Cadila Health Care Ltd.Sarkhej-Bavla road,Moraiya,Tal- Sanad,Dist. Ahmedabad- 382210

Submitted To :

Ms. UNNATI GADE

Mr. DEEPAK DOLE

Prepared By :

Himanshu Patel

PharmD candidate 2014 College of Pharmacy The University of Toledo

Duration Of training :

Summer 2009

Acknowledgement

Writing this acknowledgement has provided me

with the great opportunity to note the enormous

help & guidance given by various persons whose

work was note worthy & can’t be diminished from

my mind & soul.

I would like to mentioned name of some person

because of whose support & co-operation, I was able

to complete my training.

We would also like to thank Mr. N. K. Sinha,

Manager, Human Resources, Zydus Cadila, Mr.

Deepak Dole, Ms. Unnati Gade and Ms. Shreya Shah

who allowed us to take training in such global

industry.

We would also like to thank the entire staff

of Zydus Cadila for their kind and keen interest

during the entire period of our training.

CONTENTS

INTRODUCTION

WAREHOUSE

ASRS Raw Material Packaging Material

CENTRAL PHARMACY

Shifting Milling Dispensing pharmacy

TABLET MANUFACTURING

Granulation Compression Coating

TABLET PACKAGING

Bulk packaging Blister packaging Strip packaging

SOFT GELATIN CAPSULE DEPARTMENT

Suppository

HARD GELATIN CAPSULE DEPARTMENT

PILOT PLANT DEPARTMENT

MET FORMIN DEPARTMENT

TRANSDERMAL PATCHES

QUALITY CONTROL DEPARTMENT

LYOPHILIZATION

PARENTERAL

AEROSOL DEPARTMEN

PHARMACEUTICAL ENGINEERING DEPARTMENT

CONCLUSION

INTRODUCTION

CADILA HEALTHCARE

Cadila Laboratories was founded in 1952 by Shri Ramanbhai Patel (1925-2001), formerly a lecturer in the L.M. College of Pharmacy, and his business partner Shri Indravadan Modi. The company evolved over the next four decades into one of India's established pharmaceutical companies.

In 1995 the Patel and Modi families split, with the Modi family's share being moved into a new company called Cadila Pharmaceuticals Ltd. and Cadila Healthcare became the Patel family's holding company. Cadila Healthcare did its IPO on the Bombay Stock Exchange in 2000. Its stock code on the Bombay exchange is 532321.

In 2001 the company acquired another Indian pharmaceutical company called German Remedies. On June 25, 2007, the company signed an agreement to acquire 100 per cent stake in Brazils Quimica e Farmaceutica Nikkho do Brasil Ltda (Nikkho) for around 26 million dollars.

Zydus Cadila's major shareholder remains the Patel family. Pankaj Patel (1951 - ), son of the founder, is CEO. In 2004 Pankaj Patel was included by Forbes magazine in its annual List of India's richest people. Forbes estimated Patel's net worth at US$510m, making him India's 26th richest person.

IN INDIA:

ACTIVE PHARMACEUTICAL INGREDIENT PLANTS:

The company makes active pharmaceutical ingredients at three sites in India:

Ankleshwar plants - Zydus Cadila's plant complex at Ankleshwar in Bharuch District of Gujarat, has been producing drug material since 1972. There are around 10 plants in the complex, which is ISO 9002 and ISO 14001 certified as well as FDA Approved. Total plant capacity at Ankleshwar is around 180 million tonnes.

Vadodara plant - Zydus Cadila's plant at Dhabhasa, in Vadodara District's Padra taluka (in the eastern part of the district) in Gujarat, was commissioned in 1997 by a company called Banyan Chemicals, and acquired by Zydus Cadila in 2002. The plant has a 90 million tonnes capacity. It is an FDA-approved facility that is also approved to WHO GMP guidelines.

Patalganga plant - Zydus Cadila acquired an API plant at Patalganga in Maharashtra state, 70 km from Mumbai, in the 2001 German Remedies deal. This plant operates to WHO GMP standards.

FORMULATION PLANTS

The company operates formulation plants at six locations:

Moraiya plant - Zydus Cadila's formulation plant at

Moraiya in Sanand taluka on the outskirts of

Ahmedabad is the largest formulation plant in India.

The plant became Food and Drug Administration (FDA)-

approved in 2004/2005. The plant makes tablets,

capsules, and soft gel capsules as well as injectable

drugs in both sterile liquid and lyophilized form. Zydus

Cadila also runs a large R&D operation at Moraiya.

