Report on In Plant Training In Beximco Pharmaceuticals Limited (Part-3)

Product Development Department

Product Development department deals with both new product formulation and reformulation of the existing products.  BPL has the largest and well equipped Product Development Department ever in Bangladesh containing a group of competent and hard working personnel. The department’s concerned is to develop a better formulation to meet the patients growing need and to make it cost effective as well.

Functions of Product Development

(i)  Launching of new products

(ii)  Reformulation of existing products.

(iii) Reprocessing.

(iv)  Market compliant handling.

(v)   Troubleshooting.

(vi)   Preparation of documents for export purpose.

Process

Product development department works or formulates product on the proposal of marketing department.  The process of new product development given below:

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Recipe

To develop a new drug the product development department has to collect DAR No. from Directorate of Drug Authority, Bangladesh after submission of recipe. A recipe contains:

Technical data

  • Batch formula
  • Manufacturing instructions
  • Control data for active materials
  • Control data for finished product

Pharmacological part

  • Presentation
  • Description
  • Indications
  • Contraindications
  • Precautions
  • Dosage and administration
  • Adverse reactions
  • Drug interactions

Reformulation

In case of existing products reformulation is performed when needed to improve the quality of the product or to minimize the cost of production to increase profit.

Annexure

Annexure is a document issued by the Drug Administration containing the

  • DAR number
  • Product name
  • Pack size
  • Composition
  • Specification
  • Overage

There are two types of annexure.

  • Annexure I: For drugs except vitamins and antibiotics.
  • Annexure II: For vitamins and antibiotics.

Trial Batch

Product Development Department manufactures trial batch for feasibility study. It also called Lab batch. It is the first batch of a product but it can’t be dispensed for market.

Pilot Batch

After approval of product, Product Development Department manufactures 3 batches of product for stability study. These 3 batches called Pilot batches.

Stability Study

Stability test is done for the following purposes.

To determine the expiry range

To determine the packaging mode

There are two methods of stability study

  • Real time stability study
  • Accelerated time stability study

Products of pilot batches preserved in three separated stability chambers of three different specific conditions.

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If the degradation at accelerated stability study is less then 5% in 6 month, then the shelf life is 2 years.

Analytical Method Development

According to ICH guideline Analytical Method Development depends on the following parameters:

  • Specificity
  • Range
  • Precision
  • Linearity
  • Accuracy
  • Detection limit
  • System stability testing
  • Quantification limit

BMR & BPR processing

From the validation batches manufacturing, the validate procedures prepared as document record ship for each product. This is called Batch Manufacturing Record (BMR).

Batch Packaging Record is prepared for each product according to the product safety & cost.

List of Machines

Sl.

Name

Manufacturer/ Supplier

Origin

Uses

1

Compression machine (16 stations)Manesty Machines Ltd.EnglandTablet compression

2

Coating machineN.R. Industries Ltd.ThailandTablet coating

3

GranulatorPharmaceutical and Medical Supply Ltd.ThailandGranulation

4

Fluid bed dryerSapphire Machine Pvt. Ltd.IndiaDrying

5

Multi-mill machineRisesun Electrical & Industries Co. Ltd.Milling

6

Moister analyzer (Sartorius MA 30)Imperial Corporation Ltd.GermanyDetermination of moisture content

7

Friability testerErwekaGermanyDetermination of friability

8

StirrerSilversonEnglandMixing

9

Electronic balanceShimadzuJapanWeighing

10

Dissolution tester(DT 600)ErwekaGermanyDetermination of dissolution

11

Disintegration testerDisintegration testing

12

SonicatorUltrawave Ltd.UKShaking

13

pH meterHanna InstrumentpH determination

14

HPLC System 1ShimadzuJapanIdentification, quantification, separation

15

HPLC System 2ShimadzuJapanIdentification, quantification, separation

Solid Dosage Formulation

Solid Department of BPL comprises the maximum number of products and also covers the major portion of its sales. Its current number of products is 261 consisting 83 plain tablets, 131 coated tablets, 37 capsules and 8 powders for suspensions.

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Manufacturing Area

Granulation Unit

Granulation is the most preliminary process in the solid manufacturing area. Granulation is the process in which powder particles of raw materials are made to adhere to form larger particles called granules

  1. To improve the flow of powdered materials by forming sphere like or regularly shaped aggregates
  2. To improve the compression characteristics of the mix (blend.)
  3. To prevent segregation of the constituents in the powder mix.

Two types of granulation processes are performed in this unit:

-Dry granulation

-Wet granulation

Granulation units perform the following steps of tablet formulation to form larger particles in order to facilitate compression.

General Procedure:

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Critical parameters in granulation:

Loading ( materials adding sequence must be followed, if needed vacuum loader should be used)

Dry mixing

-Mixing time

-Agitator speed

-Mixer capacity

Wet granulation

-Agitator speed

-Chopper speed

-Solution addition pressure

-Mixing time

Wet milling

-Screen size

-Wet granule feed rate

-Mill speed

-Milling duration

Drying

-Inlet air temperature

-Bag shaking frequency

-Drying duration

-Air flow rate

-Final exhaust air temperature

-Loss on drying (LOD)

Dry milling

-Screen size

-Dry granule feed rate

-Mill speed

-Milling duration

Compression Unit

Compression is a process in which we can get the original size of a tablet containing drug or drugs with excipients on stamping machines called presses. There are two types of compression:

Direct compression

Compression after granulation

There are some tablets that are compressed directly after dispensing. E.g. Neoceptin R (Ranitidine HCl). This is an easy and less time consuming process.

