Pilot Plant Scale Up of Inject Able Sand Liquid Orals
Pilot Plant Scale Up of Inject Able Sand Liquid Orals
Pilot Plant Scale Up of Inject Able Sand Liquid Orals
Make your mistakes on a small scale and our profits on a large one.
Dr. Basavaraj K. Nanjwade M.Pharm., Ph.D Department of Pharmaceutics KLE University Belgaum.
Contents
Introduction Scale-up of parenterals Scale-up liquid orals
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Introduction
In the pilot plant, a formulae is transformed into a viable, robust product by the development of a reliable and practical method of manufacture that effect the orderly transition from laboratory to routine processing in a full scale production facility. So pilot plant is the miniature, intermediate plant between the laboratory scale and the production plant.
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Injectables
The majority of the parenteral solutions are solutions requiring a variety of tankage, piping and ancillary equipment for liquid mixing, filteration, transfer and related activities. The majority of the equipments are composed of 300 series austenitic stainless steel, with tantalum or glass lined vessels employed for preparation of formulations sensitive to iron and other metal ions. The vessels can be equipped with external jackets for heating and/or cooling and various types of agitators, depending upon the mixing requirements of the individual formulation.
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Facility Design
To provide the control of microbial, pyrogen and particles controls over the production environment are essential. Warehousing: All samples should be aseptically taken, which mandates unidirectional airflow and full operator gowning. These measures reduce the potential for contamination ingress into materials that are yet to 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 preparation area through a series of progressively cleaner environments.
First the materials are passed through class 100,000 i.e. grade D environment for presterilization.
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The preparation areas are supplied with HEPA filters. There should be more than 20 air changes per hour
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Production area
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Compounding area: The manufacture of parenterals is carried out in class 10,000 (Grade C) controlled environments in which class 100 unidirectional flow hoods are utilized to provide greater environmental control during material addition. These areas are designed to minimize the microbial, pyrogen, and particulate contamination to the formulation prior to sterilization.
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Aseptic filling rooms: The filling of the formulations is performed in an Class 100 environment. 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, air locks 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 environment and another. They are fitted with the UltraViolet lights, spray systems, or other devices that may be effectively utilized for decontamination of materials.
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Formulation aspects
Solvent:
The most widely used solvent used for parenteral production is water for injection. WFI is prepared by by distillation or reverse osmosis. Sterile water for injection is used as a vehicle for reconstitution of sterile solid products before administration and is terminally sterilized by autoclaving Solubilizers: They are used to enhance and maintain the aqueous 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, polysorbate 20, lecithin. 3. Complexing agents: cyclodextrins etc They act by reducing the dielectric constant properties of the solvent system, thereby reducing the electrical, conductance capabilities of the solvent and thus increase the solubility. Antimicrobial preservative agents:
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Buffers: They are used to maintain the pH level of a solution in the range that provides either maximum stability of the drug against hydrolytic degradation or maximum or optimal solubility of the drug in solution. Antioxidants: Antioxidants function by reacting prefentially with molecular oxygen and minimizing or terminating the free the free radical auto-oxidation reaction. Examples phenol (0.065-0.5%), m-cresol (0.160.3%) 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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Quality Assurance
Particulate matter Pyrogen test Stability test
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Liquid orals
The physical form of a drug product that is pourable displays Newtonian or pseudoplastic flow behaviour and conforms to its container at room temperature. Liquid dosage forms may be dispersed systems or solutions. In dispersed systems there are two or more phases, where one phase is distributed in another. A solution refers two or more substances mixed homogeneously.
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Agent -wetting agents Salt formation ingredients - Buffering-systems, polymers, antioxidants Colorings, suspending agent, flocculating agent. Sweeteners, flavorings
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Emulsions:
Purpose Agent
Taste/smell masking
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Solutions:
Buffers, antioxidants, preservatives Colorings, stabilizers, cosolvents, antimicrobial preservatives Sweetners, flavorings.
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Equipments
Mixer Homogenizer Filteration assembly Bottling assembly
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Filtration assembly
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Mixing
Distilled water
Filling
Packing
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 of industrial pharmacy. 3rd Edition. Varghese publication 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 You
E-mail: [email protected]
Cell No: 09742431000
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