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Questions and Answers
Which of the following components is NOT typically found in a tablet formulation?
What is the primary advantage of using wet granulation compared to dry granulation?
During the weighing process, which method ensures the highest accuracy?
Which of the following unit operations is a necessary step in both wet and dry granulation processes?
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Which of the following is a component of a tablet formulation?
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All tablets undergo a coating process.
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What is the longest granulation process among the three main methods?
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The process of __________ involves grinding, blending, and then compression to form tablets.
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Match the following granulation methods with their descriptions:
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What type of milling uses a rotating and stationary knife?
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Manual weighing methods are more accurate than automated weighing methods.
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What is the purpose of milling ingredients before mixing?
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The process of __________ involves putting products in between rollers for ointment production.
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Match the milling equipment with its description:
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Which type of mixing equipment involves loading materials once, mixing, and then discharging?
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Fixed shell mixers are typically used when adding a liquid binder during dry granulation.
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In continuous mixing processes, products are __________ continuously.
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Match the following mixing equipment with their types:
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What is the primary purpose of granulation in tablet manufacturing?
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Wet granulation is considered the least common method in tablet manufacture.
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Name one advantage of wet granulation.
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The addition of a __________ is a critical step in wet granulation.
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Which of the following is NOT a method of granulation?
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Match the types of granulation methods with their characteristics:
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Overwetting can lead to granules that are hard and difficult to disintegrate.
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What is the ideal particle size range for granulation?
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What is the primary purpose of granulation in pharmaceutical manufacturing?
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Wet granulation is the most uncommon method in tablet manufacturing.
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Granulation prevents ________ of powder components during the tableting process.
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Which of the following is NOT a control criterion for granules?
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What is the target state during the addition of liquid binder in wet granulation?
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Which of the following is NOT an advantage of dry granulation?
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All components in dry granulation are mixed before the compression process.
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Name one method of dry granulation.
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One disadvantage of dry granulation is that it can lead to the ________ of components.
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Match the following dry granulation methods with their descriptions:
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What is one significant disadvantage of direct compression?
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Direct compression is applicable for producing colored tablets.
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Direct compression produces __________ tablets compared to other methods.
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Match the features with their corresponding characteristics regarding direct compression:
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What is the role of the upper punch in the single punch tableting machine?
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The rotary tablet press machine does not require a hopper to load material.
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Describe the first step in the operation of a single punch tableting machine.
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The __________ directs the granules across the die cavity in a single punch tableting machine.
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Match the components of the single punch tableting machine with their functions:
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Which type of deformation produces irreversible changes in the material?
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Pitting occurs due to insufficient lubricant in tablet formulations.
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The process of bonding compressed powders primarily involves __________ and diffusion.
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Match the following tablet defects with their descriptions:
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What type of deformation is desired when forming tablets to ensure irreversible changes occur?
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What is NOT a purpose of coating tablets?
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Sugarcoating involves coating tablets with layers of sugar in a solution form.
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What is the initial step in the sugar coating process?
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In sugar coating, powdered substances such as ________ are used to prevent stickiness after each layer is applied.
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Match the steps of the sugar coating process with their descriptions:
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Beeswax is an example of a plasticizer used in film coating.
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Match the following terms related to film coating with their descriptions:
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Match the following coating problems with their descriptions:
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The moisture content in hard gelatin capsules should be higher than 16% for optimal performance.
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What is the purpose of using a desiccant in the preparation of hard gelatin capsules?
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The _____ Method uses a screw mechanism to fill the capsule shells with powder.
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Match the capsule filling methods with their descriptions:
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Which of the following is an added component to hard gelatin capsules to maintain the desired viscosity of the gelatin solution?
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What is a critical factor to consider when selecting the size of a capsule?
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Soft gelatin capsules contain gelatin and do not require a plasticizer.
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The stability of a tablet is assessed to ensure its functional attributes are retained throughout its shelf life.
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The term used to describe the evaluation of a tablet's appearance is called __________.
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Match the following characteristics tested for tablets with their respective tests:
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What QC test is not used to assess the flowability of granules/powders?
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Moisture content in granules can enhance powder flow during tablet production.
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IPQC tests are performed on granules and tablets at the start of the __________ process.
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Which of the following statements regarding particle size distribution is correct?
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Match the following terms with their descriptions:
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The _____ test ensures that there is no weight variation in dosage units.
