Navana Pharmaceuticals Limited

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 In Plant Training Program in

Navana Pharmaceuticals Limited

QUALITY POLICY OF

NAVANA PHARMACEUTICAL LTD.

Navana’s mission is to achieve business excellence through product quality and committed to ensure customer satisfaction by exceeding their level of expectations.

It is the policy of Navana to ensure all products manufactured in the factory pass through appropriate product development activities and to monitor product quality throughout its shelf life.

Navana is committed to comply with the WHO cGMP standards and will follow local drug regulatory norms in every phases of product development, manufacturing quality assurance and distribution of medicines.

Ensure all activities through documented quality management system (QMS) complying International standard requirements of ISO 9001:2000 through continuous developing of Human resources.

Navana will continually improve the effectiveness of quality Management System and will undertake appropriate review, evaluation and performance measurement of its operations to ensure complains Quality policy.

Purposes of in-plant training:

Pharmacy is the art and science of preparing & dispensing medications and the provision of drug & related information to the public. A pharmacist is a specialist in medications, a custodian of medical information, a companion of physician, a counselor to the patient, and above all, a guardian of the public health. Thus pharmacists, have a very important role- in the national health care system. They are rendering valuable services to the people- by making quality medicines.

In order to build up more efficient pharmacist in all aspects of this noble profession the students studying in B.Pharm (Honors) course are designed by their respective authorities to acquire practical knowledge from the renowned pharmaceutical industries because they could not have opportunities of occupying themselves with applied phenomenon on the medicinal products beyond their theoretical lessons as well as industrial operations.

With this view i.e. to make the students efficient and professionally skilled pharmacists, the Department of Pharmacy, University of Science and Technology, Chittagong (USTC) sent us to the NAVANA Pharmaceuticals Ltd. for our training. It was our great pleasure to join this In-Plant Training iin NAVANA Pharmaceuticals Ltd. which is one of the most well organized Drug manufacturing companies in Bangladesh. There we completed the In-Plant Training from 6th November, 2010 to 7th December, 2010. During this training, we were exposed to different production sites, Quality Assurance and Quality control department, Product development. We also gathered knowledge about Administration, Inventory control and planning, Marketing and Warehouse. We would try our best to summarize our gathered achievement at In-Plant Training on this report. The certificate given by the company after completing the training is to be submitted to the pharmacy council or pharmacy registration examination. Without this certificate no student will be allowed to appear in this exam.

Purpose of this report:

The report which is submitted after the training program is a reflection what the trainee have learnt. It also improves the writing and presenting skills. It also says the limitation and perfection of the company, so the report is important both for the trainee and the plant.

We, the three students of 15^th batch of Pharmacy Department of University of Science and Technology, Chittagong (USTC) have successfully completed the one month training in Navana Pharmaceuticals Ltd. We took the notes during our visit to different departments. So, this report will only represent what we have seen, what we have learnt and what we have been taught.

We hope this report will help us to implement our experiences in our working field. We will feel worthy, if this report helps other pharmacy students to learn about Navana Pharmaceuticals Ltd.

Quality of drugs:

Generally we take drug to prevent, moreover to treat a disease. If the drug is therapeutically active and has the capability to show its credit for the desired reason then we can call the drug as a quality drug. We should remember that the elegancies as well as appearance can increase the drugs acceptability.

According to ISO 8402 quality is defined as” Total of features and characteristics of a product or service that bears on its ability to satisfy a given need’’.

Aspects of the quality of a drug:

Drug is one of the prime tools for saving lives. A medicinal product must satisfy certain standards to claim it to be a quality drug. The main criteria for quality of any drug in dosage form are it’s-

· Safety · Potency

· Efficacy · Stability

· Acceptability · Regulatory compliance

QUALITY ASSURANCE:

Quality Assurance is the sum total of the organized arrangements made with the object of ensuring that the product will be of the quality require by their intended use. It is good manufacturing practice plus factors outside the scope of these guidelines. The chain of quality assurance activity stretches from the product development stage up to the end users. Quality Assurance is a wide ranging concept which covers all matters which individually or collectively influence the quality of a product. It is the sum total of the organized arrangements made with the object of ensuring that medicinal products are of the quality required for their intended use. Quality Assurance therefore incorporates Good Manufacturing Practice plus other factors outside the scope of this Guide.

