Experience of our senior brother/sister in different pharmaceutical industries of Bangladesh during their internship.

1. Quality Control DDeeppaarrttmmeenntt OOff
PPhhaarrmmaacceeuuttiiccaall CCoommppaanniieess
iinn BBaannggllaaddeesshh
Submitted to:
Adit Muktadir Pavel
Prepared by:
Nabilah Tabassum
Nurul Absar
Bodiul Alam
Mahabub Morshed Rifat
Enamul Haque
Ishfaq Ahmed

2. Pharmaceutical analysis is a branch of practical chemistry that
involves a series of process for—
Identification
Determination
Quantification
Purification of a substance
Separation of the components of a solution or mixture
Determination of structure of chemical compounds.
Quality ccoonnttrrooll ((QQCC)) is a
procedure or set of procedures
intended to ensure that a
manufactured product or
performed service adheres to a
defined set of quality criteria or
meets the requirements of the
client or customer at an
economical level.

3. AAccttiivviittiieess ooff QQCC DDeeppaarrttmmeenntt
 Testing and releasing or rejecting all incoming raw materials,
packing materials, in-process /intermediates and finished
products
 Maintaining testing records (BMR)
 Calibration of laboratory instrument / equipment
 Ensure precision and accuracy
 Performing stability study of finished products
 Real time study of marketed products at certain time intervals
(3months, 6montrrs, 9months and 12months etc.)
 Analysis of complaint samples as and when required
 Conduct technical audit / self-inspection
 Follow safety norms at all the stage during handling of chemicals
and using instruments
 Follow good laboratory practices as per GMP

4. Good Manufacturing
Practice (GMP)
GMP provides basic standards for the
manufacturers of drugs and from the
basis on which each company build its
own systems procedures to assure the
product quality. GMP ensures that
products consistently produced and
controlled to the quality standards
appropriate to their intended use.
There are number of national &
international GMP regulatory boards:
* WHO
*FDA
*TGA

5. Diagrammatic representation of Q.C. activities

6. Analysis Analysis DDoonnee iinn QQCC DDeeppaarrttmmeenntt
For Raw Material
Solid raw material
Identification
Moisture content
Bulk density
Heavy metal testing
Impurities
Melting point
Liquid raw material
Refractive index
pH
Weight per ml
Viscosity
For Finished Products
Final testing of finished product is made in
the quality control laboratories. The testing
of finished product for compliance with
predetermined standards is a critical factor
for product release. Following
characteristics are checked in finished
Solid preparation
Dissolution time
Disintegration time
Weight variation
Assay
Liquid preparation
Weight per mL
Microbiological limit test

7. Control of Packaging
materials
Following characteristics are checked
in packaging materials:
 Text of the printed materials.
 Color of the materials.
 Locking of cartoons.
 Compatibility of closures with
bottles.
 Thickness of foils.
 Pasting of cartoons.
 Weight (gram per m2) of cartoons
for checking materials.
 Transmittance test for glass
bottle
 PVC-PVDC differentiation test
Vernier Caliper

8. SSttaabbiilliittyy ssttuuddyy::
Stability test is done for the following purposes-
To determine the expiry period.
To determine the packaging mode.
There are two methods of stability study:
 Real time stability study
 Accelerated time stability study.
Products of pilot batches prescribed in three separated stability chambers of three different specific
conditions. These are:
• Room temperature and pressure Condition: 25 ± 2° C and 60±5 % Relative Humidity
• Intermediate Study: 30±°2C, 65 ±5% Relative humidity.
• Accelerated Study: 40 ±° C, 75±5% Relative humidity.
Stability parameters
Certain parameters should be followed in stability testing. Such as:
o Hardness
o pH
o LOD
o Dissolution
o Assay
o Related substance

9. UV/VIS Spectrophotometric Methods
Instrument used:
UV/Vis spectrophotometer
Principle:
It measures the intensity of light passing through a sample (I), and compares it to
the intensity of light before it passes through the sample (I0).The ratio I/I0 is
called the transmittance, and is usually expressed as a percentage (%T).
The absorbance, A , is based on the transmittance:
The UV-visible spectrophotometer can also be configured to measure reflectance
(%R). In this case, the spectrophotometer measures the intensity of light reflected
from a sample (I), and compares it to the intensity of light reflected from a reference
material (I0)

