Packaging Precision: Engineering Stability and Shelf Life for Oral Solid Dose
From capsule selection to barrier films and high-speed filling lines, ACG’s integrated approach to oral solid dose manufacturing gives pharmaceutical companies a single partner across the decisions that most affect product stability, yield, and shelf life at commercial scale.
The OSD Landscape: Diversifying Without Losing Complexity
The oral solid dose market is undergoing a structural shift that moves in two directions simultaneously. New chemical entities increasingly trend toward biologics and injectables, yet the OSD pipeline is also expanding into more sophisticated formats: combination capsules delivering immediate and delayed release in a single unit, novel polymers engineered for specific dissolution profiles, and vegetarian alternatives to gelatin serving both regulatory and patient preference requirements across key markets.
The result is a development environment in which the apparent simplicity of capsule-based drug delivery conceals a growing number of formulation-critical decisions. The choices made at R&D stage carry direct consequences for yield, shelf life, and cost of goods at commercial scale. Getting them right demands a partner with sight of the whole picture from the outset.
Selecting the Right Capsule: Science Before Aesthetics
Anil Andrade, VP Global, ACG Capsules. ACG’s capsule manufacturing operations span India, Croatia, Brazil, and a new facility in Thailand serving the Asian vegetarian capsule market.
For many development scientists, the capsule is a starting point rather than a considered choice. Its utility in early phase work is precisely that convenience: an API combined with minimal excipients, dropped into a shell and sent to the clinic. The broader questions of colour, print, and polymer come later. Beneath that practical simplicity, however, lies a set of decisions that carry real downstream consequence.
The choice between gelatin and hydroxypropyl methylcellulose capsule shells is not merely a matter of patient preference or regulatory positioning. The moisture content of a gelatin capsule typically sits between 11 and 16 per cent. An HPMC shell operates in a narrower range of 3 to 8 per cent. When a hygroscopic API is involved, the interaction between the drug substance and the capsule shell becomes a formulation variable in its own right. Choosing incorrectly can produce brittleness that is invisible at manufacture but emerges during transit, or cross-linking that only becomes apparent six months into a stability study.
Cross-linking results from an aldehyde reaction with gelatin and, while it does not affect the patient once consumed, it can prevent the shell from dissolving correctly. Reformulation at this stage is expensive. Corrective options range from the use of accelerants to a full polymer change, both requiring stability data to support. Early collaboration between the capsule manufacturer and the formulation team is the most reliable way to avoid it entirely.
“Running capsules is an art and a science. It involves a capsule, equipment, and a formulation, and everything has to align perfectly for it to work well.”
Anil Andrade · VP Global, ACG CapsulesProduct differentiation is an underappreciated function of capsule design in commercial markets. In a crowded generic landscape, where multiple manufacturers are producing equivalent molecules, the capsule becomes a branding asset. The ability to specify colour, print, and multi-compartment formats that deliver both immediate and delayed release in a single unit represents meaningful commercial value, particularly in nutrition and consumer health where OTC shelf presence influences sales volume.
Barrier Selection: Three Challenges, Many Solutions
Guy Calcagno, VP Global, ACG Packaging Materials. Based in Melbourne, Guy advises manufacturers globally on barrier selection, sustainable packaging strategy, and machinability optimisation.
Once the capsule formulation is fixed, the packaging decision begins. For oral solid dose, the three variables that drive barrier specification are consistent: moisture, oxygen, and light. The severity of each, and the combinations in which they present, determines the appropriate solution. Where all three are significant factors, cold-formed foil or high-barrier polymer laminates incorporating PVDC or PCTFE become the indicated route. Where only oxygen sensitivity is in play, a PVC/PVDC or PVC/EVOH structure may be entirely sufficient.
The pharmaceutical packaging development professional must carry this analysis across markets. The same product destined for both cold climates and humid tropical regions will not perform identically in standard PVC. Customising packaging for the API and the distribution geography is not optional for products with international ambitions. It is a regulatory and stability requirement that must be addressed at the design stage, not after market entry.
The sustainability dimension has added further complexity to what was already a technically demanding decision. A manufacturer targeting biodegradability is working in a different solution space from one seeking non-halogen compliance or lower carbon footprint. In the oral solid dose sector, a complete biodegradable solution for blister packaging does not yet exist. Partial solutions involving paper composites and certain biodegradable films are available, and regulatory guidance from the European Pharmacopoeia and the FDA is developing, but clear standards are still emerging.
