Pilot Plant Scale Up of Inject Able Sand Liquid Orals
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Transcript of Pilot Plant Scale Up of Inject Able Sand Liquid Orals
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Pilot Plant Scale-up of Injectablesand Liquid Orals
Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D
Department of PharmaceuticsKLE University
Belgaum.
Make your mistakes on a small scaleand our profits on a large one.
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Contents
Introduction
Scale-up of parenterals
Scale-up liquid orals
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Introduction
In the pilot plant, a formulae is transformed intoa viable, robust product by the development of areliable and practical method of manufacture
that effect the orderly transition from laboratoryto routine processing in a full scale productionfacility.
So pilot plant is the miniature, intermediate plant
between the laboratory scale and the productionplant.
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Why to build up a pilot-plant???
To evaluate the effect on the process of a largechange in the scale of operation and to gather otherdata so that a good design of a larger unit may bemade with a high probability of commercial success.
To produce trial lot quantities of the material inquestion so that its properties may be criticallyexamined.
To find and examine all by products or waste. Thesemay not be seen in laboratory scale. By the use ofpilot plant, it is possible to minimize the waste, hencebetter yield of prescribed dosage form.
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Scale-up for parenterals
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Injectables The majority of the parenteral solutions are
solutions requiring a variety of tankage, pipingand ancillary equipment for liquid mixing,filteration, transfer and related activities.
The majority of the equipments are composed of
300 series austenitic stainless steel, with tantalumor glass lined vessels employed for preparation offormulations sensitive to iron and other metalions.
The vessels can be equipped with externaljackets for heating and/or cooling and varioustypes of agitators, depending upon the mixingrequirements of the individual formulation.
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Working area of a parenteral pilot plant
Incoming goods are stored in special areas for Quarantine,
Released and Rejected status. A cold room is available for storage of temperature-sensitiveproducts. Entrance into the warehouse and production areasis restricted to authorized personnel.
Sampling and weighing of the raw material is performed in a
dedicated sampling area and a central weighing suite,respectively. The route for final products is separated from the incoming
goods; storage of final products is done in designated areasin the warehouse while they are awaiting shipment.
Several clothing and cleaning procedures in the controlledtransport zone and production area ensure full qualitycompliance.
In addition, a technical area is located in between theproduction zone and the area for formulation development.
Here, the water for injection equipment is located, as well asthe technical installation of the lyophilizer.
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Lay-out of the pilot-plant
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Facility Design
To provide the control of microbial, pyrogen andparticles controls over the production environmentare essential.
Warehousing:
All samples should be aseptically taken, whichmandates unidirectional airflow and full operatorgowning.
These measures reduce the potential for
contamination ingress into materials that are yetto receive any processing at any site.
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Preparation Area:The materials utilized for the production of the
sterile products move toward the preparationarea through a series of progressively cleanerenvironments.
First the materials are passed through class 100,000 i.e. grade Denvironment for presterilization.
Transfer of materials are carried out in air-locksto avoid cross contamination
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The preparation areas are supplied with HEPA filters.There should be more than 20 air changes per hour
The preparation place is Class 100 area.
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Production area
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Compounding area:
The manufacture of parenterals is carried out inclass 10,000 (Grade C) controlled environmentsin which class 100 unidirectional flow hoods areutilized to provide greater environmental control
during material addition.These areas are designed to minimize themicrobial, pyrogen, and particulatecontamination to the formulation prior tosterilization.
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Aseptic filling rooms:
The filling of the formulations is performed in an Class 100environment.
Capping and Crimp sealing areas:
The air supply in the capping line should be of Class 100
Corridors:
They serve to interconnect the various rooms. Fill rooms, airlocks and gowning rooms are assessed from the corridor.
Aseptic storage rooms.
Air-locks and pass-throughs:
Air locks serve as a transition points between one environmentand another.
They are fitted with the UltraViolet lights, spray systems, or otherdevices that may be effectively utilized for decontamination ofmaterials.
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Formulation aspects
Solvent:The most widely used solvent used forparenteral production is water for injection.
