3 week Pharma Industrial Training Programme

conducted by ClinFOX, initiated by APITCO 

and supported by WORLD BANK, DFID & SIDBI.

   

 

Submitted by P.Ramya 

 

  

                                                                   

 

  

TO WHOM IT MAY CONCERN    

This is to certify that P.Ramya, a participant from APITCO, Hyderabad, undertook a Three week Analytical instrumental training on “Various Departments in analytical laboratory” at MART Laboratories limited from 31/05/11 to 12/06/11.

We wish all success in her future endeavors.   

                                                                                                        Signature with date

      (Name)

      (Designation)

      (Company Name)     

 

TO WHOM IT MAY CONCERN   

This is to certify that P.Ramya, a participant from APITCO, Hyderabad, undertook a Three week industrial on “Various Departments in industry” at AR Life sciences Labs limited from 12/06/11 to 20/06/11.

We wish all success in her future endeavors.       

                                                                                                        Signature with date

      (Name)

      (Designation)

      (Company Name) 

   

 

TO WHOM IT MAY CONCERN  

This is to certify that P.Ramya, a participant from APITCO, Hyderabad, undertook a Three week industrial on “Various Departments in industry” at GENNEX Labs limited from 12/06/11 to 20/06/11.

We wish all success in her future endeavors.      

                                                                                                        Signature with date

      (Name)

      (Designation)

      (Company Name) 

ACKNOWLEDGEMENT  

      Firstly, I offer my adoration to God Almighty who created me, gave me the strength and courage to complete my dissertation and gave me the opportunity to thank all those people through whom His Grace was delivered to me. 

      I express my sincere gratitude to my guide Dr. Marayya garu, MART Laboratory, Mr. Gopala Krishna garu, GENNEX Labs their able guidance, continuous support and cooperation throughout my industrial training , without which the present work would not have been possible. 

      I would also like to thank the entire team of APITCO Ltd specially to Mr. Pullareddy garu and Mr. Jagadesh reddy garu, for the constant support and help in the successful completion of my project. 

      Also, I am thankful to CLINFOX International Team for giving me the opportunity be part of  this programme, for their continued guidance and invaluable encouragement

      It gives me great pleasure to express my gratitude to my parents Sri. Damodar, Smt. Savithri, brothers Anil Kumar for their support and encouragement in achieving this goal.

      . 

      Signature

                                                                                                    P.Ramya.  

 

CONTENTS 

 

   

  

CHAPTER NO.

TITLE

  1

  THEORY  SESSION

  2 ANALYTICAL INSTRUMENTAL TRAINING

  

2.1 INTRODUCTION

2.1.1 MART

2.1.2 ANALYTICAL CHEMISTRY

2.1.3 DEPARTMENTS IN THE LABORATORY

2.2 OBJECTIVES

  2.3 METHODOLOGY

  2.4 RESULTS AND DISCUSSION

  2.5 SUMMARY AND CONCLUSSION

  3 AWRENESS ON INDUSTRY

  

3.1 INTRODUCTION

3.1.1 GENNEX  LABS &AR LIFE SCIENCES

3.1.2 DEPARTMENTS IN THE INDUSTRY  3.2 PURPOSE OF TRAINING

    3.3 METHODOLOGY

    3.4 SUMMARY AND CONCLUSSION

1. THEORY SESSION: 

S. No DATE SPEAKERS TOPICS

01 17-May-2011 Dr. P.K.L.M Rao

Knowledge Partner for APITCO

1. Introduction to Pharma Industry

2. Air Handling Systems

3. Standard Operating Procedures

02 19 May-2011 A. Saritha

Senior Soft Skills Trainer

Soft Skills Training Consulting Company

1. Goal Settings

2. Interview Skills

3. Presentations Skills

20-May-2011 A. Saritha

Senior Soft Skills Trainer

Soft Skills Training Consulting Company

1. Body Language

2. Resume Writing

3. Mock Interview Sessions

03 21-May-2011

Morning Session

K. Velayutham

Research Scientist

International Specialty Products

1. Product Development

2. NDA and ANDA

3. Formulation ,Pre-formulations

4. Bio-Equivalence

5. Validations

04 21- May-2011

After Noon Session

Dr. Rama Krishna

Environment Health and Safety

Consultant

1.Introduction to Pharma Layout

2.GMP

3.GLP

05 22- May-2011 U. Venkateswar Rao

Chief Quality Control Officer

Alpha Med

Water Management System

06 23- May-2011 S.Sreedhar Regulatory Affairs

Founder & Director of ClinFOX International

07 24- May-2011 K. Annapurna

Pharma Trainer

Analog Labs

1. Chromatography

2. HPLC

3. ICH Guidelines

08 25- May-2011 K. Annapurna

Pharma Trainer

Analog Labs

1. Method Development

2. Spectroscopy

3. Overview on Clinical Trials

1) Dr. P.K.L.M Rao - 17/05/11

Topic: Presentation on Pharma Industry, Air Handling Systems, DM Plant and SOP’s.

