PHARMACEUTICS

1. IN PROCESS AND FINISHED PRODUCTS QUALITY CONTROL OF
PARENTERALS & OPTHALMICS ACCORDING TO INDIAN,USP,
AND BP.
V.VIDYADHARI
SUB: QCQA
M PHARM ANALYSIS

2. CONTENTS
• INTRODUCTION
• DEFINITION
• OBJECTIVES OF IPQC
• STERILE PRODUCTS
1) PARENTERALS
2) OPTHALMICS
• IPQC & FPQC TESTS FOR PARENTERALS & OPTHALMICS.

3.  INTRODUCTION
 All Pharmaceutical Industry aims to make products with good quality so this can be done
by allowing In- Process Quality Control (IPQC) Approaches.
 The importance of IPQC is to carry out complete testing before, after and during the
manufacturing process should be done for the Products.
 The performance of such in- process quality controls should not have any negative effect
on the quality of the product or another product.
 IPQC aims to increase the assurance of batch uniformity.

4.  Definition
Def: IPQC is concerned with providing accurate, specific and definite description of the
procedures to be employed from the receipt of raw materials to the release of the finished
dosage form.
 IPQC tests are performed at regular intervals (generally each 1 hr later) during the
manufacturing process.
 These tests are varied from dosage form to dosage form.
 In process quality control is a planned system to identify the materials, equipment's,
process and operators.

5. OBJECTIVES
OF IPQC
 To optimize the whole applied technological
procedure.
 To monitor control and improve effectively the
whole applied operations at the every stage of the
finished pharmaceutical products.
 Inspection of raw material, equipment,
environment, process, testing with respect to
specification, packing and so on.
 Quality control & Process Control

6.  Sterile Products
 Sterile products are the dosage forms of therapeutic agents that are free of viable
microorganisms. Principally these include parenteral, ophthalmic and irrigational
preparations.
 Of these, parenteral products are unique dosage forms of drugs as they are injected
through the skin or mucous membranes into the internal body compartments. They must
be free from microbial contamination and from toxic compartments as well as possess an
exceptionally high level of purity.
 All components and processes involved in the preparation of these products must be
selected and designed to eliminate, as much as possible, contamination of all types,
whether physical, chemical or microbiological origin.

7.  The In-Process Quality Control system lays emphasis on the responsibility of manufacturer’s processors in
ensuring consistency in quality during all stages of production by adopting quality control tests.
 Finished product is product which has undergone all stages of production including packaging.
 Quality control test is done for finished product to check the integrity of these products. Different
pharmacopoeia gives specific limits according to the regulatory requirements of that particular region.
 There are two types of sterile dosage forms
1. Parenteral preparations.
2. Ophthalmic formulations.

8.  Parenterals.
 Term derived from Greek words “Para” outside & “Enteron” intestine.
 Parenterals are sterile solution/suspension of drug in aqueous or oily vehicle.
 Parenteral drugs are administered directly into the veins, muscles or under the skin, or
more specialized tissues such as the spinal cord.
 Parenteral preparations are supplied in glass , plastic container and prefilled syringes
with closures are made up of plastic or elastomer.
 Categories of parenteral preparations: 1) Injections or infusions 2)Concentrates for
injections or infusions 3) Powders for injection or infusions 4) Gels for injections
5) Implants.

