Download LIQUID DOSAGE FORM

LIQUID DOSAGE FORM
T N Saifullah S
Laboratorium Teknologi Farmasi
Fakultas Farmasi UGM
Difinition
• Oral Liquids are homogeneous liquid preparations, usually consisting of a
solution, an emulsion or a suspension of one or more medicaments in a
suitable vehicle.
• All liquid dosage forms are dispersed systems in which
medical substance (the internal phase) is dispersed uniformly
though-out the external phase. Medical substances in liquid
dosage form can be in the different aggregate states: solid,
liquid and gas
CLASSIFICATION OF LIQUID ORALS
Two main types:
1.Monophasic liquids:
Solutions
Suspensions
Elixirs
Emulsions
Syrup
Liquid drops …etc
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2. Biphasic liquids:
Solution is a homogeneous mixture
composed of two or more substances. In
mixture, solute is dissolved in another
substance, known as a solvent.
Liquid dosage forms for internal use name usually mixtures
(from the Latin word of mіxturae - to mix up), the disperse
phase - water only. They are measured out to the patients
independently by spoons (table (soup)-spoon - 15 ml,
dessert-spoon - 10 ml, tea-spoon – 5ml.).
By composition
By nature of solvent.
• Simple- solutions
which include only one
substance.
• Hydrogen's
• Multiple- solutions
which include a few
ingredients.
• non-aqueous (alcoholic,
glycerin, oily).
Formulation consideration:





Solvents
Preservatives
Antioxidants
Solubilizers
Organoleptic agents etc.
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SOLVENTS
• Water
• Alcohol
• Glycerol
• Polyethylene glycol
• Propylene glycol.
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Water
• Compared to ordinary drinking water , purified water USP
is more free of solid impurities.
• When evaporated to dryness, it must not yield greater than
0.001% of residue.
• Purified water is obtained by distillation, ion-exchange
treatment, reverse osmosis and other relevant method
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PRESERVATIVES
• Preservatives are added to prevent the microbial growth
• Preservative are necessary due to chances of microbial
growth
• Raw material, processing containers & equipments, the
manufacturing environment, operators, packing materials &
the user.
• Phenol, chlorocresol, benzoic acid, etc.
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Solubilizers: Wetting Agents and Surfactants
 Wetting agents– are used in liquid dosage forms to create a homogenous
dispersion of solid particles in a liquid vehicle.
 Wetting agents are Surfactants (HLB Value 7 to 9) that when dissolved in water,
lower the contact angle and aid in spreadability of water on the particles surface
to displace the air layer at the surface and help in wetting and solubilization
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pH Modifiers and Buffering Agents
The pH– of an oral liquid formulation is a key point for API
stability, solubilization and also to prevent microbial
contamination.
Buffers are used to control pH of liquid orals. Combination of
buffers can also be used to gain a wider range of pH compared
to the individual buffer alone. Buffer selection should be
judicious to avoid incompatibility.
Suspending Agents and Viscosity-modifying Agents
Suspending agents– impart viscosity, and thus retard particle
sedimentation.
Other factors considered in the selection of the appropriate
agent include desired rheological property, suspending ability in
the system, chemical compatibility with other excipients, pH
stability, length of time to hydrate, batch-to-batch
reproducibility, and cost.
Antioxidants
Oxidation– may manifest as products with an unpleasant odor, taste, appearance,
precipitation, discoloration or even loss of activity. The oxidation of an API in an
oral liquid formulation needs to be prevented using anti-oxidents. Antioxidants act
as free radicle scavengers and terminator of chain reaction in auto oxidation
Organoleptic agents etc: colour, flavor, sweetening
agents
Sweetening
• Sugar (sucrose) or sugar substitutes (artificial sweeteners)
• One of the most popular is Sorbitol Solution USP, which contains 64% w/w sorbitol
Flavor
The flavours may be of natural origin (e.g. peppermint, lemon, herbs and spices) and
are available as oils, extracts, spirits or aqueous solutions.