Vatwa plant - Zydus Cadila's plant at Vatwa, an

industrial suburb of Ahmedabad, makes nutraceuticals.

The plant was acquired of German Remedies.

Changodar plant - Zydus Cadila's plant at Changodar,

20 kilometers from Ahmedabad on the city's outskirts,

manufactures fine chemicals. Zydus is current

constructing a facility at Changodar to make vaccines

for hepatitis B and Rabies.

Navi Mumbai plant - This operation, at Navi Mumbai

in Maharashtra, is a 50/50 joint venture with Germany's

Altana Pharma AG, makes intermediates of the drug

pantoprazole.

Goa plant - The Company’s plants at Ponda in the

southern Indian state of Goa do formulation work as

well as manufacture oncology drugs and a herbal

laxative branded Agiolax based on Psyllium seeds.

WAREHOUSE

Warehouse is a primary storage for raw material and packaging material. The material from the supplier first enters in this area.

Warehouse stores raw materials that are under test till manufacturing department need for processing.

Departments:1. Storage for active pharmaceutical ingredient (API)2. Storage for Excipient3. Storage for empty capsule shells4. Storage for packaging material5. Quality control for packaging material6. Sampling of raw material.

Storage Areas :

MATERIAL STORAGE TEMPERATUREActive pharmaceutical ings

Storage in A.C.room (below 25°c tem)

Excipient Stored at room temperatureEmpty capsule shells Stored in an A.C. room (below

25°c tem)Packaging material Stored at room temperature

Active ingredients and capsule shell are very sensitive hence stored at lower temperature.

The stored materials are labeled with different color of labels as per testing done in O.C department.

COLOUR OF LABEL POSITION OF TESTINGYellow under testGreen approvedRed rejected

All are approved samples are sent to respective department as per requirement.

Material Receipt Note are prepared for packaging

Material.

3 copies of material receipt note are required.

1st is for finance it is required for payment.

2nd is for Q.C it is required for sampling.

3rd is for store It is required for record.

For the under test area weight is according to sq route + 1.

ASRS (Automatic Storage Retrieve System):

This area is same as storage area but in this area automatic Train is present.

This Train is controled by computer system, so no more workers are required. Only 3 or 4 people are regulating this system.

Moreover, in this area,the capacity is more than storage area. In this area 5000 pellet are included.

Advantages- Temp. maintainance is easy,

Low a.c. required, Power saving, Less man power required

Q.C. For Packaging Material :

Annealing test is performed for glass ampoules Polaris cope. polarscope consists of a lens and sodium lamp. An ampoule is placed between lens and sodium lamp. Ampoule is rejected if any ring or ring like structure is observed in the lens.

Hydraulic pellet press is used to test the plastic containers. Hydraulic pellet press forms the file of plastic container whose IR spectra is taken to identify the type of plastic.

Bursting strength tester (burst o matic) is used to determine the strength of corrugated box. The pressure required to break corrugated box is measured in PSI unit.

Pinhole detector is used to check the integrity of aluminium foil. This pinhole in the foil is detected manually by keeping on light.

For Raw Material :

In warehouse, we can also store raw material.For it we must have a daily check of its weight on weighing balance.

The main difference between raw material storage and packaging material storage is :-

Temprature

Packaging material is stored only at 25. c, where as raw

material is stored according to.

1. Ambient (room temp)

Not exceed 39.c

2. below 25.c

3. 2 to 8.c (cooling temp)

In U.S. Two brands are available.

1. Tyco

2. Zygneries

In raw material. First Expiry First Out System is must.

Product name for the approved department in

packaging area are :

Losartan ,Riboflavin,Simvastatin.

If material are stored for more than one year,it must be

rechecked before using.

It is also know as Black Area. Because we can not

open any Material in that area.

CENTRAL PHARMACY

Objective :- The role of central pharmacy department in

any pharmaceutical industry is to dispense required

ingredients in required quantity.

The department has various sections as follows :-

1. Raw material staging room

2. Liquid dispensing booth

3. Sifting rooms

4. Sifting material staging room

5. Dispensing booth (total 5)

A. 2 booths for dispensing API

B. 3 booths for dispensing excipients.

1. Raw material staging room :-

According to the B.M.R raw material is issued from warehouse which is then transferred to central pharmacy and is stored in this room.

