Manufacturing Q&A: Formulations

Plant-Powered Formulations Offer a Sustainable Future

IPT spoke to Rajeev Gokhale of Roquette, who sees a strong market for innovative oral therapeutics that take account of customer preferences and target unmet needs
IPT: Sustainability is a key aspect of producing formulations. What new innovations can support this drive for sustainability?
Rajeev Gokhale: Offering environmentally friendly, innovative and competitive solutions is critical to a greener future in the pharmaceutical industry. Using plant-based resources is the key to better sustainability across the market, especially when it comes to formulation development and choosing excipients for drug products. Plant sources are renewable and can therefore be cultivated or harvested in a sustainable manner, resulting in constant availability of raw materials.

High-performing, plant-derived technologies, like those utilising pea-starch, are also helping to support innovation and sustainability practices across the nutraceutical and pharma industries. Gelatin is considered the gold standard for softgel formulation. However, despite its numerous benefits, softgel manufacturers are increasingly exploring alternative capsule materials that will help overcome challenges with gelatin, like crosslinking, while meeting evolving consumer preferences for veggie-based ingredients with greener credentials.
What more can the industry do to improve sustainability practices while driving investment in new technologies?
There are numerous actions that the pharma industry can take to innovate more sustainably. It all starts with understanding the customer need and better anticipating consumers’ expectations to develop truly innovative solutions that will help improve the health and wellbeing of people globally. When developing such solutions, manufacturers should ask questions like, ‘Can I source my raw materials more locally?’, ‘Could I optimise the transportation of my raw materials?’, or, ‘How can I strengthen the relationship with my suppliers?’.

It is equally important for brands to strengthen the sustainability of their innovation processes. This involves making sustainable development criteria a core element of any innovation project, and closely monitoring those goals to check they are being achieved. By 2025, for example, we are aiming for 80% of our company’s solutions to meet the Sustainable Development Goals of the UN.
How can investment in new facilities and innovations help to produce better formulations and serve worldwide populations?
Investment in new facilities and innovation are certainly core parts of our strategic growth plan. New facilities help us to remain close to our customers and support them throughout the drug development process to bring new products to market successfully. Meanwhile, innovation is arguably a defining characteristic of the pharma industry and, therefore, a key success factor for any organisation looking to serve unmet patient needs.

For instance, consider vaccine innovation. Currently, in this field, there is an explosion in basic scientific understanding and rapid advancements in areas such as genomics and structural biology. The result is a new wave of highly diverse approaches to vaccine development and production. As well as bringing innovation to the field, such progress has raised questions about whether conventional vaccines are enough. This has challenged leaders in the industry to think differently and push the boundaries of traditional vaccine development to get vaccines to market quicker.
What are some of the key challenges that need to be solved to improve formulations and excipients processes?
More than 60% of new drug actives exhibit low water solubility, which can lead to poor absorption in the body and reduced bioavailability when delivered orally. Encapsulation and emulsification technologies are vital for increasing the absorption of pharmaceuticals with poor water solubility, so they can reach the relevant site of action in the body and have the desired effect.

Another challenge is patient compliance. Most individuals will only comply with a treatment if it requires taking one or two tablets daily for a short period of time. However, some drug products need to be administered two-to-four times per day to be efficacious. That is where controlled release technologies are making headway, by helping to eliminate the need to take multiple tablets a day to manage a condition.

Improving the swallowability and taste of pharmaceuticals is an equally important way of improving compliance, especially in geriatric or paediatric populations, who typically struggle to swallow medications. This issue can be addressed with orally disintegrating tablets (ODTs), which dissolve rapidly when placed on the tongue, simplifying the process of taking medication and bringing greater convenience to the patient. In addition, they have a pleasant taste and mouthfeel, making them an attractive alternative to traditional oral delivery dosage forms.
Finally, with growing health awareness, more and more people are taking probiotics to maintain a healthy lifestyle. Probiotics are live microorganisms that provide a range of health benefits by improving or restoring the gut flora. However, probiotic products can be challenging to formulate, especially in terms of maintaining both the stability of the probiotic during the manufacturing process and the shelf-life of the final dosage form. Here, low water activity excipients help to support the stability of probiotics, maximising the drug’s therapeutic effectiveness and clinical applicability.
How can collaboration between the laboratories and customers bring better formulations to market?
Collaboration between researchers and customers is essential for addressing and solving complex formulation challenges and powering innovation. That is because partnership brings together individuals with diverse technical backgrounds and perspectives, and creates a space for knowledge, skill and technique sharing across teams. Ultimately this enables better problem solving and a higher possibility of bringing optimised formulations to market. That’s exactly why we plan to open a new innovation centre in Pennsylvania, US, to serve as an Applied Science and Customer Technical Support (CTS) centre. This will enable our company to work side by side with its partners and customers to provide support at every stage of development for oral prescription (small molecule) drugs, as well as nutraceutical APIs.
What does the future hold for formulations and excipients in oral dosage forms?
The oral segment has dominated the global pharmaceutical excipients market in recent years, and we expect it to maintain its dominance thanks to the growing focus on patient-centric strategies. This includes the ongoing development of oral dosage forms that get the right treatments to the right patients at the right time, all while enhancing patient compliance. In particular, pharma companies are capitalising on the demand for specialised dosage forms, including paediatric/geriatric-friendly formats and controlled-release formulations. Since traditional, solid tablets are hard to swallow, companies in the market for pharmaceutical excipients are using this opportunity to meet evolving consumer needs. As a result, they are increasingly investing in R&D to overcome the limitations of traditional approaches and enhance their capabilities to develop innovative dosage forms, such as ODTs, orally disintegrating granules, effervescent tablets, and lozenges, which are designed to be swallowed easily.

The regulatory landscape in the US is evolving, too. In recent years the FDA has approved rising numbers of oral dosage forms, owing to high patient preference for oral medication aids. Meanwhile, promotion of excipients by various institutions, such as the International Pharmaceutical Excipient Council, has influenced the choice of excipients used in drug formulations. Both of these factors are contributing to market expansion.

The expiration of blockbuster drug patents in 2022 could also be interesting for the development of the excipients market. This will usher in a new wave of product innovation among generic drug manufacturers looking to produce their own versions of once groundbreaking medicines and treatments.
When can we expect these innovations to take shape in the industry?
Patient compliance is one of the biggest challenges in disease treatment. Without patient compliance, the effectiveness of modern medicine cannot be realised. Patient-centric formulations are therefore becoming a mainstay. We have discussed two approaches to achieve patient compliance – ODTs and controlled release dosage forms. While these approaches are not new, they have significant potential thanks to the innovation and availability of novel technologies, complemented by sustainable plantbased excipients, to meet strong market acceptance and patient demand. They are also expected to play a key role in stabilising and extending the shelf-life of probiotics, and have shown great potential as a replacement of animal-soured materials, such as gelatin, in the manufacturing of pharmaceutical dosage forms.
Rajeev Gokhale is Head of Global Pharmaceutical Sciences, Pharma Solutions GBU, at Roquette. He oversees the Applied Sciences and Customer Technical Services groups in Singapore, Lestrem and the US. With over 25 years of technical leadership experience in the pharma industry, he is recognised for his expertise in solids formulations, biopharma and drug delivery systems.

Rajeev has been an Adjunct Associate Professor at the National University of Singapore, and the universities of Connecticut, Tennessee, and Illinois, US. He holds a PhD from the University of Georgia, US, an MS from the University of Kansas, US, in Pharmaceutical Sciences, and B Pharm and M Pharm degrees from the University of Mumbai, India.