radicals are capable of attacking the healthy cells of the body, causing them to loose their structure and functions
To prevent this an anti oxidant are added.
Example : Butylated hydroxy anisole , Butylated hydroxy toluene

56. CLASSIFICATION OF ANTIOXIDANT
ANTIOXIGENS
REDUCING AGENT
ANTIOXIDANT
SYNERGIST
Acts by reacting with the free radicals.
e.g.
Butylated hydroxy anisole (BHA)
Butylated hydroxy tocopherols (BHT)
(used for oil system)
Have lower redox potential than drug,hence gets oxidized first.
Ascorbic acid
Potassium and sodium metabisulfite
Thiosulfite
(used for aqueous system)
Chelating or sequestering agents, enhance the effect of anti oxidants.
Citric acid
Tartaric acid
Lacithin

57. EMULFISIERS Anionic Cationic Non ionic Alkyl sulphates Soaps
D odecyl benzene
Sulfonates
Lactylates
Sulfosuccinates
Monoglycerides
Phosphate esters
Silicones
Taurates
Quaternary ammonium compounds
alkoxyalkylamines
Polyoxyethylene
Alkyl-aryl ethers
Polyoxy ethylene
Sorbitan esters
Sorbitan fatty acid esters
Glyceryl fatty acid esters

58. Gelling agents
Gelling agent forms a gel dissolves in a liquid phase as a colloid mixture that forms a weakly cohesive internal structure.
These are organic hydro colloids or hydro phillic inorganic substances.
Example : tragacanth, sodium alginate, pectin, gelatin, cellulose derivatives.
Material %
Brook field viscosity
Carbomer 94 1 resin NF
0.15
2900
Carbomer resin NF
0.25
6300
Guar gum
1.50
8040
Methyl cellulose
2.00
5200
Sodium alginate
2.50
10400

59. Permeation enhancer
Skin can acts as a barrier with the introduction of various panetration enhancers, panetration of the drug through the skin can be improved.
Permeation enhancer
Drug used
Methanol,carvacrol,
linalool
Propranolol hydrochloride
Limonene
Indomethacin , ketoprofin
Geraniol
Nerolidol
Diclofenic sodium
Oleic acid
Piroxicam

60. Emulsifier Anionic Cationic Non ionic Alkyl sulphates Soaps
D odecyl benzene
Sulfonates
Lactylates
Sulfosuccinates
Monoglycerides
Phosphate esters
Silicones
Taurates
Quaternary ammonium compounds
alkoxyalkylamines
Polyoxyethylene
Alkyl-aryl ethers
Polyoxy ethylene
Sorbitan esters
Sorbitan fatty acid esters
Glyceryl fatty acid esters

61. Humectants
A humectant is a hygroscopic substance . It is often a molecule with several hydrophilic groups, most often hydroxl group.
Humectants are used to:
Increase the solubility of active ingredients
To elevate its skin preparation
Elevate the hydration of the skin.

62. Buffers Buffers are added to variopus purpose such as:
Compatibility with skin
Drug solubility
Drug Stability
Influence on ionization of drug
Example: Sodium acetate , Sodium Citrate , Potassium meta phosphate

63. Vehicles Purified water Water for Injection
Water for injection may be used in ophthalmic semi solid preparation like eye ointments , gels etc

64. Preservative

65. Methods of preparation

66. PREPARATION OF SEMI SOLIDS
(Ointments, creams, pastes)
Trituration method
Chemical reaction method
Ex. Ointments
creams
pastes
Ex. Ointments
creams
Emulsification method
Fusion method
Ex. Ointments
creams
pastes
Ex. Ointments
creams

67. A well-made ointment is -
(a) Uniform throughout i.e. it contains no lumps of separated high melting point ingredients of the base, there is no tendency for liquid constituents to separate and insoluble powders are evenly dispersed.
(b) Free from grittiness, i.e. insoluble powders are finely subdivided and large lumps of particles are absent. Methods of preparation must satisfy this criteria.
Two mixing techniques are frequently used in making ointments:
1. Fusion, in which ingredients are melted together and stirred to ensure homogeneity.
2. Trituration, in which finely-subdivided insoluble medicaments are evenly distributed by grinding with a small amount of the base or one of its ingredients followed by dilution with gradually increasing amounts of the base.

68. 1. Ointments prepared by Fusion method:
When an ointment base contain a number of solid ingredients such as white beeswax, cetyl alcohol, stearyl alcohol, stearic acid, hard paraffin, etc. as components of the base, it is required to melted them. The melting can be done in two methods:
Method-I
The components are melted in the decreasing order of their melting point i.e. the higher m.p. substance should be melted first, the substances with next melting point and so on. The medicament is added slowly in the melted ingredients and stirred thoroughly until the mass cools down and homogeneous product is formed.