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Which of the following tests is not part of the Quality Control Tests for Tablets?
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Match the following tests with their descriptions:
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Which of the following is NOT an ideal characteristic of a suppository base?
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Compression molding is the most common method for preparing suppositories.
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Name one alternative to cocoa butter that can be used as a suppository base.
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An ideal suppository base should be __________ with various drugs to ensure effective drug release.
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Match the following methods of preparing suppositories with their descriptions:
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What is a major disadvantage of perimeter manufacturing flow in pharmaceutical facilities?
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Circular flow layout in pharmaceutical facilities offers no intersections, thus eliminating the risk of cross-contamination.
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What is the primary advantage of a straight line flow layout in a pharmaceutical facility?
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The center warehouse layout ensures materials are __________ by personnel easily.
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Match the following flow layouts to their characteristics:
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What is the goal of maintaining negative pressure during powder handling?
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HEPA filters are used in air handling systems to ensure that dust does not enter the main area.
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What is one method used to control dust in pharmaceutical facilities?
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The airflow in a sampling area should travel from the ceiling to the sampling area, ensuring it cannot be mixed with ________ air.
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Match the following air handling components with their primary purpose:
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Potable water can be used for cleaning and sanitation purposes.
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Name one purpose of maintaining humidity and temperature control in pharmaceutical facilities.
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Match the following treatments with their functionalities:
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Study Notes
Composition of Tablets
- Tablets consist of various components, including diluent, active pharmaceutical ingredient (API), disintegrant, binder, antifrictionals, lubricant, glidant, anti-adherent, miscellaneous agents, colorants, flavorants, and sweeteners.
Summary of Unit Operations
- Key unit operations in tablet formulation include weighing, milling, blending, granulation, tableting, and coating, though not all products require every stage.
- Granulation is a crucial step and can be categorized into three main methods: wet granulation, dry granulation, and direct granulation.
Wet Granulation
- Involves multiple stages including grinding, blending, adding a liquid binder, screening, drying, and compressing.
- It's the longest process of the granulation methods and ensures that the API and raw materials are properly integrated.
Dry Granulation
- Starts with grinding and blending, followed by an initial compression to create pellets.
- Pellets are then ground and screened to achieve the desired size before lubrication and final compression into tablets.
Direct Granulation
- This method simplifies the process, involving grinding raw materials into powders or granules and blending followed directly by compression into tablets.
Weighing
- Weighing can be performed manually or automatically, requiring high accuracy and calibrated balances.
- Anyone can weigh excipients, but the weighing of regulated or scheduled drugs must be conducted by authorized personnel, typically pharmacists.
Composition of Tablets
- Tablets consist of various components, including diluent, active pharmaceutical ingredient (API), disintegrant, binder, antifrictionals, lubricant, glidant, anti-adherent, miscellaneous agents, colorants, flavorants, and sweeteners.
Summary of Unit Operations
- Key unit operations in tablet formulation include weighing, milling, blending, granulation, tableting, and coating, though not all products require every stage.
- Granulation is a crucial step and can be categorized into three main methods: wet granulation, dry granulation, and direct granulation.
Wet Granulation
- Involves multiple stages including grinding, blending, adding a liquid binder, screening, drying, and compressing.
- It's the longest process of the granulation methods and ensures that the API and raw materials are properly integrated.
Dry Granulation
- Starts with grinding and blending, followed by an initial compression to create pellets.
- Pellets are then ground and screened to achieve the desired size before lubrication and final compression into tablets.
Direct Granulation
- This method simplifies the process, involving grinding raw materials into powders or granules and blending followed directly by compression into tablets.
Weighing
- Weighing can be performed manually or automatically, requiring high accuracy and calibrated balances.
- Anyone can weigh excipients, but the weighing of regulated or scheduled drugs must be conducted by authorized personnel, typically pharmacists.
Weighing
- Weighing can be performed manually using a hand-scoop or automatically with automated dispensing machines.
- Accuracy in weighing is crucial, requiring well-calibrated balances.
- Anyone can weigh excipients; however, weighing of regulated or scheduled drugs must be carried out by authorized personnel, typically pharmacists.
Milling
- "Small scale" milling refers to trituration using a mortar and pestle.
- Milling is essential before mixing other ingredients to avoid particle segregation; small particles can easily disperse if not properly sized.
