Pilot plan scale up for semisolid and parenteral by Khushboo kunkulol

Pilot plant scale up techniques used in pharmaceutical industry

1. Pilot Plant S cale up for Semisolid and Parenterals. Presented by: khushboo kunkulol.

2. INTRODUCTION: In the pilot plant a formulae is transformed into viable, robust product by development of reliable and practical method of manufacturing that effect the orderly transition from routine laboratory to routine processing in full scale production facility . So pilot plant is miniature , intermediate plant between laboratory scale and production plant.

3. Why to build up pilot plant? T o evaluate the effect on process of large change in the scale of operation and to gather other data so that good design of larger unit may be made with high probability of commercial success. To produce trial lot quantities of material in question so that its properties may be critically examined. To gather enough data to build a full-scale production facility . A pilot plant helps in testing if equipment and control concepts perform as desired once unit operations are tied together . This is very important if recycle streams are involved as the pilot plant will demonstrate if impurities are building in recycle streams and causing operational problems. To find and examine all by-product and waste. These may not be seen in laboratory scale.

4. The majority of parenteral solution are solution requiring a variety of tankage, piping and ancillary equipment for liquid mixing, filtration, transfer and related activities. The majority of equipment are made up of stainless steel with glass lined vessel employed for preparation of formulation sensitive to iron or metals. The vessels are equipped with external heating jacket and/ or cooling and various types of agitator depending upon mixing requirement of individual formulation. Parenteral

5. Working area for parenteral. The incoming goods are stored in special area for quarantine, released and rejected purpose. The cold room is available for temperature sensitive sample. Entrance to the warehouse and production area is restricted to authorized personnel. Sampling and weighing of raw material is performed in dedicated sampling area. Storage of final product is done in designated areas in warehouse while they are awaiting for shipment. Several clothing and cleaning procedure in controlled transport zone and production area ensure the full quality compliance. Technical area is located in between production zone and area for research and formulation.

6. Layout of pilot-plant

7. Facility design: To provide the control of microbial, pyrogen and particles control over production area is 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 material that are yet to receive any processing at any site

8. Preparation area The material utilized for production of sterile product moves toward preparation area through series of progressively cleaner environment. First material are passed through grade D environment for presterilization. Then transfer of material is carried out in air-lock to avoid cross contamination. Preparation area are supplied with HEPA filters. There should be more than 20 air change per hour. The preparation place is class 100 area.

9. Production area

10. Compounding area: The manufacturing of parenteral is carried out in Grade-C controlled environment in which class 100 unidirectional flow hoods are utilized to provide greater environmental control during material addition. These area are designed to minimize microbial, pyrogen and particulate contamination to the formulation prior to sterilization. Aseptic filling room: The filling of formulation is performed in class 100 environment. Capping and crimp sealing area: The air supply in capping area should be of class 100. Corridors: They serve to interconnect various rooms, such as filling room, gowning room, air-lock room are assessed from the corridor. Air-lock and pass through: The air-lock serve as transition point between one environment and other. They are fitted with UV lights, spray system, or other device that may be effectively utilized.

11. Formulation Aspects: Solvent: The most widely used solvent for parenteral production is WFI ( water for injection) The WFI is prepared by distillation or by reverse osmosis. Sterile water for injection is used as vehicle for reconstitution of sterile solid product before administration and is terminally sterilized by autoclaving. Solubilizer: They are used to enhance and maintain the aqueous solubility of poorly water soluble drug. Solubilizing agent used in sterile product include: The co-solvent: Glycerine, Ethanol, Sorbitol etc. Surfactant: Polysorbate 80, Polysorbate 20, Lecithin. Complexing agent: Cyclodexitrine, etc. They act by reducing dielectric constant property of solvent system thereby reducing electric conductance of solvent and hence increases solubility.

12. Buffers: They are used to maintain pH level of solution in range that provide either maximum stability of drug against hydrolytic degradation or to obtain optimum stability and solubility of drug in solution. Antioxidant: The antioxidant act by reacting prefentially with molecular oxygen and minimizing and/ or terminating the free radical auto-oxidation reaction. Example: Phenol, m-cresol etc. Sterilization and depyrogentation: Steam sterilization Dry-heat sterilization. Gas and vapour sterilization. Radiation sterilization. Sterilization by filtration.

13. Instrumentation: Mixer or Homogenizer:

14. The parenteral assembly

15. Filling and closing machinery:

16. Quality assurance: The dissolution of drug in solution. Potency of drug in suspension. Temperature uniformity in suspension. Microbial control. Product uniformity. Final volume. Stability.

17. Scale up for semi-solid. In general semisolid dosage form are complex formulation having complex structure. Often they are composed of two phases (oil and water) one of which is continues phase and other is dispersed phase. The active ingredient is dissolved in one phase although occasionally the drug is not fully soluble in the system and is dispersed in one or both phases thus creating the three-phases system. The physical properties of dosage form depend upon various factor including the size of dispersed particle coefficient of active ingredient between phases and product rheology. These factors combine to determine the release characteristic of drug as well as other characteristic such as viscosity.

18. Formulation of semi solid dosage form : Ingredient used in preparation of semi-solid dosage form are: Active pharmaceutical ingredient. Bases Preservative Humectant Antioxidant Emulsifier Gelling agent Permeation enhancer Buffer.

19. Suppositories: The manufacturing of suppositories on laboratory scale usually requires: The preparation of molten mass. Casting of suppositories in suitable mould. Cooling of mould. Open and remove suppositories.

20. Critical manufacturing parameter: For a true solution the order in which solute is added to solvent is usually unimportant. The same cannot be said for dispersed formulation however, because dispersed differently depending on to which phase a particulate substance is added. In a typical manufacturing process the critical points are generally initially separation of one phase system into two phase and the point at which active ingredient is added. Because the solubility of each added ingredient is important for determining whether a mixture is visually a single homogeneous phase, such data possibly supported by optical microscopy should usually be available for review. This is particularly important for solute added to formulation at conc. Near or exceeding that of their solubility at any temperature to which the product may be exposed.

21. Variation in manufacturing procedure that occur after either these event likely to be critical to the characteristic of finished product. This is especially true of any process intended to increase the degree of dispersion through reducing droplet or particle size. Aging of finished bulked formulation prior to packaging is critical and should be specifically addressed in-process validation study.

22. General stability consideration: The effect that SUPAC changes may have on the stability of drug product should be evaluated. For SUPAC submission the following point must be considered : In most cases, expect those involving scale-up, stability data for pilot scale batches will be acceptable to support the proposed change. Where stability data shows a trend toward potency loss or degrading increase under accelerated condition, it is recommended that historical accelerated stability data from a representative pre-change batch be submitted for comparison. It is also recommended that under these circumstance all available long term data on test batches from ongoing studies be provided in supplement. Submission of historical accelerated and available long term data would facilitate review and approval of supplement.

23. New era of drug product: Health care is one of the important indicator of any country's development and status of health care indicate nature of development of country. Pharma company are working consistently towards improvement of health care among people. Drug are one of the important component of health care management. The increase in income and change in lifestyle are contributing to increase expenses of health care management.

24. Indian pharmaceutical industries: Evaluation of Indian pharmaceutical sector Phase 1- In 1901 Acharya Chandra Roy established Bengal chemical and pharmaceutical work limited in Kolkata and in 1907 alembic chemical work in Vadodara. After independence Hindustan antibiotic ltd was established in 1954. Phase 2- The private companies like sun pharma established in 1983 and dr. reddy lab in 1984 The government also took initiative to export the pharmaceutical product.

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