In-Plant Training Programme In Aristopharma Ltd. (Manufacturer Of Pharmaceutical Products)
Introduction
Plant training for the professionals is now essential to know in details the application mode of modern scientific and management issues aiming to familiar them correctly.
This training is the bridge between the theories and principles with their practices, in other words between the institution and commercial organization.
For gathering complete knowledge about pharmaceutical aspect of microbiology there is no alternative for in-plant or industrial training program. This training is conducted by the pharmaceutical industries in our country. By this training, each microbiology student can achieve vast experience many of which is almost new to us; can correlate the theoretical knowledge with the practical experience. Thus we can develop ourself completely for microbiology related job in pharmaceutical company. To take part in such type of training program we have been selected THE ARISTOPHARMA LTD. This ensures manufacturing and marketing of essential medicines with highest quality by following cGMP, GLP and ISO-2000 by all modern technologies. The main dosage form manufacturing by the respective company are solid such as tablet, capsule and dry syrup. Semisolid such as ointments, creams and liquid such as suspension and syrup. Sterile products include ophthalmic, injectable product, MDI and lyophilized product. Special microbiological precautions have to maintain in sterile and liquid section. In order to GMP, every procedure and equipment has its own Standard Operating Procedure (SOP).
Policies of Aristopharma Ltd.
”Quality the Unit We Count”
To maintain and improve status of an integrated healthcare company through
v acquisition of state of arts skills and facilities and enhance competency of human resources through appropriate relevant training program.
v To adhere strictly with WHO cGMP regulations in respect to manufacturing, Quality assurance, Marketing and distribution of medicinal products and to keep compliance of regulatory specifications of local authority.
v To practice and continually improve Quality Management System (QMS) in it’s totally to consistency meet customers needs in the global context.
v To review and upgrade “Quality Audit Programme” to match with regulatory requirements.
The Journey of Aristopharma Ltd.
1986
The journey started through the formation of a proprietorship firm under the dynamic guidance of Mr. M. A. Hassan, present Chairman & Managing Director of the company. It was a modest start with the introduction of a few products in oral liquid & tablet form.
1990
The new manufacturing unit was commissioned at Shampur-Kadamtali with highly sophisticated and advanced facilities.
1998
Production line was diversified with the addition of cream and ointment in the portfolio.
2000
Company starts its international operation – Vietnam being the first country to export.
2001
Export starts to Sri Lanka
2002
Sterile Products Block is commissioned & Ophthalmic Products are introduced in the market.As the first Pharmaceutical Company in Bangladesh, ARISTOPHARMA exports to Hong Kong – one of the most developed markets of Asia.
2003
The diversification rolls on – parenteral dosage form is introduced.
2004
Company touches another landmark in international operation – export starts to Singapore.
Export of highly sophisticated Ophthalmic Products starts to Hong Kong. Export also strarts to another country – Macau.
2005
Company crosses the continental boundary export start to Ukraine of East Europe.
2006
Export starts to Mauritius of Africa. Became No. 1 in Ophthalmic market in Bangladesh. Enters the top 10 chart of Bangladesh Pharmaceutical Market.
2009
Agreement is signed with APC, Australia to set up its 3rd plant at Gacha, Gazipur for Europe/American Market. Export starts to United Arab Emirates of Middle East and Nigeria of Africa.
2010
Export starts to Pakistan. The new expansion building of factory starts operation with the facilities for inhalers, lyophilized injections, pre-filled injections, suppositories etc.
2012
New plant is under construction in Gazipur (Gacha). Manufacturing of insulin, suppository,amino acid will be started this year.And the journey continues…
SOLID DEPARTMENT (TABLET)
Drug substances are most frequently administered orally by means of solid dosage forms, such as tablets and capsules. Solid dosage forms are some of the least expensive, most popular and convenient methods for drug delivery. Here we would focus different aspects of tablet making procedure and the equipment involved in it.
Total Units in Solid Department
Manufacturing area Packaging area
Granulation unit Compression unit Coating unit Capsule filling unit
Contents of a tablet
1. Active Ingredients
2. Filler/Diluents
3. Disintegrant
4. Binder
5. Lubricant
6. Glidant Excipients
7. Antiadherent
8. Flavourings
9. Colourings
· Filler/Diluents – to increase the size (bulk) of the tablet. It is necessary as, sometimes, the active ingredient used is in very small quantity and thus would be too small to handle the tablet.