QA = Product design + GMP + QC + Quality goal activities

Objectives of quality assurance:

1. Raw material specifications

2. Packaging material specifications

3. Intermediate product specifications

4. Bulk product specifications

5. Finished product specifications

Quality control:

Quality control is a part of quality assurance. Quality control refers to the process of striving to produce a perfect product by a series of measures requiring an organized effort by the entire company to prevent or eliminate errors at every stage in production. It concerns quality control of raw materials, finished products and packaging materials.

Quality control is a comprehensive course which will help all students quickly and easily identify and correct error in quality control procedure.

QC = Test +Assessment

Raw materials specification depends upon the following parameters:

• Appearance · Odor

• Solubility · Water Content

• PH · Residue on ignition

• Heavy metals · Absorptivity

• Assay (HPLC/IR/UV) · Loss on drying

• Viscosity · Melting point

• Turbidity · Bulk density

• Sterility/Pyrogen · Screen test

• Specific gravity · Specific volume

In process control:

The In-process control is the checks made during the course of manufacturing process which aims to ensure that product will comply with specifications. Thus quality is built into the product. Although these checks are not a part of final product specifications but done as a part of control evidence that the correct operations did apply during manufacture.

Advantages of IPC:

· Allows timely action

· Improves productivity

· Reduces rejection cost

· Reduces the chance of batch failure

Some commonly performed IPC checks:

Process	In-Process checks
1.Dispensing	Weighing and recording.
2.Mixing	Time and speed, Temperature.
3.Granulation	Time and speed, Homogeneity of the content.
4.Drying	Temperature (Inlet and outlet air), Time, Pressure, LOD (Loss on drying).
5.Tableting	Machine speed, Compression pressure, Thickness, Hardness, Appearance, Friability, Disintegration time, Dissolution test.
6.Coating	Temperature, speed, Uniformity, Spray rate, Degree of atomization and Weight.
7.Oral liquid	Temperature curve of heating jacket.

In process quality control depends on the following parameters:

A) For Tablet:

• Blend uniformity · Loss on drying

• Appearance · Average weight

• Dosage uniformity · Hardness

• Thickness · Friability

• Weight variation · Disintegration

• Dissolution

B) For Liquids:

• Appearance · pH

• Specific gravity · Viscosity

• Re-suspendability · Flavor

· Preservative · Average fill intent

Quality control after granulation:

Only moisture content will be detected after granulation.

Quality control after mixing:

• Moisture content.

• Blend assay (for those drug, which has very small quantity of drug content)

Quality control after compression:

• Length · Width

• Thickness · Hardness

• Friability · Disintegration time

Quality control for coating approval:

· Hardness · Friability

• Moisture content · Disintegration time

• Average weight of tablet · Drug content

In process quality control for Blistering:

• sealing temperature · Pre heat temperature

• Air press in bar · Room temp.

• Humidity · Batch coding

• Visible defects · Foil Alignment

• Leak test.

In process quality control for Packaging Materials:

• Faulty container or closure

• Mislabeled product

• Printing errors

Finished Product:

Finished product testing should be performed by the quality unit & should conform to written specification.

Finished product specification depends on the following parameters:

For Tablets:

· -Dosage uniformity · Loss on drying (LOD)

· Hardness of tablets · Thickness of tablets

· -Disintegration · Dissolution

· -Average weight

For coating:

· Temperature ‹Inlet and outlet air› · Speed and time

· Uniformity and weight · Appearance

· Disintegration time Dissolution test

For Liquid:

· Appearance · P^H

· Specific Gravity · Foreign matter

· Assay · Viscosity

· Fill variation · Volume in container

For Capsule:

· Moisture Content

· Disintegration

· Average weight

· Sealing

· Polishing

For Dry syrup:

· P^{H ?}Viscosity

· Moisture Content Potency

· Weight variation

Documentation:

Documentation is a prime necessity in quality assurance. Its purpose is to define the system control, to reduce the risk of error, so that personnel are instructed in details of and follow the procedures concerned and to permit investigation and tracing of defective products.