Colours
• These are generally natural or synthetic watersoluble, photo-stable ingredients
that are selected according to the flavour of the preparation.
• For example, mint-flavoured formulations are commonly a green colour,
whereas in banana-flavoured solutions a yellow colour is commonly employed.
Stages of operations:
1.Tank selection
• Material of the tank must not be additive
to the product
• The shape and size of equipment must be
selected according to the batch size
• The tanks are usually constructed of
polished stainless steel of different grades
• Teflon and glass lined tank.
• Adequate clean-up procedures developed.
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2.Mixing
• Simple mixing is essential to increase flow of liquids.
• If the liquid is of high viscosity, high electrical stirrer
may be used.
• Addition of ingredients in proper order have vital
important.
• At high viscosity the chance of air entrapment.
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Air entrapment Minimize:• By reducing agitator speed
• By caring out the mixing procedure in enclosed tank under
vacuum
• The alternative procedure to the all is versator
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3. Dispersion
•
Suspensions and emulsions require considerably greater
shear forces
•
Laboratory formulation is difficult to duplicate at large
scale
•
Dispersion produced by colloidal mill or an immersion
homogenizer
•
Variety
results.
Homogenizer
of equipment should evaluated for better
Colloidal mill
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4. Filtration and clarification—
•
Filtration procedure, requires careful evaluation to ensure that pilot scale-ups
exhibit the same degree of clarity as their laboratory counterparts.
•
During the pilot run the clarity of the filtrate should be checked periodically, in
order to establish schedule for changing pads, cake, or cartridges, depending on the
type of filtration employed.
•
In filtration, filter pads are used which is made up of asbestos and cellulose.
Selection of filtration depends on
•
The product viscosity
•
Volumes
•
Rate requirement
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will
5. Transfer and filling
• Filling – important parameter in the transfer of liquids
from tank to tank and into containers.
• New batches should not be started until the previous
batches are completely filled and the tanks are emptied.
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Methods for filling of liquids:• The selection of equipment depends on
characteristic of liquid such as, viscosity,
type of packaging, surface tension.
•
Gravimetric (specific weight)
•
Volumetric (specific volume)
•
Constant volume filling
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Gravimetric
Volumetric
Containers and closures:
• Glass
• Plastic
• It is more important to store the final product in container
until its expiration.
• Most oral liquids are packed in either amber or flint glass
containers with plastic or metal caps.
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Raw materials
Weighing &
Measuring
Mixing
Distilled
water
Filling
Packing
Pilot Plant Scale-Up
Techniques for
liquid orals
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Finished
Product
storage
Quality
Assurance
Manufacturing of Monophasic liquids:
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Manufacturing of Biphasic liquids:
WATER
SURFACTANTS
OTHER
HELPING
AGENTS
PRESERVATIVES
CONTINUOUS
PHASE
DISPERSE PHASE
FOR SUSPENSION
FOR EMULSION
MIXING
GRINDING OF
DRUG &
OTHER SOLIDS
DISSOLVED
DRUG IN OIL
AQUEOUS SOLUTION
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MILLED DRUG
DRUG SOLUTION
IN OIL
Continuous
phase
Disperse
phase
PRE – MIX
OR
CRUDE DISPERSION
pHADJUSTMENT
OTHER ADDITIVES
(FLAVOURS,
COLOURING AGENT)
VOLUME ADJUSTMENT
HOMOGENIZE
FINE DISPERSE DELIVERY SYSTEM
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Test parameters for solution, emulsion and suspension
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Test parameter
Solution
Suspension Emulsion
Appearance
yes
yes
yes
Specific gravity
yes
yes
yes
Viscosity
yes
yes
yes
PH
yes
yes
yes
Content uniformity
yes
yes
yes
Sedimentation
No
yes
No
Resuspendability
No
yes
No
Particle size
No
yes
yes
Release rate/disolution
No
yes
yes
Microbial cont.
yes
yes
yes
Storage area
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Terimakasih
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