9.  Opthalmics
 These are the sterile liquids, semisolids or solid preparations intended for administration upon the
eyeball and/or conjunctiva in the conjunctival sac.
 Categories of ophthalmics:
 Eye drops
 Eye lotions
 Powder for eye drops
 Powders for eye lotions
 Semisolids eye preparations
 Ophthalmic inserts

10. • IPQC & FPQC Tests For Parenterals.
 The In-process quality control test includes the leakage and clarity testing. The quality
control of finished product required the pyrogen and sterility testing.
 These are of 5 types:
 Leakage Test
i) Dye Bath Test.
 Clarity Test
 Pyrogen Test
i) Limulus Amoebocyte Lysate (LAL) Test.
 Sterility Test
i) Membrane Filtration Method
ii) Direct Inoculation Method
 Content Uniformity & Weight

11. 1. Leakage Test
 Leakage test is employed to test the package integrity.
 Package integrity reflects its ability to keep the product in and to keep potential contamination out”.
 It is because leakage occurs when a discontinuity exists in the wall of a package that can allow the
passage of gas under pressure or concentration differential existing across the wall.
 Leakage test can be done by dye bath test.
 Dye Bath Test
• The test container is immersed in a dye bath. Vacuum and pressure is applied for some time. The container
is removed from the dye bath and washed.
• The container is then inspected for the presence of dye either visually or by means of UV spectroscopy

12.  The dye used may be of blue, green, yellowish-green color. The dye test can be optimized by use of a
surfactant and or a low viscosity fluid in the dye solution to increase the capillary migration through the
pores.
 The dye test is widely accepted in industry and is approved in drug use.
 The test is inexpensive and is requires no special equipment required for visual dye detection.
 However, the test is qualitative, destructive and slow. The test is used for ampoules and vials.

13. 2. Clarity Test
 Clarity testing is carried out to check the particulate matter in the sample. In this test
transparent particles or white particles observed against the black background and the
black or dark particles observed against the white background.
 Particulate matter is defined as unwanted mobile insoluble matter other than gas bubble
present in the product.
 If the particle size of foreign matter is larger than the size of R.B.C.. It can block the
blood vessel.
 The permit limits of particulate matter as per I.P. are follows:

14.  Particulate matter can be detected in parenteral product by two methods, including visual inspection and
electronic particulate counting.
a. Visual methods
b. Visual inspection by naked eye
c. Automated visual inspection

15. 3. Pyrogen Test
 Pyrogens are fever producing metabolic products of micro organisms.
 The presence of pyrogens in parenteral preparations is evaluated by a qualitative fever response test in
rabbits.
 Test for pyrogens can be carried out by in-vitro and in-vivo methods.
 A) Rabbit test (in-vivo)
 B) LAL test (Limulus amoebocyte lysate) (in-vitro)

16.  Limulus Amoebocyte Lysate (LAL) Test.
 The LAL Assay is an in vitro assay used to detect the presence and concentration of bacterial
endotoxins in drugs and biological products.
 Endotoxins, which are a type of pyrogen, are lipopolysaccharides present in the cell walls of
gram-negative bacteria.
 This test is based upon the gelling property of an enzyme, the limulus amebocyte lysate extracted
from the horse shoe crab.
Principle:
 The addition of a test solution containing of endotoxin to a solution of lysate produce turbidity or
precipitation. The rate of reaction depends on the concentration of the endotoxin .

17. Interpretati
on of
results.
 Into each test tubes dispense a volume appropriate to chosen receptacle
of positive control, negative control and test solution
 Add to each test tube equal volume of the appropriately constituted lysate.
 Place and incubate at 37± 10c for 1 hr.
 The preparation or substance being examined complies with pyrogen test
if result of the positive product control is positive and negative product
control is negative.
 LAL test is cheaper, quicker and more accurate than other tests.

19. 4. Sterility Test
 The tests for sterility are intended for detecting the presence of viable microorganism in pharmaceutical preparation that is designed to be
sterile.
 The test is based on the principle that if micro-organism are placed in a medium that provide optimum condition of nutrition, moisture , they can
grow and their presence will be indicated by the presence of turbidity in clear medium.
 Test for sterility may be carried out by one of the following two methods.
1. Membrane Filtration Method
2. Direct Inoculation Method
Media Used :
1. Fluid thioglycollate medium
2. Soya bean casein digest medium