On the other hand, there are some tablets that cannot be gone through the direct compression due to their hardness problem. These are first passed through the wet granulation and then the compression is done. E.g.  Flatameal DS.

Flow diagram of compression

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Coating Unit

Some of the tablet dosage forms manufactured by BEXIMCO Pharma are coated for the following reasons:

  1. To improve the pharmaceutical elegance of the product by use of special colors.
  2. To mask the unpleasant taste, odor, or color of the drug.
  3. To control the release of the drug from the tablet.
  4. To protect physical and chemical protection for the drug

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Sugar Coating Procedure:

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Film Coating Procedure

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Packaging Unit

Packing can be defined as an economical means of providing, presentation, protection, identification/information, containment, convenience, and compliance for a product during storage, carriage, display and use until such time as the product is used or administered. After   compression of tablets and coating [if required] the tablets are packed either in blister pack or in the strip.

There are two packaging areas:

a)      Primary packaging area

In the primary packaging area, 10 machines are involved for packing. Among them, 8 for blister pack & 2 for strip pack.

b)      Secondary packaging area. 

Types of packaging:

Packaging of Solid dosage form is of two types:

1) Strip packaging:

Striping materials is:

a) ALU-ALU type

b) PVC-ALU-PVC type

2) Blister Packaging:

Blistering materials are of three types-

a) ALU-ALU type

                   b) ALU-PVC type

                   c) ALU-PVDC type

Different parts of a blister pack machine

Different parts of a blister pack machine and their functions are giver in the following table:

Parts of blister machine

Function

1. Base gridDraws the base material, which may be PVC, PVDC, Aluminum foil.
2. Forming StationForms blister in the base material either by hydraulic pressure or by air pressure and temperature
3. HopperTablets are kept in the hopper
4. Chute and Spiral FeederRegulate the vibration so that table can move and fall in the feeding channel
5. Feeding ChannelFeed the blister with tablet
6. DedusterCollects dust by creating vacuum
7. ScannerScan the empty blister
8. Sealing stationSeal the blister pack
9. Cooling stationCool the blister pack
10. Marking stationMarks the empty blister
11. Code embosserEmboss code number
12. Slitting stationSlit the blister pack
13. Web clumpDraws the blister
14. Punching StationCut the blister and slit down
15. TimerRegulate the passage of blisters
16. DetectorDetect the empty packet
17. RejecterRejects the empty blister packet
18. Conveyer beltConvey the pack for further processing.

Steps of Blister packing

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Steps of Strip Packing

beximco

List of Machines in Solid Department

Sl.

 

Name of Instrument

Manufacturer/ Supplier

Origin

Capacity

 

Granulation Unit #1

1

Planetary MixerGansonsIndia60 Kg

2

Fluid Bed DryerSaphireIndia60 Kg

3

Multi MillGansonsIndia100 Kg/h

4

Vac-U-MaxBellevilleUSA2000 Kg/h

 

Granulation Unit #2

5

Planetary MixerGansonsIndia120 Kg

6

Fluid Bed DryerSaphireIndia120 Kg

7

Multi MillGansonsIndia100 Kg/h

8

Vac-U-MaxBellevilleUSA2000 Kg/h

 

 

Granulation Unit #3

9

High Speed Mixer Granulator (HSMG)Thailand250 Kg

10

Fluid Bed DryerSaphireIndia150 Kg

11

Fluid Bed DryerSaphireIndia150 Kg

12

Multi MillMarkBangladesh

13

Vac-U-MaxBellevilleUSA2000 Kg/h

14

Lift Lever (Stacker)Toyota Tuscho Corp.Japan650 Kg

 

Granulation Unit #4

15

Solace Aero DryerSolaceIndia120 Kg

16

High Speed Mixer Granulator (HSMG)Thailand250 Kg

17

Multi MillGansonsIndia100 Kg/h

18

Vac-U-MaxBellevilleUSA2000 Kg/h

 

                                                 Compression Units

19

16 Station Rotary PressManestyEngland10560-29760 TPH

20

35 Station Rotary Press (Double Channel) (BB4)ManestyEngland70000-210000 TPH

21

35 Station Rotary Press (Double Channel) (BB4)ManestyEngland70000-210000 TPH

22

35 Station Rotary Press (Double Channel) (BB4)ManestyEngland70000-210000 TPH

23

Fette P3100 (55 Station)FetteGermanyMax. 594000 TPH

24

Fette P1200 (30 Station)FetteGermanyMax. 216000 TPH

25

SEJONG (45 Station)SejongSouth KoreaMax. 380000 TPH

26

Weighing BalancesSartoriusGermany

 

Coating Units

27

Accela Cota 150ManestyEngland150 Kg

28

Accela Cota 350 AManestyEngland350 Kg

29

Accela Cota 350 BManestyEngland350 Kg

30

Sejong CotaSejong Pharmatek Ltd.South Korea450 kg

 

 

Packaging Area

31

Blister Machine (PG)Precision GearIndia66000 TPH (4 Track)

32

Blister Machine (085)Klockner HanselGermany50000 TPH (2 Track)

33

Blister Machine (042)Otto HanselGermany

34

Blister Machine (043)

35

Blister Machine (074)Klockner HanselGermany48000 TPH (2 Track)

36

ELMAC PACK Blister MachineELMACIndia36000 TPH (usually)

37

PAM-PAC Blister MachineIndia120000 TPH

38

HOONG-A Blister MachineKorea

39

Strip MachineGansonsIndiaMax. 80/min

40

Strip MachineHemson