Gattefossé Pharma

INTERVIEW WITH STEVE AMOUSSOU-GUENOU, ROQUETTE

Steve Amoussou-Guenou is a Global Technical Developer with Roquette. In this role, Mr Amoussou-Guenou leads all aspects of technical support for Roquette pharma customers, including helping them in the use of Roquette excipients for their pharmaceutical development projects, offering technical guidance in formulation/process development, quality and regulatory affairs, and contributing to the development of innovative solutions.

Mr Amoussou-Guenou has more than 12 years of experience in the pharmaceutical industry. Before joining Roquette in 2016, he worked for eight years for a variety of organisations, including big pharma, research institutes and CDMOs. His responsibilities included leading pharmaceutical development and technology transfer projects, managing communication with internal and external stakeholders and business development.

Mr Amoussou-Guenou is a qualified industrial pharmacist and holds a Master of Science degree from Laboratory of Pharmaceutical Industrial Technology from the University of Bordeaux 2 (France).

In this interview, Mr Amoussou discusses how Roquette developed the LYCAGEL™ system and how this plant-based alternative compares with traditional gelatin softgel capsules.

Q Historically, there have been several hurdles to the adoption of softgel technologies in the pharmaceutical industry, including cost, solubility, shelf-life and others. What makes LYCAGEL different and what new formulation opportunities does it present for pharmaceutical manufacturers?

A Although there are other plant-based softgel products on the market, LYCAGEL™ is the first pharmaceutical-grade plant-based softgel alternative to gelatin – meeting both EU and US pharmacopeia standards (Figure 1).

A key ingredient in the LYCAGEL™ system, hydroxypropyl (HP) pea starch, is the first of its kind to market. Its benefits include increased capsule strength, improved seal integrity, quick drying time with no stickiness and – when compared with gelatin – no cross-linking and higher processing temperature suitability. As well as offering advanced performance, the pea starch system delivers on consumer visual appeal, too – resulting in capsules with a shiny, transparent finish and excellent reproducibility.

Figure 1: Roquette’s LYCAGEL™ capsules, a plant-based pharmaceutical-grade alternative to gelatin for softgel capsules.

LYCAGEL™ also accommodates a wide range of active fills for different capsule shapes and sizes, including ingredients that require higher processing temperatures and complex multi-ingredient formulations. For example, it is ideal for the encapsulation of over-the-counter analgesics – its ability to disintegrate quickly means that manufacturers can offer rapid pain relief, a feature often required by such products.

Follow this link to request more information about LYCAGEL™ or download the LYCAGEL™ Technical Data Sheet.

Q How long has LYCAGEL been in development for and how was Roquette able to create the first plant-based softgel to successfully meet both EU and US pharmacopoeial standards?

A Roquette has been investing in research and development for LYCAGEL™ for the past two years. The decision to launch now is supported by the validation of its reproducibility at scale when encapsulating varying fills for different capsule sizes and shapes. Meanwhile, with demand for plant-based alternatives to gelatin showing no signs of abating, pharmaceutical and nutraceutical manufacturers alike require a solution that can help them meet discerning consumer preferences for sustainable, non-animal derived ingredients.

When it came to formulation, the project team defined a target product profile that covered several parameters; everything from the capsule’s physical attributes to regulatory requirements, including the ability to meet both pharma- and food-grade standards.

When it came to formulation, the project team defined a target product profile that covered several parameters; everything from the capsule’s physical attributes to regulatory requirements, including the ability to meet both pharma- and food-grade standards. Using Roquette’s expertise in starches and hydrocolloids, we carefully selected some excipient candidates that successfully met our objectives. Finally, using experimental design techniques, we optimised the softgel formulation and manufacturing process.

Q What were the primary technical challenges in creating LYCAGEL™ and how were they overcome?

A The basis of the LYCAGEL™ system is a tailored HP pea starch. Unlike gelatin, it does not possess the gelling properties needed to form a homogeneous softgel film. As such, we needed to explore ingredient combinations to ensure we could achieve this essential characteristic – ultimately, we selected carrageenan as the solution. However, when mixed together, pea starch and carrageenan are more viscous. In addition, we found that the formulation was jellifying at temperatures below approximately 85°C, so, compared with gelatin, the preparation of the gel mass required a higher temperature, the same being true for film casting and capsule sealing. We also experienced some challenges with capsule sealing during the initial stages of the development; we found that the capsules were leaking, or the films were too thick, with heterogeneous structure or containing some air bubbles.

To overcome these challenges, we developed a specific cooking procedure for the pea starch and carrageenan system and implemented some equipment adjustments to avoid the immediate jellifying of the gel mass. Following multiple testing phases, a new temperature setting profile was established. Our efforts to optimise and adjust the process parameters for LYCAGEL™ subsequently overcame the initial challenges with film texture homogeneity, capsule leakage and sealing marks.

Q How does LYCAGEL compare with gelatin? Does it have the same performance characteristics and what studies have been carried out?