WFI is prepared by by distillation or reverseosmosis. Sterile water for injection is used as avehicle for reconstitution of sterile solid productsbefore administration and is terminally sterilizedby autoclaving
Solubilizers:They are used to enhance and maintain theaqueous solubility of poorly water-soluble drugs.
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Solubilizing agents used in sterile products include:1. co-solvents: glycerine, ethanol, sorbitol, etc.
2. Surface active agents: polysorbate 80, polysorbate20, lecithin.
3. Complexing agents: cyclodextrins etc
They act by reducing the dielectric constantproperties of the solvent system, thereby reducingthe electrical, conductance capabilities of thesolvent and thus increase the solubility.
Antimicrobial preservative agents:
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Buffers:
They are used to maintain the pH level of asolution in the range that provides eithermaximum stability of the drug against hydrolyticdegradation or maximum or optimal solubility of
the drug in solution. Antioxidants:
Antioxidants function by reacting prefentially withmolecular oxygen and minimizing or terminating
the free the free radical auto-oxidation reaction.Examples phenol (0.065-0.5%), m-cresol (0.16-0.3%) etc.
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Instrumentation
Mixer
Homogenizer
Filteration assembly
Filling machinery
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Mixer/Homogenizer
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Filtration assembly
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Bottling/Filling machinery
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Sterilization and Depyrogenation
Steam sterilization Dry-heat sterilization and depyrogenation
Gas and vapour sterilization
Radiation sterilization Sterilization by filteration
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Aseptic processing control and evaluation
In-process Testing:
End-product Testing:
Process simulations:
Quality Assurance Particulate matter
Pyrogen test
Stability test
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Particulate matter detector
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Liquid orals
The physical form of a drug product that is pourabledisplays Newtonian or pseudoplastic flow behaviourand conforms to its container at room temperature.
Liquid dosage forms may be dispersed systems orsolutions.
In dispersed systems there are two or more phases,where one phase is distributed in another.
A solution refers two or more substances mixedhomogeneously.
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Steps of liquid manufacturing process
Planning of material requirements:
Liquid preparation:
Filling and Packing:
Quality assurance:
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Critical aspects of liquid manufacturing
Physical Plant: Heating, ventilation and air controlling system:
the effect of long processing times at suboptimal
temperatures should be considered in terms ofconsequences on the physical or chemicalstability of ingredients as well as product.
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Formulation aspects of oral liquids
Suspensions:
Purpose Agent
Facilitating the connection
between API and vehicle
-wetting agents
Salt formation ingredientsProtecting the API - Buffering-systems, polymers,
antioxidants
Maintaining the suspension
appearance
Colorings, suspending agent,
flocculating agent.Masking the unpleasanttaste/smell
Sweeteners, flavorings
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Emulsions:
Purpose Agent
Particle Size Solid particles, Dropletparticles
Protecting the API Buffering-systems,antioxidants, polymers
Maintaining the appearance Colorings, Emulsifying
agents, Penetrationenhancers, gelling agents
Taste/smell masking Sweetners, flavorings
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Solutions:
Protecting the API Buffers, antioxidants,preservatives
Maintaining theappearance
Colorings, stabilizers,cosolvents, antimicrobialpreservatives
Taste/smell masking Sweetners, flavorings.
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Layout of the pilot plant
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Equipments
Mixer
Homogenizer
Filteration assembly
Bottling assembly
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Filtration assembly
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General flow chart
Raw Materials Measured andweighed
Mixing
Filling
Packing
Distilled water
Finished products storage
Quality Assurance
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Quality assurance
Dissolution of drugs in solution
Potency of drugs in suspension
Temperature uniformity in emulsions Microbiological control
Product uniformity
Final volume Stability
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References
Lachman L. The Theory and practice ofindustrial pharmacy. 3rd Edition. Varghesepublication house.
www.google.com
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Expected questions?
Pilot plant scale up of parenterals
Pilot plant scale up of suspensions
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Thank YouE-mail: [email protected]
Cell No: 09742431000
mailto:[email protected]:[email protected]