Discussion:

Sir explained about,

A. Pharma Industry:

The Main departments of the Pharma industry are ware house, Production, QA, QC, RA, R & D, rules and regulations of the each department, job opportunities in each department.

B. DM Plant:

It is De-mineralised Plant, used to remove minerals from the water. MPN (Most Probable Number of Organisms) is the important parameter to check the water purity.

C. Air Handling System:

AHS (Air handling system) or AHU (Air handling unit) is a device used to produce conditioned air and circulate that air to the heating, ventilating, and air-conditioning system. Air handlers usually connect to Ductwork that distributes the conditioned air through the building and returns it to the AHU. Air ducts are one method of ensuring acceptable indoor air quality as well as thermal comfort.

D. Standard Operating Procedures:

Another presentation on SOP (Standard operating procedures) sir shown some SOPs of the product, how they are preparing according to the SOPs and making of documentation etc. 

Conclusion: This session was very interactive and we gained a lot of information.

2) A. Saritha - 19/05/11 to 20/05/11

Topic: Goal settings, Interview skills and Resume writing

Discussion and conclusion:

Madam discussed about the resume writing in that she explained difference between the curriculum vitae, resume and bio-data. How to write the resume, what are the different techniques in writing the resume etc.

She had given a demo on interview skills i.e. how to behave with the recruiter, common mistakes doing at the time of interview, dress sense, how to sit in front of the recruiter, about handshake etc. and she shown practically. This session is very helpful. 

In goal setting commitment is necessary to achieve the goal. Try and try until you succeed.

3) K. Velayutham - 21/05/11

Morning Session

Topic: Product Development

Discussion and conclusion:

In this session sir gave presentation  about the product development i.e. what are the different organizations involved in the product development like NDA (new drug application) & ANDA (abbreviated new drug application),difference between the Generic and patent drugs, how to apply for the patents and preformulation studies. Through this presentation I got full idea about the new drug development, what is the process involved.

4) Dr. Rama Krishna - 21/05/11

Afternoon session

Topic: presentation on Pharma layout, GMP (Good manufacturing practices) and GLP (Good laboratory practices)

Discussion and Conclusion

Through this session I known about the good practices for designing the premises, cleaning the area and equipments, sanitation, production operation and Good practices in quality control.

I known about the effluent treatment plant, statutory requirements for the industry and very important interesting topic i.e. Safety and health environment in this I am clear about common

hazards (mechanical, chemical and biological) occurring in the industry. This information is very useful when we exposed to industry.

 

5) U. Venkateswar Rao - 22/05/11

Topic: water management systems

Discussion and Conclusion

Sir had given presentation on water systems, source of water contamination like industrial, agricultural and domestic, types of waters as softened water, process water, purified water, water for injection and sterile water, types of contaminations, pre treatment of raw water, and removal of dissolved salts in the water and infrastructure of the purification process. 

6) S.Sreedhar - 23/05/11

Topic: Regulatory Affairs

Discussion and Conclusion

Sir had given a detailed explanation on Reulatory affairs. The history behind the requirement importance of regulatory affairs in Pharma industry development in the respect of Quality and Safety of consumers, The importance of awareness of the various abbreviations, and the job oppurtunities, and how to acquire them. He had given a good scope in this field.

7) K. Annapurna - 24/05/11

Topic: Chromatography, HPLC, ICH guide lines

Discussion

Madam had explained briefly about ICH guidelines, detailed information on mainly Quality guidelines, Importance of Stability & Shelflife. These are the basic points to be known to work in QC & QA departments. Presentations on Chromatography and HPLC had also been delivered.

8) K. Annapurna - 25/05/11

Topic: Method Development, Spectroscopy, Overview on Clinical Trials.

Discussion

Madam explained about the definition and parameters involved in Method development and Method Validation with respect to HPLC analysis. Also given a breif account on Overview of Clinical Trails i.e stages of clinical trails, basic components involved in it. Presentation on Spectroscopy had been delivered.

Conclusion : Madam had given an important notes which is essential to get aware of the basic points of the Analytical department.

***** 

2. ANALYTICAL INSTRUMENTAL TRAINING

2.1 INTRODUCTION:

2.1.1 MART LABORATORY

  MART it is an Analytical and Research Testing Laboratory established in 2010. It offers testing services. There are wide range of analytical testing includes nutraceuticals, herbals, enzymes, microbial, metals, dioxins, PCBs, solvent residues, and mycotoxins. They also provide services for full nutritional panels and food analysis.

      There facility is GMP licensed and employs state-of-the-art equipment and the most up-to-date testing methodologies in accordance with USFDA regulations. They are service-oriented professionals whose only business is your testing needs.

` 2.1.2. Analytical chemistry

From the time of BC the chemist worked with meager equipment in small laboratory, pharmacist have made main importance in the field of medicinal chemistry i.e. both in discovering and isolating the new drug entity and in developing methods for standardization. Now a day such activities are done by the prescription laboratory or analytical laboratory.