To facilitate proper and effective use of documents they should be designed and prepared with care.

1. The title, nature and purpose of the document is to be clearly stated.

2. The way the document is to be used, and by whom, should be clearly apparent from the document itself.

3. Where documents bear instruction they should be written in the imperative. They should be clear, precise and in language the user can understand.

4. Documents, which require the entry of data, should provide sufficient space for the entry.

5. Reproduced documents should be clear and legible.

Flow chart for Quality Assurance activity:

Receiving of Raw & packaging Attachment of quarantine

Materials by visual inspection Tag of yellow color

Sampling of raw & packaging

Materials for QC analysis

Release / rejection Attachment of respective

tag for raw & packaging

materials.

Dispensing of raw & packaging

Material

Checking of cleanliness,

Approval of equipment

& area of manufacturing

In process checking of Sampling of in process

Some parameters during Product to Q.C.

Compression, filling etc.

In process checking of

Packing operation

Transfer of finished product

For distribution after

Collecting the retention sample

Investigation of product complaints,

product recall returned product from

market

Equipment in Quality Assurance:

Name	Source	Scope	Calibration Time Interval	Calibration Factor
Digital Polarimeter	England	Determination of Specific Optical Rotation	6 month	Quartz control cell
Karl Fischer		Bound moister determination	1 month	Electrode sensitivity
High Pressures Liquid Chromatography (HPLC)	Poland	Qualitative and Quantitative analysis	6 month	Retention time, Peak area.
Fourier Transform Infra-Red Spectrophotometer (FTIR-8101A)	Japan	Sample identification	3 month	Shape of power spectrum , Wavelength (accuracy, resolution, reproducibility)
UV-Spectrophotometer (UV-1601pc)	Japan	Identification and Potency determination	3 month	Control of absorbance (235, 257, 313 and 350 nm.),Cell (Holmium and Didymium cells )
Disintegration Tester	India	Disintegration time	6 month	Temperature and cycle.
Dissolution Tester 8 stage basket system‹TDT-08L›	India	Dissolution	6 month	Temperature and rpm
Tablet Friability Test apparatus USP	India	Friability	6 month	rpm
Digital Tablet Hardness Tester‹TSF-1000›	England	Determination of Tablet Hardness
Analytical balance	Switzerland	Weight	3 month	Wight (BSTI approval).
Melting point Apparatus	England	Identification	1 year	Vanillin, Phenacetin and Caffeine
Slide Caliper	Poland	Size, Diameter, Thickness
Centrifuge Machine‹ S-549›	UK	Analytical Work in QA		rpm
Magnetic stirrer	Germany	Mixing
Opti-melt ‹Automated melting point system›	England	Determination of Melting Point.	1 year	Vanillin, Phenacetin and Caffeine
Vacuum Oven	England	Drying		Temperatre
Laminar Air flow cabinet (HEPA)		To avoid cross contamination
Sartorius PH meter	Germany	PH	daily	PH (4,7,11)
Moister Analyser	USA	LOD	3 month	Wight
Digital Automatic Tap density test Apparatus(350T)	Germany	Determination of Density
Micrometer(PAT No.200959)	Japan	Thickness of package

Figure: UV machine (Double beam spectrophotometry)

Figure; F510 FT-IR Spectrophotometry

Some of the reagents:

?Karl-Fischer reagent, ? Bromocresol green,

?Crystal violet, ?a-Naphthol benzene,

? Methanol, ?Methyl orange/ red,

?Phenolphthalein, ?Chloroform,

?Starch, ?Na-acetale buffer,

?Potassium iodide, ? Acetic acid.

?Iodine solution, ?Acetonitrile,

? 2- Butanol, ?Citric acid,

?Cyclohexane, ? Hexane,

?Ether, ?Dithiozone etc.

All reagents are of pharmaceutical standard sources.

Some of the glass wares:

?Conical flask, ? Burette,

?Pipette, ?Volumetric flask,

?Beaker, ?Graduated cylinder,

?Separating funnel. ?Glass bottles,

? Round bottom flask, ? Desicator etc.