2. Liquid dispensing booth :-

This room is meant for dispensing of liquid Materials.The liquid material is dispensed through a Pump which is air operated pump. The top of the drum of the liquid to be dispensed is attached to one of the pipe of the pump which withdraws the liquid from the drum due to pressure and the required quantity of liquid coming out is transferred

to the respective drums. The pump has two separate divisions for dispensing.

a) For propylene glycol.b) For liquid other than glycol

Special care is taken for propylene glycol because it is used in manufacturing of parenteral solutions. so the sole aim here to avoid contamination of Propylene Glycol with other liquids.

3 Sifting rooms :-

Equipments : Vibro sifter. Communicating mill.

The solid materials to be dispensed needs to be sifted according to the B.M.R before dispensing. The material is sifted in a sifter. Sifting is done in order to make all the particle of uniform size. For some product even Air Jet Mill is also use to ensure uniformity in particles of given powder. In vibro sifter different type of mesh size is used. For sifting and milling 4 rooms are available.

4 Sifted material staging room :-

Material after sifting are transferred in this room and stored before dispensing. This room serves as store room of sifted materials.

5 Dispensing booths :-

Dispensing booth is a place where actual dispensing takes place. The booths are air locked to prevent the interference of outside air currents. It has reverse laminar air flow so no unwanted air currents are formed inside the rooms. Each booth has 2 weighing machine. one for big quantity dispense and other for small quantity dispense. which are used according to quantities of the materials to be dispensed. The weighing machines are connected to the computer so the quantity of the material dispensed is noted down followed by generation of slip by computer which has all the details of the dispensed drug like. Name of material dispensed.

Temperature of this area NMT 30 ‘C’

Humidity of this area is NMT 60%

The material which is not used must be returned to the warehouse.

Central pharmacy is also known as Grey area because here the material can be Opened.

TABLET MANUFACTURING

Tablet manufacturing is one of the important area as tablets form the major bulk of solid dosage form. The various areas are :-

1 Granulation area2 Granule quarantine area3 Approved granule store4 Tablet compression area5 Tablet quarantine area6 IPQC7 Tablet inspection area8 Coating area9 Approved tablet area

Various methods of tablet manufacturing are :-1 Wet granulation2 Dry granulation (using roller compactor e.g.

chilsonator)3 Direct compression.

General scheme of manufacturing includes :-1 Milling2 Sieving3 Mixing4 Granulation5 Granule drying6 Sieving7 Lubrication8 Compression

The various equipments used are :-

1 Rapid mixer granulator

2

2. High speed mixer granulator

2 3. Oscillating granulator

4. Turbo sifter

5. Multimill

6. Fluidised Bed Drier

1. Egg shell blender1. Rotary press 2. Gans coater 1500 (Gasons)

The various Tablet Ingredient are :-

1 Active ingredient (drug)2 Diluents-lactose. spray dried lactose. mannitol.

Avicel PII 101/102/112 dextrose, Emulex. Celutab etc.

3 Binders-maize starch. PVP, IIPMC, MCCssss4 Disintegrents-Primogel. Explotab. Ac-Di-Sol-MCC5 Lubricants-magnesium stearate6 Chiants –Aerosol Cab-O-Sil talc7 Sweeters-aspartame, eyelamate8 Colors & Flavors.

The various Tablet Defects are :-1 Capping2 Lamination

3 Picking4 Sticking5 Chipping6 Mottling7 Black spots8 Weight variation

Granulation:

For granulation, total 5 areas are available.It is grouped based on the capacity difference.

Area CapacityGra-1 60 kg 150 literGra-2 100 kg 400 literGra-3 300 kg 650 literGra-4 400 kg 750 literGra-5 500 kg 12000 liter

In the process of granulation, ingredients are loaded with The help of vacuum then binder solutions are added in the Rapid mixture granulator.

So wet mass will form. In it impeller is used for good Mixings & cheaper is used for avoid lump formation.

Then drying of the wet mass will done in fluid bed dryer In it with the help of hot air. material get fluidized.

Then material are transferred from different sieves to get In powder form of mixture.

Area 5 is the one of the most biggest area in the granulation process & area 1 is smallest area in this process.

Compression:

In the compression different station machine are available in tablet manufacturing.Total 12 compression machine are in the compression.

Some machine are as follows :

32 station cad mach machine.

12 station cad mach machine.55 station cad mach machine.75 station cad mach machine.

Here cavin & cadmach machine are available in the compression machine.

Generally, in this process first material is passed from the hopper after in the fidder powder filled in die then going in roller and compress the material.