· Disintegrant – helps the tablet to break down into small fragments, when it is ingested. This helps the medicine to dissolve and be taken up by the body quickly for it to act swiftly.
· Binder – to hold the tablet together after it has been compressed, stopping it from breaking down into its separate ingredients.
· Lubricant – to ensure that the tablet has a smooth surface and that the powder does not stick to the equipment used to make the tablet.
· Glidant– to help to keep the powder, used to make a tablet, flowing as the tablet and stopping it from forming lumps.
· Antiadherent– to stop the powder from sticking to the equipment as the tablet is being made.
· Flavourings – to make the tablets smell and taste better.
· Colourings – to distinguish one tablet from another.
Process of tablet making
Dispensing
Granulation
Blending
Powder compression
Coating
Blistering
Secondary Packaging
q Several categories of tablets for oral use may be distinguished as:
· Uncoated tablets
· Coated tablets
· Effervescent tablets
· Soluble tablets
· Dispersible tablets
· Orodispersible tablets
· Gastro-resistant tablets
· Modified-release tablets
· Tablets for use in the mouth
Granulation
Granulation is the process in which the powder particles of raw materials are made to form larger particles in order to facilitate compression for the production of tablet.
The purposes of granulation are:
– 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.
Granulation Processes which are performed in the Aristopharma 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. 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.
Dry granulation
This process is used when the product needed to be granulated may be 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.
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
Difference between Wet and Dry Granlation
| Wet granulation | Dry granulation | ||||||||||||
| Weighing of active ingredient as well as excipients and sieving it
¯ Dry mixing ¯ Wet mixing (addition of wet binder) ¯ Initial phase drying in Fluid Bed Dryer (FBD) ¯ Milling in the Multimill ¯ Partial drying in FBD ¯ Milling in the Multimill ¯ Terminal/Final drying in the FBD ¯ Sieving in the Vibratory Sifter according to the required particle/granule size ¯ Check moisture content and dry accordingly. Add lubricant. ¯ Granules of desired size ready for blending. |
Weighing of drugs and excipients; then sieving them.
Dry mixing of drugs and diluents
Slugging or pre-compression
Milling and sieving
Lubrication
Discharge for compression |
Condition for manufacturing of Granules:
– Relative humidity: Not more than 55%.
– Temperature: Below 250C.
Mixing & Blending:
A powder blend should be as uniform as possible to assure the proper amount of medication in each dosages unit. The blending of solid particles is affected by the shape, density, size & size range of the particles, and surface effects such as absorbed liquid film, electrostatic charges & Van der Waals forces. Small particles are difficult to blend because they exhibit poor fluidity. However, more important than actual particle size is particle size range. All drugs & chemicals should be reduced to approximately the same size prior to weighing & mixing
Machinery:
Tablet Processing unit: 1
| Name of the machines | Purpose |
| 1.Planetary mixer-60 kg,
Gansons, India. |
To mix the active ingredient and binder to form granules. |
| 2.FBD-1-10 kg, Alliance Eng. Co. India | To Dry granules. |
| 3.Multi mill-1 | To reduce the size of granules. |
| 4.Double cone Blender | To mix uniformly all the excipients. |
| 5.Tablet oscillating Granulator | To reduce the size of granules. |
| 6.Paste Kettle | Preparation of slurry |
| Pam Glatt Fluid Bed Processor India | Preparation of granules |
Tablet Processing unit: 2
| Name of the machines | Purpose |
| 1.RMG– 160 kg, Saral ENG. Company LTD. | To mix the active ingredient and binder to form granules. |
| To Dry granules. | |
| 2. Y- cone and Double cone blenders. | To mix the processed granules with lubricating agents. |
Fig: Rapid mixing granulator (RMG) Fig: Fluid bed dryer
Fig: Multi Miller Fig: Double cone blender
Features Specifications: Rapid Mixer Granulator:
Technical Specifications
- Standard processing duration
- Dry mixing approx 3 – 5 minutes
- Wet mixing approx 5 – 10 minutes
- Wet granulation approx 5 – 10 minutes
- Discharge approx 1-15 minutes
Unique features:
- RMG improved processing
- Uniform distribution of all formulation ingredients
- Reduced mixing and granulation time
- Useful working capacity of up to 80% to 40% of bowl volume
- Uniform granules by gentle processing
- Widely applicable
- Easy scale up & scale down between machine sizes
- Bowl shape design to have no dead spaces
- Homogeneous binder distribution
- Enclosed moving parts
- Ensured safety
- Air purge sealing for main shaft and Chopper shaft.
