Wet Granulation Technique in Pharma Manufacturing How to Optimize Your Granulation Process
The perfect ‘wet granulation process’ underlies many different parameters. The numerous points to consider while designing a granulation process is described in this article.
Wet granulation technique
Wet granulation is the most used technique in the pharmaceutical industry. The process aims to achieve a mix of desired properties which is suitable for further steps like tableting, coating, etc. The granulation process should be robust, repeatable, controlled, and also provide the best possible yield. The wet granulation technique is primarily used to improve flow, compressibility, bioavailability, and homogeneity of low dose blends, electrostatic properties of powders, and stability of dosage forms.
The granulation process
A granulation process has a lot of parameters that can have a significant impact on the process quality. For instance, the most critical effects resulting from raw material properties like particle size, structure, density, solubility, or stability. Some of them might be predicted or anticipated but should always be under control.
In general, the granulation process includes some or all the following steps:
2. Spraying the granulation agent to distribute the liquid into the blend
3. Wet massing/granulation phase
4. Discharging and continuing to the drying or sizing process
In many cases, the process development, scale-up, and the final quality of the granules depend on the formulation.
Selecting the suitable equipment
Proper selection of the equipment will maximize the success of wet granulation, even with limitations from API or formulation. There is a variety of equipment based on the same principle but with significant differences in their design. For example, there are different varieties of high shear granulators available based on the location of the main impeller (top drive or bottom drive) and the configuration of the granulators (side-mounted or vertical mounted).
Defining the endpoint
There is no universal definition of how the granules should look like at the end of wet granulation but they should provide good flowability, compressibility, and the desired dissolution profile. Proper selection of the endpoint should be based on the consideration of the whole process and aim to provide repeatable results.
Even with the best formulation, process, and equipment, the endpoint will consist of granules with different sizes, shapes, different moisture contents, and strengths. It is crucial to evaluate the impact on the performance of the final dosage by the different design of endpoint, for example, dissolution failure due to heavy endpoint for IR dosage form. The process should consider the impact on subsequent drying, milling, compression, and coating processes.
The particle size of granules is determined by the quantity and feeding rate of the granulating liquid.
The mean granule size depends on the specific surface area of the excipients, the moisture content, and the liquid saturation of the agglomerate. Moisture content is also a crucial parameter as, during the granulation process, issues like sticking on bowl sides can arise.
A granulation endpoint can be defined by the formulator as a target particle size mean or distribution. It has been shown that once you have reached the desired endpoint, the granule properties and the subsequent tablet properties are very similar, regardless of the granulation processing factors, such as impeller or chopper speed or binder addition rate.
Five steps to an optimal process design
Designing a robust process is one of the most common challenges in wet granulation. With proper considerations to the design during formulation and process development, failures can be reduced or avoided. For this, five steps can be recommended:
1. Identify the impact of API and raw materials
2. Proper selection of which type of equipment should be used
3. Understand the impact of process parameters
4. Select designs that can reduce the sensitivity of endpoint determination
5. Utilize the contribution from each step (from beginning to end) and balance the design based on the overall process.
It is always necessary to consider the various input parameters along with the required properties of processed products that will be suitable for subsequent process steps.
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