- Various milling equipment is used:
- Shearing - Involves stationary and rotating knives, effective for fibrous materials.
- Compression - Utilizes heavy products to press materials against a mortar, often referred to as "Mortar and Pestle" for large-scale grinding.
- Impact - Materials are crushed using hammers or bars to reduce particle size, commonly done with Hammer Mills and Vibration Mills.
- Attrition - Involves a rubbing mechanism where products are placed between rollers, typically used for ointments, such as in Roller Mills.
- Combined Impact and Attrition - Achieved with Ball Mills, providing efficient particle size reduction.
Blending
- The goal of blending is to achieve a uniform mix of raw materials.
- Equipment types include:
- Batch-type - Loads once for mixing and then discharges, providing a controlled blending environment.
- Rotating Shell - Includes drum blenders, double-cone blenders, and V-blenders, where the vessel is inverted to facilitate mixing.
- Fixed Shell - Involves ribbon mixers, sigma blade mixers, and planetary mixers, typically used when liquid binders are added during wet granulation.
- Continuous-type - Ensures ongoing mixing and discharge of products, suitable for larger quantities with the use of motionless or static mixers.
Blending Overview
- Aim is to achieve a uniform mixture of raw materials.
- Different blending techniques and equipment are used based on the material properties and desired outcome.
Equipment Types
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Batch-Type Mixers:
- Operate by loading materials once, mixing them, and then discharging the final blend.
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Rotating Shell Mixers:
- Include various types such as:
- Drum blenders
- Double-cone blenders
- V-blenders
- Utilize the rotation of the vessel to combine materials effectively.
- Include various types such as:
Fixed Shell Mixers
- Types include:
- Ribbon mixers
- Sigma blade mixers
- Planetary mixers
- Commonly employed when introducing liquid binders during the wet granulation process.
Continuous-Type Mixers
- Designed for ongoing mixing and the continuous discharge of blended products.
- Suitable for large quantities, providing efficiency in production environments.
Motionless/Static Mixers
- Preferred for processing larger volumes without the need for moving parts.
- Effective in ensuring consistent mixing in continuous operations.
Granulation Overview
- Aggregation process transforms powders into larger particles ranging from ~0.2-4.0 mm in diameter.
- Reduces segregation of powder components, enhancing performance during tableting and storage.
- Improves flow properties and compaction characteristics.
- Minimizes dust production during handling.
Main Granulation Methods
- Wet Granulation: Involves adding a liquid binder to powdered components, the most common method in tablet manufacturing.
- Dry Granulation: Also known as pre-compression or double compression method, does not require liquid.
- Direct Compression: Involves compressing powders directly into tablets without any granulation process.
In-Process Quality Control (IPQC)
- Must be conducted for all granules from both wet and dry granulation.
- Flowability is assessed using the Angle of Repose.
- Compressibility is evaluated via Bulk and Tapped Density, along with Hausner’s Ratio and Compressibility Index.
Wet Granulation Process
- Mixing: Combines powders with a suitable fluid, usually a liquid binder.
- Common Liquid Binders: Include starch, povidone, glucose, and various cellulose derivatives; colorants can also be incorporated.
Advantages
- Utilizes conventional excipients in formulation.
- Tablets made are compatible with further processing steps.
Disadvantages
- Involves multiple processing steps.
- Addition of liquid can be unsuitable for moisture-sensitive materials.
Liquid Binder Application
- Formation of liquid bridges during granulation:
- Pendular: Small liquid bridge.
- Funicular: Liquid bridges extending surface-to-surface between particles.
- Capillary: Liquid fills pores between particles.
Importance of Moisture Control
- Overwetting: Results in hard granules that prohibit disintegration.
- Underwetting: Leads to weak granules that may not compress effectively.
Screening of Damp Mass
- Utilizes mesh sizes 6 or 8 during the screening process.
- Can be done manually or with mechanical devices such as oscillating granulators or extrusion machines.
Drying of Granules
- Performed using ovens or tray/shelf driers to promote the formation of solid bridges.
- Avoidance of overdrying is crucial as it can affect granule integrity.
Screening of Dried Granules
- Ensures uniform particle size distribution using mesh sizes 12-20.
- Mills or oscillating granulators are commonly employed for this purpose.