Modern pharmaceutical formulations are complex mixtures of different APIs and diluents, disintegrants, colors etc. To ensure the quality and stability of the final product, the analyst must be able to separate the mixture into individual components prior to quantitative analysis. We want to know the purity and impurities, % of impurities these analytical techniques are playing an important role. Continual advances in the instrumental methods of analysis have helped for the development analytical laboratory

Analytical chemistry is the science of making quantitative measurements. In practice, quantifying an analyte in a complex sample becomes an exercise in problem solving. To be efficient and effective, an analytical chemist must know the tools that are available to tackle a wide variety of problems. For this reason, analytical chemistry courses are often structured along the lines of the analytical methods.

2.1.3. Departments in the laboratory:

a. Stability zoneb. Chemical labc. Chromatography labd. Spectroscopy labe. Microbiology lab

f. Validation lab

2.2. OBJECTIVE

Aim: The Main aim of this Analytical lab training is to get experienced with practical environment of an analytical lab.

THE MAIN OBJECTIVES OF THE PROPOSED WORK ARE:

To get expose to the analytical instruments. To learn the various analytical techniques in brief. To learn the manner of handling, and minor precautions to be taken during analysis. To take the opportunity to get idea about advanced analytical instrumentation.

2. 3. METHODOLOGY

2.3.1. CHEMICAL LAB

I heard demo on the following equipments in chemical lab. They are as follows

1. Mufflle Furnace2. Mantel3. Magnetic stirrer4. Centrifuge5. Melting point apparatus6. Bulk density apparatus7. Sieve analysis Apparatus8. Vacuum Oven9. Hot air Oven10. PH meter 11. Disintegration Apparatus12. Friability Apparatus13. Hardness Tester14. UV cabinet15.Conductometric Titration apparatus

1. Muffle Furnace: It is used for ignition purpose up to 12000c.

2. Mantel:  It is used for heating or boiling purpose. It works under power.3. Magnetic stirrer:  It is automatic stirrer for well mixing purpose using magnetic bar.4. Centrifuge:  It is used for the separation of components (solids from solutions) using

centrifugal force.

5. Melting point apparatus: It is used for the determination of the melting point of the solid substances. Here mostly unknown sample are determined.

a. Maker: labindiab. Model: ID(M/MP/01)

6. Bulk density apparatus: It is used to determine the Bulk density apparatus of the powders based on the weight of the sample kept in cylinder having 2 positions (USP I & USP II ). Model: V Tap

7. Sieve shaker: It is used to sieving the granules or powders for getting uniform size. Here the sieves are arranged in vertical manner of 3 size sieves. If the powder does not pass in one of the sieve it passes in another one.

a. Make: Retschb. Model: AS200

8. Vacuum oven: It is used where the thermal processes occur in an airtight chamber, where a desired level of vacuum has been applied using an external vacuum pump with 500 mm hg pressure is used. Purposes are following:

o Moisture Determinationo Chemical Resistance Studieso Drying of Paper, Rubber, and Textileso Desiccatingo Dry Sterilizationo Vacuum Storage

9. Hot air oven: used for the sterilization of the glass equipments, plates etc...10. PH meter: used for the determination of the pH of the given sample.

Model: Labindia

11. Disintegration apparatus: It is used for the determination of the disintegration time of the tablets or capsules. It is one of the important official evaluation test for the tablets or capsules.12. Friability apparatus: It is used for the Determination of the mechanical strength of the

solid dosage forms like tablets. It is one of the official evaluation test for the tablets.13. Hardness tester: it is used to test the hardness of the tablet.14. UV Cabinet: It is used for the identification of the spotted molecules on the TLC plates

under 2 fixed wave lengths i.e. 254nm (short wavelength) & 365nm (long wavelength) under normal light.

15. Conductometric Titration apparatus: It is a titration apparatus working on the principle conductivity of the sample. It consists of the conductance bridge, detector & cell (dip type cell) which is in contact with the solution. The cell is immersed in a thermostatically controlled bath.

2.3.2. SPECTROSCOPY LAB

Spectroscopy

Definition: It is a branch of science which deals with the interaction of EMR with matter. It is the measurement and interpretation of the EMR absorbed (or) emitted when molecules or atoms or ions of a sample exited from one energy state to another state

Various types of spectroscopy:

UV VIS IR NMR MS FT-IR AAS LC-MS GC-MS

 I heard demo on the following equipments in spectroscopy lab.1. Polarimeter2. FT-IR3. Autotritator4. UV-VIS5. AAS6. Dissolution apparatus (labindia DS8000)

    POLARIMETER

MODEL    : Autopol V

MAKE       : Rudolpf research analytical

SOFTWARE  : Rudolph pc interface

PRINCIPLE   : Non symmetrical structures which rotate the plane polarized light are called Optically active compounds. If it rotate the plane polarized light to the left, sample is called levorotatory, if it rotate right side it is dextrorotatory.