10. Solvents
The choice of the solvent to be used in ultraviolet spectroscopy
is quite important.
Some common UV-Spectroscopy solvents are :
 Acetonitrile,
 Chloroform,
 1,4-Dioxane,
 95% Ethanol,
 Cyclohexane,
 Methanol,
 Water,
 n- Hexane, and
 Trimethyl Phosphate

11. Applications:
Chemical analysis
Food safety analysis
Blood analysis
DNA/RNA Conc. Analysis
Residual Pesticide analysis
Residual chlorine analysis
Drugs analyzed:
Ephedrine
Ketoprofen
Procaine
Phenylephrine
Amoxycillin Trihydrate
Folic Acid
Glyceryl Trinitrate Tablets

12. CCHHRROOMMAATTOOGGRRAAPPHHYY
Chromatography may be defined as a process by which components of
molecular mixtures can be separated by distributing them between two
phases—
i.Mobile phase -- gas or liquid; run over the stationary phases to facilitate
the separation of the components in a mixture and
ii.Stationary phase -- immiscible and immobile; finely powdered Silica
(SiO2), Alumina (Al2O3) or cellulose; capable of retaining both solvents and
solutes.
Different types of chromatographic techniques are used in pharmaceutical
analysis like—
•Thin-layer chromatography (TLC)
•Gas chromatography (GC)
•High performance liquid chromatography (HPLC)

13. HHPPLLCC
HPLC is a form of liquid chromatography used to separate compounds that are
dissolved in solution. The components of a basic high-performance liquid
chromatography [HPLC] system are shown in the simple diagram in the following
figure.
HPLC instruments consist of---
a reservoir of mobile phase
a pump
an injector
a separation column
a detector.
Compounds are separated by injecting a sample mixture onto the column. The
different components in the mixture pass through the column at different rates
due to differences in their partition behavior between the mobile phase and the
stationary phase

14. http://www.youtube.com/watch?v=kz_egMtdnL4

15. Applications:
Isolating natural products
Ensure the purity of raw materials
Controlling and improving process yields
Quantifying assays of final products
Evaluating product stability
Monitoring degradation
Drugs Analyzed:
Isoniazid
Pyrazinamide
Rifampicin
Ethambutol
Anti-tuberculosis compounds

16. GGaass CChhrroommaattooggrraapphhyy
Gas chromatography (GC), is a common type of chromatography used in
analytical chemistry for separating and analyzing compounds that can be
vaporized without decomposition
Instrument used:
Gas chromatograph
Principle:
The analyte is vaporized and introduced into a stream of carrier gas
(conducted through a chromatographic column) and separated into its
constituents
These fractions pass through the column at characteristic rates, and are
detected as they emerge in a time sequence.
The detecting cell responses are recorded on a chart, from which the
components can be identified both qualitatively and quantitatively.

18. Applications:
Testing the purity of a particular substance
Separating the different components of a mixture
Amounts of components can also be determined
In identifying a compound
To prepare pure compounds from a mixture
In forensic investigation
Drugs Analyzed:
Amphetamine
Cocaine
Morphine
Codein

19. Vibrational spectroscopic methods consist of three main tools –
I.Mid-IR spectroscopy, more commonly named Fourier transform IR (FTIR)
spectroscopy
II.Near-IR (NIR) spectroscopy and
III.Raman spectroscopy.
Among these FTIR is more frequently used in Bangladesh.
FFTTIIRR
FTIR (Fourier Transform Infrared Spectrophotometer) is used for
identification of compounds.
The principle of FTIR is based on the fact that bonds and groups of
bonds vibrate at characteristic frequencies.
A molecule that is exposed to infrared rays absorbs infrared energy at
frequencies which are characteristic to that molecule.

