1. QUALITY CONTROL TESTS OF DIFFERENT PHARMACEUTICAL DOSAGE FORMS
Lecture (11)

2. IPQC Tests For Liquid Dosage Forms
Prof.D.M.Shinkar, Asst.Professor, KCTS R.G.S.College Of Pharmacy,Anjaneri, Nashik.

3. 1. Purified vehicle (water)
The water is filtered and purified at the plant to destroy any micro-organisms and to remove particles from the water. Water is tested frequently to ensure that it is clean and pure before the preparation.
  2. Volume in container
Ensure that the final pack contain the desired volume.

4. 3. Organoleptic properties (Appearance)
By Visual examination:
The color (by Light Transmittance Meter for syrup)
The clarity (for syrup)
The odor
The taste

5. 4. Specific gravity (for suspension & syrup)
Decrease in density indicates the presence of entrapped air.
It can be determined with density bottle or Hydrometer.
5. Rheological studies
The viscosity can be determined with Brookfield or Cone and plate Viscometers.

6. 7. Uniformity of dosage unit
6. pH determination
It can be determined with pH meter
7. Uniformity of dosage unit
Susp, emulsion in single unit container or capsule for systemic use ( )
Solution in single unit container or capsule for systemic use ( )
Solution for inhalation through nebulizer ( )
Otherwise, CU.

7. 8. Zeta potential (for suspension & emulsion)
Zeta potential has practical application in the future stability of systems containing dispersed particles since this potential governs the degree of repulsion between the adjacent similarly charged dispersed particles.

8. 9. Seal integrity
Using E-scan HVLD (high voltage leak detection) by scanning the product to detect small pinholes, micro cracks and defective seals.

9. Special Tests for Syrup 1. Sucrose concentration (66.7%, BP):
if the concentration Sucrose in the syrup is very high it may crystallize the syrup and less sucrose concentrations give favor for the microbial growth.
use HPLC and UV-spectroscopy for this purpose.
2. Physical stability:
its appearance (no crystallization and microbial growth)
Color
Odor and taste (palatable)
Solid material is completely miscible in liquid.

10. Special Tests for Elixir 1. Determination of alcohol concentration:
Elixir usually contains 5 to 40% alcohol.
By using Alcoholmeter.

11. Special Tests for Suspensions 1. Sedimentation volume (F)
It is the ratio of the ultimate volume (Vu) of the sediment to the original volume (Vo) of the suspension.
N.B.;
The F value is between the limits 0 to 1
The larger this ratio, the better is the redispersibility.
F = Vu / Vo

12. 2. Redispersibility
Redispersibility describes the ease of redispersion of the formed sediment by moderate shaking to yield a homogeneous system.
Ease of redispersion of the suspension can be determined either by:
Simple agitation of the suspension in the container.
The use of a mechanical shaking device which simulates human arm motion during the shaking process and can give more reproducible results.

13. 3. Particle size changes
Any change in the particle size of the suspension can give an indication of crystal growth.
The freeze-thaw cycling technique is applicable to stress the suspension to promote crystal growth and the particle size can be measured by using:
Microscope.
Coulter counter device .
Laser diffraction device.
Suspension must be firstly diluted and deflocculated to ensure that each individual particle is measured rather than each floccule.
This method indicates the probable future state of suspensions after long storage at room temperature.

14. Special Tests for Emulsions 1. Dilution test
This test is used to identify the emulsion type.
Take a few drops of the emulsion in a test tube and dilute it with drops of water.
If the water is distributed uniformly in the emulsion, then the emulsion is o/w type, but if the water separates out as a layer, then the emulsion is w/o type.
Special Tests for Emulsions 1. Dilution test

15. 2. Creaming, sedimentation and coalescence (separation)
It could be initiated by centrifugation at rpm at room temperature.
Creaming
The dispersed globules move upward and form a thick layer at the surface of the emulsion
It is a temporary phase because it can be re-distributed by mild shaking or stirring to get a homogeneous product.
Sedimentation
The dispersed globules move downward and form a thick layer over the bottom of the container.
Coalescence
The dispersed globules coalesce together and two separate layers of the dispersed phase and continuous phase are formed which are difficult to redisperse by shaking or stirring to get the original product.
It is more serious in comparison to creaming. And sedimentation.