- Auto / Manual controls
- Hydraulic/ Pneumatic lifting of main shaft for cleaning
q Tablet Compression
Compression is the reduction of the bulk size of a tablet due to high pressure. In the compression of active pharmaceutical ingredients, overall control is essential to ensure high quality.
Flow chart of Compression
Granules (previously made)
Transfer of granules in the Hooper of tablet press machine
By hand or auto powder/granules loader
Rising of upper punch & dropping of lower punch
¯
Filling of die cavity through feed frame
¯
Removal of extra granules by scrape off plate
¯
Coming down of upper punch for
Compression to produce tablet
Raising of both upper & lower punches
To certain extent
Ejection of tablet with the help of take out plate
Conventional Uncoated Tablets
Of desired shape and size
Tablet-machine parts:
| Ø Hopper
Ø Main compression roller Ø Feed frame Ø Compression station Ø Feed paddles Ø Ejection cam Ø Draw down cam Ø Take off blade Ø Weight controller fills station Ø Ejection station Ø Pre-compression roller Ø Take off chute. |
Machines used in the Tablet Press unit for Compression:
# B-tooling machine ? Die 30 mm & punch 19 mm (35 punches)
# D-tooling machine ? Die 38 mm & punch 25 mm (27, 35 punches)
There are 08 compression machines:
# 1 automatic machine 30 station. (Sejong)
# Press machines {Station: -16, 23(1), 27(1), 35(3), and 37(1)}
Automatic tablet compression machine:
New Se Jong Model 37 Station Rotary Tablet Press. Machine
Features:
1) Unit has the capacity to deliver 54,000 to 216,000 tablets per hour.
2) Maximum Tablet Diameter: 16mm, Maximum Tablet Thickness: 8.5 mm, Filling Depth: 4.5 to 10mm, 8.5 to 14mm, 12.5 to 18mm
(3) Lubrication System: Automatic lubrication by cycle pump, Lubricating interval and amount can be reset
(4) Feeding System: Mechanical feeder as standard, open feeder is available as an option, Stainless Steel hopper with sight port.
(5) Tooling: ‘B’ Type.
Common Problems that arise during Compression:
Common Problems that generally arise during compression are-
· Capping
· Chipping
· Sticking
· Weight variation
· Mottling
· Hardness problem
· Lamination
Tablet Coating:
Coated tablets have a smooth surface which is often colored and may be polished; a broken section, when examined under a lens, shows a core surrounded by one or more continuous layers with a different texture.
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
Aqueous coating Organic coating
Sugar Coating
In suitable sugar- coating equipment, the tablet cores are successively treated with aqueous sucrose solutions which, depending on the stage of the coating reached, may contain other functional ingredients e.g. fillers, colors etc. The build up of coating material is due to transference of coating medium from one tablet to another.
Stages of Sugar Coating-
- Sealing
- Subcoating
Film coating
In film coating two polymers are highly used. One is HPMC and another is Eudragit-L100 and L-50 (liquid). In aqueous solution water is used as solvent but in organic solution – methanol, methylene chloride and PEG 6000 are used. The distance between spray gun and tablet bed, incase of organic solvent is 3-4 inch and incase of aqueous solvents is 8 inch. Pan rotation is within 3-15/hr. it varies from product to product. Air pressure is maintained to 1.5-4 kg.
Steam temperature:
| Coating | Inlet | Outlet |
| Organic | 750c | 650c |
| Aqueous | 60/650c | 50/550c |
? 200 kg coating machine containing spray guns.