Now tooling is decided according to the product.Tooling is divide in the 3 ports like.

Upper Punch Dye Lower Punch

Function of dye cavity :-

In the dye cavity the material is fill and compressed the both punch & ejected in out side and according to shape product is out side and according to shape product is out side the dye cavity.

75 & 55 station cadmach machine are more high speed in the compressed machine.

55 & 75 station machine are doubled rotary machine in the compression.

Product name : Atenolal

I.P.Q.C. of the compression :-

1. Balance

2. Friabilator To check the friability and tablet strength.

3. Disintegration tester (USP)

4. Weight variation.

Product name : loridine

Coating :-

In the coating process ganscoater machine is used. The capacity of ganscoater machine is 1200 mm.

In this process first the material is sprayed through the spray gun and a film of coat is developed which is then left for 10 min for its drying.

Product name : Simvastatin

I.P.Q.C of the coating :

1 to check the roughness of the tablet2 orange peel3 Sticking & picking

In the tablet manufacturing total bunker area is 12.

Tablet packaging

In the pharmaceutical industry. it is vital step that the package selected adequately preserve the integrity of the product. The selection of a package therefore begins with a determination of the products physical and chemical characteristics. The materials selected must have the following :

1 They must protected the preparation from the Environment Condition.

2 They must not reactive with product.3 They must not impart to product tastes or odors.4 They must be nontoxic.5 They must be a FDA approved.6 High speed packaging material.

The whole packing department is divided into main four areas.

1 Primary packaging storage2 Approved tablet store3 (3) Tablet quarantine store4 Tablet inspection store

There are mainly three type of tablet packaging :1 Packaging of tablet into strips2 Packaging of tablet into blister3 Packaging of tablet into plastic bottle (bulk

packaging)

Blister Packaging :-It is the type of packing in which the tablet is filled into plastic pockets covered with aluminum foil.

The step of packaging are :1 Formation of cavity into PVC foil temp =

100-180c2 Filling of tablet into cavity3 Coding of aluminum foil

4 Sealing of two film temp = 120-230c

5 Cooling6 Cutting of blister7 Packing into final paper box.

The rejected blister are separated from tablet by de-blister machine.

Strip packaging :-

Strip packing is same as blister packing but instead of the plastic foil both the film are of aluminum.

The equipment working on this principle is ROTOVAC 210+.This equipment is also known as ALU-ALU packaging

machine.

The step of packaging are :-

1 Filling of tablet between to foil2 Coding of aluminum foil3 Sealing of two film temp=125-

200c4 Cooling5 Cutting of strip6 Packing into final paper box7 Printing on paper box (mfg & exp date)

Packaging area are of two type :-

1 primary packaging area2 secondary packaging area

Tablet packaging area contain 12 lines :-

1. line 1 Product name-pantodac 10 type blister packing

2. line 2 product name- BQL 10 type-strip packing

3. line 3

product name-MEL.OD 7.5 type-blister packing.

4. line 4 product name-citalipram type-blister packing.

5. line 5 product name- promethazine type-container packing

6. line 7 & 8 product name-losacar H. type-blister packing

7. line 9 product name-warfarin

8. line 10 product name-atenolol type-container packing.

9. line 12 product name-atenolol type-container packing

Packaging :-

The containers used are mainly made up from glass and plastic

Plastic containers :-

The principal ingredient if the various materials used for container is the thermoplastic polymer : Although most of the plastic materials used in the medical field have a relatively low amount of added ingredients, some contain a substantial amount of plasticizers, fillers, antistatic agents, antioxidants and other ingredients added for special purposes.

The ingredients are not usually chemically bound in the formulation and, therefore. may migrate out of the plastic and into the product under the conditions of production and storage.

Considerable variability also has been encountered in the purity of the commercially available polymers.problem of leaching, absorption and permeation.

Glass containers :-

The glass that is most resistant chemically is composed almost entirely of silicon dioxide, but it is relatively brittle and can only be melted and molded at high temperatures.

Boric oxide somewhat modifies the above characteristics as it enters the structural configuration, but most of the other oxides apparently enter the spaces within the structure and reduce the strength of the interatomic forces between the silicon and oxygen.

Therefore, the latter oxides lower the melting point of the glass and are comparatively free to migrate.

Consequently they also lower the chemical resistance of the glass that is, they may migrate into a product over a prolonged period of contact, particularly with aqueous solutions.

Advantages are visibility and cheap and easily made by tubing and molding. The disadvantages are that they are easily breakable.

