PILOT PLANT SCALE UP FOR SEMI-SOLID
PILOT PLANT SCALE UP FOR SEMI-SOLID
• Pastes, gels, ointments and creams are closely related to suspensions, liquids and emulsions except that they are products with higher viscosities
• The scale up involves many of the same factors that are considered in lower viscosity products but high viscosity renders certain aspects of the scale up of semi-solid products more critical
• The natural turbulence created by mixers used to make liquid suspensions or emulsions is not adequate to produce a homogenous product or cream
• The mixing equipment must be capable of effectively and continuously moving the semi-solid mass from the outside walls of the mixing kettle to the centre and from the bottom to the top of the kettle
Distribution of ingredients
Efficient heat transfer during heating and cooling
High Shear homo mixer
Power required for Mixing
• Power required for mixing depends on the viscosity of the product
• Motors used to drive the mixing system must be appropriate to handle the product at its most viscous stage
• They need to have variable speed mixing
Low speed à Low viscosity
Moderate speed à High viscosity
High speed mixing à causes à Air entrapment
High speed mixing à Prevented by à Use of vessels that operate under controlled vacuum
Temperature of process
• Mixing of oil and water phases during emulsification, homogenization, addition of ingredients, product transfer are carried out at carefully predetermined temperatures
• Temperature is critical to the quality of final product
Temperature of process‐ Emulsions
• In the formation of cream, the aqueous phase and oil phase must be heated to a temperature above the solidification point of the oil phase and then emulsified
If temperature of both phases are not maintained correctly:
èImproperly dispersed wax leading to a poor quality product
èWide ranges in product vicosity
Temperature of process ‐ Suspensions
• Improper temperature control can have adverse effects on the particle size of poorly soluble active ingredients
If insoluble ingredients added at high temperatures
Solubility is artificially increased creating a metastable product
On cooling – crystal growth or recrystallisation from a saturate solution
Change of particle size distribution, gritty product, altered stability and biologic activity
Many cream formulations and gel products are shear sensitive
Shear sensitive liquids change viscosity when under stress or pressure, such as when they are hit by the impeller inside a pump:
Some liquids become less viscous with increased force (called shear thinning or pseudoplastic)
Some become more viscous with increased force (called shear thickening or dilatant)
Shear thinning or pseudoplastic à Ketchup‐ becomes runnier when shaken
Shear thickening or dilatant à Corn starch suspended in water ‐ when stirred slowly it looks milky, when stirred vigorously it feels like a very viscous liquid.
• Handling such products during transfer from the manufacturing kettle to holding tanks to filling lines require consideration of shear properties
• Changes in measured viscosity are seen when viscous products are pumped through long transfer lines or during filtration
Critical processing steps
• Emulsification of 2 phases
• Dispersion of any suspended active ingredients
• Hence equipment selection is important
High Shear homo mixer
• Transfer pumps (must be able to move viscous material without applying excessive shear and without incorporating air)
• While choosing the size and type of pump,
a. Product viscosity
b. pumping rate
c. Product compatibility with the pump surface
d. Pumping pressure
Challenges in Semi-Solid Scale-Up
Scaling up semi-solid formulations presents various challenges, including:
Homogeneity: Achieving uniform mixing of ingredients in larger batches can be challenging.
Equipment Adaptation: Adapting laboratory processes to larger-scale equipment requires careful consideration.
Quality Assurance: Ensuring stringent quality control throughout the scale-up process is essential.
What is pilot plant scale-up in the context of semi-solid pharmaceuticals?
Pilot plant scale-up is the process of transitioning from laboratory-scale development and testing of semi-solid pharmaceuticals (such as creams, ointments, and gels) to producing larger quantities suitable for commercial distribution.
Why is pilot plant scale-up important in the pharmaceutical industry?
Pilot plant scale-up is crucial because it ensures that pharmaceutical companies can efficiently produce high-quality semi-solid medications at a scale that meets market demand while adhering to regulatory standards.
What are the key considerations when scaling up semi-solid pharmaceuticals?
Key considerations include formulation optimization, equipment selection, process validation, and maintaining product quality and consistency during the scaling process.
What are the challenges associated with scaling up semi-solid formulations?
Challenges include achieving homogeneity in larger batches, adapting laboratory processes to larger equipment, and maintaining stringent quality control throughout the scale-up process.
What are some best practices for a successful pilot plant scale-up of semi-solid pharmaceuticals?
Best practices include detailed planning, risk assessment, continuous monitoring and testing, and strict adherence to regulatory guidelines.
How does pilot plant scale-up impact the cost efficiency of semi-solid pharmaceutical production?
Scaling up allows for the production of larger batches, which typically reduces manufacturing costs per unit, making the process more cost-efficient.
Why is regulatory compliance crucial during pilot plant scale-up?
Regulatory compliance is essential to ensure that the final product meets safety and efficacy standards, allowing for its approval and distribution in the market.
What are the benefits of successful pilot plant scale-up for semi-solid pharmaceuticals?
Benefits include cost-efficient production, consistent product quality, compliance with regulatory requirements, and timely availability of medications in the market.
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