16. 3. freeze-thaw cycling
As an accelerated stability testing, the emulsion is exposed to freeze-thaw cycling and visually examined for any creaming, sedimentation or coalescence.

17. IPQC Tests For Sterile Products
Parenteral products
Ophthalmic products

18. 1. Volume in container (solution)
The volume of :
one container (for > 10 ml sterile solution)
3 containers (for 3-10 m1 sterile solution)
5 containers (for < 3 m1 sterile solution)
is carefully transferred to a graduated cylinder to be measured.
For oily injections the containers are warmed to be easily transferred to a graduated cylinder before measuring the volume.
N.B.;
A certain volume excess is allowed and it ranges from 2-20% according to the volume of the injection. As volume of the injection increases, volume excess decreases.
e.g., for 1 ml injection, volume excess is 20%, and for 50 m1 injection, volume excess is 2%.

19. 2. Uniformity of dosage unit (WV or CU ?!!), (USP, BP)
Solution ?!!
Suspension, emulsion, gel ?!!
Ointment ?!!

20. 3. Sterility testing
Sterility testing is carried out by the Direct Incubation Technique.
A specified volume of the tested product is transferred aseptically to culture tubes containing a suitable culture medium.
The tubes are plugged with sterilized cotton wool and incubated for 7 days at a temperature of 30 to 35°C.
The tubes are then examined visually for turbidity which indicates microbial growth.
Thus, if the tubes remain clear, this indicates that the product is sterile.

21. 4. Pyrogen testing
Pyrogens are the metabolic products of cell wall of microorganisms. They are lipopolysaccharide in nature.
The most dangerous pyrogens are those produced by Gm -ve bacilli.
Pyrogens cause fever, anaphylactic shock and may lead to death in large doses.
Pyrogens can withstand heat, pH change and pass through many filters.

22. Pyrogen test (rabbit method) (USP,BP)
Carry out the test using a group of three rabbits.
The tested solution injected in the ear vein of the rabbit (not less than 0.5 mL/kg and not more than 10 mL/kg of body mass).
The body temperature is recorded at least 90 min before the injection of the product to be examined and continuing 3 h after the injection.
If there is any rise in temperature of O.6°C or more above the normal temperature which has been measured before injection, then the test solution is considered pyrogenic.

24. LAL (Limulus amebocyte lysate) test
Fred Bang reported in 1956 that Limulus Polyphemus, even if killed, will cause the blood of the Atlantic horseshoe crab to turn into a semi-solid mass.
LAL test is widely used for the detection and quantification of bacterial endotoxins.
Horseshoe crabs are collected and blood is removed. The blood cells are separated from the serum using centrifugation and are then placed in few distilled water, which causes them to swell and burst ("lyse"). This releases the chemicals from the inside of the cell (the "lysate"), which is then freeze-dried. To test a sample for endotoxins, it is mixed with lysate and water; endotoxins are present if coagulation occurs.

25. 5. Clarity testing It is a test for particulate matter.
The presence of particulate matter in ophthalmic preparations will be irritating to the eye.
The presence of particulate matter in parentral preparations particularly those which are given intravenously will be dangerous as they may block the blood vessels with serious results (embolism).
Sources of particulate matter include:
Raw materials
Processing equipment
Container
Environmental contamination

26. Procedure
Mix the contents of the sample by slowly inverting the container 20 times successively.
For large-volume parenterals, single unit is tested. For small-volume parenterals less than 25 mL in volume, the contents of 10 or more units is combined in a cleaned container to obtain a volume of not less than 25 mL.
Remove four portions, each of not less than 5 mL, and count the number of particles equal to or greater than 10 µm and 25 µm. Disregard the result obtained for the first portion.
Particles can be counted using Light obscuration and Microscopical methods.
The solution under test is examined visually in presence of a source of light against black & white backgrounds for the detection of light-colored and dark­-colored particles respectively.
If any particulate matter is visible (˃100 μm), the package is rejected.

27. USP & BP limits:
Light obscuration method
Microscopic method