Ask an Expert -- Can I Deliver a Complex Probiotic Formulation Effectively in a Softgel Capsule?

Consumer preference for softgel capsule technology to deliver pharmaceutical and nutraceutical products is growing fast¹. Pill fatigue has boosted the popularity of consumer-friendly dosage forms including softgels, in alignment with consumer needs for fast, safe, and efficient supplement delivery systems. Softgels’ luster also imbues quality and efficacy, and, for most consumers, they’re perceived as easier to swallow.

However, not all formulations can be successfully delivered using softgels. Encapsulating probiotic bacteria formulations in softgels has been notoriously problematic because of two fundamental issues:

1. Softgel capsules traditionally required high temperatures and humidity to manufacture--which leads to the destruction of probiotics--making most probiotics in softgel formulations unviable.
2. Common softgel shell formulations are challenged to maintain a market-standard product shelf life (typically 2 years), especially at room temperature. 

Probiotic softgel formulations are challenged to maintain desired viability (often measured in colony forming units or CFUs) during the designed shelf life of the product (typically 2 years), especially at room temperature. This is thought to be due in part to the high free-water activity (Aw) inside the softgel. The Aw gradient is associated with the softgel manufacturing process, particularly during the encapsulation stage. During encapsulation, some of the water present in the shell moves to the formulation in the shell, where it is retained in free form. With formulations containing probiotic bacteria, the free/or available water activates the probiotic bacteria and leads to a loss of viability. Therefore, softgel manufacturing process can stress probiotic bacteria even when encased in oil, thereby reducing viability and stability.

Practical innovation delivering a better process and product

Innovation and technical advancement on several fronts over the last decade are finally creating a practical pathway to deliver high-potential probiotics via softgel in the gut successfully. Refining chemistry, formulation and process, recent patented innovation enables the manufacture of softgel capsules combining uncoated probiotic bacteria with at least one oil – e.g., fish oil with either DHA or EPA, in a softgel.

Popular probiotic formulations are increasingly being delivered in softgels on a commercial basis. Lactobacillus and Bifidobacterium are some of the more well-documented strains that can be delivered via this methodology in a softgel format, but it can work with many different types. As noted, combining popular probiotics with fish oil is a prerequisite. But research and patent development over the last 10 years has demonstrated Omega 3 is one lipid that can support an extremely effective and marketable formulation strategy for consumer probiotics. By delivering probiotics with Omega 3, developers have the capability to deliver more active probiotics in fewer individual doses to meet their supplement needs.

The key to mitigating loss and ensuring the viability and therapeutic performance of probiotics involves precisely tuning process parameters to dramatically improve probiotic actives’ survival rates and preserve shelf life. First comes formulation, putting the probiotic bacteria into a suspension. In general, the oily matrix or oily based suspension formulation effectively limits the contact between the bacteria and the free water entry from the shell of the softgel capsule into its internal environment.

The key to a processable formulation, and the key to bacteria viability in softgels lies in reducing heat and energy from the manufacturing process. Reducing shear and other forces, as well as maintaining product temperatures in a range between 5 and 15 can help mitigate damage, loss and support better viability of the probiotics in a softgel. This is the key area of probiotic formulation and process innovation that is now permitting nutraceutical developers a truly consumer-friendly probiotic delivery system with distinct benefits and few compromises.

Fostering a healthier relationship with softgel technology

The global probiotics market size is expected to reach $111B by 2030 and is expected to expand at a compound annual growth rate of 7.5% from 2021 to 2030 ². With access to process innovation and new capabilities probiotic innovation has even fewer limitations and more possibilities, especially when it comes to creating dose forms more patients prefer.

References

1. https://pharma-trends.com/2021/02/09/current-trends-in-oral-solid-dosage-forms/
2. https://www.businesswire.com/news/home/20220426005686/en/Global-Probiotics-Market-Analysis-Report-2021-2030-Food-Beverages-Dietary-Supplements---Growing-Inclination-Towards-Preventive-Healthcare---ResearchAndMarkets.com