- Lubricant is introduced at the end of the process due to its hydrophobic nature, assisting in granule compression during tablet formation.
Enhanced Techniques
- Fluid Bed Granulator: A method that involves spraying for more consistent granule production and improved quality.
Granulation Overview
- Aggregation process transforms powders into larger particles ranging from ~0.2-4.0 mm in diameter.
- Reduces segregation of powder components, enhancing performance during tableting and storage.
- Improves flow properties and compaction characteristics.
- Minimizes dust production during handling.
Main Granulation Methods
- Wet Granulation: Involves adding a liquid binder to powdered components, the most common method in tablet manufacturing.
- Dry Granulation: Also known as pre-compression or double compression method, does not require liquid.
- Direct Compression: Involves compressing powders directly into tablets without any granulation process.
In-Process Quality Control (IPQC)
- Must be conducted for all granules from both wet and dry granulation.
- Flowability is assessed using the Angle of Repose.
- Compressibility is evaluated via Bulk and Tapped Density, along with Hausner’s Ratio and Compressibility Index.
Wet Granulation Process
- Mixing: Combines powders with a suitable fluid, usually a liquid binder.
- Common Liquid Binders: Include starch, povidone, glucose, and various cellulose derivatives; colorants can also be incorporated.
Advantages
- Utilizes conventional excipients in formulation.
- Tablets made are compatible with further processing steps.
Disadvantages
- Involves multiple processing steps.
- Addition of liquid can be unsuitable for moisture-sensitive materials.
Liquid Binder Application
- Formation of liquid bridges during granulation:
- Pendular: Small liquid bridge.
- Funicular: Liquid bridges extending surface-to-surface between particles.
- Capillary: Liquid fills pores between particles.
Importance of Moisture Control
- Overwetting: Results in hard granules that prohibit disintegration.
- Underwetting: Leads to weak granules that may not compress effectively.
Screening of Damp Mass
- Utilizes mesh sizes 6 or 8 during the screening process.
- Can be done manually or with mechanical devices such as oscillating granulators or extrusion machines.
Drying of Granules
- Performed using ovens or tray/shelf driers to promote the formation of solid bridges.
- Avoidance of overdrying is crucial as it can affect granule integrity.
Screening of Dried Granules
- Ensures uniform particle size distribution using mesh sizes 12-20.
- Mills or oscillating granulators are commonly employed for this purpose.
- Lubricant is introduced at the end of the process due to its hydrophobic nature, assisting in granule compression during tablet formation.
Enhanced Techniques
- Fluid Bed Granulator: A method that involves spraying for more consistent granule production and improved quality.
Dry Granulation Overview
- Aggregation of particles occurs through high stresses applied to mixed powders.
- Key forces aiding aggregation include electrostatic forces and Van der Waals interactions.
- Melting of components within the powder mix enhances bonding and granulation.
Methods of Dry Granulation
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Slugging:
- Involves pre-compressing the powder into large, flat tablets known as slugs (~1 inch in diameter).
- Slugs are subsequently broken down into smaller granules using a tableting machine adapted with specific punches and dies.
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Roller Compaction:
- The powder mix is compressed into thin sheets using a roller compactor.
- Material is flattened and pushed through a roller mechanism, creating uniformly sized granules.
Advantages of Dry Granulation
- Utilizes conventional excipients, maintaining compatibility with standard formulations.
- Eliminates the need for heat or solvents, preserving the integrity of heat-sensitive materials.
Disadvantages of Dry Granulation
- Requires additional equipment specific to roller compaction processes.
- Potential for component segregation, adversely affecting uniformity.
- Produces softer tablets, which may be less desirable for certain applications.
- Process can generate dust, posing handling and safety concerns.
Direct Compression Overview
- Direct compression skips the granulation step, allowing for a more streamlined manufacturing process.
- Steps involved in direct compression lead directly to tablet formation without intermediate processes.
Advantages of Direct Compression
- Reduces processing steps, enhancing efficiency in tablet production.
- Eliminates the need for solvents, making the method cleaner and potentially safer.
Disadvantages of Direct Compression
- Requires special excipients, which may not be standard in traditional formulations.
- Excipients used must be both flowable and compressible, potentially leading to higher costs.
- Common diluent, lactose, is typically inexpensive, but direct compression requires more costly spray-dried lactose with specific particle geometry (circular particles).