Blister packaging :-

The vials are packed in the blister and for that the machine is automatic in which one side the PVC roll came and then by means of vacuum the sufficient size of pocket is made and then from the other side the aluminum roll came and then by means of heat the sealing is done and finally at downwards the cutting of the strip occur.

EVALUTION PARAMETERS FOR THE PRODUCTS :-

1 Leak test by means of vacuum is done. if any crack or not properly sealed ampoules easily breaks and

removed. 2 For checking the alkalinity of the glass the test is

performed.3 The BREWITY INSPECTION MACHINE was there for

checking the glass particles, fibers, black particle and white particle in the vials. There are 3 cameras, two of them used for same purpose for glass and fiber particle checking while another with red LED used to check black particle and volume determination.

4 Black particles and white particles is checked against the white and black background respectively manually for ampoules.

Soft Gelatin capsule

Product name1. globac z 2. depin 10 3. depin 5 4. globac PM 5. calcit SG

Manufacturing it is carried out by rotary die process which is a

continuous process & riquires less man power

Manufacturing devided into 2 unit.1. gelatin prepparation2. medicine preparation – 1. sensitice area (Na lamp used)

2. non sensitive area

For benzonatate capsulefor gelatin preparation, 3 equipment are used.

1. gelatin preparation tank. temperature- (55-65’c)

2. colloid mill

3. gelatin paste storage tank . temprature- (45-55’c), humidity-(15-35)

Material added to form gelatin solution are :1. glycerin water mixter2. sorvitol-as plasticize3. methayl & propyl paraben-as preservative4. titanium dioxide5. colour6. flavorPackaging product name- Amlodipin capsule blister packaging sealing temp.210’c top-122’c bottom-123’c

Suppositories :

In this Morayia plant suppository Department is not separately, but it s situated behind the soft gel department.

A suppository is a drug delivery system that is inserted either into the rectum (rectal suppository), vagina (vaginal suppository) or urethra (urethral suppository) where it dissolves.

They are used to deliver both systemically-acting and locally-acting medications.

The alternative term for delivery of medicine via such routes is pharmaceutical pessary.

The general principle is that the suppository is inserted as a solid, and will dissolve inside the body to deliver the medicine

HARD GELATIN CAPSULE

Capsule is an important oral dosage from and has properly to mast the unpleasant taste pf drug. It is one of the leading dosage forms after tablet.

Advantage of Capsule over other dosage formulation :

Good elegance Ease and convenient of use Smooth slippery and easily swallowed Can be used for enteric coating

Departments of hard gelatin capsule manufacturing :

1. Empty capsule storage area2. Filling area3. Coating area4. I.P.Q.C (In Process Quality Control )5. Packaging6. Dispensed material storage area

Actual Manufacturing Process :

Production of pellets :- Equipments used to produce

Coating of Pellets :- Solace aero coater is used for Pellet coating

Five coatings are done on sugar seed to produce enteric coated pallets (of omeprazole)

Name of coating material UseHydrozyl propyl methyl cellulose

provide hardness to sugar seed

Drug (omeprazole) Active ingredientHydroxyl propyl methyl cellulose

Barrier coating

Sodim alginate Separating layerEndragit Enteric coating.

The sugar seeds are placed in solace aero cotter and the coating material is sparaved thought a fine no---less. Before coating process the coating solution is filtered by 1000 sieve to prevent any clogging of fine orifice.

Capsule filling :-

Equipment :- AF-40 and zanasi filling machine.

Empty capsule shell are separated in caps and body which are then passed through filling line where drug is filled in the body. Then cap is inserted on body and filled capsuled are ejected out. These capsules are then passed through polishing machine for finishing.

Temperature :- 22-24.cHumidity :- NMT 55%

I.P.Q.C (In Process Quality Control).

Some filled capsules are randomly selected for Q.C testing. Test for - weight variation.- Content uniformity.- Disintegration time.are performed. Any deviation from standard value leads to rejection of whole batch.

Packaging.

1. Blister packaging :-

It is the type of packing in which the CAPSULE is filled

into Plastic pockets covered with aluminum foil.

The instrument used this principal is

PAM PAC 240 MACHINE .

The step of packaging are :-

1. Formation of cavity into PVC foil.

Temp = 100-180.c

2. Filling of capsule into cavity

3. Coding of aluminum foil

4. Sealing of two file Temp=140-200.c

5. Cooling

6. Cutting of blister

7. Packing into final paper box

Name of some products :-

Piricam-20 capsule. (pyroxicam)

Ocid capsule.

