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.

44. 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
For example teeth paste

45. 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
Jellies are transparent or translucent non greasy semisolid and contain more water than gels.
Example of gelling agent; Gelatin, agar, pectin, tragacanth form gels by this mechanism

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

47. 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.

48. composition 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

49. Bases
It is one of the most important ingredient used in the formulation of semisolid dosage form
Ointments (oleaginous base, absorption base, water soluble base, water miscible base)
Cream (w/o emulsion, o/w emulsion)
Gel, should contained polymeric matrix
Plaster- should contain resin (waxy material)

50. Presevatives Some bases , although, resist microbial attack
Commonly used preservative include:
Methyl hydroxy benzoate
Benzoic acid

51. Antioxidant To prevent hydrolysis of active ingredient.
Example : Butylated hydroxy toluene (BHT)
vitamin _E

52. EMULFISIERS: Quaternary ammonium compounds (cetrimide)

53. Gelling agents
Gelling agent forms a gel dissolves in a liquid phase as a colloid mixture that forms a weakly cohesive internal structure.
Example of gelling agent; Gelatin, agar, pectin, tragacanth form gels by this mechanism

54. 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. For example – methanol.

55. Humectants
A humectant is a hygroscopic substance . For example glycerin

56. 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

57. Methods of preparation

58. 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

59. 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

61. FOR YOUR KIND ATTENTION