20. In a molecule, the differences of
charges in the electric fields of its
atoms produce the dipole moment of
the molecule. Molecules with a dipole
moment allow infrared photons to
interact with the molecule causing
excitation to higher vibrational states.
Diatomic molecules do not have a
dipole moment since the electric fields
of their atoms are equal.
During FTIR analysis, a spot on the
specimen is subjected to a modulated
IR beam. The specimen's transmittance
and reflectance of the infrared rays at
different frequencies is translated into
an IR absorption plot consisting of
reverse peaks. The resulting FTIR
spectral pattern is then analyzed and
matched with known signatures of
identified materials in the FTIR library.

21. Although titrimetry has already been extensively used in past years, a
literature search reveals that there are few recent methods that employ
this technique for analysis of pharmaceuticals.
PPootteennttiioommeettrriicc ttiittrraattiioonn
A potentiometric titration is a technique in which the end-point is
detected by measuring the change in potential of a suitable electrode
during the titration. It is used for all kinds of titration like:
• Acid base
• Redox
• Complexometry
Potentiometric titration is a technique in which two electrodes are
used, an indicator electrode and a reference electrode. The indicator
electrode forms an electrochemical half cell with the interested ions in
the test solution. The reference electrode forms the other half cell,
holding a consistent electric potential.

22. Advantages:
It gives a sharp end point in every case
Apparatus used is not sophisticated thus easy to handle
It is used for very dilute solution
Disadvantages:
It has high temperature
Plotting of titration curve is too time consuming

23. KKaarrll FFiisscchheerr ttiittrraattiioonn
Karl Fischer titration is a classic titration
method in analytical chemistry that uses–
Coulometer or
Volumetric titration,
to determine trace amounts of water in a
sample.

24. CCoolloorriimmeettrriicc ttiittrraattiioonn
The main compartment of the titration cell contains the anode
solution plus the analyte. The anode solution consists of an alcohol
(ROH), a base (B), SO2 and I2. A typical alcohol that may be used is
methanol or diethvlene glvcol monoethvl ether, and a common base
is imidazole.
The titration cell also consists of a smaller compartment with a
cathode immersed in the anode solution of the main compartment.
The two compartments are separated by an ion-permeable
membrane.
The end point is detected most commonly by a bi-potentiometric
method.

25. VVoolluummeettrriicc ttiittrraattiioonn
The volumetric titration is based on the same principles as the
colorimetric titration except that the anode solution above now
is used as the titrate solution.
The titrant consists of an alcohol (ROH), base (B), SO2 and a
known concentration of I2.
The end point may be detected by a bi- potentiometric method
as described above.
Application:
Karl Fischer Titration is used to calculate bound and unbound
moisture to determine the moisture content in drug substances.

26. Advantages of Karl Fischer Titration:
The popularity of the Karl Fischer titration is due in large part to several
practical advantages that it holds over other methods of moisture
determination, including:
•High accuracy and precision
•Selectivity for water
•Small sample quantities required
•Easy sample preparation
•Short analysis duration
•Nearly unlimited measuring range (Ippm to 100%)
•Suitability for analyzing:
Solids
Liquids
Gases
•Independence of presence of other volatiles
•Suitability for automation
 The major disadvantage is that the water has to be accessible .

27. Other Instruments Used
Instruments Application
Atomic Absorption Spectroscopy Used to identfy and quantify metal
Particle Counter Particle size of different preparation.
UPLC Qualitative and Quantitative analysis
Polarimeter "Levo"(L) or "Dextro" (D) from of a Isomer
Refractrometer Determine the reflective index of a chemical
Vaccum dryer Used to dry unbound moisture of a compound
Hot Stage Microscope Combination of microscopy and thermal analysis
Muffle Furnace Burn chemical compound sat high temperature of 2600°C
Sonicator To solubilize compound in a solvent
Dissolution Tester In vitro drug release information
Disintegration Disntegration rate
Centrifuge For Separation of Samples
Stampfvolumeter Measures tap density
pH meter Measures pH
Viscometer Measure viscosity

28. Conclusion