All instruments are of pharmaceutical standard.

General Introduction:

Solid dosage forms are some of the least expensive, most popular and convenient methods for drug delivery. They can be produced in a non-sterile environment and the technology is well-known after more than 100 years of development. Since most pharmaceuticals are produced in solid dosage forms, it is important that the unit operations for their production be thoroughly understood. This course focuses on the fundamentals of each discrete processing step (unit operation) required for the manufacture and packaging of tablets and capsules, the most common of solid dosage forms.

Total Units in Production Area

Manufacturing area Packaging area

?

Liquid manufacturing Solid manufacturing

?

Granulation unit Compression unit Coating unit Capsule filling unit

1. Introduction of Tablet

DEFINITION:

Tablets may be defined as a solid unit dosages form of medicament or medicaments with or without suitable diluents and prepared either by molding or by compression. They vary greatly in shape, size and weight which depend upon the amount of medicament and mode of administration.

Tablet contents:

Compressed tablets usually consist of active medicaments mixed with a number of inert substances known as excipients. These additives are added to given the qualities of good tablet. Although these additives are termed as inert but they have a great influence on stability, bioavailability and the process by which the dosage forms are prepared. According to the functions, which these additives play in the preparation of tablets, they are follows:

1.Diluent 5.Lubricants

2.Binders 6.Colouring agent

3.Granulation agent 7.Flavouring agent

4.Disintegrating agent 8.Sweetening agent

Diluent

When the quantity of the drug for an individual dose is very small and it is not practicable to compress such small amount in the form of a tablet then the inert substances which are to increase the bulk of powder to be easily compressed are known as diluent. For example-lactose, sucrose, mannitol, dextrose, calcium sulfate dehydrate, starch, microcrystalline cellulose (Avicel PH101,RC 591), sorbitol.

Binder:

Agents that are used to convert granules from crystalline form before compression to impart cohesiveness to the powdered substance are known as binders. e.g: Polyvinyl pyrrolidone (povidone K-90),Crosspovidone,Starch-1500 partially pregalatinize maize starch.

Disintegrant

They help the tablet to break down into small fragments, when it is ingested to dissolve and be taken up by the body so that it can act more quickly. For example-Sodium starch glycolate (Primojel), veegum, bentonite, agar, CMC, MC, Na-alginate, citrus pulp, microcrystalline cellulose (Avicel), maize starch(dry).

Glidant:

The glidant helps to make the powder free flowing stopping it from forming lumps.e.g: Talc, corn starch, aerosil, colloidal silica etc.

Lubricant

Lubricants ensure that the tablet has a smooth surface and that the powder does not stick to the equipment used to make the tablet. eg : stearic acid, Mg-stearate.

Switeening agents

These are used for tablets need to be dissolved in buccal cavity.eg: Sucrose, lactose, mannitol, saccharin, aspartame, Acesulfame potassium ,Sorbitol solution 70% etc.

Flavour:

Flavouring agents help to make the tablet taste better. Example: Cherry cream, Lemon, Orange, Pineapple, Raspberry, vanillia etc.

Colorant:

Colours are added to help you to recognize your tablet and to make it easier to take your medicine correctly.e.g: Color iron oxide (red,yellow), Color lake brilliant(blue), Color lake orange (yellow), Color lake quinoline (yellow), color raspberry (red), Color red 2G, Color lake erythrocine(red) etc.

Tablets are usually right, circular solid cylinders, the end surfaces of which are flat or convex and the edges of which may be beveled. They may have break-marks and may bear a symbol or other markings. Tablets may be coated.

2. Production of tablet:

In tablet production there are several steps involved which are following:

• Dispensing and Granulation.
• Blending
• Powder compression
• Coating
• Blistering / Striping /Filling.
• Secondary Packaging.

GRANULATION UNIT

DEFINITION:

Granulation may be defined as a size enlargement process which converts small particles into physically stronger and larger agglomerates in order to facilitate the flow and compression for the production of tablet. All the materials are received from the dispensing unit and granulation is performed. For suitable granulation, it is required to have 30-40% powder and 60-70% granules and also 1-5% moisture in compressing particles.

