Pharmaceutical Industry training. Summer training of chemical Engineering at Ind swift laboratories.

1. IND SWIFT LABORTARIES
LTD.
DCRUST, MURTHAL

2. Overview
 Company Profile
 Major Reaction and Reagents Capabilities
 Company Products
 Different Units of the company

3. Company Profile
 Ind-Swift Laboratories Ltd. (ISLL) is a USD ~ 200 million, fast growing active
pharmaceutical ingredient (API) and contract research and manufacturing
services (CRAMS) company, based in Chandigarh, North India.
 Established in 1995 Ind-Swift has fast evolved towards a business model
that is focused on deep-rooted domestic presence and leveraged on high-
value mature regulated markets along with considerable growth in emerging
markets:
 Ind-Swift Laboratories Ltd. (Manufacturer of APIs)
 Ind-Swift Laboratories Inc. (US Subsidiary)
 Ind Swift Menthol
 With manufacturing sites at 6 different locations across India and an
independent State-of-the-Art R&D Centre, the Group has embarked upon a
journey to establish itself as reliable partner in the Global Pharmaceutical
Industry. In house capabilities for Development of APIs, Finished Dosage
forms, Non-Infringing Process & World Class facilities for Contract
Manufacturing are the inherent strengths.
 ISLL–CRAMS offers world class services across early phase drug
development, process R&D, contract manufacturing to analytical and
regulatory services.

4. Major Reaction and Reagents
Capabilities
 Grignard Reaction
 Friedel-crafts Acylation
 Hydrogenation
 Halogenation
 Witting Reaction
 Stetter Reaction
 Arbuzov Reaction

5. Company Products
 Few of the major products that are produced in here are :-
 Clarithromycin
 Roxithromycin
 Azithromycin
 Ezetimbe
 Clopidogrel Hydrogen Sulphate
 Fexofenadine HCl
 Nateglinide

6. Different Sections
Research & Development Centre
Quality Control Unit
High Performance Liquid Chromatography
Gas Chromatography
Microbiology
Production Unit

7. Research & Development
 R&D includes basically the fulfillment of the demands of the masses by
thoroughly researching and developing new ways or products as per their
requirements. Few of the basic products that are produced here are :-
 Clarithromycin
 Roxithromycin
 Azithromycin
 Ezetimbe
 Clopidogrel Hydrogen Sulphate
 Fexofenadine HCl
 Nateglinide

8. Quality Control & Quality Assurance
 Quality control (QC) 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 masses. QC is similar to, but not identical
with quality assurance (QA). QA is defined as a procedure or set of procedures
intended to ensure that a product or service under development (before work is
complete, as opposed to afterwards) meets specified requirements. QA is
sometimes expressed together with QC as a single expression, quality assurance
and control (QA/QC).

9. Quality Control Unit
Quality Control Unit consists :
HPLC lab (High performance liquid chromatography lab)
 GC lab (Gas chromatography lab)
Microbiology lab

10. High Performance Liquid
Chromatography
 High-performance liquid chromatography (formerly referred to as high-
pressure liquid chromatography), HPLC, is a chromatographic technique used to
separate the components in a mixture, to identify each component, and to quantify
each component.
 In general, the method involves a liquid sample being passed over a solid adsorbent
material packed into a column using a flow of liquid solvent. Each analyte in the
sample interacts slightly differently with the adsorbent material, thus retarding the
flow of the analytes. If the interaction is weak, the analytes flow off the column in a
short amount of time, and if the interaction is strong, then the elution time is long.
 HPLC has been used in medical (e.g. detecting vitamin D levels in blood serum),
legal (e.g. detecting performance enhancement drugs in urine), research (e.g.
separating the components of a complex biological sample, or of similar synthetic
chemicals from each other), and manufacturing (e.g. during the production process
of pharmaceutical and biological products).

11. High Performance Liquid
Chromatography Lab
 The lab consists of three basic instruments which are :
 Reservoir
 Column
 Detector
 The reservoir brings the sample mixture into the mobile phase stream which carries
it into the column. The pumps deliver the desired flow and composition of the
mobile phase through the column. The detector generates a signal proportional to
the amount of sample component emerging from the column, hence allowing for
quantitative analysis of the sample components.