- Results in softer tablets, which may not be desirable for all formulations.
- This method is not suitable for colored tablets due to difficulties in incorporating dry colors. Mixing colors into a dry powder is challenging.
- To achieve color uniformity, wet granulation is preferred, allowing for better integration of colors into the mixture.
Single Punch Tableting Machine
- Hopper serves as a reservoir for granules, funneling them into the compression area.
- Upper punch is crucial for compressing the granules within the die cavity.
- Feed shoe effectively directs granules from the hopper into the die cavity during operation.
- Die is the designated mold where granules are compressed into tablets.
- Lower punch must be adjusted according to the desired volume of the die cavity.
- Process involves filling the die cavity with granules, followed by the upper punch lowering to achieve compression.
- After compression, the upper punch returns to its initial position, allowing the lower punch to raise and eject the tablet.
Rotary Tablet Press Machine
- Operates through a rotary mechanism and requires loading of powder or granules into a hopper or feeder.
- As the rotary turret turns, it fills die cavities with a specific amount of material.
- The upper punch descends to compress the material in the die cavity.
- Upon compression completion, the upper punch ascends, leaving the formed tablet within the die.
- The rotary turret continues its motion, facilitating the ejection of the finished tablet from the die cavity.
Types of Deformation
- Stress leads to various deformation types in granules, including elastic, plastic, and fragmentation.
- Initial steps involve rearranging the powder bed or granule structure, followed by the deformation of powders, impacting shape and porosity.
- Bonding between compressed powders occurs through:
- Adsorption: Involves the adhesion of particles at the surface.
- Van der Waals forces: Enhanced by close proximity; more compact granules exhibit stronger interactions due to increased Van der Waals forces.
- Diffusion: Movement of particles can alter the mechanical properties of the powder.
- Deformation alters mechanical properties, especially during melting, enhancing interactions among particles, leading to better tablet integrity.
- It is essential to exceed the elastic deformation stage and move into the plastic region to induce irreversible deformation, facilitating stronger bonding.
- Increased granule density enhances interaction, potentially benefiting the final tablet formation.
Tablet Defects
- Pitting: Characterized by pit marks on the tablet surface, caused by insufficient lubricant leading to unfilled dye cavities and rough edges.
- Capping: Refers to the fracture occurring at the top of the tablet, resulting in separation of the upper portion from the lower.
- Lamination: Internal fractures dividing the tablet's main body, typically stemming from stress-induced failures, causing structural integrity loss.
- Excessive porosity can generate too much internal pressure, leading to material displacement and product failure.
- Chipping: Involves the loss of small edges of the tablet due to inadequate binder application, often assessed through a friability test.
- Mottling: Results in uneven color distribution on the tablet’s surface, impacting the aesthetic quality and possibly indicating formulation issues.
Types of Deformation
- Stress leads to various deformation types in granules, including elastic, plastic, and fragmentation.
- Initial steps involve rearranging the powder bed or granule structure, followed by the deformation of powders, impacting shape and porosity.
- Bonding between compressed powders occurs through:
- Adsorption: Involves the adhesion of particles at the surface.
- Van der Waals forces: Enhanced by close proximity; more compact granules exhibit stronger interactions due to increased Van der Waals forces.
- Diffusion: Movement of particles can alter the mechanical properties of the powder.
- Deformation alters mechanical properties, especially during melting, enhancing interactions among particles, leading to better tablet integrity.
- It is essential to exceed the elastic deformation stage and move into the plastic region to induce irreversible deformation, facilitating stronger bonding.
- Increased granule density enhances interaction, potentially benefiting the final tablet formation.
Tablet Defects
- Pitting: Characterized by pit marks on the tablet surface, caused by insufficient lubricant leading to unfilled dye cavities and rough edges.
- Capping: Refers to the fracture occurring at the top of the tablet, resulting in separation of the upper portion from the lower.
- Lamination: Internal fractures dividing the tablet's main body, typically stemming from stress-induced failures, causing structural integrity loss.
- Excessive porosity can generate too much internal pressure, leading to material displacement and product failure.
- Chipping: Involves the loss of small edges of the tablet due to inadequate binder application, often assessed through a friability test.
- Mottling: Results in uneven color distribution on the tablet’s surface, impacting the aesthetic quality and possibly indicating formulation issues.