Purposes of granulation:

-To produce tablets of appropriate size.

– To prevent segregation of the constituents in the powder mix.

-To improve the flow properties of the powder mix.

-To improve compression nature of powder.

Types of granules:

Two types of granules are produced in the four-granulation units of the industry, which include;

· Granules with active ingredient/s

· Placebo granules without any active ingredient/s for moisture sensitive active/s or drug/s

Granulation Processes which are performed in the NAVANA plant are following:

· Wet Granulation.

· Dry Granulation.

· Direct compression

Wet granulation:

Wet granulation is a process of using a liquid binder or adhesive to the powder mixture to produce the granules. The amount of liquid can be properly managed, and over wetting will cause the granules to be too hard and under wetting will cause them to be too soft and friable. Aqueous solutions have the advantage of being safer to deal with than solvents.

Weighing of active ingredient as well as excipients ¯ Dry mixing ¯ Wet mixing (in case of wet granulation) by addition of de-mineralized (DM) water or Maize starch paste in Rapid Mixer Granulator (RMG) for a certain time period specified in the Batch Production Record (BPR) ¯ Initial Phase drying in Fluid Bed Dryer (FBD) ¯ Milling in the Multi mill ¯ Partial drying in FBD ¯ Milling in the Multi mill ¯ Terminal/Final drying in the FBD ¯ Sieving in the Vibratory Sifter according to the required particle/granule size ¯ Measurement of Loss on Drying (LOD) ¯ Granules of desired size ready for blending.

Dry granulation:

This process is used when the materials needed to be granulated are sensitive to moisture and heat. Dry granulation can be conducted on a press using slugging tooling or on a roller compactor commonly referred to as a chilsonator. Dry granulation equipment offers a wide range of pressure and roll types to attain proper densification. However, the process may require repeated compaction steps to attain the proper granule end point.

Dry granulation

Weighing of drugs and excipients   Dry mixing of drugs and diluents   Slugging or pre-compression   Milling and sieving   Lubrication   Discharge for compression

Direct compression:

This method is used when a group of ingredients can be blended and placed in a tablet press to make a tablet without any of the ingredients having to be changed. This is not very common because many tablets have active pharmaceutical ingredients which will not allow for direct compression due to their concentration or the excipients used in formulation are not conducive to direct compression.

Mixing & Blending:

Mixing/blending may be defined as a process where two or more components or substances are treated so as to lie as nearly as possible in contact with particle of each of the other components or substances with uniform distribution of each component. A powder blend should be as uniform as possible to assure the proper amount of medication in each dosages unit. Small particles are difficult to blend because they exhibit poor fluidity. However, more important than actual particle size is particle size range.

EQUMPMENT IN PRODUCTION UNITS:

Name Source Capacity

High speed mixer Thailand 120Kg/300L

Granulator (MG -300)

Mechanical Shifter-30”M India

Multi mill-SMT India

GFG High Efficiency Fluid Bed Dryer China 120Kg

Oil Jacked Vessel for Bangladesh 40L

Paste preparation

Double Cone blender (DCB-120) India 150Kg

Double Rotary Tab Compression India 65000/hr

Machine (Clit-27 station)

Double Rotary Tab Compression India 52000/hr

Machine (Adept-25 station)

Excella-2000(20 Station) India 33000/hr

Thai-coater 32” Thailand 50Kg

NR-Cotar-39”‹FC-39› Thailand 80Kg

Features	Excella-2000(20 Station)	Double Rotary Tab Compression Machine (Adept-25 station	Double Rotary Tab Compression Machine (Clit-27 station)
Source	India	India	India
Based on pressure	Dtooling	Dtooling	Btooling
rpm	28	18	22
Capacity	33000?hr	52000/hr	65000/hr
No. of station	20	25	27

Rapid mixing granulator(RMG)	Fluid bed dryer
Fig: Double cone blender

Tablet compression:

Compression of powders or granules means a reduction or bulk volume of a material as a result of displacement of the gaseous phase. Compression may also be defined a s the process of applying external mechanical forces to the material or the process of pressing materials to make it more firm and rigid solid. Compression is used for the manufacturing of tablet.