20. 1. Membrane Filtration Method
Parenteral preparation
membrane filter ( having a nominal size of 0.45 µ and diameter of 47 mm )
The solution to be examined can be introduced and filtered under aseptic
conditions.
Cut aseptically the filter paper in to two halves
Transfer one of the parts to each type of culture media meant for the growth of the bacteria and incubate under prescribed
conditions 30 to 35°C for not less than 7 days.
The another halve is transferred to 100 ml of culture medium meant for fungi and incubated at 20 - 25 o C for not less
than 7 days

21. 2. Direct Inoculation Method
In this method, the test sample is added directly into a measured quantity of a suitable culture medium.
The culture is incubated at appropriate temperature for not less than 14 days.
The culture medium is observed at periodic intervals during the incubation period and at the end to detect
presence of any microbial growth.

22.  IPQC Tests For Opthalmics
 Evaluation of the ophthalmic product is done by following tests :
• 1. Sterility Test.
• 2. Clarity Test.
• 3. Leaker Test.
• 4. Metal particles in ophthalmic ointment.

23. 1. Sterility Test
I. Direct Inoculation Method
It involves the direct introduction of product test samples into the culture media.
II. Membrane filtration Method
It involves filtering test sample through membrane filter, washing the filter with fluid to
remove inhibitory property and transferring the membrane aseptically to appropriate culture
media.
Detection of contamination used to two culture media : -
A) Soyabean-casein digest medium :- Incubated at 20 to 25⁰C
B) fluid thioglycolate medium :- Incubated at 30 to 35⁰C on 7 days

25. 2. CLARITY TEST
 Visual Inspection :
Under a good light, baffled against reflection into the eye and viewed against a black and white
background with contact set in motion with swilling action.
 Instrumental method :
It is utilizing the principle of light scattering, light absorption and electrical resistance to obtain
particle count and size distribution – destruction of product units only for quality control testing.
Instrumental method utilizing video image projection detects moving particles without destruction of
product units used for detection.

26. 3. Leaker Test
 Select 10 tubes of the ointment with seals applied when specified.
 Thoroughly clean and dry the exterior surfaces of each tube with an absorbent cloth.
 Place the tubes in horizontal position on a sheet of absorbent blotting paper in an oven maintained at
temperature of 60 + 3 for 8 hours.
 No significant leakage occurs during or at the completion of the test.
 If leakage is observed from one, but more than one of the tubes repeat the test with 20 additional tubes of
the ointment.
 The requirement is met if no leakage is observed from the first 10 tubes tested or if leakage is observed from
not more than one of 30 tubes tested.

27. 4. Metal Particles In Opthalmic Ointment
 Extrude as completely as practicable the content of 10 tubes individually into separate, clear, flat-bottom,
60-mm petridishes that are free from scratches.
 Cover the dishes and heat at 85⁰c for 2 hours, increasing the temperature slightly if necessary to ensure
that a fully fluid state is obtained.
 Taking precautions against disturbing the melted sample, allow each to cool to room temperature and to
solidify.
 Remove the covers and invert each Petri dish n the stage of suitable microscope adjusted to furnish 30
times magnification and equipped with an eye pieces micrometer disk that has been calibrated at the
magnification being used.
 Examine the entire bottom of the Petri dish for metal particles.

28. Contd….
 Count the number of metal particles that are 50µm on larger in any dimension. The requirements are met
if the total number of such particles in all 10 tubes does not exceed 50 and if not more than 1 tube is found
to count more than 8 such particles.
 If these results are not obtained, repeat the test on 20 additional tubes.

29. REFERENCES
• International Journal of Pharmaceutical Sciences -
In-Process and Finished Products Quality Control
Tests for Sterile and Non Sterile Dosage Form
(Research Article).
• IP 2007 VOL-1. Pg. No: 42-57.
• Lachman& Liberman – Theory and Practice of
Industrial Pharmacy.
• https://www.slideshare.//evaluation of ophthalmic
preparation.