“When you are targeting different markets around the world for the same product, the solution will be slightly different as per your need. You must customise your packaging for your API and excipients.”
Guy Calcagno · VP Global, ACG Packaging MaterialsWhat does exist are non-PVC alternatives for markets where halogen-containing packaging is being restricted. South Korea’s PVC ban, effective July 2023, prompted ACG to develop a cold-form foil solution using HDPE in the mid-layer in place of PVC. The aesthetic outcome for the consumer was identical to the original format. The transition required minimal changes to existing production lines. The cost premium at raw material level was approximately 25 per cent, but expressed as a proportion of total product cost per unit, this represented only one to two per cent. The manufacturer gained a credible sustainability claim for its OTC channel with negligible impact on the economics of the finished product.
Equipment and Integration: Where Yield Is Won or Lost
The filling and packaging equipment sits at the intersection of every upstream decision. A capsule specified for a high-speed line must perform with the consistency that high-speed filling demands. A barrier film selected for moisture resistance must run without delamination or pocket cutting at the temperatures and pressures of the blister forming machine. These are not theoretical concerns. They represent the daily reality of pharmaceutical manufacturing, and they account for a disproportionate share of production losses when not managed correctly.
A case study from a large North American generic manufacturer illustrates the scale of impact. The product was gabapentin, produced in volumes approaching three billion capsules annually across ten high-speed filling lines. The customer’s yield stood at 96 per cent. Analysis revealed that 88 per cent of the four per cent loss was occurring at the dedusting unit, with further losses distributed across the machine table and defect rejection. Modifications to the filling process and installation of purpose-designed components increased yield by 1.3 percentage points. On a product at that volume, the financial recovery was between five and seven million US dollars per machine per year, across a fleet of ten.
A parallel case in the packaging materials space involved Levothyroxine for export to the North American market from Bangladesh. The innovator product was packaged in PCTFE, and the generic manufacturer’s instinct was to replicate that format. Concerns centred on regulatory speed to market, cost, and raw material supply reliability. ACG worked with the development team to demonstrate that a high-barrier PVDC solution at 180gsm would meet the regulatory requirements, deliver equivalent protection, and bring the product to market within 12 to 18 months at a unit packaging cost 25 to 30 per cent lower. In both cases the value delivered was not simply the supply of a component. It was the technical guidance to make a better decision than the manufacturer had initially proposed.
AI and the Global Lighthouse Network
ACG’s capsule manufacturing operations were recognised by the World Economic Forum as a Global Lighthouse Network facility, a designation awarded for the deployment of advanced manufacturing technologies, including artificial intelligence and digitalisation, to improve operational performance. The case studies underpinning the recognition involved applying AI to quality management, production speed, and changeover time across a pilot facility, with measurable improvements in yield and reductions in production cost now being replicated across the group’s global capsule manufacturing estate.
The internal dimension of this programme deserves equal attention. Introducing AI-enabled production management required active engagement with the workforce to reframe the technology as a capability-enhancing tool rather than a source of job displacement. That process of communication and cultural alignment is as much a part of the transformation as the technology itself, and it must be replicated at each site. The ambition is to extend the same approach to films and foils and to engineering in due course.
The Case for Integration
The structural argument for ACG’s integrated model is demonstrated at the level of individual interventions rather than abstract principle. A technical services team that spends a month on a customer’s production floor. A packaging technologist who works alongside an equipment engineer during a new filling line installation. A film and foil team that increases reel size to reduce downtime and improve OEE on a machine that ACG also manufactured. Each of these represents a value that is only possible when capsules, materials, and equipment are designed and supported by the same organisation.
The geographic footprint supports the model. Capsule manufacturing operations span India, Croatia, Brazil, and a Thailand facility coming online for the vegetarian capsule market in Asia Pacific. Packaging materials are produced in India and Brazil, with warehousing positioned in North America, Europe, and China to service multinational contract manufacturers on just-in-time terms. A recent acquisition in the UAE strengthens the group’s position in the Middle East. For oral solid dose manufacturers navigating increasing regulatory complexity, evolving sustainability requirements, and persistent pressure on cost of goods, the question of supplier integration has become less a philosophical preference than a practical imperative.
The full presentation, including ACG’s case studies on yield improvement, barrier selection, and sustainable packaging alternatives, is available on demand via the Pharma D-mand webinar library.
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