In the compression of active pharmaceutical ingredients, overall control is essential to ensure high quality.

Physics of tablet compression:

· ?Transitional packing

· ?Deformation

· ?Fragmentation

· ?Bonding

· ?Deformation of solid body

· ?Ejection

Fig: Tablet compression cycle.

Common Problems that arise during Compression:

Common Problems that generally arise during compression are-

? binding to the dies and punches

· Capping and splitting

· Lamination and Chipping

· Picking and Sticking

· Weight variation

· Mottling

· Hardness variation

· Double impression

· Pitted surface

· Drug instability

TABLET Coating:

Fig: NR-Cotar-39”‹FC-39›

DEFINITION:

Coating is the process of compressing a granulating layer around the preformed or pre-compressed tablet that is the core tablet. It is an additional step for manufacturing of tablet. The substances used as coating substances are usually applied as a solution or suspension in conditions in which evaporation of the vehicle occurs leaving a polymeric layer.

Classification of Coating:

Mainly three types of coating are performed in the solid section. They are as follows:

Coating

Sugar coating Film coating Enteric coating

1 Aqueous coating

2 Non aqueous coating

1. Film coating:

Film coating is the process which involves the deposition of polymeric substances as continuous and non-porous membrane over the surface of the core tablet. In film coating the thickness of the coat is 30-100µ.

Film coating process is based on two distinct phenomena-

1. Formation of film over the surface of the core tablet known as cohesion,
2. Bonding between polymeric film and the surface of the core tablet known as adhesion.

Polymers used in film coating:

Hydroxy propyl methyl cellulose, methyl hydroxy ethyl cellulose, ethyl cellulose, hydroxy propyl cellulose,Na-CMC, Poly ethylene glycol, acrylate polymer.

Steam temperature:

Coating	Inlet	Outlet
Organic	62-650c	42-450c
Aqueous	70-750c	50-550c
Enteric	5o0c	320c

3. Enteric coating:

It is a coating technique applied to tablets to protect the tablet core from disintegration in acid environment of the stomach to protect the acid labile drug and to avoid gastric discomfort or to delay disintegration until they reach the upper intestine.

There are two steps for enteric coating

?.Sub-coating: By using HPMC as polymer with either organic or aqueous solution. This process performs for 5 hours.

??.Enteric coating: By using udragil L-100 or L-50 over the sub coating. This is done for 15 hours.

Polymers used in enteric coating:

Hydroxy propyl methyl cellulose phthalate, poly vinyl acetate phthalate, cellulose acetate phthalate, methacrylic acid‹Udragil›-L-100, S-100,L-300.

Condition required during Coating:

· Relative Humidity: Not more than 50%.

· Temperature: Below 25⁰C.

Common problems associated with tablet coating:

1. Logo bridging

2. Core erosion

3. Edge chipping/erosion

4. Picking/sticking:

5. Cracking: 6. Peeling

7. Orange peel/roughness

8. Twinning:

9. Tablet-to-tablet color variation

Number of tablet being produced in Navana Pharmaceuticals ltd.

· 2. Capsule

DEFINITION

The word “capsule” is derived from the Latin word “capsula” meaning small box. Dosages forms in which unit doses of powder, semisolid or liquid drugs are enclosed within either a hard or a soft envelope or a shell are called capsules. Usually the shells are composed of gelatin.

Several categories of capsules may be distinguished:

• hard capsules;

• soft capsules;

• gastro-resistant capsules;

• modified-release capsules;

Steps involves in capsule manufacturing:

?Developing and preparing the formulation and selecting the capsule size

?Filling capsule shells (encapsulation),

?Sealing and

?Polishing the filled capsule (if required)

(The industry does not manufacture any capsule shell.

The active is filled in the empty the hard gelatin capsule shell in the form of-

Ø Powder

Ø Pellets

The different sizes of hard gelatin capsule shells used in pharmaceutical manufacturing are- –

SHELL SIZE FILL VOLUME‹in ml›

000 1.36

00 0.95

0 0.67

1 0.50

2 0.37

3 0.30

4 0.21

5 0.12

The capsule sizes used in Navana Pharmaceuricals Ltd. for general production-

Size-0, 1, 2, 4.