Zylin 150 capsule.

Omeprazole.

PILOT PLANT

Pilot plant is used for the drugs which are under research work. They are prepared in the plant and sent to the research labs and the other batch is discarded. The processes are same as the tablet manufacturing and mat forming but only difference is that only it is small scale production.

The manufacturing procedure is same as in the tablet manufacturing. There are two pilot plants in the zydus cadila, sanand.

Metformin

Category – hypoglycemic agent

Metformin tablet manufacturing involve 7 different area :

1. Dispensing area equipment capacity-500 kg

- 850 kg - 1000 kg

for milling CODDRO mill is used.

2. Staging area

3. Granulation area Equipment used are :

1. RMG-Rapid Mixture Granulator. IPA (isopropyl alcohol)+ water used for binding. temp.- NMT 30’c humidity NMT 60%

2. FBD-Fluidised Bed Dryer used for drying the powder material.

3. OG mill-Ocillating Granulator used to get uniform size granule

4. EGG SHELL Blender Mg stearate MCC (micro crystalline cellulose)

both used as binding agent.

4. Compression area

45 station double rotatory machine used

5. Costing area opadry white=water(aq base)-used for coating.

6. Inspection area

7. Packaging area

Transdermal

A transdermal patch or skin patch is a medicated adhesive patch that is placed on the skin to deliver a specific dose of medication through the skin and

into the bloodstream. Often, this promot es healing to an injured area of the body. An advantage of a transdermal drug delivery route over other types such as oral, topical, etc is that it provides a controlled release of the medicament into the patient. A disadvantage to development however, stems from the fact that the skin is a very effective barrier. A wide variety of pharmaceuticals can be delivered by transdermal patches.

Adverse events

In 2005, the FDA announced that they are investigating reports of death and other serious adverse events related to narcotic overdose in patients using duragesics, the fentanyl transdermal patch for pain control. The Duragesic product label was subsequently updated to add safety information in June 2005.

Types of transdermal patches

1. Single layer drug inadhesive2. multi-layer drug inadhesive

Transdermal manufacturingIn manufacturing of transdermals, fully

automatic machine named transdermal slot die

coater dryer is used The following steps are included.1. blending of drug with proper exipients2. binding of drug with adhesive strip3. adhesive strip covered wuth the covering

strip4. cutting of patches5. Q.C.

6. blister packing

The diclofenac patches were manufactured.

Q.C. DEPARTMENTQuality Assurance systems and test regimens must be in place to ensure that medicines are made reliably and reproducibly, i.e the contents of the container match the label claim.Quality Control evaluation is performed on materials prior to blending to confirm identification, purity and impurities for medicine ingredients and packaging components are as per specifications.The level of active ingredients and other physical and chemical parameters are tested at the completion of the dose form manufacture. As appropriate, microbiological testing is also performed.For all dose forms, tests include appearance, identification/content/concentration of the active ingredient

Other tests may include:

LiquidsColour/flavourpHTabletsRate of disintegration/dissolution in waterHardnessFriability (toughness)SuppositoriesMelting pointSmoothnessHardnessCreams and LotionspHConsistencyLiquid InjectionsFormation of particulates

pH changePackaging integrityVolumeStabilityMajor criteria of medicine R & D and ongoing production are to ensure that a medicine is stable during the shelf life period. By (temperature) accelerated and real time storage, the shelf life of the medicine is established.A stability evaluation program is an ongoing requirement for commercial medicines.Parameters evaluated for stability evaluation include:LiquidsChange of active concentrationIncrease in impuritiesChanges of colour/flavourChanges in pHEvaporation from containersFormation of sediment or crystallisationTablets/CapsulesChange of active concentrationIncrease in impuritiesRate of disintegration/dissolution in waterChanges of colour and appearanceSuppositoriesChange of active concentrationIncrease in impuritiesChange in appearance

Creams and LotionsChange of active ingredient concentrationIncrease in impuritiespHEvaporation and “skinning”Change of colour

Liquid Injections

Change of active ingredient concentrationIncrease in impuritiesFormation of particulatespH changePackaging integrity to maintain sterilityAnalytical instrumental techniques used include high performance liquid chromatography (HPLC), infra red and ultraviolet spectroscopy , coulometric water measurement,pH meters ,gas liquid chromatography. A variety of non-instrumental techniques and wet chemistry methods are used also.

