Introduction to Unites States Pharmacopeia – USP
United States Pharmacopeia is the set of standards published for the healthcare sector. Divided into various chapters or sections, it addresses issues related to different areas of public health and provides practical solutions for quality operations and effective products. It covers the entire pharma product area, such as processes, methods, equipment, areas, and all the relevant subjects.
Chapter 1062, written as USP <1062>, TABLET COMPRESSION CHARACTERIZATION, provides guidelines for the tablet form of dosages such as equipment, compression process, and associated areas. As discussed above, It also offers some insight into common problems during the compression process and how these can be solved.
USP <1062> Tablet compression characterization
The USP 1062 is divided into fourteen chapters. Each chapter intends to provide guidance related to processes related to compression equipment and associated areas.
Let’s discuss a brief description of each chapter in USP 1062
Chapter 1 – Background
This chapter introduces tablet and tablet compression, tablet properties, and what the USP 1062 includes. It starts by stating that tablet is the widely used dosage form, referencing another USP document, USP <1151>.
It also states that tablet compression is a critical process for manufacturing tablet form and mentions some common problems faced during the tablet compression process. Examples of problems this chapter indicates include capping, lamination, high friability, sticking, and insufficient mechanical strength.
It also mentions ambient conditions, such as temperature and humidity, that play an important role in affecting the tablet’s characteristics.
Some other factors that affect the final tablet product includes
Chapter 2 COMPRESSION PHASES
This chapter focuses on aspects of the compression process, such as pressure, strain, and strain rate. It provides information about compression forces and states that there are four stages during tablet compression or formation, as indicated below
Particle rearrangement
In this stage, product particles rearrange themselves to reduce or eliminate pores without deforming individual product particles. Particles undergo slippage, rotation, or translational movement for re-arrangement, and after this process, particles are denser than their initial stage due to the elimination of pores.
Compression
Compression occurs when they are compressed against each other, die walls, and punch. It increases the powder density and reduces the powder volume.
Compression occurs in the die when the powder is compressed against upper and lower punches. For compressing, upper and lower punches move down and up simultaneously in a die.
Decompression
During decompression, punches release pressure on powder by retracting from the die. The upper punch moves upward, while the lower punch moves downward at its initial position.
In this stage, particles undergo controlled elastic recovery. Because uncontrolled elastic recovery could decrease the bonding and mechanical strength. As a result, the tablet will lack the desired physical characteristics, and chances are that the quality department can reject these tablets.
Ejection
This is the final stage, where tablet comes out of lower die in a final finished form.
Chapter 3 Tablet Compression Characterization Equipment
This chapter addresses different types of table compression machines in the pharmaceutical industry. Each machine has its features and benefits. The USP <1061> describes the following four types of tablet compression equipment
Hydraulic Press
In hydraulic press, compression and decompression speeds cannot be precisely controlled. Testing tablets produced through a hydraulic press for various parameters such as tablet strength, density, friability, disintegration, and dissolution is necessary.
Instrumented Research Tablet Press
These are small-scale compression equipment used during the product development stage. These machines have smaller capacities and speeds as compared to the production scale.
There are two instrumented research tablet press types – Eccentric single-station and rotary multi-station presses.
A single station has only one station, while a multi-station has more than one.
Tablet press emulator
They are like rotary tablet press machines, but the difference is that their compression track is linear. It increases the tablet press cycle compared to the rotary tablet press.
Compaction Simulator
They are single-station press that uses hydraulic power for operation and compression. They use a computer or electronic controller to control the tableting function.
Chapter 4 Tooling
This chapter of USP 1062 addresses tooling for tablet compression machines.
Tooling on tablet compression is the mechanical assemblies used to give tablets their physical properties. They combine an upper punch, a lower punch, and a die. Common tooling shapes include flat-faced, flat-faced with a beveled edge, and standard round concave.
The selection of particular tooling depends upon the technical aspect of tablets and market requirements.
Chapter 5 Punch Displacement – Time Profiles
Tablet press can produce various punch displacement – time profiles, some of them include saw-tooth profile, square profile, and modified sinusoidal profile. These profiles depend upon compression speed, compression pressure, and compression profile.
These profiles can be measured by using instrumentation. Punch displacement profiles for most production scale tableting machines combine sinusoidal and square profiles.
