1. LIQUID DOSAGE FORM T N Saifullah S
Laboratorium Teknologi Farmasi Fakultas Farmasi UGM

2. 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

3. CLASSIFICATION OF LIQUID ORALS
Two main types:
1.Monophasic liquids:
Solutions Elixirs Syrup
Liquid drops …etc
2. Biphasic liquids:
Suspensions Emulsions 3

6. Solution is a homogeneous mixture composed of two or more substances
Solution is a homogeneous mixture composed of two or more substances. In mixture, solute is dissolved in another substance, known as a solvent.

7. 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.).

8. By composition
By nature of solvent.
Simple-
solutions
Hydrogen's
non-aqueous (alcoholic, glycerin, oily).
which include only one substance.
Multiple- solutions which include a few ingredients.

9. Formulation consideration:
Solvents
Preservatives
Antioxidants
Solubilizers
Organoleptic agents etc. 9

10. SOLVENTS Water Alcohol Glycerol Polyethylene glycol Propylene glycol.10

11. 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 % of residue.
Purified water is obtained by distillation, ion-exchange treatment, reverse osmosis and other relevant method 11

12. PRESERVATIVES Preservatives are added to prevent the microbial growth
Preservative growth
are necessary due
to chances
of microbial
Raw material, processing containers & equipments, the manufacturing environment, operators, packing materials & the user.
Phenol, chlorocresol, benzoic acid, etc. 12

15. 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 15

17. 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.

18. 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.

20. 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

21. Organoleptic agents etc: colour, flavor, sweetening agents
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.

22. Stages of operations: 1.Tank selection Material of the to the product
must not
be additive •
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. 22

23. 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 important.
ingredients
in proper
order
have
vital
At high viscosity the chance of air entrapment. 23

24. 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 24

25. 3. Dispersion Suspensions and emulsions require considerably greater
shear forces
Homogenizer
Laboratory formulation is difficult to duplicate at large scale
Dispersion produced by colloidal mill or an immersion homogenizer
of equipment
should
evaluated
for better
Variety results.
Colloidal mill 25

26. 4. Filtration and clarification—
Filtration procedure, requires careful evaluation to ensure that pilot scale-ups will
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 26

27. 5. Transfer and filling
Filling – important parameter in the from tank to tank and into containers.
transfer of
liquids
New batches should not be started until the previous batches are completely filled and the tanks are emptied. 27

28. Methods for filling of liquids:-
The selection of equipment depends on characteristic of liquid such as, viscosity, type of packaging, surface tension.
Volumetric
Gravimetric (specific weight)
Gravimetric
Volumetric (specific volume)
Constant volume filling 28

29. 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. 29

30. Pilot Plant Scale-Up Techniques for liquid orals
Raw materials
Weighing & Measuring
Mixing
Distilled water
Filling
Packing
Finished Product storage
Pilot Plant Scale-Up Techniques for liquid orals
Quality Assurance 30

31. Manufacturing of Monophasic liquids:31

32. Manufacturing of Biphasic liquids:
WATER
SURFACTANTS
OTHER HELPING AGENTS
PRESERVATIVES
DISPERSE PHASE
CONTINUOUS PHASE
FOR SUSPENSION
FOR EMULSION
MIXING
GRINDING OF DRUG & OTHER SOLIDS
DISSOLVED DRUG IN OIL
AQUEOUS SOLUTION
DRUG SOLUTION IN OIL
MILLED DRUG 32

33. OTHER ADDITIVES (FLAVOURS, COLOURING AGENT)
Continuous phase
Disperse phase
PRE – MIX OR
CRUDE DISPERSION
OTHER ADDITIVES (FLAVOURS, COLOURING AGENT)
pH ADJUSTMENT
VOLUME ADJUSTMENT
HOMOGENIZE
FINE DISPERSE DELIVERY SYSTEM 33

34. Test parameters for solution, emulsion and suspension
Appearance
yes
Specific gravity
Viscosity PH
Content uniformity
Sedimentation No
Resuspendability
Particle size
Release rate/disolution
Microbial cont. 34

36. Storage area 36

37. Terimakasih
Hp:
WA: