The manufacturing of pharmaceutical tablets involves several main steps including blending, granulation, drying and milling. Each step is known as a unit operation and will be outlined below.
The ingredients to make a pharmaceutical tablet will include the active pharmaceutical ingredients [API], and may require a bulking or binding agent which allows the tablet to be sufficiently large for consumption and provides sufficient surface properties of the particles within the mixture to facilitate suitable agglomeration for proper mixing and tableting, these ingredients are known as excipients.
Tablets used for medication often require a precise quantity of API and as such, an evenly distributed or ‘homogenous’ mix throughout the stages of production is necessary. The stages of production will vary depending on the formulation of the constituents, some require only blending, while others may require a granulation process. A homogenous mix with good flow must be achieved for proper dosage of API in each tablet and so that the tablets may be compressed at high speeds without disruption to the production line or equipment. [1] Mixing and Blending The most common and also efficient methods for mixing two or more powders is to use a tumbling unit, which takes the powder bed through repeated 360˚ turns at speeds and duration dependent on the formulation of the powder mixture. …show more content…
Each powder mixture has unique characteristics, and so have a unique optimization curve to achieve an acceptable state of uniformity and particle size distribution.
Many blending units are available which offer differing shear, convective and dispersion properties on the powder bed. Convective forces refer to large groups of particles moving in an orthogonal direction to the axis of rotation. Dispersion is random motion of particles due to collisions, usually parallel to the axis of rotation, and shear forces separate particles that may have agglomerated due to surface characteristics of the particles. Particles often have an irregular shape, size, density or surface characteristics and do not flow well which will cause them to segregate within the unit operation or when transferring from one unit operation to another. For this reason, and for end point determination statistical, analysis must take place with minimal disturbance to the powder bed. [3] Sampling can be taken with a sample thief [Figure 1] which is a metal rod or cylinder with one or more recessed cavities that can receive a sample of the powder bed at various locations in the tumbler and at various times during the mixing period. Samples must be taken with diligence, as weak points or ‘dead zones’ are common in blenders depending on their shape, illustrated in Figure 2. [12] In addition, studies have shown operator technique can introduce sampling errors in the statistical analysis. New technologies for sampling are being developed using optical methods, near infrared and nuclear magnetic resonance, but have not been used widely in industry yet. [4] An agitator or intensifier bar is included in some designs, which markedly increases shear forces if required for the particular formulation. The agitator can rotate independently of the rotating shell and can act as a delivery system for binders or granulating liquid. [11] Bin tumbling The bin blender, also known as an intermediary bulk container [IBC] was originally designed so that the contents could be transferred to the next phase in the operation after blending had completed, without having to remove the contents into a secondary vessel. …show more content…
This decreases the risk of segregation and also minimises delays and operator contact that could be hazardous or contaminate the mixture. The design shown in Figure 3 is of a square pyramidal shaped bin or tote, which can be lifted on a vertical shaft and rotated on a horizontal or slightly angled axis. The bin is filled or ‘charged’ on the square face, and after blending, can be raised or lowered and removed for discharging at the apex of the prism. V tumbling The V-Blender as shown in Figure 4, is a V Shaped Double cone that is usually joined at a 75˚ or 90˚ angle, the unit rotates on an axis to allow the powder mixture to split and diverge continuously. V-Blenders can provide high degree of homogeneity, which is particularly important when some ingredients may be as little of 5% of the total mix. [4] The
The ingredients to make a pharmaceutical tablet will include the active pharmaceutical ingredients [API], and may require a bulking or binding agent which allows the tablet to be sufficiently large for consumption and provides sufficient surface properties of the particles within the mixture to facilitate suitable agglomeration for proper mixing and tableting, these ingredients are known as excipients.
Tablets used for medication often require a precise quantity of API and as such, an evenly distributed or ‘homogenous’ mix throughout the stages of production is necessary. The stages of production will vary depending on the formulation of the constituents, some require only blending, while others may require a granulation process. A homogenous mix with good flow must be achieved for proper dosage of API in each tablet and so that the tablets may be compressed at high speeds without disruption to the production line or equipment. [1] Mixing and Blending The most common and also efficient methods for mixing two or more powders is to use a tumbling unit, which takes the powder bed through repeated 360˚ turns at speeds and duration dependent on the formulation of the powder mixture. …show more content…
Each powder mixture has unique characteristics, and so have a unique optimization curve to achieve an acceptable state of uniformity and particle size distribution.
Many blending units are available which offer differing shear, convective and dispersion properties on the powder bed. Convective forces refer to large groups of particles moving in an orthogonal direction to the axis of rotation. Dispersion is random motion of particles due to collisions, usually parallel to the axis of rotation, and shear forces separate particles that may have agglomerated due to surface characteristics of the particles. Particles often have an irregular shape, size, density or surface characteristics and do not flow well which will cause them to segregate within the unit operation or when transferring from one unit operation to another. For this reason, and for end point determination statistical, analysis must take place with minimal disturbance to the powder bed. [3] Sampling can be taken with a sample thief [Figure 1] which is a metal rod or cylinder with one or more recessed cavities that can receive a sample of the powder bed at various locations in the tumbler and at various times during the mixing period. Samples must be taken with diligence, as weak points or ‘dead zones’ are common in blenders depending on their shape, illustrated in Figure 2. [12] In addition, studies have shown operator technique can introduce sampling errors in the statistical analysis. New technologies for sampling are being developed using optical methods, near infrared and nuclear magnetic resonance, but have not been used widely in industry yet. [4] An agitator or intensifier bar is included in some designs, which markedly increases shear forces if required for the particular formulation. The agitator can rotate independently of the rotating shell and can act as a delivery system for binders or granulating liquid. [11] Bin tumbling The bin blender, also known as an intermediary bulk container [IBC] was originally designed so that the contents could be transferred to the next phase in the operation after blending had completed, without having to remove the contents into a secondary vessel. …show more content…
This decreases the risk of segregation and also minimises delays and operator contact that could be hazardous or contaminate the mixture. The design shown in Figure 3 is of a square pyramidal shaped bin or tote, which can be lifted on a vertical shaft and rotated on a horizontal or slightly angled axis. The bin is filled or ‘charged’ on the square face, and after blending, can be raised or lowered and removed for discharging at the apex of the prism. V tumbling The V-Blender as shown in Figure 4, is a V Shaped Double cone that is usually joined at a 75˚ or 90˚ angle, the unit rotates on an axis to allow the powder mixture to split and diverge continuously. V-Blenders can provide high degree of homogeneity, which is particularly important when some ingredients may be as little of 5% of the total mix. [4] The