# Encapsulation Process by Automatic Capsule Filling Machine:

For encapsulation of pellets the following procedure is done with the help of Automatic Capsule Filling Machinein the capsule filling units of Navana Pharmaceuricals Ltd.

Blend Pellets with NPS

¯

Encapsulation

¯

For encapsulation of powder,

¯

Blending

¯

Slugging

¯

Granulation

¯

Sieving

¯

Encapsulation

Encapsulation Process by Manual Capsule Filling Machine by Hand:

For encapsulation of powder the following procedure is done with the help of Manual Capsule Filling Machineby hand in the capsule filling units of the industry:

Loading of capsule in the loading plate

¯

Removal of caps of the shells

¯

Filling of powder

¯

Rejoining of caps of the shells

¯

Encapsulation

¯

Sorting of Capsules

¯

Polishing of Capsule

Machineries used in capsule manufacturing:

Machine name	Machine specification	No of station/hole	Model	Manufacturer
Semi automatic Capsule filling machine (Scorpio)	Capacity: 18000/hr Capsule fill	600	MEC-MX.115-1	P+am pharmaceuticals, India.
Automatic Cap-filling machine	Capacity: 40000/hr Capsule fill	48	AF-40T	P+am pharmaceuticals, India.
Hand filling capsule machine	Capacity: 12000/hr	300	MF-30	P+am pharmaceuticals, India
Double cone Blender(DCB150)	Capacity: 150Kg(rpm:25)			India
Capsule polishing machine				Hoong-a corporation,korea.

Number of Capsule being produced in Navana Pharmaceuticals Ltd.

Trade name	Generic Name
OMETAC	Omepraxole
DINAC-TR	Diclofac-Na
NAVACEF	Ciprofloxacin
NAVAMOX	Amoxacillin
NORTIN 10	Nortriptyline

Dry Syrup

Manufactured method in Navana Pharmaceuticals Ltd,

Ø Direct Mixing,

Flow chart for Direct Mixing for the manufacturing of Dry Syrup:

Crushing the sucrose in mill at 3000 rpm

¯

Transfer of half portion of sucrose from step-1 into a double cone blender by passing through a 20 mesh screen

¯

Transfer of all other excipients in the blender to blend for 30 minute

¯

Transfer the mix from the double cone blender by Passing through a 20 mash screen

· Machines used in the Dry Syrup Manufacturing unit:

Name of the Machine	Function
Double cone Blender	Blending/Mixing
Bottle Filling Machine	Filling of Dry Syrup
Bottle Sealing Machine	Sealing of Dry Syrup Bottle

· Condition for manufacturing Dry Syrup:

· Relative Humidity: Not more than 45%.

· Temperature: Below 27⁰

Purpose of packaging:

· To increase the acceptability of the drug

· To increase the stability of the drug

· To minimize the transport/shipping hazards

· To improve patients compliance

· To improve the pharmaceutical elegance by use of special color or contrasting printing

At Navana Pharmaceuricals Ltd. Three types of combination is use depending on the upper & lower layers as well as product requirement. They are;

· PVC-Aluminium Blister

· Aluminium -Aluminium Blister

· PVDC- Aluminium Blister

Besides blister packaging, at other packaging includes;

· Striping ‹Alu-Alu›

· Filling of tablets &capsules in bottles

· Labeling of bottles

· Secondary Packaging (Both on-line & off-line)

Packaging machineries:

Name Model source capacity

Automatic blister DPP-250DII China 60000/hr

Packing Machine

MINISTAR VAT Automatic M.S dal Hooga-A South Korea 12000-90000/hr

blister Packing Machine

(Scorpio)

Automatic Strip Leo-4 India 30000/hr

Packing Machine

Material Used:

?Alu.Foil (Blister/Strip) ?PVC/PVDC Film

?Alu-Alu Foil(Bottom) ?PP Cap

?Label ?Unit Carton

?Inset ?Plastic Spoon

?Plastic Cap ?Stopper

?Shipping Carton ?Cotton.