69. Advantages: Cautions:
This will avoid over-heating of substances having low melting point.
Method-II
All the components are taken in subdivided state and melted together.
The maximum temperature reached is lower than Method-I, and less time was taken possibly due to the solvent action of the lower melting point substances on the rest of the ingredients.
Cautions:
(i) Melting time is shortened by grating waxy components (i.e. beeswax, wool alcohols, hard-paraffin, higher fatty alcohols and emulsifying waxes) by stirring during melting and by lowering the dish as far as possible into the water bath so that the maximum surface area is heated.

70. (ii) The surface of some ingredients discolors due to oxidation e. g
(ii) The surface of some ingredients discolors due to oxidation e.g. wool fats and wool alcohols and this discolored layers should be removed before use.
(iii) After melting, the ingredients should be stirred until the ointment is cool, taking care not to cause localized cooling, e.g. by using a cold spatula or stirrer, placing the dish on a cold surface (e.g. a plastic bench top) or transferring to a cold container before the ointment has fully set. If these precautions are ignored, hard lumps may separate.
(iv) Vigorous-stirring, after the ointment has begun to thicken, causes excessive aeration and should be avoided.
(v) Because of their greasy nature, many constituents of ointment bases pickup dirt during storage, which can be seen after melting. This is removed from the melt by allowing it to sediment and decanting the supernatant, or by passage through muslin supported by a warm strainer. In both instances the clarified liquid is collected in another hot basin.
(vi) If the product is granular after cooling, due to separation of high m.p. constituents, it should be remelted, using the minimum of heat, and again stirred and cooled.

71. dissolve oil soluble drug add small volume phase in large volume phase
Fusion method
Grate the waxy base
melt using water bath
high m.p base 1st
mix low m.p in it
melt base together
dissolve oil soluble drug
add small volume phase in large volume phase
cooling unde stirring
soft mass of 40⁰ c
homogenization
filling

72. 2. OINTMENT PREPARED BY TRITURATION
This method is applicable in the base or a liquid present in small amount.
(i)     Solids are finely powdered are passed through a sieve (# 250, # 180, #125).
(ii)   The powder is taken on an ointment-slab and triturated with a small amount of the base. A steel spatula with long, broad blade is used. To this additional quantities of the base are incorporated and triturated until the medicament is mixed with the base.
(iii) Finally liquid ingredients are incorporated. To avoid loss from splashing, a small volume of liquid is poured into a depression in the ointment an thoroughly incorporated before more is added in the same way. Splashing is more easily controlled in a mortar than on a tile.
Example:
(i) Whitfield ointment (Compound benzoic acid ointment B.P.C.)
(ii) Salicylic acid sulphur ointment B.P.C.

73. Trituration Method SIZE REDUCTION LEVIGATION MIXING WITH BASE
SPATULATION OR TRITURATION
MIXING BASE TO PRODUCE FINAL WEIGHT
HOMOGENIZATION
FILLING

74. 3. OINTMENT PREPARATION BY CHEMICAL REACTION
Chemical reactions were involved in the preparation of several famous ointments of the past, e.g. Strong Mercuric Nitrate Ointment, of the 1959 B.P.C.
(a) Ointment containing free iodine
Iodine is only slightly soluble in most fats and oils but readily soluble.
Iodine is readily soluble in concentrated solution of potassium iodide due to the formation of molecular complexes KI.I2, KI.2I2, KI.3I2 etc.
These solutions may be incorporated in absorption-type ointment bases.
e.g. Strong Iodine Ointment B.Vet.C (British Veterinary Pharmacopoeia) is used to treat ringworm in cattle. It contains free iodine. At one time this type of ointments were used as counter-irritants in the treatment of human rheumatic diseases but they were not popular because: They stain the skin a deep red color.

75. (i)     Due to improper storage the water dries up and the iodine crystals irritate the skin, hence glycerol was some times added to dissolve the iodine-potassium iodide complex instead of water.
Example: Strong Iodine Ointment B. Vet.C.
                              Iodine
                              Woolfat
                              Yellow soft paraffin
                              Potassium iodide
                              Water
Procedure:
(i)     KI is dissolved in water. I2 is dissolved in it.
(ii)   Woolfat and yellow soft paraffin are melted together over water bath. Melted mass is cooled to about 400C.
(iii) I2 solution is added to the melted mass in small quantities at a time with continuos stirring until a uniform mass is obtained.
(iv)  It is cooled to room temperature and packed.
Use: - Ringworm in cattle.

77. Fourth lecture

78. MANUFACTURE OF OINTMENTS / CREAMS IN INDUSTRIAL SCALE PREPARATION OF OIL AND AQUEOUS PHASES

79. The components of the oil mixtures are placed into a stainless steel steam jacketed kettle, melted and mixed.
Some of the solid components e.g. stearic acid, cetyl alchol are available in many different forms like cakes, flakes or powder. The flakes are more preferable because of the convenience of handling.
Petrolatum is inconvenient to handle unless it is melted and transferred by pumping or pouring from its drum.
The oil phase is then strained through several layers of cheese cloth to remove any foreign matter.
If petrolatum is used as oil phase then it should be passed through filter medium particularly in ophthalmic preparations.
The oil phase is transferred by gravity or pump to the emulsion mixing kettle.
The components of the aqueous phase are dissolved in the purified water and filtered, A soluble drug may be added to this aqueous phase.