Coating Overview
- Coating serves multiple purposes: protection against environmental factors, prevention of stomach irritation, taste masking, modification of drug release characteristics, and improving aesthetic and identification aspects.
Main Types of Coatings
- Two primary coating methods: sugar coating and film coating.
Sugar Coating
- Involves applying layers of sugar in solution form onto tablets.
-
Step-by-Step Process:
- Seal Coating: Initial application of a polymeric alcoholic solution (e.g., shellac).
- Subcoating: Initial layers (3-5) using sugar-based syrup enriched with acacia, gelatin, or PVP; dusting powder like talc prevents stickiness.
- Smoothing: 5 to 10 additional syrup coatings; dusting powder used between layers.
- Color Coating: Final thin layers of colored sugar syrup achieve aesthetic appeal.
- Polishing: Application of wax (e.g., carnauba wax, beeswax) for a shiny finish.
-
Challenges:
- Significant weight gain from multiple layers affects shipping and packaging costs.
- Each layer requires a drying process for uniform coating, which is time-consuming.
Film Coating
- Utilizes a thin, plastic-like coating applied tightly over a compressed tablet.
- Generally applies one layer, minimizing weight gain.
-
Components:
-
Non-Aqueous:
- Film formers include polymers such as PVA, PVP, cellulose acetate phthalate (similar to Elmer's glue).
- Alloying substances like polyethylene glycol enhance fluid penetration.
- Plasticizers (e.g., castor oil) provide flexibility.
- Surfactants improve film spreadability (e.g., Tweens).
- opaquant (e.g., TiO2) and colorants (e.g., FD&C or D&C dyes) are added for appearance.
- Sweeteners (e.g., saccharin) and flavors (e.g., vanillin) can be incorporated for taste.
- Glossants (e.g., beeswax) add luster.
- Volatile solvents such as alcohol and acetone ensure rapid evaporation.
-
Aqueous:
- Film formers include cellulose polymers but utilize water as the solvent.
- Plasticizers like glycerin, PEG, or PPG for flexibility.
- Similar colorants and opacifiers as in non-aqueous coatings apply here.
-
Non-Aqueous:
Coating Equipment
- Spraying techniques utilized during drum rotation ensure a uniform application of the coating layer.
Coating Problems Overview
- Coating issues can significantly affect the quality of tablets and their effectiveness.
Blistering
- Occurs due to the detachment of the film layer from the tablet surface.
- Often a result of overheating during the coating process.
Pitting
- Involves the deformation of the core tablet itself, leading to irregularities.
- High temperatures increase the likelihood of core deformation.
Chipping
- Surface defects manifest as broken tablet edges.
- Related to issues with excipient material used in formulation.
Cratering
- Occurs when a tablet absorbs moisture, resulting in deformation.
- Can compromise the structural integrity and appearance of the tablet.
Blooming
- Refers to the fading or dulling of the tablet's color over time.
- May indicate instability in the coating materials.
Sticking or Picking
- Happens when the polymer in the coating becomes excessively sticky.
- Can result in tablets sticking to each other or the machinery.
Color Variation
- Involves noticeable changes in the color of the coating.
- Can affect consumer acceptance and perceived quality.
Blushing
- Characterized by a whitish or cloudy appearance on the tablet surface.
- May indicate moisture issues or improper coating application.
Infilling
- Surface irregularities result in an uneven coating application.
- Can lead to inadequate protection and compromised shelf life.
Cracking or Splitting
- Triggered when the film coating lacks flexibility due to over-compression.
- Can lead to the loss of active ingredients and reduced efficacy.
Orange Peel or Roughness
- Results in a rough texture on the tablet’s surface.
- Affects both appearance and mouthfeel, possibly impacting patient compliance.
Twinning
- Occurs when the coating becomes too sticky, causing tablets to adhere together.
- Can complicate product handling and packaging.
Bridging
- A specific form of infilling where coating material collects at gaps.
- Can hinder the release of the active ingredient.
Erosion
- Results from an excess of water in the coating solution.
- Leads to compromised film integrity and potential loss of product potency.
Hard Gelatin Capsule
- Capsule shell composition includes gelatin (35-40% w/w) and moisture content (13-16% w/w).
- Desiccants are added to minimize moisture and prevent capsule softening; excessive dryness leads to brittleness and cracking.
