Chapter 7 Semi-Solid
Chapter 7 Semi-Solid
Chapter 7 Semi-Solid
DOSAGE FORMS
OINTMENTS, CREAMS, PASTES & GELS
Topics to be Covered …
INDUSTRIAL PROCESSING
PREPARATION OF OIL AND AQUEOUS PHASES
STORAGE CONDITIONS OF SEMISOLIDS
INDUSTRIAL PROCESSING
BASIC INTRODUCTION
• 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.
Ideal properties of
Semi solid dosage form
Physical properties
a) Smooth texture
b) Elegant in appearance
c) Non dehydrating
d) Non gritty
e) Non greasy and non staining
f) Non hygroscopic
g)
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
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
Penetrometer are used to measure the consistency and viscosity of ointments.
Collapsible Tubes = the container of choice for ointments
OINTMENTS (cont.)
Ointment Bases
• Oleaginous Bases
• Absorption Bases
• Water-Removable Bases
• Water-Soluble Bases
Preparation of Ointments
• Incorporation
• Fusion method = the oil & aqueous phase are mixed at a controlled temp
range from 70-72⁰C to avoid separation of water from oil.
Compendial Requirements for Ointments
• Microbial Content
• Minimum Fill
• Packaging, Storage, and Labeling
• Additional Standards
In levigation, the suitable non-solvent added to the solid material is term as levigating agent,
example of which are mineral oil and glycerin. This is a process used to incorporate solids into
dermatological and ophthalmic ointments and suspensions
CREAMS
• Viscous semi solid emulsion with opaque appearance as
• Contrasted with translucent ointments
• Consistency depends on whether the cream is W/O or O/W
• PEG (Polyols, polyethylene glycol) is a prototype example of a water soluble base
which are use as humactants in creams
w/o creams
Contain lipophyllic emulsifying agent
Used as emollient or as cleansing agent
o/w creams
Contains O/W emulsifying agent
O/W creams are elegant drug delivery system
PASTES
Contains high percentage of insoluble solid(usually 50% or more)
Pastes are usually prepared
by incorporating solids directly into a congealed system by levigation with a portion of base
to form paste like mass.
They have good adhesion
on skin and less greasy.
GELS/JELLY
• 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
• Gels are aqueous colloidal system of hydrated forms of insoluble medicaments.
It demonstrated the characteristic of Thixotropy (shake before use – to liquify &
enable pouring)
• 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.
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
Gel Composition
• Gelling agent
• Water
• Cosolvents
• Preservatives
• Stabilizers
Gelation
• 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
FORMULATION OF SEMI-SOLIDS
Ingredients used in preparation of semi solid dosage form:
Active pharmaceutical ingredients
Bases
Preservatives
Humectants
Anti oxidants
Emulsifier
Gelling agent
Buffers
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
IDEAL PROPERTIES
• BASES
• WATER SOLUBLE BASE
• EMULSION BASE
• ABSORPTION BASE
• OLEAGINOUS BASE
EXAMPLES of bases
Oleaginous 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)
Absorption Bases
• Hydrophilic petrolatum
• Aquaphor
• Aquabase
Emulsion Bases
• Water-in-oil:
• Cold Cream (Petrolatum-Rose Water Ointment)
• Lanolin
• Oil-in-water:
• Hydrophilic Ointment
Water Soluble Bases
• Velvachol
• Polyethylene Glycol Ointment
• Biozyme Ointment, Desenex Ointment, Whitfields Ointment
• Veegum 10% Dermatological base
• Veegum 5% Thixotropic lotion
PRESERVATIVES
Preservatives are substances added to formulations to prevent the growth of bacteria, molds
and yeast therefore preventing the decomposition of deterioration of the product.
Some bases , although, resist microbial attack but because of their high water content, it
require an anti microbial preservative.
Commonly used preservative for semi-solids include:
Methyl hydroxy benzoate
Propyl hydroxy benzoate
Chorocresol
Benzoic acid
Phenyl mercuric nitrate
• Commonly used preservative in dosage forms: propylparaben, methylparaben, sod.
benzoate
ANTI-OXIDANTS
(with classification)
• 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
ANTIOXIGENS
Acts by reacting with the free radicals.
e.g.
• Butylated hydroxy anisole (BHA)
• Butylated hydroxy tocopherols (BHT)
(used for oil system)
REDUCING AGENT
Have lower redox potential than drug,hence gets oxidized first.
e.g.
• Ascorbic acid
• Potassium and sodium metabisulfite
• Thiosulfite
(used for aqueous system)
ANTIOXIDANT
SYNERGIST
Chelating or sequestering agents, enhance the effect of anti oxidants.
e.g.
• Citric acid
• Tartaric acid
• Lacithin
Humectants
A humectant is a hygroscopic substance . It is often a molecule with several hydrophilic groups,
most often hydroxyl group.
Gelling agents
Gelling agent forms a gel dissolves in a liquid phase as a colloid mixture that forms a
weakly cohesive internal structure.
EMULFISIERS
Anionic
• Alkyl sulphates
• Soaps
• D odecyl benzene
• Sulfonates
• Lactylates
• Sulfosuccinates
• Monoglycerides
• Sulfonates
• Phosphate esters
• Silicones
• Taurates
Cationic
• Quaternary ammonium compounds
• alkoxyalkylamines
Non ionic
• Polyoxyethylene
• Alkyl-aryl ethers
• Polyoxy ethylene
• Sorbitan esters
• Sorbitan fatty acid esters
• Glyceryl fatty acid esters
BUFFERS
Buffers are added to various purpose such as:
Compatibility with skin
Drug solubility
Drug Stability
Influence on ionization of drug
Example: Sodium acetate ,
Sodium Citrate ,
Potassium meta phosphate
SEMI SOLIDS
Methods of PREPARATION
(Ointments, creams, pastes)
Trituration
method Chemical reaction Fusion method Emulsification
Ex. Ointments method Ex. Ointments method
creams Ex. Ointments creams Ex. Ointments
pastes creams pastes creams
Trituration Method
• SIZE REDUCTION
• LEVIGATION
• SPATULATION OR TRITURATION
• HOMOGENIZATION
• FILLING
Fusion Method
Homogenization
Filling
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.
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.
MIXING OF PHASES
• 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.
The simultaneous blending of the phases requires the use of a proportioning pump and a
continuous mixer.
The second method is used for emulsion systems that have a low volume of dispersed
phase.
• Agitator mixers
• Shear mixers
The mechanism of mixing is shearing. The sigma shaped blades creates high shear.
Advantages:
Disadvantages:
Colloidal mill/rotostator
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.
It is used primarily to reduce the solid particle size & for dispersion of suspension containing
particles, as well as for emulsions that are too viscous.
Advantages:
Disadvantages:
Roller Mill
• It is used to reduce the particle size of powders in ointments
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.
• 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.
• 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.
• They should be flushed with chlorinated water, formalin, or other suitable sterilant
followed by a bacteria-free water rinse.
Types of Containers
1. Tight container = protects the contents from contamination by extraneous liquids, solids,
or vapors, from loss of the article, and from efflorescence, deliquescence, or evaporation
under conditions of handling, shipment, storage & distribution.
2. Hermetic container = impervious to air or any other gas under condition of handling, etc.
3. Well-closed container = protects the contents from extraneous solids & loss of article
under conditions of handling, etc.
4. Light resistant container = protects the article from phytochemical degradation.
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