12. High Performance Liquid
Chromatography Lab

13. Schematic Diagram for HPLC

14. Reservoir
 The reservoir in HPLC is generally preferred mobile phase reservoir .
 Mobile phase reservoir will carry the mobile phase solution and through the
pump it will be pumped into the column. This movement is according to the
gravitational force. The mobile phase reservoir is a solvent with different
polarities such as water, methanol, and acetonitrile.
 These solvents should be highly pure. For an example, water should be
used as de-ionized water. Hygienic conditions are facilitated with the use of
0.45 µm filter. The solvent is filtered through this filter mesh to remove all
particulate matter. This is termed as Millipore filtering. Degas is done to
minimize errors which occur when compounds interact with several gases. If
degas or the removal of all the gases, is not done correctly then it may spoil
the column.

15. Column
Column is considered as the “Heart “ of the whole process .
The separation of the compound mixture takes place in this column or HPLC tube.
The HPLC tube is made up of stainless steel. The stationary phase is packed in the
column and it is usually a solid adsorbent. In some instances the solid adsorbent is
packed with a thin layer of water. Thus the physical principle or the mode of
separation in HPLC is partition.
As in other chromatographic techniques in HPLC the mobile phase with the test
sample is gone through the stationary phase. And the compounds in the test sample
are separated in here. Mobile phase serves only as a carrier of the test sample.
According to the solubility differences (in other words polarity differences) the
mixed compounds are separated
Many different types of columns are available, filled with sorbents varying in
particle size, and in the nature of their surface ("surface chemistry"). The use of
smaller particle size packing materials requires the use of higher operational
pressure ("backpressure") and typically improves chromatographic resolution (i.e.
the degree of separation between consecutive analytes emerging from the column).

16. Column

17. Detector
 Detector records the relative concentrations of different components of the
test sample with respect to their retention time. Retention time is the time
taken by the compound to elute from the column. Retention time is
calculated from the time of injection until the compound is eluted. Detection
is based on several different physical principals.
 Those are UV absorption, fluorescence, radioactivity, IR absorption and
electrochemical gradient. Depending on the characteristics of the mixture
the physical principals will be different.
 The one we use here is Dual wavelength absorbance detector or PDA
Detector .

18. The Process
 The microprocessor shows the chromatograms which consists of small peaks and
major peaks hence defining the amount of the required substance to be separated.
 The pressure required is 5000 psi in case of HPLC and 15000 psi for UPLC which
is at times preferred for the separation in industry.
 This way the whole process takes place in 24 – 48 hrs depending upon the product
to be manufactured.
 For Clarithromycin it takes 28 hrs of separation process.

19. The Process
 The process begins with the mixing of various chemical required to prepare the
requirement as discussed in STP (Standard Testing Procedure) and is then further
placed in sampler so as to begin the process of chromatography which proceeds
towards column.
 The column is filled with tiny silica particles, and the solvent is non-polar -
hexane, for example. A typical column has an internal diameter of 4.6 mm
(and may be less than that), and a length of 150 to 250 mm.
 Polar compounds in the mixture being passed through the column will stick
longer to the polar silica than non-polar compounds will. The non-polar ones
will therefore pass more quickly through the column.
 Then after moving from column it goes to detector where the required things
are detected and that is shown on a digital microprocessor and user
software controls the HPLC instrument and provide data analysis

20. HPLC Chromatogram

21. Gas Chromatography Lab
 Gas chromatography is used in
analytical chemistry for separating
and analyzing compounds that can be
vaporized without decomposition.
the mobile phase is a carrier gas,
usually an inert gas such as He or an
unreactive gas such as N2
The stationary phase is a microscopic
layer of liquid or polymer on an
inert solid support, inside a piece
of glass or metal tubing called a
column .

22. Gas Chromatography Lab

23. The Process
 A known volume of gaseous or liquid analyte is injected into the "entrance" (head)
of the column, usually using a microsyringe (or, solid phase microextraction fibers,
or a gas source switching system). As the carrier gas sweeps the analyte molecules
through the column, this motion is inhibited by the adsorption of the
analyte molecules either onto the column walls or onto packing materials in the
column. The rate at which the molecules progress along the column depends on the
strength of adsorption, which in turn depends on the type of molecule and on the
stationary phase materials. Since each type of molecule has a different rate of
progression, the various components of the analyte mixture are separated as they
progress along the column and reach the end of the column at different times
(retention time). A detector is used to monitor the outlet stream from the column;
thus, the time at which each component reaches the outlet and the amount of that
component can be determined.

24. Gas Chromatogram