- Other shell components may include wetting agents, lubricants, viscosity-modifying agents, colorants, and opacifying agents.
- Fill material typically consists of powders with diluents, disintegrants, lubricants, glidants, and surfactants to enhance API solubility.
- Disintegrants help separate compact powders within the capsule.
- Various forms of fill materials can be employed, including oils, eutectic mixtures, suspensions, pastes, tablets, and other capsules.
Preparation of Hard Gelatin Capsules
- Gelatin solution preparation is the first step, followed by incorporation of other constituents.
- Viscosity of the gelatin solution must be controlled for proper fillability.
- The dip-coating method applies the gelatin solution to metal pins or molds.
Preparation of Filled Hard Gelatin Capsules
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Development of the formulation includes capsule size selection, ensuring accurate dosage, bioavailability, ease of filling, production stability, and aesthetic qualities.
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Capsule size is determined through trial and must ensure the body is filled but not the cap.
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Filling methods include:
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Dependent Method (Auger Method): Material is placed in a hopper and pushed through a screw mechanism into rotating turntable slots containing empty capsules.
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Independent Method (Dosator Method): An open dosator collects powder from a powder bed and transfers it into the empty capsule shells.
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-
Capsule sealing options include:
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Pre-closed: Sealing one groove.
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Closed: Both grooves sealed using gelatin band sealing or hydroalcoholic solvent seal.
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Cleaning and polishing procedures involve rubbing with cloth or gauze and using vacuum systems at machine ends to ensure clean capsules.
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Weight checks verify capsule consistency post-filling.
Soft Gelatin Capsule
- Capsule shell consists of gelatin plus a plasticizer (20-30% w/w) such as glycerin or sorbitol, with moisture content between 5-8%.
- Additional shell components may include preservatives, colorants, and opacifying agents.
- Fill material is primarily lipophilic and may include self-emulsifying systems or water-miscible liquids, but powders are used less frequently.
Preparation of Soft Gelatin Capsules
- The preparation process for soft gelatin capsules combines shell and fill formulation simultaneously.
- The Rotary Die Process employs two plates to form the capsule: gelatin is poured into one plate, allowed to partially set, then the fill material is added, followed by placement of a second plate with set gelatin to complete encapsulation.
Testing Hardness and Breaking Forces of Tablets
- Tablets must have uniform weight and drug content for efficacy.
- Key characteristics tested include weight variation and content uniformity.
- Important for clinical settings to ensure appropriate dosing for patients.
Bioavailability of Active Pharmaceutical Ingredient (API)
- API must be bioavailable, meaning it should be able to be released effectively from the tablet.
- Critical characteristics include disintegration and dissolution of the tablet.
Aesthetic and Stability Requirements
- Tablets should have an elegant appearance.
- Organoleptic evaluation assesses the sensory properties of the tablet.
- Stability testing is necessary to confirm that all functional attributes are retained over time.
Quality Control Tests for Tablets and Powders
- Flowability is assessed through the angle of repose.
- Compressibility is evaluated using the Hausner Ratio and Compressibility Ratio.
- In-Process Quality Control (IPQC) is performed on granules and tablets at the start of compression to ensure they are suitable for tableting.
Granule and Powder Testing Methods
- Granules need to be flowable and compressible for effective tableting.
- Bulk Density can be measured using graduated cylinders or volumeters.
Key Properties of Powders
- Particle Size Distribution is crucial, especially for particles over 75µm.
- Bulk and tapped density are indicative of flow properties.
- Moisture content should be minimized to maintain powder flow and prevent sticking to equipment.
Equipment for Quality Control
- Friability tester machines assess the durability of tablets during storage and handling.
- Tablets are rotated in a drum to check for weight loss or signs of breakage.
Bioavailability and Dosage Uniformity
- Important tests for tablets include disintegration and dissolution.
- Uniformity of dosage units ensures consistent weight and content across tablets.
- Assay methods can include titration or spectrophotometry, depending on the specific monograph requirements.
In-Process Quality Control (IPQC)
- IPQC tests such as organoleptic evaluation, thickness, and weight validation contribute to overall tablet quality.
- Thickness can impact tablet uniformity and consistency during manufacturing.
Suppositories
- Solid dosage forms designed for insertion into rectum, vagina, or urethra.
- Typically medicated, varying in shapes and weights.
Suppository Bases
- Cocoa Butter is the most common base used.
