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Manufacturers must consider key components of manufacturing solid versus semi-solid drugs to create a successful end product.
When it comes to solid vs. semi-solid drugs, there are many
considerations for manufacturers to take in regards to the process in which the end product is made. While solid dosage drugs may be easier to manufacture, they present more challenges regarding regulatory requirements. While semi-solid dosage drugs are more challenging to manufacture, they are subject to fewer regulatory obstacles.
To learn more about the manufacturing processes for solid and semi-solid dosage drugs, Pharmaceutical Technology spoke with Shankar Gupta, chief sales officer at ACG.
PharmTech: What are the pros and cons of solid dosage versus semi solid dosage, or capsules vs. soft gels?
Gupta: Each of them have their own pros and cons. On the one hand, from a manufacturing standpoint, capsules are fairly straightforward. The capsules are filled using a filling machine,
and the product is ready. However, there are a number of standard and regulatory requirements that need to be met before they are approved for consumption and marketing.
Although soft-gel capsules are subject to fewer regulations, the manufacturing process is both longer and more complex, requiring a larger manufacturing space. Additionally, the processes require greater numbers of staff with a wide range of skills. Also, processes result in more wastage. Before they can be packed, they [also] need to be dried, which adds to the time, complexity, and cost.
PharmTech: How can the formulation of a drug impact the quality of the resultant oral solid dosage form and the tableting process altogether?
Gupta:The formulation of a drug is governed by a number of key factors. For a contract manufacturer, this would be determined by the customer’s preference or need. Otherwise, the formulation of a drug is generally dictated by the patient’s experience, compliance, and the appropriate packaging for the product.
In the case of needing to taste mask to achieve a neutral product or to add color, capsules would be the preferred choice.
Although capsules have a good shelf life, when exposed to humidity, temperature fluctuations, or if they are subjected to prolonged light exposure, they can become brittle. Despite these variances, the packaging for capsules is quite simple.
[On the other hand,] tablet packaging has a higher degree of complexity due to varied shapes, sizes, and consistency of the end product.
PharmTech: What processes can be used to ensure uniformity/equal distribution of ingredients in capsules/tablets during manufacturing?
Gupta: From a mechanical perspective, the machinery utilized to ensure the uniformity or equal distribution of ingredients depends on the requirement of the formulation, and also determines the process. For example, in cases of a high degree of content uniformity, the processes may rely on the utilization of a fluid bed drier, processor, or a high-shear mixer.
Other dependencies include the dissolution time, [need] for fast delivery, or the disintegration requirement.
PharmTech: Can you explain tablet tooling and provide some considerations to make when deciding what methods to use?
Gupta: Tablet tooling refers to a tooling method that uses upper and lower punches, and compression force with a die and cup to shape granules or powder into a tablet. The die is used in conjunction with the punches to accept the granules or powder for compression and creates the tablet’s perimeter size. The cup depth determines the tablet’s depth.
The end product will influence the tooling parameters including the tablet size, based on economies and end-user price point. This goes from low-cost packaging through to the creation or innovative shapes to drive product differentiation and competition in a particular category and market.
PharmTech: What are some of the main challenges drug manufacturers face when trying to process oral solid dosage forms/tablets quickly and cost-effectively while also maintaining high quality?
Gupta: It is widely known that efficiencies in pharmaceutical productivity are not comparable to productivity gains in other manufacturing sectors. Running at an efficiency of 60–65%, the biggest challenge across the sector is by far productivity.
Also, as accuracy and quality are vital in cases where products are exported to regulatory markets, the levels of inspection are hugely increased. This, in turn, can hamper the ability to streamline and drive efficiencies.
The other challenges facing pharmaceutical manufacturing are varied, from API variations to labor shortages, speed of product inspection, production timelines, and speed of adopting new technology. However, the industry is accelerating its digital Industry 4.0 transformation in pursuit of data-controlled processes, which should help the sector to increase efficiencies, as well as speed to market.
PharmTech: Have you witnessed any significant trends in tableting over the past decade that have had a positive/negative impact on the industry?
Gupta: We are seeing a rise in multi-unit pellet system tablets. This is a solid dosage form that is the outcome of compressing a mixture of pellets that contain drugs and powder excipients [in order] to control drug release.
We have also seen a significant change in the adoption of inspection technology. The COVID-19 pandemic made it more evident that human inspection regarding the quality of products must be reduced, for example, by removing processes such as hand-picking products to test. Companies that focus on cost control, through the use of more efficient equipment and less onerous inspection processes, will not only reduce waste and the need for costly labor, but will also benefit from a reduction in costly product recall.
Manufacturers who adopt inspection technology benefit from microlevel distinction differentiation of the product; inside and outside. These inspections are efficient performing at high speed and in real-time, meaning samples do not have to be taken off the line to be tested. Inspection technology assesses every single product and provides real-time intelligence regarding rejections so the quality of the products in the batch that haven’t been rejected can be guaranteed.
Where as the sample method of testing means the entire batch quality is based on the test results of a subset of the batch and the remaining products in the batch are assumed to be of the same quality but can’t be guaranteed.
PharmTech: Could you give us your predictions on the trends within tableting for the coming decade?
Gupta: A growing and ageing global population, along with new emerging markets, are creating high demand in the pharmaceutical sector globally. With an increase in competition, speed to market is vital. Those who are customer-centric, provide safety assurance, and deliver faster will ultimately win.
We are seeing the nascent signs of demand for high-output machines. This is coupled with the need to drive efficiencies in the sector. The combination of advancements in Industry 4.0 and the need for leaner workforces will drive the analysis of multiple sources of data to provide information such as predictive maintenance and even remote maintenance. Where machine uptime and efficient running costs are improved, cost savings will be achieved without compromising the quality of the product.
Additionally, we are starting to see a greater uptake in 3D printing in the sector. Being able to print in small batches results in waste reduction, coupled with reliable outputs and efficiencies. It will have a useful place in the set-up of new product development and has the potential to revolutionize the delivery of personalized medicine.
Alivia Leon is assistant editor at Pharmaceutical Technology.
Vol. 47, No. 1
When referring to this article, please cite it as A. Leon, "Considerations for Manufacturing Solid Versus Semi-solid Drugs," Pharmaceutical Technology 47 (1) (2023).