This document discusses in-process quality control tests for pharmaceutical suspensions. Some key tests mentioned include visual inspection of appearance and purity, measuring properties like density, pH, clarity and sedimentation volume over time. Electrokinetic methods like zeta potential measurement and microscopic analysis of particle size distribution are also described. Content uniformity testing and ensuring redispersibility upon shaking are emphasized for control during production.

1. By
ADITI ROY
RAHUL BRAHMA
M.Pharm. (Sem - II)
Dept. of Pharmaceutical sciences & Technology
BIRLA INSTITUTE OF TECHNOLOGY
MESRA, RANCHI

2.  A suspension is a heterogeneous mixture in which the solute
particles do not dissolve, but get suspended throughout the
bulk of the solvent ,let floating around freely in the medium.
 A Pharmaceutical suspension is a coarse dispersion in which
internal phase (therapeutically active ingredient)is dispersed
uniformly throughout the external phase.

3. Based on general classes-
 Oral suspension (eg: Paracetamol suspension antacids,
Tetracycline)
 Externally applied suspension (eg :Calamine lotion).
 Parenteral suspension (eg: Procaine penicillin G Insulin Zinc
Suspension C)
Based on electrokinetic nature of solid particle-
 Flocculating-
 Deflocculating-

4. Based on Size of Solid Particles –
 Colloidal suspensions (< 1 micron) -Suspensions having particle sizes of
suspended solid less than about 1micron in size are called as colloidal
suspensions.
 Coarse suspensions (>1 micron) -Suspensions having particle sizes of
greater than about 1micron in diameter are called as coarse suspensions.
 Nanosuspensions- Suspensions are the biphasic colloidal dispersions of
nanosized drug particles stabilized by surfactants.
Size of the drug particles is less than 1mm.

5. Advantages-
 Suspension can improve chemical stability of certain drug. E.g. Procaine
penicillin G.
 Drug in suspension exhibits higher rate of bioavailability than other
dosage forms.
 Solution > Suspension > Capsule > Compressed Tablet > Coated tablet
¾Duration and onset of action can be controlled. E.g. Protamine Zinc-
Insulin suspension.
 Suspension can mask the unpleasant/ bitter taste of drug. E.g.
Chloramphenicol .

6. Disadvantages-
1. Physical stability , sedimentation and compaction can causes problems.
2. It is bulky sufficient care must be taken during handling and transport.
3.It is difficult to formulate.
4.Uniform and accurate dose can not be achieved unless suspension are
packed in unit dosage form.

7.  The formulation of a suspension depends on whether the
suspension is flocculated or deflocculated.
 Three approaches are commonly involved-
1. Use of structured vehicle
2. Use of controlled flocculation
3.Combination of both of the methods

8.  Structured vehicles are also called thickening or suspending
agents.
 They are aqueous solutions of natural and synthetic gums.
 These are used to increase the viscosity of the suspension.
 It is applicable only to deflocculated suspensions. E.g. methyl
cellulose, sodium carboxy methyl cellulose, acacia, gelatin
and tragacanth
 These structured vehicles entrapped the particle and reduces
the sedimentation of particles. Thus, the use of
deflocculated particles in a structure vehicle may form solid
hard cake upon long storage.

9.  Too high viscosity is not desirable as: a) It causes difficulty in
pouring and administration. b) It may affect drug absorption
since they adsorb on the surface of particle and suppress the
dissolution rate.
 Structured vehicle is not useful for Parenteral suspension
because they may create problem in syringeability due to
high viscosity.

10. Controlled flocculation of particles is obtained by adding
flocculating agents, which are:
(1) electrolCytes
(2) surfactants
(3) polymers.

11.  Wetting agents -They are added to disperse solids in continuous liquid phase.
 Flocculating agents- They are added to floc the drug particles.
 Thickeners- They are added to increase the viscosity of suspension.
 Buffers and pH adjusting agents -They are added to stabilize the suspension to
a desired pH range.
 Osmotic agents- They are added to adjust osmotic pressure comparable to
biological fluid.
 Coloring agents- They are added to impart desired color to suspension and
improve elegance.
 Preservatives They are added to prevent microbial growth.
 External liquid vehicle They are added to construct structure of the final
suspension.