LYOPHILIZATION

Lyophilization is a dehydration process typically used to preserve a perishable material or make the material more convenient for transport.

Freeze-drying works by freezing the material and then reducing the surrounding pressure and adding enough heat to allow the frozen water in the material to sublime directly from the solid phase to gas.

PRIMARY DRYING

During the primary drying phase, the pressure is lowered (to the range of a few millibars), and enough heat is supplied to the material for the water to sublimate. In this initial drying phase, about 95% of the water in the material is sublimated.

In this phase, pressure is controlled through the application of partial vacuum. Furthermore, a cold condenser chamber and/or condenser plates provide a surface(s) for the water vapor to re-solidify on. Condenser temperatures are typically below −50 °c (−60 °f). During the primary drying phase, the pressure is

lowered (to the range of a few millibars), and enough heat is supplied to the material for the water to sublimate. In this initial drying phase, about 95% of the water in the material is sublimated.

In this phase, pressure is controlled through the application of partial vacuum. Furthermore, a cold condenser chamber and/or condenser plates provide a surface(s) for the water vapor to re-solidify on. Condenser temperatures are typically below −50 °c (−60 °f).

SECONDARY DRYING

The secondary drying phase aims to remove unfrozen water molecules, since the ice was removed in the primary drying phase. This part of the freeze-drying process is governed by the material’s adsorption isotherms. NOTE:After both the phases of the drying process are completed the temperature of the product is about 30ºC and the product is in fine and solidified free flowing form. Also the freeze dried material is supplied along with WFI with which it is to be reconstituted before use.

PARENTRAL DEPARTMENT

Parentral [par- beyond, enteral- git] are injectables containing one or more medicament dissolved or suspended in a suitable vehicle and are introduced into body from any route other than oral. It is administered by means of an injection.

PARENTERAL SECTION -

Gray zone of parentrals.

Storage room Wasting Decartoning area Washing and sterilization area Quarantine I.P.Q.C Janitor room Inspection area

White zone of Parentral.

Filling and sealing area -Sterilization area.

PROCEDURE-

Raw material from ware house -Raw material is supplied by the ware house as per BMR and is stored in storage room at suitable temperature and humidity.

Decartoning of ampoules and vials. Washing and sterilization –

Equipments- Ampoule washing machine

Ampoule sterilizing tunnel Depyrogenating tunnel

Washing - It is carried out by-

* Highly purified water (60c) passed through 1 Om filter.

* Air jet (0.2 m filter) of compressed air. Two jets of air

* Water for Injection (WFI)* Air jet.

Sterlization-Ampoules are then passed to Ampoule

sterilizing tunnel to dry heat sterilizer (Pejroklenz co.) where they are dry heat sterilized at a temperature of 330-370ºc.

Cooling- They are then cooled by air and HEPA filters.

Ampoule filling and sealing -This is carried out in class 100 aseptic area with:Vertical laminar air flow system.

Equipments - Ampoule filling machine

ampoules are filling at one time.

Filling-

Ampoules are first exposed to nitrogen gas to remove 02 present in it. Then they are filled with accurate close of medicament are re-exposed to nitrogen.

Sealing-

Ampoule sealing is done by pull-sealing method using a flame of Oxygen and LPG. The ampoules are allowed to rotate and the flame is concentrated on sealing point. As the glass is sealed, remaining part pulled off.

Moist heat sterlization-

Sterilization is done in order to remove and kill all micro organisms and bacteria from preparations.

Equipment- Double door autoclave. Temperature- 121 -124ºc.

Time- 20 minutes.

o One door of autoclave opens to filling and sealing area while other opens to unit operation area. There are certain loading patterns which are strictly to be followed.

o PLC (Programmable Logical Curve) display reveals - temperature relationship used during sterilization process. The room also consists of an LAF of efficiency 100/f per min. + 10.

o Leak test of ampoules- Ampoules are kept in inverted position in autoclave (0.15 vacuums) for 5 minutes. Then they are weight to analyze lose of fluid.

Inspection-

The stored finished product is transferred to inspection room from quarantine. There are three methods of inspection- Visual inspection- This is done manually by

checking in front of black and white backgrounds respectively.

Semi- automatic inspection-Equinity- checking machine. It is used only for fibers and particles. Four ampoules are checked at one time. Inspection is manual.

Automatic Inspection-Equipment-Automatic inspection machine.

Optical rejection can be done due to presence of fibre, black particle, glass particle, improper sealing and less volume.