? 110 kg coating machine containing spray guns
? 100,70, 20 kg coating machine containing spray guns
Enteric coating
There are two steps for enteric coating
? Sub-coating: Sub coating is performed by using HPMC as polymer with either organic or aqueous solution. This process performs for 5 hours.
? Enteric coating: Enteric coating is performed by using eudragit L-100 or L-50 over the sub coating. This is done for 15 hours.
| Name of the Machine | CAPACITY |
| NR-COTA (FC) TC-TC9. NR INDS. THAILAND. | 90-110 KG. |
| ECO COTA TC-TC2 F D & C Pvt. LTD. PAKISTAN | Max:100 KG |
| SUGAR COATING PAN, BANGLADESH&INDIA. | Max:70 KG |
| RAMA COTA (EC) TC-TC-1 RAMA PROD. COM. LTD. | Max:20 KG |
| N R COTA 2 TC TC-11, NR INDS. THAILAND | Max:200 KG |
q Condition required during Coating:
Ø Relative Humidity: Not more than 50%.
Ø Temperature: Below 250C.
Common problem associated with tablet coating:
1. Logo bridging
Cause:
– Surface characteristics of the product being coated
– Inadequate adhesion of film coating
– Inadequate design of logo (e.g. too detail/fine logo)
Solution:
– Modify core formulation to include more hydrophilic ingredients
– Increase core porosity
– Using formulation with increased adhesion property.
– Increase area within the debossing and modified angles.
–
2. Core erosion
Cause:
– Inherent softness or high friability of core.
– Excessive pan speed in coating process.
– Spray rate too low.
– High sensitivity of core to moisture as coating is applied.
Solution:
– Increase mechanical strength of core.
– Decrease pan speed.
– Increase spray rate.
3. Edge chipping/erosion
Cause:
– Low mechanical strength of coating
– Excessive pan speed
– Low solid content in coating liquid
– Low spray rate
– Sharp edges on tablets
– Worn tablet punches
Solution:
– Using formulation with increased mechanical strength
– Decreased pan speed
– Increase solid content in coating liquid
– Decrease spray rate
– Use modified punch design
4. Picking/sticking:
Cause:
– Spray rate too high
– Inadequate drying condition
– Pan speed too low
– Inadequate atomization of coating liquid
– Poor distribution of coating liquid
Solution:
– Decrease spray rate
– Increase drying condition
– Increase pan speed
– Increase atomizing air pressure/volume
– Increase number of spray gun
5. Cracking
Cause:
– Low mechanical strength of coating, exacerbated by inadequate plasticization, excessive pigmentation.
– Core has significantly different thermal expansion characteristics than coating.
– Extended strain relaxation of core after compaction.
Solution:
– Selecting formulation with increased mechanical strength and elasticity properties.
– Avoid use of mineral type fillers (e.g. CaCO3, CaSO4, MgCO3 etc.)
– Extend holding period of tablets prior to submitting them to coating process.
6. Peeling
Cause:
– Low mechanical strength of coating
– Poor adhesion of coating to tablet surface
Solution:
– Using ingredients of improved mechanical strength.
– Using ingredients with improved adhesion properties.
7. Orange peel/roughness
Cause:
– Viscosity of coating liquid is too high
– Poor atomization of coating liquid
– Excessive drying condition
– Over wetting (causing coating too rub)
Solution:
– Decrease solid content of coating liquid
– Increase atomizing air pressure/volume
– Decrease inlet air temperature/flow rate
8. Twinning
Cause:
– Spray rate too high
– Pan speed too low
– Inappropriate tablet shape
Solution:
– Decrease spray rate
– Increase atomizing efficiency
– Increase pan speed
– Select new tablet shape that decrease chances of flat surfaces coming into contact during application of coating liquid. (e.g. avoid capsule shape tablet with thick side wall)
q SOLID DEPARTMENT (CAPSULE)
Capsules are solid dosage forms in which the drug substance is enclosed in either a hard or soft soluble shell of a suitable form of gelatin, usually containing a single dose of active substance(s). They are intended for oral administration.
The capsule shells are made of gelatin or other substances, the consistency of which may be adjusted by the addition of substances such as glycerol or sorbitol. Excipients such as surface-active agents, opaque fillers, antimicrobial preservatives, sweeteners, coloring matter and flavoring substances may be added
In this pharmaceutical industry encapsulation, sealing and polishing of capsules of hard gelatin shell are done during manufacturing, as the industry does not manufacture any capsule shell and has to be brought separately. The active is filled in the empty the hard gelatin capsule shell in the form of powder and pellets.
There are 6 different sizes of empty hard gelatin capsule shells used in AristopharmaLtd. for general production, which include–
§ Capsule shell size 0
§ Capsule shell size 00
§ Capsule shell size 1
§ Capsule shell size 2
§ Capsule shell size 3
§ Capsule shell size 4
Encapsulation Process by Automatic Capsule Filling Machine:
Blend Pellets with NPS
¯
Encapsulation
¯
For encapsulation of powder,
Blending
¯
Slugging
¯
Granulation
¯
Sieving
¯
Encapsulation
Encapsulation Process by Manual Capsule Filling Machine by Hand:
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 Capsul
Machinery:
| Machine name | Machine specification | Manufacturer | Origin |
| Semi automatic Capsule filling machine | Capacity: 15000-17000/hr Capsule fill | P+am pharmaceuticals | India |
| Automatic Capsule filling machine | Capacity: 30000/hr Capsule fill | Hanli | Korea |
| Automatic Capsule filling machine | Capacity:90000/hr
Capsule fill |
Se jong | Korea |
| S.S.Drum -Blender | Capacity: 200 kg | Gansons | India. |
| Charge Vat | Capacity: 50 kg | Myth | Bangladesh |
| Cap. polishing machine | P+am pharmaceuticals | India | |
| Hand fill machine | Capacity:8000/hr | Pharmachem | India |
SOLID DEPARTMENT (DRY SYRUP)
Dry syrup, in Aristopharma, is manufactured by dry mixing method.
Dry mixing procedure flow chart
Crushing the sucrose in FITZ 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
Condition for manufacturing Dry Syrup
– Relative Humidity: Not more than 45%.
– Temperature: Below 250
q Machines used in the Dry Syrup Manufacturing unit:
| Name of the Machine | Function |
| Double cone Blender | Blending/Mixing |
| FITZ Mill | Crushing/ Milling |
| Dust Collector | Removal of dust |
| Bottle Filling Machine | Filling of Dry Syrup |
| Bottle Sealing Machine | Sealing of Dry Syrup Bottle |
q Packaging
Packaging can be described as a coordinated system 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.
Purpose of packaging
Ø To increase the acceptability of the drug
Ø Physical protection and barrier protection to increase the stability of the drug
Ø To minimize the transport/shipping hazards
Ø To improve patients’ compliance
Ø Containment or agglomeration. Liquids, powders, and granular materials need containment.
Ø Information transmission and marketing
Ø To improve the pharmaceutical elegance by the use of special color or contrasting printing
At Aristopharma, two types of blister, PVC- Aluminium Blister and Aluminium Blistercombination are used.
Packaging can be divided into two categories mainly; primary packaging and secondary packaging.
Primary packaging is the material that first envelops the product and holds it.
Secondary packaging is outside the primary packaging, perhaps used to group primary packages together.
There is also tertiary packaging which is used for bulk handling, warehouse storage and transport shipping.
Primary Packaging Materials
| Materials | Thickness |
|
250-300 ?m
250 ?m 20 ?m (top) 130 ?m (Bottom) |
Packaging Machineries:
| Machine Name | Machine specification | No. of Machine | Manufactured by | Origin |
| Automatic Blister Pack machine | Capacity:
80000/hr |
1 | Buchon | Korea |
| Automatic Blister Pack machine | Capacity:
72000/hr |
1 | Buchon | Korea |
| Automatic Blister Pack machine | Capacity:
60000/hr |
1 | Buchon | Korea |
| Automatic Blister Pack machine | Capacity:
90000/hr |
1 | Hoong-A | Korea |
| Automatic Blister Pack machine | Capacity:
82000/hr |
1 | Hoong-A | Korea |
| Automatic Blister Pack machine | Capacity:
60000/hr |
2 | Elmapack | India. |
| Strip Packing machine | Capacity:
120000/hr |
1 | Gansons | India. |
Major Steps of blister packaging:
PVC sheet
Heating plate
Foil softens by hot plate at temp. 125-145°C
Passed through desired dies plate which is keptcold& air pressure is applied to make pocket for small time & desired shape is resulted (air pressure 6-8 bar)
Tablets or capsules are filled into the pockets
Pressed by two plates simultaneously (upper plate temp. 160-180°C for PVC & lower plate is cold)
Passed through cutter
Desired blister pack
Major steps of strip packaging:
Tablets or capsules in hopper
Tablets/capsules in vibrating disc
Enter through tode channel
Tablets or capsules enter between two alu roll strips
Hot roller having particular dies shape
Pressing
Poly-coated alu rolls (coated with plastic materials) come from two sides
Strip packaging
Trouble shooting
Ø Preheating problem – malleability
Ø Forming problem
Ø Sealing problem
Ø Slitting problem – perforation
Ø Loading problem
Ø Air pressure
Ø Scanner problem
Ø Emboss problem
Ø Heat exchanger
Ø Feeding problem –
o Chute channel
o Gate transfer
o Spiral
o Brush
In-process check:
Ø Observation no.
Ø Leakage test (at 400 mm Hg )
Ø Room condition
o Temperature & humidity
o Segregation of bulk materials/finished packs
o Product identity
o Line, display board
Ø Aluminum foil leaving in machine and stock
Ø Number of individual strips/blisters checked
Ø Number of finished products checked
Ø Quality and identity of components compliant slip/labels/cartons/leaflets/outer labels/outer box/ spoon
Ø Identity and appearance of product in packs
Ø Quantity: No./volume/weight
Ø Overprinting/embossing: batch no./MFD/Exp date/MRP
Ø Label/carton with product name, Batch no, Mfg date, price, and Exp date.
q LIQUID SECTION
The liquid department in Aristopharma Ltd. is divided into four sections. They are:
Ø Liquid
Ø Cream,ointment& gel
Ø Topical
Ø suppository
General working procedure of liquid
Receive monthly product schedule
¯
Analysis the monthly product schedule
¯
BMR &BPR prepared
¯
QA approval
¯
Sent BMR, BPR to RM &PM
¯
Receive the materials
?
Processing
?
Filling
?
Packaging
?
Transferring to finished goods
Procedure of a liquid formation
Active ingradient
?
Suspending agent (guargum)
?
Solvent (purified water)
?
Sweeting agent (aspartame,saccharineetc)
?
Buffering agent (citric acid, sodium citrate etc )
?
Preservatives (sodium benzoate, methyl paraphene)
?
Co-solvent (propylene glycol)
?
Coloring agent
?
Flavouring agent
?
Viscosity enhancer (glycerine)
Suspension preparation Steps
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
Condition For Manufacturing Of Oral Liquids:
– Relative Humidity: Not more than 55%.
– Temperature: Below 30oc
q Machines used in the Oral Liquid Manufacturing unit:
| Name of the Machine | Function | Capacity |
| Steam Jacketed Vessel | Mixing | 1000 Liter |
| Charge Vessel | Manufacturing | 2000 Liter |
| Storage Vessel | Storage | 2000 Liter |
| Cartridge Filter | Filtration | – |
| Bottle Filling & Sealing Machine | Filling &Sealing of Oral Liquid Bottles | 2500 bottles /hour |
q Condition for manufacturing of Oral Liquids:
Ø Relative Humidity: Not more than 55%.
Ø Temperature: Below 30oc
Cream, Ointment & Gel
Cream, ointment and gel fall into topical product. Semi sterile condition is maintained here.
Cream is made of two ways; firstly water in oil; secondly, oil in water.
In ointment, no water is used, only oil.
In gel, both water and oil is used.