12. Step 1: Suspensions are prepared by grinding (or) levigating the insoluble materials in the mortar to a smooth paste with a
vehicle containing the wetting agent.
Step 2: ƒll all soluble ingredients are dissolved in same portion of the vehicle and added to the smooth paste to step1 to get
slurry.
Step 3: The slurry is transformed to a graduated cylinder, the mortar is rinsed with successive portion of the vehicle.
Step 4:Decide whether the solids are Suspended in a structured vehicle, Flocculated ,and then suspended Add
the vehicle containing the suspending agent (or) flocculating agent.
Step 5: Make up the dispersion to the final volume . Thus suspension is prepared.

14. In Process
Quality Control
Test 0f
Suspension

15.  IPQC stands for IN PROCESS QUALITY CONTROL . These are checks that
are carried out before the manufacturing process is completed. The
function of of in-process controls is monitoring and if necessary
adaption of the manufacturing process in order to comply with the
specifications .this may include control of equipment and
environment too. In-process materials should be tested for identity,
strength, quality and purity as appropriate and approved or rejected
by the quality control unit during the production process. Rejected in-
process materials should be identified and controlled under a
quarantine system designed to prevent their use in manufacturing
.Written procedure should be established and followed that describe
the inprocess controls and tests as specified

16. 1.Visual inspection-
 With visual inspection the API and final products are carefully
examined for purity and for appearance.
 Physical appearance of products are critical for the product
acceptability to the patients.
2. Color, odour, taste-
Those are very important ipqc tests for suspension as changes in
color, odour and taste indicates chemical instability.

17.  2.Density measurement-
Density measurement is very important for suspension. Decrease in
density indicates that entrapped air is there in the structure of the
suspension.
It can be measured by hydrometer.

18. 3. Ph values-
 pH of the suspension is checked to maintain the stability as well as
formulation characteristics.
 So pH of the different vehicles, phases of suspension before and after
mixing, pH should be checked time to time to monitor optimum pH.
 It can be checked using pH meter or pH paper.
4. Clarity testing –
Clarity testing is carried out to check whether any particulate is there in
the formulation or not.

19.  This test is carried out to ensure that there will be no problem during the
suspension filling during the manufacturing process and patient handling.
6. Sedimentation volume –
The suspension formulation( 50 ml) is poured into separate measuring cylinder
100ml and sedimentation volume is read after 1,2,3, 7 days interval for 12 weeks.
Triplicate results are obtained for each preparation.
Sedimentation vol. is calculated using the formula F= Vu/Vo
Where f= sedimentation volume, Vu= ultimate vol of sediment, initial vol
of total suspension.

20.  It provides information about the settling behaviour .
 The arrangements of the vehicle and the particles structural features.
 Brookfield viscometer is used to study the viscosity of the suspension.
8.Electrokinetic method-
- Zeta potential can be measured by zeta plus and microelectrophoresis
apparatus.
-It shows stability of a disperse system by applying EMF which propels zeta
particles (+/-).
-approximately 1 ml of suspension was transferred to plastic cuvette using a
pipette and diluted with distilled water.
-25◦c and refractive index 1.33 is set.
-The zeta potential of the sample was measured on day 0,7,14, 21 and 28th day
post formulation.

21.  Determine the content of the active ingredients of each of 10 containers
taken at random using any suitable analytical method.
 The preparation complies with the test if the individual values that
obtained thus are all between 85 to 115 percent of the average value.
 The preparation fails to comply the test if any one individual lies outside
75 to 125 percent of the average value or more then one of the
individual lies outside the range 75 to 125 percent of the average value.

22.  The stability of the suspension depends on the particle size
distribution with respect to time of the dispersed phase.
 A change in particle size can be measured by microscopy or
coulter counter method.
 Photomicroscopic technique is also a important tool for this.
 By attaching polaroid camera with photo microscopes , a rapid
processing of photomicrographs of the suspension can be
achieved.

23.  If the particles in the suspension settle , they should be easily
dispersed by application of shaking. For maintaining the
consistency and stability this is a very important ipqc test.