Fig: Aluminium foil

Fig: Blister machine

NAME OF THE PVC/PVDC FILM USED:

Name of the item Width (mm) Thickness (mm)

1. Coffee brown 146 0.250
2. Glass Clear 160 0.250
3. Glass clear PVDC 202 0.350
4. Alu-Alu Bottom 221 0.250

Name of the Bottle size:

• 35 ml bottle Round Amber
• 70 ml bottle Round Amber
• 100 ml bottle Round Amber
• 130 ml bottle Round Amber
• 200 ml bottle Oval
• Plastic Container with Cap & Washer

Primary Packaging Materials:

Automatic Blister Packing Machine:

Machine Parts:

?Bottle Foil (P.V.C) uncoiler ?Drive Motor

?Pre-heating & forming station ?Pneumatic Circuit

?Hopper ?Sealing Station

?Feeding System ?Cooling & Slitting System

?Cover Foil ?Punching Station

?Embossing Station ?Waste Foil coiler

?Conveyor ?Refrigerator & Cooling Unit

?Control Panel

Flow Chart of Blister packaging Machine:

Pocket formation (By Compression air & temperature)

Filling Station (Channel, feeder, dosage channel)

Sealing (temperature)

Cooling

Code embossing

Slitting

Punching

Pneumatic Actuator

Automatic Strip Packing Machine:

Flow Chart of Strip packaging Machine:

Pocket formation

Filling Station

Sealing (temperature station)

Cooling

Batch Printing

Slitting

Secondary Packaging (Both on-line & off-line):

Secondary packaging includes-

· Unit Cartooning with

-Container

-Leaflet

-Spoon/dropper (in case of liquid)

-Security seal/ Hologrammed Seal

· Master Cartooning with

– Unit cartoons

In-process check:

1. Observation no.
2. Leak test
3. Room condition

a) Temperature & humidity

b) Segregation of bulk materials/finished packs

c) Product identity

d) line, display board

5. Aluminum foil leaving in machine and stock

6. Number of individual strips/blisters checked

7. Number of finished products checked

8. Quality and identity of components compliant slip/labels/cartons/leaflets/outer labels/outer box/ spoon

9. Identity and appearance of product in packs

10. Quantity: No./volume/weight

11. Overprinting/embossing: batch no./MFD/Exp date/MRP

12. Label/carton with product name, batch no., Mfg date, price and Exp date.

Liquid

Oral liquid preparations include-

· Oral Syrup

· Suspension

General Manufacturing Process of Oral Liquids:

The general manufacturing of oral liquids in the liquid section of Navana Pharmeceuticals Ltd isbriefly described below with a flowchart;

Weighing of active ingredient/s along with excipients

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Mixing of excipients with certain amount of demineralized (DM) water as specified in the Batch Production Record (BPR) by the aid of a mechanical stirrer

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Addition of active ingredient/s

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Passing through a pump to the storage vessel to the

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Transfer of the solution to the filling vessel through 0.5m Cartridge filter.

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Filling, Flushing of Nitrogen (N₂) & Sealing of Bottles (glass or pet) containing oral liquids

Machines used in the Oral Liquid & Suspension Manufacturing units:

Name Speed Source

Variable speed stirrer 1400rpm India

Emulsifying Stirrer 2800rpm China

Horizontal Filter Press 1400rpm India

Inline emulsifier mixer 800 rpm India

Colloid mill 2810rpm England

Stainless steel Vessel

Semiautomatic liquid

Filling Machine

Cap sealing Machine.

Fig: Inline emulsifier mixer

Condition for manufacturing of Oral Liquids:

· Relative Humidity: Not more than 55%.

· Temperature: Below 30⁰

Steps involved in Suspension Preparation:

Dispersion of suspending agent

Transfer to compounding vessel containing sucrose solution

Addition of drugs & other ingredient

Mixing with continuous stirring

Adjustment of final volume with purified water

Filling & sealing

Packaging

Research and Development:

To launch a new product, the Research and Development department develops a formulation and manufactures the product on a laboratory scale. The stability tests are performed on these new products. After passing the tests the product is manufactured commercially. Research & development department prepares the manufacturing instruction, coating instruction (if necessary), packaging instruction, product specification and testing procedure file of the new product.

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