Trends in Solid Dosage Forms and their Challenges for R&D and Manufacture

Innovation has always been the lifeblood of the pharmaceutical industry and while new active ingredients are of vital importance, improvements in drug delivery and drug targeting systems, in both device and dosage form, provide many more opportunities for enhancing efficacy, improving the patient experience and achieving commercial differentiation.

However, working with new dosage forms can present numerous challenges for R&D, production and quality control.

"At CI Precision we have spent over 50 years helping pharmaceutical companies to find solutions for weighing and sorting every kind of solid dosage form."

Growing demand for alternative solid dosage forms

As ever more products become available over the counter, consumer choice is a major driver of pharmaceutical innovation. From flavour and mouthfeel to colour, size, appearance and even novelty, in many product categories there are many opportunities beyond the API and excipients.

Healthcare professionals, meanwhile, are always seeking ways of improving patient compliance and overcoming barriers to taking medication. This is focused in particularly on those who struggle with traditional dosage forms, including children, but also in groups who are more likely to forget and/or suffer serious consequences from missing their medication.

Previously underserved populations can also be reached with some newer dosage forms where others have proved impractical.

Innovations in solid dosage forms are also being driven by more technical challenges, including the need for more sophisticated release profiles and/or combinations of APIs. With some drugs, improving their bioavailability remains a priority.

And, as more APIs come out of patent and are made available as generics, there is also a commercial imperative to create new, differentiated and where possible patentable dosage forms.

Trends in oral solid dosages and implantable dosages

Very few advances are truly unique, and the pharmaceutical sector has achieved numerous successes by adopting developments from other areas, notably food and beverage but increasingly from the tech sector.

Gummies and soft chews are a prime example of a product which started as pure confectionary, was adopted for nutraceuticals and is now achieving substantial traction wherever drugs need to be easier to chew and swallow, taken without water or made more appealing for paediatrics.

• Mini tabs and multiparticulate systems have started to become widespread since their commercial introduction in the early 2000s. As well as being easier for patients with dysphagia (difficulty swallowing), the ability to combine multiple mini tabs in a capsule is opening up new possibilities for personalised medicine.
• Orodispersible tablets and films (ODTs and ODFs) have existed for many years but, with advances in taste masking agents and other factors, they are seeing a growth in popularity for both over the counter and prescription medicines. Designed to dissolve rapidly in the mouth, they are valuable for rapid release drugs such as migraine treatments, as well as increasing the bioavailability of drugs with a high first pass effect.
• Implanted dosages were first used in the 1960s for contraceptives but despite tremendous potential have only recently started to be used in more applications and with wider uptake. Because they require medical administration, they are best suited to high value treatments and/or where the risks from non-adherence are high.
• Digitally integrated devices are a more recent innovation in solid dosages. In their simplest form, these comprise a tablet or capsule with API and excipients plus a radio transmitter which is paired with a receiver worn on the skin. By recording exactly when a dosage is taken, these can provide remote monitoring of patient adherence. Within the context of a clinical trial, this same information can provide valuable assurance of quality and consistency.
• 3D printing of solid dosages is truly at the cutting edge of personalised medicine. It has tremendous potential for precise, automated production of unique dosage forms, with drug combinations, quantities and release profiles tailored for each patient. However there are many hurdles before this is ready for commercialisation, not least the need for greater speed and proof for regulators that this technology can deliver with high precision and consistency.

Manufacturing challenges with new dosage forms

These newer dosage forms are not inherently more difficult to produce, but they do require some new approaches to manufacture that will present different challenges to production specialists:

Non-standard shapes and sizes. Volume production of tablets is highly optimised for a very narrow range of sizes and shapes of dosages. Many of the machines used for making, weight checking and sorting tablets would require substantial modification to handle different dosage forms. If you are making a variety of different dosage forms, you need to optimise manufacturing in a different way, to balance setup time, sensitivity/resilience and running speed.

• Stickiness and static cling. A significant advantage of regular tablets is that they move smoothly through production processes. In contrast, gummies and similar soft dosages can be sticky. Dusting powders may be helpful but could have an unpredictable impact on weight conformance for quality control. Mini tabs also present handling challenges, as their very small size makes them prone to static build-up, which needs to be safely discharged to prevent them adhering to machinery or to one another.

• Formulation challenges. As with any dosage form, the move from R&D to production can require formulation changes. Foremost is the need to ensure even distribution of APIs and excipients, although some newer dosage forms bring other formulation challenges. For example, mini tabs are more prone to friability than regular tablets, due to the greater surface to volume ratio and a fundamental lack of structural integrity at that very small size. Equally, gummies can suffer from shear effects when cut, which has to be balanced with achieving an acceptable disintegration rate and providing patients with a pleasant level of firmness.
• Need for controlled atmosphere or aseptic environment. The operational challenges and additional costs of aseptic manufacturing for implants are well understood. However, gummies with their higher water content and often no protective coating also need protection against microbial contamination. Furthermore, gummies and orodispersible dosage forms require a controlled atmosphere to prevent them being spoiled by exposure to moisture in the air.
• Manual handling issues. When working with small batches, whether for research, personalised medicine or specialised drugs, manual handling often forms part of the production process. This is particularly common in quality control with weight checking. However, when the dosages are very small and hard to handle, as with mini tabs, or need to be kept in containment, then the flexibility and cost of manual operations cease to be advantageous.

Ensuring conformance and patient safety

The implications for non-conformant doses reaching the consumer are far reaching, not just in terms of patient safety, but also from reputational, contractual and regulatory perspectives. With innovative and high-value dosage forms, any production problems and malformed product also represents costly and time-consuming waste.

Regulators are pushing for more data to be gathered throughout R&D and manufacturing processes rather than relying on assumptions about the performance of machines. So, while weight checking the finished product may be appropriate for regular tablets, this approach is inadequate for dosage forms such as implantable devices or multiparticulate systems. There, it is essential that all the constituent parts are individually precision weighed to verify physical conformance, for both compliance and commercial reasons.

Given the challenges discussed above, this additional measuring and checking may require new ways of thinking about the processes and the machinery used.

About CI Precision

At CI Precision we are specialists in fast, flexible, high precision weight sorting. For over 50 years we have been helping pharmaceutical companies to find solutions for weighing and sorting in R&D, in clinical trials, validating processes as they go into manufacture, and ensuring quality and conformance throughout production.

Our precision weight sorters are highly adaptable and can be moved from one product type to another without the need for change parts. They work within containment systems and are well suited to aseptic manufacture.

If you need to weight check and sort an unusual or challenging dosage form, please read about our solutions or contact us to discuss how we could help.

Learn more about solving weight control and analysis issues for small and novel dosage forms