STANDARD COMPOUNDS: These are used as reference samples. The commonly used samples are

D-glucose      : 52.7 (d) Tartaric acid   : 14.1 (d) D-fructose      : -92.4 (l) Sucrose          : 66.5 (d)

INSTRUMENTATION:

           Light source        : Na vapor lamp

Prisms                :  2 prisms are used (Nichol Prism & Calcite Prism with quartz windows).

           Sample holder      : Temptrol  

Length of tube     : 1 decimeter = 10cm

Detector               : PDA detector

Wavelength          : 365nm, 405nm, 436nm, 589nm, 633nm

Temperature        : 20 to 25 ˚c

The polarimeter consists of 2 openings, sample is injected through one hole and care should be taken while injecting the sample so that no air bubbles are formed. The other opening is meant for checking the temperature.

TROUBLE SHOOTS:  air bubbles, temperature limits

PROCEDURE:

Steps for sample preparation:

1. 0.5 g of sample is taken in 100ml volumetric flask2. To this add 60 to 70 ml of 50% methanol (v/v).3. Keep the flask in sonicator (for proper mixing).4. Then measure the absorbance at 589nm at temp 20˚.

 

FORMULA:

SOR   =    Average angle of rotation*100/Length of the tube*Wt of the sample*(100- % of Water content)

The limit range varies from 14 -18. If the value obtained is in these values the sample passes the test

APPLICATIONS:

o This equipment is used for measurement of SOR (specific optical rotation).o It is also used to analyze the compound whether it is levorotatory or dextrorotatory.

 

FT-IR (Fourier transform infra-red spectroscopy)

MODEL     : Nicolet IS10

MAKE    : Thermoscientific

SOFTWARE   : Omnic

PRINCIPLE   : For every functional group there is fundamental vibrational frequency and whenever sample is subjected to IR radiation and the natural frequency of vibration is equal to applied frequency then it absorbs radiation and gives peak, plotted as % of  transmittance vs. wave length .                                                                INSTRUMENTATION

1. Source : Nichrome coil, Nearnst glower, Globar source 2. Monochromator : Gratings

3. Sample : There are 4 sample preparation methods

a. Solid preparation (KBr-100mg, sample-0.5-1mg).

b. Liquid preparation ( NaCl plates – NMT 0.01mm thickness)

c. Mull preparation: mull prepared using mulling reagent, nujol oil (light paraffin oil).

d. Gas preparation

PROCEDURE:

Sample is prepared as pellet using KBr press with 200kg/cm2 pressure.

Blank(KBr) is placed in IR beam and sample with KBr pellet was scanned and then compare the sample with  standard  

TROUBLE SHOOT  : Care should be taken about pellet preparation, it should be free of cracks (which may lead to noise peaks)

CALIBRATION  : It is calibrated using polystyerene film.

APPLICATION  : It is majorly used for qualification of sample and quantification of sample is minor application.

AUTO TITRATER

MODEL  : 1) 808 Titrando (normal titrations)

2) 795 KFT Titrino (Moisture content determination)

MAKE   : metrohm

SOFTWARE  : tiamo 1.2.1

PRINCIPLE  : the principle involved in autotitration is potentiometric titration i.e. based on potential difference(voltage) of sample. End point can be detected using Indicator Electrodes, without indicator                                                                               

INSTRUMENTATION:

1. Reaction Vessel : a) 804 Ti stand – for Normal titrations ( aqueous, nonaqueous, complexometric, redox titrations)

b) 803 Ti stand, 703 Ti stand - for Karlfiesher titrations

2. Indicator Electrode : pH, pH+9.2buffer, Ag ring, Pt ring eleectrodes3. Reservoir : for storage of titrate

4. Burette of 10ml volume & burette dispensor

PROCEDURE:

o It is an automatic processo The sample is taken in reaction vessel and fixed it to instrument. The burette automatically

gives(or) delivers the solution in the burette to the solution in vessel based on the data given in software. The electrode filled with 2 M Licl3 in acetic acid.finally the

concentration of the unknown sample can be found. The end point can be detected by the software attached.

FORMULA  :  Titer value X equivalent factorX100X Dilution factor/wt. of the sample

TROUBLESHOOT : silica gel patches should be used for avoidance of moisture

CALIBRATION : 1. 0.1N NaOH & Potassium hydrogen pthalate

For Aqueous titrations – 4,7,9.2 buffers, For nonaqueous – 4,7 buffers

2. For complexometric - HCl-silvernitrate titration

APPLICATION  : To determine the concentration of the sample at micro level

To assay various compounds with high accuracy

To determine the moisture content of the given sample accurately with high sensitivity

UV –VISIBLE SPECTROPHOTOMETER

MODEL : Evolution 300(uv –visble)

MAKE  : Thermo photometer

SOFTWARE : vision pro

PRINCIPLE : The Principle involved is Beer-Lamberts law

INSTRUMENTATION:    Double beam UV-Visible spectroscopy

Light source  : Xenon lamp (UV), Deuterium lamp(VIS).