General process for manufacturing of cream
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General process for manufacturing ointments
Machinery
| Machine Name | Specification and Origin |
| Vacuum Emulsifying Mixer | China |
| Auto tube filling and sealing machine | China |
| Automatic tube filling machine | Precitechindustries,india |
| Automatic tube filling machine | Pharmachemmachinaries,india |
| Colloid mill | Cadmach ,India |
| Charging vessel | Mythindustries,Bangladesh |
| High speed emulsifier | India |
| Vacuum homogeniger | China |
| Transfer pump | U.S.A |
| Automatic labeling machine | Korea |
| Automatic liquid filling, Cap Sealing and labeling machine | India |
| Machine Name | Specification and Origin |
| Vacuum Emulsifying Mixer | China |
| Auto tube filling and sealing machine | China |
| Automatic tube filling machine | Precitechindustries,india |
| Automatic tube filling machine | Pharmachemmachinaries,india |
| Colloid mill | Cadmach ,India |
| Charging vessel | Mythindustries,Bangladesh |
| High speed emulsifier | India |
| Vacuum homogeniger | China |
| Transfer pump | U.S.A |
| Automatic labeling machine | Korea |
| Automatic liquid filling, Cap Sealing and labeling machine | India |
q SUPPOSITORY
A suppository is a drug delivery system that is inserted intotherectum (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 general principle is that the suppository is inserted as a solid, and will dissolve inside the body to deliver the medicine pseudo received by the many blood vessels that follow the larger intestine.
Condition:
Temperature– 45-50oC
Base– Carnauba Wax
STERILE DEPARTMENT
Aristopharma is a leading pharmaceutical company in Bangladesh and leading to produce ophthalmic product in Bangladesh. Aristopharma is now manufacturing different types of sterile dosages form including ophthalmic eye drop, eye ointment, eye cream, nasal drop, ear drop as well as IV and IM injection and recently included lyophilized product. Recently they have launched their MDI and Insulin product. They have a future plan for manufacturing of amino acid product,hormone& anti cancer product.
Doses forms in Sterile Department
§ Liquid injection (suspension)
§ Eye drop
§ Eye ointment
§ Dry vial
§ Lyophilized vial
§ Pre-filled syringe
§ Lyophilized injection
§ Insulin
Generally the products are manufactured by two ways:
– Aseptically Sterilized
– Terminally Sterilized
Injectable Products in Ampoule
Injectable products are dispensed in ampoules in the following procedure:
| Ampoule De-boxing
¯ Ampoule washing ¯ Sterilization (in case of aseptically filled ampoules) ¯ Ampoule filling (under laminar air flow) ¯ Ampoule Sealing ¯ Terminal Sterilization ¯ Ampoule Inspection ¯ Sealed Ampoules |
Ampoule washing sequence
DM water (inner-outer) ? Compressed air spray ? Distilled water ? WFI
Ampoule Filling & Sealing (under laminar air flow)
Ampoule on the filling belt®N2 flush ®Filling ® N2 flush ® Sealing by flame ® Ejection
Ampoule Inspection
– The white zone detects visually the black particles,
– The black zone detects the white particles.
– The volume is measured visually by taking 4 ampoules at a time in hand
Different Sterilization Techniques & their uses
| Sterilization Technique | Temperature
( 0C) |
Exposure Time
(hrs) |
Pressure
(Bar) |
Uses |
| Dry Heat Sterilization (DHS) | 180 | 3 | 1.1 | Vials |
| 220 | 2.5 | 1.1 | ||
| 250 | 1 | 1.1 | ||
| Steam Sterilization /Autoclave | 121 | 0.5 | 1.1 | Ampoules, Gloves, Filters, Gourmets |
Manufacturing of injectable preparations require a clean room which should have the following standard:
| Class | Cfu/m3 | Particle of 0.5 micron/ft3 | Particle of 5 micron /ft3 |
| 100 | <1 | NMT 100 | 0 |
| 1000 | NMT 10 | NMT 1000 | NMT 7 |
| 10,000 | NMT 100 | NMT 10,000 | NMT 70 |
| 1,00,000 | NMT 1,00,000 | NMT 700 |
Category of different vial processing area
| Area | Clean room standard |
| Filling point | 100 |
| Filling room | 1,000 |
| Vial washing & sterilization room | 10,000 |
| Filling room corridor | 10,000 |
| Fabrics change room | 10,000 |
Category of different ampoule processing area
| Area | Clean room standard |
| Filling point | 100 |
| Filling room | 1,000 |
| Mixing room | 10,000 |
| Filling room corridor | 10,000 |
| Fabrics change room | 10,000 |
Injectable products (powder or solution) in Via
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