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Pilot Plant Scale-up Considerations for Solids, Liquid orals, Semi solids and Relevant Documentation

Pilot plant can be understood as a small-scale production system or a pre-commercial system of the giant pharmaceutical industry.
Pilot Plant - It can be understood as a small-scale production system or a pre-commercial system of the giant pharmaceutical industry. Here, a small preliminary lab-scale formula is developed and transformed into an operational product by the development of the liable and practical procedure of manufacture.

Scale-up - The art designing of a prototype to increase the batch size of a product using the data obtained from the pilot plant model.

Objectives:
  • Before investing a large sum of money on a production unit this small preliminary lab-scale formula can be carried out on a model of the proposed plant.
  • To conduct an examination of the formula to check its robustness and ability to withstand large scale or Batch-scale production and if process modification is needed.
  • To conduct an evaluation of equipment and process validation.
  • Assessment of the crucial or vital step of the process.
  • Guidelines to be followed strictly for production and process controls.
  • Master manufacturing formula is provided with instructions for manufacturing procedure.
  • To avoid or minimize the scale-up problems.

Why conduct pilot plant studies?
  • Evaluation of a product and process validation on an intermediary scale can be carried out by a pilot plant setup before investing large amounts of money to full-scale production.
  • It is not feasible to predict the effects of a many-fold increase in the scale of batch production without a pilot plant study.
  • It is beyond everyone’s scope to design a large-scale manufacturing unit from laboratory data alone without any degree of relevant success.
Pilot plant scale-up checkpoints for liquid orals
  1. Personal requirements: A person with good theoretical knowledge of pharmaceutics with a perfect blend of rich practical experience in liquid orals manufacturing are the basic requirement.
  2. Space requirements:
  • Administration and information processing: A place for any paper work, any discussion, documentation purpose desk, space for meetings , computer junction
  • Physical testing area: A place where samples are laid out, examined and physically tested.
  • Equipment floor space: A place designated for equipments needed for manufacturing liquid orals.
  • Storage area: It includes storage for active ingredients and equipment, inprocess materials, finished bulk products, packaging materials.
Raw material → Weighing and measuring → Mixing (Addition of distilled water) → Filling → Packing (Finished Product Storage) → Quality Assurance

Pilot plant scale-up checkpoints for semi-solids
  1. Pastes, gels, ointment, and creams are categorized as semi-solid dosage forms with higher viscosities.
  2. The scale-up considerations of these products include many of the same factors that must be considered in the scale-up of the liquid orals.
  3. A concerning factor is the high viscosity of semisolids which play a definitive step in the scale-up technique. For example - Ointments or creams with homogenous mixture can be manufactured by the use of specialized mixers that are not used for liquid suspensions.
  4. The mixing equipment which is used for semisolids must be capable of continuously rotating the semisolids mass or to prevent sticking from the outside walls of the mixing equipment.
  5. Mixing of ingredients involves the uniform distribution of the ingredients and brings about a heat transfer during the heating and cooling steps.
Steps of the semisolids manufacturing process:
  1. Planning of requirement of material
  2. Preparation of semisolids
  3. Filling and Packing
  4. Quality Assurance

Pilot plant scale-up checkpoints for solids:
1. Material handling system
  • In large-scale production, proper handling of materials is necessary.
  • Accurate quantity of the ingredient should be delivered to the destination.
  • Selection of the the type of system depends on the characteristics of the materials.
  • Different material handling systems are vacuum loading systems, devices to lift & tilt drums, metering pumps, screw feed systems.
2. Dry Blending
  • Granulated powders must be well blended to ensure proper distribution of drug.
  • An inadequate blending of powders could result in uneven portion of the batch which result in either high or low in potency.
  • To ensure that all the ingredients are free of lumps and agglomerates prior to blending, proper steps should be taken care of or else flow problems can occur.
  • Prior screening and/or milling of the ingredients should be carried out before blending.
3. Granulation
  • The process involves the transformation of fine powders into free-flowing powders that are definitely easy to compress.
4. Binders
  • Used in tablet formulations to make powders more compressible and resistant to breakage during handling.
5. Drying
  • Drying of granulation takes place by circulating hot air oven, which is heated by either steam or electricity.
  • Drying times at specified temperatures and airflow rates must be taken care of for each product.
6. Slugging (Dry granulation)
  • The forces used for slugging should be taken care of, the diameter of the punches and the sizing and screening operations.
  • Optimization of these variables affects particle size and particle distribution.
7. Compression
  • The process involves where the granulation can be compressed on a high-speed tablet press and produce tablets.
8. Tablet Coating
  • Tablet formulation can be put into test to check whether the granulation can be compressed on a high-speed tablet press.
9. Quality control and stability
  • In-process quality control facilities to check the formulations are as follow:
  • There are also separate areas for carrying out:
  • Stability studies
  • Accelerated stability studies
  • accelerated light stability studies
  • forced degradation studies in accordance with ICH guidelines

Importance of Pilot plant scale-up
Below are the few key points which explains the importance of pilot plant scale up as follow:
  • Examination of formulae can be carried out.
  • Review of range of relevant processing equipments.
  • The specification of the raw materials can be understood.
  • Production rates can be checked.
  • The physical space area required can be checked.
  • Appropriate records and reports can be obtained to support GMP.





Ankur Choudhary is India's first professional pharmaceutical blogger, author and founder of Pharmaceutical Guidelines, a widely-read pharmaceutical blog since 2008. Sign-up for the free email updates for your daily dose of pharmaceutical tips.
.moc.enilediugamrahp@ofni :liamENeed Help: Ask Question


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