Tablet Scoring: Challenges and opportunities are describe in this post.
Tablet splitting can lead to medication errors. One of the main reasons is that the tablets may not have been partitioned into the appropriate dosage. This can lead to overdose or underdoes.
Tablet Scoring
Other factors to take into consideration include:
(a) Lack of drug substance uniformity with a single tablet. Although a tablet may fall within specified specification of dosage strength, the active ingredient may not be equally distributed within that tablet.
(b) Non-conventional shaped tablets. Certain tablet shapes may be difficult to partition, since the geometry of the tablet plays a crucial role in positioning the embossing scored line in the tablet.
(c) Fragments or crumble tablets. This issue is related to the lack of robust tablet physical property. The right selection of excipients can circumvent the fragmentation issue.
We discuss below the factors that can potentially influence tablet scoring. These factors are identified here on the basis of knowledge of tablet formulation, as there have been no published studies available that explicitly address these issues.
(1) Particle Size
Particle size can affect granule flow properties, which can influence tablet weight variation. Particle size can cause powder segregation, which can affect blend uniformity. Segregation typically occurs during blend or granulation discharge. Several studies have shown data in which segregated blends were evaluated using a segregation tester. To overcome the issue of segregation in the final blend, and to reduce the risk of poor content uniformity, it is preferable to used excipients having similar particle sizes.
When there is a greater disparity in the particle size of the granulation components, segregation effects can happen making homogenous mixing difficult. Segregation occurs as a result of differences in particle size, density, and structural identities of the materials used.
In the pharmaceutical industry, a conical mill (or conical screen mill) is often used to reduce the size of material in a uniform manner. Sieves of different screen mesh opening are used to target the desired granule particle size. Size reduction is a step that is commonly used after the granulation step to eliminate the oversize granules. For formulations that are designed for tablet splitting, this step plays a crucial role.
(2) Blending and Mixing (Blend Uniformity)
The uniformity of a powder blend is dependent on the excipients used in the formulation and the mixing approach. Mixing is an energy consuming process which produces a random distribution of particles. Poor blend uniformity can potentially produce tablets with poor content uniformity.
The efficiency of the mixer dictates the uniformity of the blend. Mixer efficiency is dependent on the following factors:
- type of mixer used,
- operating speed,
- mixing time,
- blend volume.
- Particle size, shape, density, and cohesively can also influence mixing.
Mixing involves the following steps:
- Convective movement of the particles from various location within the mixer.
- Shear movement, which is the cascading effect of the particles within the mixer.
- Diffusive movement of the particles as a result of increasing mobility.
Blend uniformity is an important factor to consider when developing a formulation suitable for tablet splitting. Blend uniformity ensures content uniformity within the tablets. For tablet splitting it is important to have homogenous distribution of the drug substance in the powder blend, to ensure content uniformity in the split tablets.
(3) Tablet Compression and Tooling Design
Powder segregation should be controlled during tablet compression. Discharging the powder blend from the tote to the hopper tablet press introduces powder transportation effects. During the transport of powders, there is a constant migration of particles. Due to differences in trajectories of particles with different masses and/or sizes, these particles will be separated during transportation. The shape of the particles also plays an important role during this type of segregation process. Special precautions must be taken during handling of these powders by reducing the transportation velocity or the falling height segregation is minimized. In order to overcome this effect, a valve is designed and placed with a certain angle at the junction of the mixer to the hopper of the tablet press.
The speed of the turret can introduce percolation effect where gravity causes smaller particles to move into the voids between larger particles, due to relatively larger differences in particle sizes.
The tablet press turret and feeder speed should be optimized in order to control powder vibration. Smaller sized particles will gradually move under the bigger sized particles, leading to a separation between differently sized particles.
In addition, tablet compression forces should be controlled in order to produce tablets with physical properties that are amenable for scoring. Tablet splitting effectiveness is dependent on the following tablet properties.
- Hardness (good breakability will not crumble during splitting)
- Thickness (bulkier tablets can be difficult to split)
- Good friability (tablets are not brittle and do not loose mass during splitting)
Finally, tablet tooling design is also important, as tooling geometry and the depth of the debossed score line influence the ability to effectively score tablets.
Ineffective, tablet splitting may result in the administration of an inaccurate dose, which can be of significant risk if the split medication is a narrow therapeutic index medication. The current United States Pharmacopeia (USP) guidelines for drug content of split tablets are loosely defined.
7. Conclusions
Tablet scoring refers to the breakage of a tablet in order to attain a desired dose efficacy. Tablet scoring provides benefits regarding dose flexibility, ease of administration and cost mitigation. This practice is more common among the pediatric and geriatric patient populations.
Tablet scoring is an emerging concept in the pharmaceutical industry, however, the nuances of tablet scoring are not well understood. Because of the lack of available data to address the complexity of this practice, patients and health care practitioners are confronted with half tablets that lack weight and uniformity accuracy. This can pose adverse reaction concerns with clinicians, particularly in cases where higher potency tablets are used.
In order to overcome the issues associated with tablet scoring, the design of the formulation has to be well thought out. The selection of excipients with appropriate chemical and physical attributes is crucial. The processing parameters are also important, as some of the methods currently used can potentially modify the physical characteristic of the excipients. The use of compression tooling with adequate debossing is important, as the geometrical position of the score line can influence the partitioning of the tablets.
This review aims to highlight the current state of knowledge in the field and provide an impetus toward further studies on the fundamentals underlying tablet scoring.
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