Packaging and Labeling-

Ampoules are blister packed with one foil of PVDC and another printed aluminum foil which consist of following information-

Name of medicament Quantity Composition Dosage Name of manufacture Marketed by Batch no. Expiry date Equipment -HSP ampoule sticker labeling

machine.

HOW TO USE AMPOULE:

According to WHO, ampoule has an OPC (One Point Cut) mark from where they are to be broken. Force is applied on head of ampoule by thumb tip and is broken at OPC.

MARKETED PRODUCTS OF ZYDUS CADILA:

Dexamethasone Fosoline

Ranitidine injection LP (R-loc)

R-hu-erythropoitin injection Brand name- Zyrop 2000 with WFI.

Dexona injection.

AEROSOL DEPARTMENT

Aerosol is defined as a pressurized dosage form which contains active pharmaceutical ingredients and works by actuation and thus produces a dispersion of liquid alone/ liquid with solid.

COMPONENTS OF AN AEROSOL Material air lock propellant area Washing area Manufacturing area Can cleaning and filling area Quarantine area Spray checking area Pre packing area Labeling and packing hall Space for finished goods and package

APPARATUS USED FOR MANUFACTURING OF AEROSOL

Can cleaning machine Aerosol filling machine Weighing machine Spray checking and labelling machine Over wrap machine Carton sealing machine Procedure:

Aluminium cans cleaning & washing Add the API(active product ingredient) and

additives Filling in the al. cans with propellent-11 as in liquid

form Capping of these cans Add the propllent-12 as in gas form for pressurized

spray Store in Qurtanine area for 28 days as in inverted

position Check the leak test Al. cans put in water for 4-5 minutes as check leak

test. Check the pressure gauze and crimp test Packing

NOTE:

Temp. of mixing of propellent & api is 4-3c as chillerTemp. of manufacturing area is 25-27c and humidity is 30% HrJacket temp is 4-12cPropellant -11 is in liquid form, chemically it is tri chloro mono floro methane, it is required for mixing with api.Propellent -12 is in gas form, chemically it is di chloro di floro methane, it is required for pressurized of api, But it is harmless to ozone layer of

environment, so it is less used, In place of this ,HFA may used.

PRODUCTS OF AEROSOL AS NASAL SPRAY:

Tiotropium Bromide & formotenolTiomistFormoterol fumaral & fluticasoneNovolizerPlaceboSalbutamolFormonidePropionate dry powderBudesonide and formoterol fumarate

PHARMACEUTICAL ENGINEERING DEPARTMENT

Two Bore wellsApplication: Raw water generation

1. Near canteen 2. Behind pump house

Depth - 274 meter (900 ft.)

Diameter - 200 mm (8 inch)

Water level -50 meter (164 ft)

Capacity -45-55 m3/hr

Pump -KSB

Type -submersible

Motor -33 HP

Multigrade filer -

Filter media 1200 mm

Diameter x 200 mm ht. Mixture of 6 - 14And 16-30 mesh sand up to 950 mm ht. and 1/4 ' t o 1/16 " gravel (400 kg) for 100

Mm depthPiping-PVCCartridge filter Membrane - expanded PTFE RO Unit feed water flow - 24.5 m3 / hr

Permeate flow - 19.6 m3/hr Reject flow - 4.9 m3/hrTotal recover 80 %

Control panel for ROConductivity < 200 us /cmPH range 6.5 to 7.5

RO water

50 KL SS tankConductivity - < 200 µs /cm

Used for DM plant & Softening plant

Boiler feed water to make steam

DM plant Cation unit: Remove cationic impurities

Anion Unit: Remove

7th & 8th RCC Tank

Processing water for drinking &

anionic impurities

List of systems:1. Pre-treatment system2. RO system3. Demineralization unit4. Softener

Pretreatment system scheme

BorewellSectionWater

Row water-

Storage tank

MGF RO

NaOCLFeCL-i dosins

Drinking water usage

CONCLUSION.

It was a great experience for me to take training in such a renowned & well established pharmaceutical company.

This training period. during my educational period was very important for me to improve myself as a pharmacist. It helped me a lot in gaining practical knowledge & what are the latest invention & research going on. Also this training was beneficial for me because it was a chance where I was able to imply my theoretical knowledge & for this.

I am thankful to ZYDUS CADILA Pharmaceutical & my college Institute of Pharmacy.

I am sure this training will help me a lot in future as a Professional pharmacist.

Himanshu PatelStudent Pharmacist,UT college of pharmacy