Transcript semisoliddosageform-1

OINTMENTS, CREAMS, PASTES, GELS,
Poulice and PLaster

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.
Paste
s
Ointm
ents
Cream
s
Gels/
Jelly
Poultices
Plaster
Physical properties
a) Smooth texture
b) Elegant in
appearence
c) Non dehydrating
d) Non gritty
e) Non greasy and non
staining
f) Non hygroscopic
Physiological
properties
a) Non irritating
b) Do not alter
membrane function
c) Miscible with skin
secretion
Application properties
a. Easy applicable with efficient drug release
b. High aqueous washibility
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.
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.
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.
•
•
Ointment
Creams
Pastes
Gels
Poultices
Plaster
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
(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
CLASSIFICATION OF BASES
BASES
WATER
SOLUBLE BASE
EMULSION
BASE
ABSORPTION
BASE
OLEAGINOUS
BASE
I. OLEAGINOUS BASES
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.
(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.
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.
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.
II. ABSORPTION BASE
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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.
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.
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.
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
Hydrous
Will absorb water
Will absorb water
Insoluble in water
Insoluble in water
Not washable
washable
e.g. Hydrophilic ointment
sodium lauryl sulfate 1%
steryl alcohol 25%
while petrolatum25%
PEG
12%
water 37%
emulsifying agent
emulsifying ointment
oleaginous base
aqueous phase
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.
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.
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.
EXAMPLES OF BASES
Hydrocarbons (mineral oils, petrolatums, paraffins, waxes)
Oleaginous
Animal fats/vegetable oils (castor oil, cottonseed oil, olive oil)
Bases
Synthetic esters (glyceryl monostearate, butyl stearate,
isopropyl lanolate, stearyl alcohol)
Hydrophilic petrolatum
Aquaphor
Absorption
Bases
Aquabase
Water-in-oil:
Cold Cream (Petrolatum-Rose Water Ointment)
Lanolin
Oil-in-water:
Emulsion
Bases
Hydrophilic Ointment
Velvachol
Polyethylene Glycol Ointment
Biozyme Ointment, Desenex Ointment, Whitfields Ointment
Veegum 10% Dermatological base
Veegum 5%
Thixotropic lotion
Water
Soluble
Bases
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
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
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.
Oleaginous
Ointment
Bases
Comp
osition
oleaginous
compounds
Water
Conte
nt
anhydrous
Absorption
Oint. Bases
Waterabsorption
Oil/Water
Water-miscible
Emulsion
Ointment Bases
Oint.Bases
Water soluble
Water-misicble
oleaginous
base + w/o
surfactant
oleaginous
Polyethylene
base + water (> Glycols (PEGs)
45% w/w) + o/w
surfactant (HLB
>9)
anhydrous
hydrous
anhydrous,
hydrous
Affinity hydrophobic hydrophilic
for
Water
difficult
difficult
Sprea
dability
Washa nonwashable nonwashable
bility
hydrophilic
hydrophilic
easy
moderate to easy
washable
washable
Stability
oils poor;
oils poor;
unstable,
stable
hydrocarbo hydrocarbo especially
ns better
ns better alkali soaps
and natural
colloids;
nonionics
better
Drug
solids or solids, oils, solid and solid and aqueous
Incorporatio
oils (oil
and
aqueous
solutions
n Potential
solubles
aqueous
solutions
only)
solutions
(small
(small
amounts)
amounts)
Drug
poor
poor, but > fair to good
good
Release
oleaginous
Potential*
Occlusivene
yes
yes
no
no
ss
Uses
Examples
protectants,
emollients
(+/-),
vehicles for
hydrolyzabl
e drugs
protectants, emollients,
emollients vehicles for
(+/-),
solid, liquid,
vehicles for or nonaqueous hydrolyzabl
solutions,
e drugs
solids, and
nonhydrolyzabl
e drugs
White
Hydrophilic Hydrophilic
Petrolatum, Petrolatum, Ointment,
White
Anhydrous Dermabase
Ointment
Lanolin,
™,
Aquabase Velvachol®,
™,
Unibase®
Aquaphor®,
Polysorb®
drug vehicles
PEG Ointment,
Polybase™
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
Physicochemical Factors
1
The desired release rate of the drug from the ointment base
2
The desired enhancement of the percutaneous absorption
of the drug
3
The desired occlusion of moisture from the skin by the base
4
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
5
The influence of the drug on the consistency of the ointment
base
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.
 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
stratum corneum.
through
the
1
2
Transepidermal transport means that
molecules cross the intact horny layer
stratum corneum
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.
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
 Factors concerning the nature of the drug
1. Drug concentration
2.
Percutaneous absorption
Drug partition coefficient (greater attraction to the skin
than to the vehicle)
3.
Percutaneous absorption
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 vehicle
1. Spreadability of the vehicle
Percutaneous absorption
2. Mixing with the sebum
Percutaneous absorption
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.
 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.
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
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.
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
i.
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
ii. Jellies are transparent or translucent non greasy
semisolid and contain more water than gels.
iii. Example of gelling agent; Gelatin, agar, pectin,
tragacanth form gels by this mechanism
1. (Cataplasma) It is a soft mass of vegetable constituents
or clay, usually heated before application.
2. 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.
3. After heating the preparation is spread on dressing and
applied to the affected area of the skin.
4. 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.
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.
Ingredients used in preparation of semi
solid dosage form:
Active pharmaceutical ingredients
Bases
Preservatives
Humectants
Anti oxidants
Emulsifier
Gelling agent
Permeation enhancer
Buffers
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)
Some bases , although, resist microbial attack
Commonly used preservative include:
Methyl hydroxy benzoate
Benzoic acid
To prevent hydrolysis of active ingredient.
Example : Butylated hydroxy toluene (BHT)
vitamin _E
EMULFISIERS:
QUATERNARY AMMONIUM COMPOUNDS (CETRIMIDE)
Gelling agents
 Gelling agent forms a gel dissolves in a liquid phase as a
colloid mixture that forms a weakly cohesive internal
structure.
i.
Example of gelling agent; Gelatin, agar, pectin, tragacanth
form gels by this mechanism
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.
A humectant is a hygroscopic substance . For
example glycerin
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
Methods of
preparation
PREPARATION OF SEMI SOLIDS
(Ointments, creams, pastes)
Trituration
method
Chemical
reaction
method
Ex. Ointments
creams
pastes
Ex. Ointments
creams
Fusion
method
Emulsification
method
Ex. Ointments
creams
pastes
Ex. Ointments
creams
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
• http://ijpsr.com/bft-article/recentadvances-in-semisolid-dosageform/?view=fulltext
• http://4my5151.blogspot.com/2013/12/c
hapter-6.html?m=1
• https://www.slideshare.net/mobile/rab
abambreen1/semisolid-dosage-form
• https://www.slideshare.net/mobile/doc
mano15/semi-solid-dosage-forms
FOR YOUR KIND ATTENTION