Sample cell  : 2 Quartz cells ( for standard & sample)

Detector  : PhotoMultiplierTude

FORMULA:

Absorbance = (Std absX sample dilution factorX%purityX100) /(smp abs. X std DF X (100-LOD))

CALIBRATION: It is calibrated by 4 parameters.

a. control of absorbance  -Potassium dichromate, Sulphuricacid

(at wavelengths 235,257,313,315,430nm)

b. control of wavelength – holmium oxide, Perchloricacid

(at wavelengths 240.9,2870.2,261.5,536.3nm)

c. Limit of straight light – KCl, 200nmd. Resolution  - NLT-1.8, Toulene and dil n-hexane.

APPLICATION:

o Identification of unknown sample concentrationo To determine whether the different concentrations of sample follows linearity or noto Determination of λ max or specific wavelength of unknown substance

ATOMIC ABSORPTION SPECTROPHOTOMETER

MODEL  : AA-6300

MAKE    : Shimadzu

SOFTWARE   : Wizard

PRINCIPLE   : The main principle involved  is Atomization of sample.

INSTRUMENTATION  

SOURCE  : Various light sources are used based on sample nature i.e detection of element nature

CARRIER GASES : Acetylene and air for palladium

ANALYSERS  : Mainly 3 analysers are present

      1. Mercury vaporizing unit - MVU-1A

      2. Graphite furnace unit - GFA-EX7i

      3. Hydride vapour generator – HVG-1

SAMPLE CELL   : It is like a test tube but it is made of rubber

CAPACITY     : 10 ml automatic sample collection/injection

CAPACITY OF INJECTOR  : 10 µl

PROCEDURE

Blank used is Aquaresia (HCl:HNo3=1:3) We observe sample i.e. sample for detection of pd different concentrations 10,25

and 50 ppm Here blank different concentrations of sample and unknown sample conc. Are filled

in different sample cells and in same manner as that can enter into software

In software adjust washing time, repeatability time .If linearity follow, then only that can detect the concentration of unknown sample

FORMULA:

Unknown sample conc. = (Sample absorbance/Std abs) X (std conc./sample conc) X 100 

2.3.3. VALIDATION LAB

TGA (Thermo gravimetric analysis) : It is used for analysis of loss on drying

DSC (differential scanning colorimeter) : Used for detection of melting point, purity, stability

ELEMENTOR    : Used for analysis of mainly 4 elements (C, H, N,S) 

2.3.4.  CHROMATOGRAPHY LAB

The primary goal of chromatographic separations is to separate the components (of interest) in the sample. The condition of separation is achieved when the resolution (Rs) between individual components is greater than a numerical value of 2.0. Resolution can be measured from a chromatogram. However, the measurement of resolution does not direct the approach to achieving resolution.

 I heard demo on the following equipments in chromatography lab.

1. HPLC2. GC

3. GCMS-QP 2010

4. GC-HS

5. Ultrapure water system-SG

6. Ultrasonic Bath sonicator

HIGH PERFORMANCE LIQUID CHROMATOGRAPHY

HPLC is a chromatographic technique that can separate a mixture of compounds and is used in biochemistry   and analytical chemistry   to identify, quantify and purify the individual components of the mixture.

MAKE             :  Waters

MODEL               : 2695

SOFT WARE      : EM POWER

DETECTORS      :  PDI (Photodiodide detector) – Waters 2996 PDA

                                  Refractive index detector – Waters 2414 RI

PRINCIPLE        : The Partition is major principle involved, adsorption to minor extent.

Ultra violet detectors UV detectors are the most commonly used detector. They measure the ability of a sample to absorb UV radiation.  PDA is an UV detector.

PROCEDURE

The solution moved through the column is slowed by specific chemical or physical interactions with the stationary phase present within the column. A normal gradient for reversed phase chromatography might start at 5% methanol and progress linearly to 50% methanol over 25 minutes; the gradient depends on how hydrophobic   sample

PARAMETER

Larger ID columns (over 10 mm) are used to purify usable amounts of material because of their    large loading capacity.

Analytical scale columns (4.6 mm) have been the most common type of columns, They are used in traditional quantitative analysis of samples and often use a UV-Vis absorbance detector.

Narrow-bore columns (1–2 mm) are used when more sensitivity is desired either with special UV-visible detectors, fluorescence   detection

Capillary columns (under 0.3 mm) are used almost exclusively with alternative detection means such as mass spectrometry. They are usually made from fused silica   capillaries,

PARTICLE SIZE

The stationary phase attached to the outside of small spherical silica   particles these particles come in a variety of sizes with 5 μm. But the pressure required for linear velocity increases by the inverse of the particle diameter, squared isocratic flow and gradient elution

Parameters to be measured :

Retention time

Resolution

Rt ratio,Tailing factor

Area

Formula: N1 sin θ = N2 sin θ

ISOCRATIC AND GRADIENT ELUTION

The mobile phase composition remains constant throughout the procedure is termed isocratic (meaning constant temp).