A Historically, gelatin has been considered the go-to softgel solution for pharmaceutical manufacturers. However, gelatin is animal-derived and exhibits cross-linking and incompatibility issues with fill ingredients that can shorten the softgel product’s shelf life. At the same time, consumers, for a variety of reasons, including religious and dietary, are demanding companies use non-animal derived ingredients. Based on experience of working with other plant-based softgel solutions, some formulators are concerned that plant-based soft capsules don’t match up to gelatin when it comes to performance. Moreover, many manufacturers think that the manufacturing process is much slower for plant-based softgels, making them inefficient and more expensive.

As a high-performing ingredient developed from pea starch, LYCAGEL™ helps to meet the consumer demand for plant-based options, without compromising on performance or quality.

As a high-performing ingredient developed from pea starch, LYCAGEL™ helps to meet the consumer demand for plant-based options, without compromising on performance or quality. When developing LYCAGEL™, we conducted a thorough performance study, looking at process parameters, capsule performance and stability. Contrary to popular belief around plant-based softgels, our research has found that the total manufacturing time for LYCAGEL™ is actually equivalent to that of gelatin, with a drying time of 4-5 days, compared with the 3-4 days observed with traditional gelatin softgels. Additionally, LYCAGEL™ is processed at higher temperatures, removing the temperature limitations experienced with gelatin. This offers manufacturers greater formulation utility to use multi-ingredient and complex formulations, and the flexibility to include ingredients that require higher processing temperatures, such as pastes or waxes.

In terms of capsule performance, one of the greatest advantages of LYCAGEL™ is its strength compared with gelatin, and its ability to maintain structural integrity during production and throughout storage. For example, LYCAGEL™ retained a hardness of 19.1 N after six months at 25°C/60% relative humidity and 17.3 N after 12 months at 20°C for example.1 Unlike gelatin-based capsules, LYCAGEL™ softgels also exhibit no cross-linking, which means there is no significant increase in the capsule’s disintegration time during storage due to alteration of the shell composition. The results of our performance study confirmed this, demonstrating a disintegration time of less than eight minutes after 12 months at 20°C and six months at 40°C/75% relative humidity due to no cross-linking.1 Further tests also revealed that LYCAGEL™ capsules showed no leakage or sticking, and do not exceed 8% moisture content in 25°C/60% RH and 20°C conditions.

Q Are there any drawbacks to LYCAGEL™ as an oral delivery system or could it render gelatin obsolete?

A Gelatin has a long-standing history of use as a key ingredient in softgel formulations. It is a proven film-former material and unlikely to be replaced entirely by plant-based softgel alternatives. In fact, most softgel manufacturing processes today are designed to accommodate gelatin. However, since gelatin has performance issues – primarily temperature limitations for encapsulation of select APIs and cross-linking that can impact the release of capsule fills – there is certainly a gap in the market for a more robust solution (Figure 2).

Q Is LYCAGEL™ suitable for all the same applications as gelatin softgels? Is it necessary to modify manufacturing lines?

A Because of the higher processing temperatures, LYCAGEL™ unlocks new possibilities for fill materials that require these higher temperatures, in addition to standard fills like fish oil.

Because of the higher processing temperatures, LYCAGEL™ unlocks new possibilities for fill materials that require these higher temperatures, in addition to standard fills like fish oil.

One drawback of LYCAGEL™, or any other non-gelatin alternative, is the need to make minor modifications to gelatin softgel manufacturing equipment to handle the higher gel mass viscosity and temperature requirements. Despite this, Roquette’s LYCAGEL™ system comes close to the gelatin process in terms of total process time and encapsulation speed.

Plus, Roquette offers a full technical package as part of the LYCAGEL™ system, ensuring that regardless of whether the drug manufacturer is developing their first softgel product or is looking to switch from gelatin or alternative plant-based softgel solution, they are fully supported every step of the way.

Q How does LYCAGEL™ compare to other plant-based products on the market?

A Currently, we don’t have a complete set of data to support claims that LYCAGEL™ offers superior performance over other plant-based softgel solutions available on the market. That said, as part of our rigorous R&D process, we conducted a full review of existing products and worked in collaboration with select partners to understand where such products may be falling short of expectation. We then built on these insights to deliver a truly advanced solution.

Q In which regions will LYCAGEL™ be available and what R&D support is available to pharmaceutical manufacturers?

A As our LYCAGEL™ system is available for sale worldwide, we can expect nutraceutical supplements featuring LYCAGEL™ to launch globally as early as late 2021 or early 2022, although pharmaceutical drug products naturally have a longer development lead time. We can also offer some LYCAGEL™ premix samples for accelerated development and scale-up.

The LYCAGEL™ technical support package will help ensure manufacturers get their products to market faster. This includes a technical data package which summarises the formulation, equipment and processing know-how, as well as either remote or on-site technical support.

Follow this link to request more information about LYCAGEL™ or download the LYCAGEL™ Technical Data Sheet.

REFERENCE

  1. “Pea starch performance study.” Internal study, Roquette, 2020.

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