Factors ranging from inertia to fear of failure can dominate conversations on the shop floor and in boardrooms, subsequently hindering plans for innovation and growth
The adoption of HPMC capsules is a classic example of this reticence.
Despite their growing use in nutraceuticals, their versatility, customisable release profiles, insusceptibility to the dangers of crosslinking and their consumer-friendly traits (vegetarian and biodegradable), there remains a reluctance in the industry to embrace HPMC.
Conversations with many pharmaceutical manufacturers suggest that their preference is to stick with gelatin as the status quo … and that the true value and benefits of HPMC are yet to be understood or acted upon within the industry.
To help quell these fears and encourage scientists to add HPMC capsules to their product lines, this article aims to bust some of the most common myths, misconceptions and excuses we’ve heard about HPMC — aiming to highlight the importance of HPMC in the future of capsule technology, drug delivery and, ultimately, patient care.
Myth: gelatin is the best material for capsules
Although HPMC has been around for decades, is already in use globally as a coating for tablets and is recognised as safe by major global regulatory agencies, including the UK’s Medicines & Healthcare products Regulatory Agency (MHRA) and the US Food and Drug Administration (FDA), gelatin is still seen by most pharmaceutical manufacturers and formulation specialists as the “default” option when it comes to developing generic capsule formulations.
This is largely because gelatin came first. Gelatin was well established as the safest, most versatile and only option for capsules for decades until the latter half of the 20th century.
Owing to a lack of viable alternatives in the past, recognised challenges with gelatin, such as an unpredictable shelf-life because of cross-linking issues, were skirted around … despite causing quality challenges during the storage and transportation of the product.
With safe and viable alternatives such as HPMC now readily available and widely used, it is important to note that inconsistent and costly workarounds — like adding enzymes to overcome challenges related to cross-linking in gelatin — are no longer necessary.
Gelatin should no longer be thought of as the default or only option.
Instead of spending valuable resources fighting and bending over backwards to accommodate gelatin’s limitations, R&D teams’ brainpower, time and budgets can be better spent investing in cellulose derivative materials such as HPMC to unlock new opportunities in capsule product innovation and development.
Myth: the burden of regulatory requirements is too great to warrant investment in HPMC
Pharmaceutical generic manufacturers often express concerns about the regulatory flexibility involved in adopting different types of capsules, even those with similar dissolution behaviours to gelatin (such as HPMC).
To avoid any regulatory headaches, they choose to limit their development to what has previously been done. This perspective not only overlooks the benefits that HPMC can bring but also its contribution to mitigating risk.
This “guidance” provided by the regulatory bodies, however, is just a recommendation and not a mandatory requirement.
Regardless of which capsule material they choose, each company must conduct their own studies, submit regulatory data and perform bioequivalence testing when introducing any generic products to market.
If the product meets the bioequivalence requirements, the type of capsules will not be questioned; so, despite the implication, adopting HPMC should not cause any undue regulatory burden.
In addition, after the upfront regulatory work, manufacturers generally have a more varied product portfolio with HPMC and also experience reduced market complaints and recalls. This saves both time and costs and improves their brand image and reputation.
Myth: gelatin is the more cost-effective option
Although gelatin capsules generally have a lower price tag than HPMC alternatives, this cost difference primarily reflects current economies of scale rather than inherent value.
As HPMC adoption continues to accelerate throughout the pharmaceutical industry, growing demand and increased competition are driving material costs down.
More importantly, HPMC offers pricing stability that gelatin does not. Gelatin prices fluctuate significantly based on the availability of its raw materials — animal bones, skin and cartilage — which are subject to market volatility and supply chain disruptions.
Beyond direct material costs, HPMC capsules deliver operational advantages that improve the overall economic equation.
Their robust nature renders them "machine-friendly,” making them compatible with existing encapsulation equipment without requiring costly production line investments or upgrades.
This eliminates any hidden transition costs that might otherwise undermine the business case for adoption.
By evaluating the total cost of ownership, rather than simply comparing unit prices, factors such as improved stability, reduced rework owing to cross-interactions, fewer regulatory concerns and better compatibility with a broader range of formulations illustrate that HPMC capsules can offer significant long-term advantages compared with gelatin.
Moreover, the cost of the empty hard capsule typically represents only a small fraction of the total product cost.
As such, a marginal increase in capsule cost to achieve higher quality and reduce unforeseen quality issues will have minimal impact on the overall product pricing or profitability, except in cases of extremely cost-sensitive or highly commoditised products.
For most formulations, this investment in quality pays dividends in product consistency, brand reputation and long-term efficiency.
Myth: HPMC capsules are not proven in the market
Understandably, manufacturers want to work with materials that are reliable and well-established in the marketplace.
Despite gaining popularity as early as the 1990s as a vegetarian alternative to gelatin, a misconception that HPMC lacks sufficient market validation still exists. This is simply untrue.
Today, HPMC capsules are used widely throughout the nutraceutical industry, are considered to be safe and have been approved by major regulatory agencies, including the FDA and the European Medicines Agency, for pharmaceutical and nutraceutical applications.
Since 2007, approximately 40 products in HPMC capsules have been approved by the FDA for different pharmaceutical products.
This regulatory acceptance is complemented by extensive commercial adoption and documented performance.
In addition, HPMC products — such as ACG's H+, HR, HA and HX capsules — offer formulation scientists the opportunity to modify drug release profiles, including valuable options for delayed-release applications.
This versatility not only represents an alternative to gelatin but also the opportunity to safely use HPMC to address complex drug delivery challenges.
Myth: pharmaceutical manufacturers must choose between HPMC and gelatin capsules
Adopting HPMC capsules does not mean eliminating or even phasing out the use of gelatin ones.
It is not an either/or proposition; in fact, using gelatin alongside HPMC can act as a failsafe, thereby reducing risk and ensuring that there is no wasted time in product redevelopment while new offerings are being tested.
Gelatin continues to be an established, reliable and widely used material in the capsules market and a suitable choice for formulations with compatible/moisture-insensitive ingredients.
For products containing sensitive APIs or excipients that react to moisture, however, HPMC offers clear advantages and should be considered.
The key is for formulation developers to critically evaluate different capsule materials in parallel for each specific product.
This method prevents wasted time and resources in terms of failed stability studies or market complaints after many months or years of R&D, enabling a “first-time-right” approach to product launches.
By making evidence-based selections, manufacturers can make room for both materials to ensure long-term market success while addressing diverse formulation needs.
The future of HPMC
Far from being risky or unproven, HPMC capsules have established a substantial track record of safety, regulatory compliance and formulation versatility in multiple market segments.
We believe that the growing demand for industry advancements in areas including delayed release formulations, as well as the consumer-driven call for plant-based alternatives, will continue to bring HPMC and other alternatives to gelatin to the forefront.
In short, HPMC is here to stay.