The mobile phase composition does not have to remain constant. A separation in which the mobile phase composition is changed during the separation process is described as a gradient elutio

GAS CHROMATOGRAPHY

                     It is a common type of chromatography used in analytical chemistry for separating and analyzing compounds that can be vaporized without decomposition In  the mobile phase  is a carrier gas, usually an inert gas such as helium or an un reactive gas such as nitrogen. 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 (a homage to the fractionating column used in distillation).these is called as gas chromatography

Make :        Shimadzu

Software            :       GC solution

Model                :        GC 2010                                                         

Principle:-

Gas chromatography is in principle similar to column chromatography but has several notable differences. Firstly, the process of separating the compounds in a mixture is carried out between a liquid stationary phase and a gas mobile phase, whereas in column chromatography the stationary phase is a solid and the mobile phase is a liquid.  The column through which the gas phase passes is located in an oven where the temperature of the gas can be controlled, whereas column chromatography (typically) has no such temperature control.

Two major types Gas Chromatography:-

• Gas-solid chromatography (Stationary phase: solid)

• Gas-liquid chromatography (Stationary phase: immobilized

liquid)                                                              

Retention Volume:-

VR = tR F (related)

Vm= tm.F (non-related)

average volumetric flow rate (mL/min)

F can be estimated by measuring flow rate exiting the column.

                       The process of gas chromatography is carried out in a specially designed instrument. A very small amount of liquid mixture is injected into the instrument and is volatilized in a hot injection chamber. A stream of inert carrier gas through a heated column which contains the stationary, high-boiling liquid.

AUTO SAMPLER:-

The auto sampler is a sample automatically into the inlets. Manual insertion of the sample is possible but is no longer common. Automatic insertion provides better reproducibility and time-optimization. Different  kinds of auto samplers exist. Auto samplers can be classified in  relation to sample capacity.

COLUMNS:-

Two types of columns are used in GC:                                                                                   

Packed columns are 1.5 – 10 m in length and internal diameter of 2 – 4 mm. These is usually made of stainless steel or glass and contains apacking of finely divided, inert, solid support material (e.g. diatomaceous earth) that is coated with a liquid or solid stationary phase.

Capillary columns have a very small internal diameter, on the order of a few tenths of millimeters, and lengths between 25–60 meters are common. The inner column walls are coated with the active materials (WCOT columns), some columns are quasi solid filled with many parallel micropores (PLOT columns).

DETECTORS:- 

FID (Flame ionization detectors), TCD (Thermal conductivity detector)                           

A number of detectors are used in gas chromatography. The most common are the flame ionization detector (FID) and thethermal conductivity detector (TCD). Both are sensitive to a wide range of components, and both work over a wide range of concentrations.

The Biochemical compounds such as proteins, nucleotides, and pharmaceuticals can be studied with flame ionization as well as other detectors, like thermal conductivity, thermionic, or electrolytic conductivity due

to the presence of nitrogen, phosphorus, or sulfur atoms or because of the universality of the thermal conductivity detector

      Some gas chromatographs are connected to a mass spectrometer which acts as the detector. The combination is known as GC-MS. Some GC-MS are connected to an NMR spectrometer which acts as a backup detector. This combination is known as GC-MS-NMR.

SAMPLE INJECTION:-

The chromatographic analysis with the introduction of the sample onto the  column. The development of capillary gas chromatography resulted in many practical problems with the injection technique. The technique of on-column injection, often used with packed columns, is usually not possible with capillary columns.

APPLICATIONS:-                                                                                                                                    

Used for Food, Beverage and Perfume Analysis                                                                               GC-MS is extensively used for the analysis of these compounds which include esters, fatty acids, alcohols, aldehydes, tarpons etc. Cheek the impurities and residual limits of unknown sample

Here manufactures are two types:

Bulk manufacture: determine residual limits in different processing steps of API

Formulations manufacture: cheek the impurities of drugs pre finishing products.

HEAD SPACE GAS CHROMATOGRAPHY(GC-HS)

       The difference between GC-HS is only in the auto sampler. sample is kept in vials is injected by automatically. Here around 60 samples can be analyse at the time of injection

HS-GC can be used for gas phase analysis of simple or complex gas and liquid mixtures

• Head space oven allows a controlled sample preparation

• Competitive solubility data of several gases (e.g. absorption isotherms) can be examined with high accuracy with a TCD (or) FAD

INSTRUMENTATION:-

Vial preparation with liquids and gases (e.g. ionic liquid + gas mixture)

• Cap with septum keeps the gas phase in the vial

• Several functions allow a controlled sample preparation

• Temperature control for the head space oven

• Shaking device for faster equilibration

• Inert gas insertion for reproducible injection.

RESULTS AND DISCUSSION:

Chromatographically instruments like HPLC, GC are playing major role in pharma industry, which are majorly used in the qualitative and quantitative analysis, the spectroscopic instruments are also more advanced and sophisticated.

CONCLUSION:

After attending the training classes, being with knowledge of analytical instruments is very helpful for completing and continuing a operation in pharma industry and in R&D laboratory.