80. 1 2 3 MIXING OF PHASES Ways of Mixing the Phase
The phases are usually mixed at a temperature of 70 to 720C,because at this temperature intimate mixing of the liquid phases can occur.
The properties of some emulsions depend on the temperature at which the phases are mixed. The initial mixing temperature must be raised above 70 to 72 0C.
Simultaneous blending of the phases
Addition of the discontinuous phase to the continuous phase
Addition of the continuous phase to the discontinuous phase 1
Ways of
Mixing
the Phase 2 3

81. MIXING OF PHASES (cont.)
The simultaneous blending of the phases requires the use of a proportioning pump and a continuous mixer.
This method is used for continuous or large batch operation.
The second method is used for emulsion systems that have a low volume of dispersed phase.
The third process is preferred for many emulsion systems.

82. Equipments used for mixing of phases
Agitator mixers
Sigma mixer and planetary mixer
Shear mixers
Triple roller mill and Colloidal mill

83. Sigma blade mixer:
The mechanism of mixing is shearing. The sigma shaped blades creates high shear. Advantages: 1.It creates a minimum dead space during mixing. 2.It is used for wet granulation process. Disadvantages: 1.It works at a fixed speed.

84. Colloidal mill:
It consists of two steel discs. Here one disc rotates and another one is stationary. When the material is passed through these discs they get sheared. Thus coarse particles are break down to small particles due to shear. Advantages: 1.It can be used in the production of sterile products. Disadvantages: 1.It is not used for dry milling. 2.Heat is generated during milling.

86. STORAGE CONDITIONS OF SEMISOLIDS

87. STORAGE OF SEMI-SOLIDS
Unless rapid in process methods of analysis are developed, it is the usual practice to store the semisolid until the specified quality control tests have been completed before packaging into appropriate.
containers: tubes, jars, or single dose packets.
A product is considered to be in process until it has been packaged.
The active substance in the cream or ointment may react with the storage container unless a Highly resistant, stainless steel, is used for bulk storage.
Evaporation of water from a cream must be retarded; this can be effectively accomplished by placing non-reactive plastic sheeting in direct contact with the cream, as well as covering the storage container with a tight-fitting stainless steel lid.

88. TRANSFER OF MATERIAL FOR PACKAGING
The semi-solid may be gravity fed, if it is a two-Level operation or pumped to the filling equipment.
It must be able to resist the shear stress developed in the transfer of the product, as well as that due to the mechanical action of the filling equipment.
Once a formal manufacturing procedure has been established, there should be no deviation from it.
The manufacturing and packaging equipment should be sanitized following thorough cleaning with detergents.
They should be flushed with chlorinated water, formalin, or other suitable sterilant followed by a bacteria-free water rinse.
Water and swab samples should be taken to verify microbial elimination.

89. The ointments should remain stable from the time of preparation to the time when the whole of it is consumed by the user.
(i) To stop microbial growth preservatives are added. Preservatives for ointment includes : p-hydroxy benzoates, phenol, benzoic acid, sorbic acid, methyl paraben, propyl paraben, quaternary ammonium compounds, mercury compounds etc.
(ii) The preservatives should not react with any of the component of the formulation. Plastic containers may absorb the preservative and thereby decreasing the concentration of preservative available for killing the bacteria.
(iii) Some ingredients like wool fat and wool alcohols are susceptible to oxidation. Therefore, a suitable antioxidant may be incorporated to protect the active ingredients from oxidation.
(iv) Incompatible drugs, emulsifying agents and preservatives must be avoided. The drugs which are likely to hydrolyze must be dispensed in an anhydrous base.
(v) Humectants such as, glycerin, propylene glycol and sorbitol may be added to prevent the loss of moisture from the preparation.
(vi) Ointment must be stored at an optimum temperature otherwise separation of phases may take place in the emulsified products which may be very difficult to remix to get a uniform product.

90. Label Protect from moisture.
For emulsified systems, temperature extremes can lead to physical instability of the preparation. When this is the case products should be clearly labeled to specify appropriate storage conditions.
Ointments typically are packaged either in ointment jars or ointment tubes. Ointment jars are often used for more viscous ointments that do not require sterility.
Ointment tubes typically are used for less viscous ointments and those such as ophthalmic ointments that require the maintenance of sterility.
The package sizes for ophthalmic preparations are controlled to minimize the likelihood of contamination and loss of sterility

91. REFRENCES Remington: The Science and Practice of Pharmacy
Pharmaceutics: The Science of Dosage Form Design by Aulton
Ansel's Pharmaceutical Dosage Forms and Drug Delivery Systems

93. FOR YOUR KIND ATTENTION