In this online exclusive, Tomasz Bokas, European CMO sales manager at Saneca Pharma, discusses the benefits of soft gel capsules, the manufacturing and handling considerations that should be considered and overcoming the potential barriers to their adoption by manufacturers.
Soft gels
Soft gel capsules provide pharmaceutical companies with an effective means of delivering poorly soluble active pharmaceutical ingredients (APIs). As with any dosage form there are pros and cons to the adoption of soft gels, from initial investment costs to challenges around solubility, and all must be considered by drug makers.
The benefits of soft gel capsules
Soft gels allow for rapid absorption of the ingredient and they minimise the amount of excipients required compared with tablets. In addition, modern technologies allow the production of soft gels in a variety of shapes, colours, finishes and flavours.
The decision to adopt soft gels is often driven by their ability to deliver poorly bioavailable APIs. This is becoming increasingly important for drug developers and manufacturers as, according to some estimates, 40% of the new chemical entities (NCE) being worked on by the drug industry have poor biopharmaceutical properties, specifically low solubility.1 Insoluble compounds — those that belong to biopharmaceutics classification system (BCS) class II or class IV -are poorly absorbed by the body which ultimately impacts the efficacy of the drug. Soft gels can help resolve this issue because the APIs they contain are in a solution.
Challenges in materials and design
There are several considerations manufacturers need to keep in mind when producing soft gel formulations. One of the major constraints is that gelatin, an animal derived material used to make the polymer shell, is highly water soluble. Gelatine’s solubility is an advantage in some respects; soft gel capsules rapidly dissolve when ingested which is ideal for the delivery of fast-acting medicines, and during production, water is used to make gelatine pourable.
However, this solubility causes soft gel capsules to be very sensitive to heat and humidity, consequently, the shelf life of these formulations can vary considerably depending on the conditions in which they are stored. It also impacts the types of APIs soft gel capsules can be used to deliver. The liquid fill must be oil-based rather than water-based to prevent it interacting with the outer shell, which means drug developers need to find ways of dissolving their APIs in an oil-based suspension using excipients.
Prompted by these issues and a growing demand for non-animal-based products, drug makers are also exploring alternative materials including synthetic polymers or plant-derived hydrocolloids, with hydroxypropyl methylcellulose (HMPC) being one of the best-known examples.
Soft gel formulations offer a similarly dichotomous challenge when it comes to their design. The shape of a soft gel capsule can be modified to make it easier for patients to swallow and manufacturers can incorporate taste masking technologies into capsule shells to make otherwise unpalatable medicines more pleasant.In both instances, a soft gel is being tailored to ultimately improve patient compliance. However, manufacturers must consider any potential interaction between the soft gel’s liquid fill and the shell. One of the more prominent areas for consideration is that certain shell colouring agents can react with liquid contents, dramatically reducing stability and sometimes leading to leakage.2
Cost as a barrier
Cost is likely to be one of the major hurdles for drug-makers looking to use soft gels. Production requires specialist technologywhich can be expensive to install for manufacturers that are more familiar with making traditional tablets.3 Developing the liquid fill can also be time consuming and therefore costly in terms of internal resource and is likely to involve specialist excipients.
While the initial set-up and formulation development costs may be prohibitive, there are several long-term returns on the investment. Soft gel capsules are relatively cheap to mass produce, minimise the amount of excipient required.
Outsourcing soft gel development and production to contract development and manufacturing organisations (CDMOs) with expertise and capacity is a viable option for pharmaceutical companies looking to minimising these costs.
Conclusion
For the right API, soft gel capsules are an ideal delivery technology that can be used to improve the bioavailability of poorly soluble drug ingredients and deliver precise dosages, quickly and efficiently.
Like all dosage forms, it is important that pharmaceutical developers fully understand the stability characteristics and manufacturing considerations involved in making soft gel products. Where resources are strained, soft gel expertise and production capacity are fast-becoming the benchmark of modern, full-service CDMOs.
References
1. https://www.ncbi.nlm.nih.gov/pubmed/20737624
2. https://pdfs.semanticscholar.org/c337/bf900f572a447cf62036fe4b79ddbfc410b5.pdf