As a APITCO participant I got the chance of becoming a instrumentally skilled person, I utilised this great opportunity. On the exposure to the industrial staff we found that the Lab staff is really hard working sincere & very co- operative in nature.

3.1.1GENNEX LABORATORIES LIMITED

BULK DRUG MANUFACTURING AND FORMERLY PRUDENTIAL PHARMACEUTICALS LIMITED

Sy.No.133, IDA Bollaram(Village), Jinnaram Mandal, Medak District 

3.1.1. History about the Industry Gennex Laboratory Limited is a Public Limited Company established in the year 1995 and is a ISO 1900-2000 company & engaged in the manufacture of Active Pharmaceutical ingredients and Intermediates.

 

3.1.2 Departments in the gennex lab:

1. WARE HOUSE/RAW MATERIAL  STORAGE 2. QUALITY CONTROL3. PRODUCTION4. PHARMA AREA5. QUALITY ASSURANCE6. STABILITY ROOM7. STORE HOUSE8. HUMAN RESOURCES

 

3.2 Purpose Of Training:

The purpose of visit is to get a firsthand information about the operative system, machines, procedures adopted by the industries in practice and to gain some work experience. Industrial visits provide vital information about the organization, its performances and various functioning process of the organization. It also enables to understand the internal working environment. As organizational behaviour is a part of the management, it is necessary for a manager to understand and get accustomed to the atmosphere of the organization.

3.3 What I have learned

Raw material store/ Ware house Department:

      Required dose of the raw material is purchased by the company and received by the raw material stores.These raw materials are stored under suitable conditions depending upon their requirements. Approved& rejected materials are placed in different places with different colour indications.

Quality control department:

This department is heart of the production department. After receiving the raw material  the material is checked by the QC members for the impurities and for the standards. If the results are negative the product is rejected. these QC testes are done by using

o PH meter

Used for the detection of pH of the sample and  also at the time of reaction some solvents are added at particular pH

o Conductivity meters

It is a temperature depended Automatic electrical conductivity meter (EC meter) measures the electrical conductivity in a solution.

o TDS Analyser:

It is used for the measurement of total contents i.e  inorganic and organic substances present in the liquid in the form of ions or micro-granular (colloidal sol) suspended and molecular form

o Bulk density apparatus:

It is used  to study  the packing down of powder beds of different pharmaceuticals and chemicals in the process of tablet manufacturing and capsule filling

o KER (Karl Fischer reagent) Appartus

For determining the moisture content present in the sample

o MP apparatus

Used for the determination of  melting point

o GC (Gas chromatography)

The instrument used for gas chromatography is known as “aerograph” or “gas separator”.

Make: Chemito

Model: 8610HTgc

Software:N2000

Detector :FID (flame ionization detector).

GC used for qualitative and quantitative analysis. Substances that vaporize below 3000C can be measured quantitatively.

o Vaccum dryer : To remove water content in solid samples

o Sonicator : It is used in the fast dissolution of  solids in liquid samples.

o HPLC (High performance liquid chromatography).

Make: Shimadzu

Model: SPD-M20A

Software:LC solutions

Detector: PDA(prominence diiodide array detector).

Detect the residual limits and impurities of unknown sample and also impurities present in the drug preparations and finished products.

Quality assurance

This department maintains the all records i.e. BMR (batch manufacturing record) and BPR(batch process record)  about the product from the entry of the material to exit of the product. After checking Raw material in QC if it passes the limit it is approved by QA. The final product is also checked and approved by QA.

Production

After  getting approval from QC the product is passed to the production. In gennex laboratories at present 4 types of drugs are manufacturing of different categories.

Bioreactor is a vessel where reaction occurs.4 types of reactors are available, they are 

      SSR     (stainless steel reactor)

        GLR    (glass lined reactor)

        MSR   (mild steel reactor)

       GR      (graphite reactor)

Totally 8 reactors are available in gennex labs, out of 8, 2 are glass lined reactors,6 are stainless steel reactors.Reactor contains motor, gear box, jacket, manhole, vent, light,  scanner, condenser, pressure guage, chargers. There are 2 inlets and 2 outlets they are coloured as follows. 

Colour indications for

                            Steam       - white

                            Vaccum      - blue

                             Air       - yellow

                            Brine solution - black

                            RT out/inlet     - green       

Pharma Area

          Reactor is connected to centrifuge.After completion of reaction in reactor the product is transferred to centrifuge where separation of mother liquor and pure form of product occurs. Then mother liquor is again distilled for solvent recovery.

       Centrifuge

Model:CF101

Rpm:140

Capacity:4000 lt of 48 inches

Here the centrifuge separator cloth is made with polypropylene

Crystalizer: For the recovery of the product from the solvent.

Dryer: drying is done by using FBD(Fluidised bed dryer)

After drying the product is subjected to milling and sieving.finally to the packing.