- Alternatives include:
- Polyethylene glycols
- Glycol-surfactant combinations
- Glycerinated gelatin
Ideal Suppository Base
- Should be nontoxic and non-irritating to the user.
- Must be compatible with a wide range of drugs.
- Melts or dissolves in body fluids, facilitating drug release.
- Must remain stable during storage, retaining its properties without melting.
- Should not interfere with the drug's release and absorption process.
Methods of Preparing Suppositories
- Rolling and Hand-Shaping: An outdated method that is inefficient.
- Compression Molding: Rarely used as it resembles tablet procedures; risk of introducing air, which can oxidize wax components.
- Fusion or Melt-Molding: A preferred method that involves melting materials for easier shaping.
Pharmaceutical Facility Overview
- Layout is crucial for controlling material flow and preventing cross-contamination.
- Essential controls include humidity and temperature management, water quality, and pest control.
Layout Types
- Effective layouts separate released materials from quarantined or rejected materials.
- Common layouts include:
- Perimeter manufacturing with a central warehouse
- Circular flow
- Straight line flow
Perimeter Manufacturing / Center Warehouse
- Warehouse located at facility center facilitates quick access to materials by personnel.
- Flow of materials includes:
- Warehouse → Dispensing → Tablet Granulation → In-Process Quarantine → Approved Bulk Materials → Packaging Areas
- Advantages:
- Centralized location simplifies material sourcing.
- Disadvantages:
- Increased risk of cross-contamination due to intersections in workflow.
Circular Flow
- Characterized by a circular pathway minimizing intersections in the workflow.
- Advantages:
- Simpler processing due to streamlined flow.
- Reduced risk of cross-contamination.
- Disadvantages:
- Some work areas may be farther apart, leading to potential inefficiencies.
Straight Line Flow
- Utilizes a straight pathway for material movement.
- Advantages:
- Lowers the probability of cross-contamination.
- Disadvantages:
- Larger space requirements may limit feasibility; spatial constraints can challenge the facility's design.
Control of Cross-Contamination
- Air handling systems are crucial to maintain cleanliness and prevent contamination in controlled environments.
- Filtration systems are essential for removing particulate matter from the air to maintain air quality.
- Recirculation of air helps in maintaining uniform temperature and humidity levels while reducing the risk of contamination.
- Positive pressure areas protect clean zones by preventing unfiltered air from entering.
- Negative pressure areas contain potential contaminants, ensuring they do not escape into clean zones.
- Dust collection and exhaust systems are implemented to efficiently remove dust and airborne particles.
Dust Control
- Dust control measures are particularly important in areas such as sampling and weighing.
- Air flows are strategically directed from the ceiling toward sampling and weighing areas to prevent contamination.
- The separation of airflows is vital; mixing airflow can lead to cross-contamination.
- An effective exhaust system directs airflow appropriately to keep work zones clean.
- During granulation, proper dust control is achieved through pressure management.
- Handling powders requires a negative pressure setup to minimize dust escape.
- Negative pressure indicates that the pressure inside the rooms is lower than in adjacent main areas, preventing dust release.
- The ultimate goal is to ensure dust remains contained and does not disperse into the main area.
- Compression tasks are conducted with specific room configurations, where HEPA-filtered air maintains cleanliness in negative pressure environments.
- Several rooms are separated from the main area to enhance contamination control systems.
Humidity and Temperature Control
- Protects products and ensures employee comfort.
- Maintains stable conditions, minimizing impact from external ambient temperatures.
- Requires adequate ventilation for optimal airflow, such as large roof fans in warehouses.
- Installation of dehumidifiers is essential to control moisture levels.
Water Systems
- Supply of potable water must be defect-free and free from contamination.
- Purification methods include ion-exchange treatment, reverse osmosis, and distillation.
- Non-manufacturing operations may utilize well water.
- Potable (drinking) water is necessary for personnel as well as cleaning and sanitation.
- Non-sterile conditions may allow for the use of purified water instead of sterile water.
- Purified water is crucial for various applications, particularly in solid manufacturing processes.
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Description
Explore the essential components that make up pharmaceutical tablets, including various agents such as diluents, APIs, and binders. Understand the key unit operations involved in tablet production, such as weighing, milling, and granulation. This quiz covers the methods and processes critical to tablet formulation and manufacturing.