Chapter 6 Tablet Mechanical Strength
The mechanical strength of a tablet is influenced by particle–particle bond and surface area of each particle.
The mechanical strength can be examined by measuring the maximum stress that a tablet can sustain. Common tests include placing the tablet between two plates and exerting force on both sides. The instrument continuously calculates the force, and the instant tablet breaks, the instrument records the exerted force, and it is the tablet’s mechanical strength. The tablet strength is often referred to as hardness, and the instrument is called a Hardness tester.
According to USP<1062>, tablet strength is affected by various factors, including
Chapter 7 Tablet Porosity and Solid Fraction
In the previous section, it was mentioned that powders rearrange themselves to eliminate pores. However, still, there are pores present in tablets. Porosity is the measure of the volume of tablets that consists of pores.
Porosity is critical when quantitatively characterizing tableting properties, as it substantially affects measured compact properties.
Pharmaceutical tablets commonly have porosities between 0.1 and 0.4. 0.1 indicates minimum pores, while 0.4 indicates maximum pores in a tablet.
One way to improve porosity is to increase the use of compression force. Increased force improves the rearrangement of powder in the die.
Chapter 8 Manufacturability Profile
The relationship between the tablet breaking and compression forces is called manufacturability. This relationship is often used during tableting to monitor and classify compression. It is also helpful in monitoring the tableting behavior of powder.
Chapter 9 Tabletability Profile
Tabletability is the relationship between tablet tensile strength and compression pressure. For a limited pressure, tensile strength increases with the increase in pressure. However, after a particular force, tensile strength decreases, called overpressure.
The decrease in tablet strength at higher compression pressure results from defects in tablet properties.
To obtain an authentic tablet ability profile, it is useful to calculate the strength over the compression force range rather than calculating strength on a single compression force value.
Chapter 10 Compressibility Profile
This chapter describes the compressibility profile of a tablet and shows how a solid fraction of tablet changes with the increasing compaction force.
The solid fraction is inversely proportional to the tablet’s porosity, i.e., the higher the porosity lower the solid fraction, and vice versa.
A reference value of 0.85 can be compared for many pharmaceutical materials because most pharma materials can be compressed to this solid fraction and can be easily compared for monitoring tablet properties.
Compressibility can also be defined using the Heckel equation, as mentioned below.
−ln(porosity) = K × (compression pressure) + B (5), where 5, K and B are constants
Chapter 11 Compactibility Profile
This chapter describes the COMPACTIBILITY of a pharma tablet and describes the relationship between tablet strength and porosity. According to this chapter, there is an exponential relationship between tablet tensile strength and solid fraction.
Chapter 12 Tablet Compression Profile
This chapter guides the compression force of tablet press equipment and discusses its impact on tablet strength and solid fraction. Generally speaking, it shows a direct relationship between these parameters.
Increasing the compression force increases the tablet strength and solid fraction, while decreasing the force decreases the strength and solid fraction.
Chapter 13 Machine Speed Sensitivity
This chapter discusses the impact of machine speed on tablet properties. It focuses on comparing different machine speeds on tablet’s compaction.
Using the machine speed data, the following equation can be used to calculate the Stain Rate Sensitivity of a powder using the tablet’s properties, such as tensile strength, hardness, and porosity.
SRS = property(SR2) - property(SR1) / property(SR1)
SR1 = low strain rates (e.g., low compression speed)
SR2 = high strain rates (e.g., high compression speed)
Chapter 14 Conclusions and Recommendations
In this final chapter, USP<1062 provides a detailed list of properties that must be considered for analyzing compression because tablet compression depends on many factors, such as material composition, product properties, manufacturing process parameters, environmental conditions, and machine characteristics.
Some properties that are helpful in determining the compression properties include the following
Tooling types
Tooling size
Compression speed
Punch displacement – time profile
Compression pressure range
Slid fraction range
Tablet properties (such as weight and dimensions)
Powder equilibrium
Lubrication
Tablet storage ( time, temperature and RH)
Tablet press configuration
Compressibility
Compactibility
Tabletability
Ejection force
SRS
About the Author
Muhammad Asim Niazi has a vast experience of about 11 years in a Pharmaceutical company. During his tenure he worked in their different departments and had been part of many initiatives within the company. He now uses his experience and skill to write interested content for audiences at PharmaSources.com.
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