                                                       Reacted product

                                                         Centrifugation       

                                                          Crystallization

                                                                 Drying(FBD)

                                

                                                                    Milling

            Seiving

                                                                                                                                                                                                                          

                                                                       Packing 

Here for packing the product 2 types of materials are used HDPE (high density polyethylene) & fibre drums depending upon the customer requirements. After approved by the QA the product is packed and placed in the store room.    

STORE ROOM

After QA approval the packed products are labeled according to their quantity, date &storage conditions.

STABILITY TESTING ROOM

The approved samples are collected and sent to stability testing room to test the stability of the product.

BOILER

It is a closed vessel in which water or other fluid is heated. The heated or vaporized fluid exits the boiler for use in various processes or heating applications.

COOLING TOWER

It is a heat rejection device, which extracts waste heat to the atmosphere though the cooling of a water stream to a lower temperature.   *****   

3.1.1(b) AR. Life Sciences Private Limited ,Behind Allahabad Bank, Madhuranagar, Yousufguda Road 

Hyderabad, Andhra Pradesh. 

I have visited another company AR Life sciences

3.1.1 History about the company

      A.R. Life Sciences Private Limited, take immense pride to announce as a recognized manufacturer & exporter of Pharmaceutical Intermediates & APIs. We are an ISO 9001:2008 certified organization; we offer a wide range of qualitative range of products. Our entire range is manufactured in accordance with the GMP guidelines. Our teams of QC and QA stringently test all the products using HPLC and GC instruments in our well equipped laboratory.

3.1.2 Departments in industry

Manufacturing QC QA Warehouse RA R&D Engineering HR

 

3.2 Purpose of Training:

The purpose of visit is to get a firsthand information about the operative system, machines, procedures adopted by the industries in practice and to gain some work experience. Industrial visits provide vital information about the organization, its performances and various functioning process of the organization. It also enables to understand the internal working environment. As organizational behaviour is a part of the management, it is necessary for a manager to understand and get accustomed to the atmosphere of the organization.  

3.3 What I have learn: 

WAREHOUSE

It is place of storage of ingredients. It consists of both imported and exported ingredients. It consists of 3 sub divisions based on the type of ingredient analyzed. Those which are successfully analyzed  are placed in green block and those which are yet to be analyzed are placed in yellow block and finally those which does not meet the fulfillments are placed in red block.The place of warehouse are maintained well in the standard temperatures and relative humidities inorder to avoid deteriation of products

R&D

The products from warehouse are taken in small quantities and are sent for analysis at R&D

Then they are analysed and if they reach the standards they are sent to manufacturing department if not they are sent to rejection block at warehouse.This is department where method of synthesis of sample is done according to the requirement of customer. The details of drug is sent to production department for further synthesis.

MANUFACTURING

It is a place where the successfully analyzed samples are subjected to manufacturing.

This can be done by various types of reactors based on the nature of the sample taken.

REACTORS

There are 16 reactors present in the manufacturing unit. It consists of 2 inlets and 2 outlets which are used for flow of steam ,brine solution etc etc. the differentiation of flow can be distinguished by the colour present on the pipeline

Some of the colour patterns used in this industry are

Stripes of Yellow black    : stream Green                                : RT(room temp) inlet&outlet Sriped Black                     : brine water Yellow                              : air Dotted black                     : chilled water Blue                                  : vaccum Continuous Red               : vents Stripes of red and white   : flow of hydrogen Stripes of yellow and white: flow of nitrogen

Various types of reactors present are

SSR(stainless steel reactor) GLR(glass liquid reactor) GR(glass reactor)

SSR is used to manufacture the samples which are basic in nature.                                                                          

GLR is used to manufacture the samples which are acidic in nature.                                                                            

GR is used to manufacture the samples which are volatile in nature.

Then the finished product from manufacturing are then subjected to centrifuse inorder to separate the solid and the liquid present in the sample and then finally the product from centrifuse is then subjected to drying inorder to remove the moisture content present in the sample.the drying can be done in any one way of 3 processes present depending on the type of sample.

3 types of drying equipments are present. They are

Tray dryer Vaccum dryer RCVD(rotate  cone vaccum dryer)

QC

This is the place where whether the sample taken reaching the standards are not even if any impurity found can be detected. They can be detected by HPLC , PHmeter, conductometry, potentiometry and GC

QA

This is the place where monitoring and evaluation of the various aspects of a project, service or facility is done to maximize the probability so that the minimum standards of quality are being attained by the production process. QA cannot absolutely guarantee the production of quality products.

3.4 CONCLUSION

The three weeks industrial training proved to be a golden opportunity for us in letting us understand various operations involved in pharmaceutical industry.  During our training period we came very close to all the aspects and analysis which we are carried out in the industry at the same time we learn how to follow the rules & regulation as per CGMP and GLP & according to WHO & ISO 9001.

           . I am hundred percent agree that the industrial training program have achieve its entire primary objective. It’s also the best ways to prepare student in facing the real working life. As a result of the program now I am more confident to enter the employment world and build my future career.