(M1230-02-12) Improving Stability and Sustainability of an Auto-Oxidative Excipient, Polyethylene Oxide, with Foil-Lined Packaging

Purpose: Packaging plays a crucial role in medicinal products and the excipients that go into those products. However, traditional excipient packaging methods, like thick, difficult to recycle fiber drums formed with metal top and bottom chimes, sealed with polyethylene lids, can contribute significantly to landfill waste and carbon emissions via transportation. The pharmaceutical industry is witnessing a shift towards sustainable packaging solutions driven by environmental awareness, regulatory pressures, and consumer demand [1]. Key trends include the adoption of recyclable materials, like cardboard, and minimalist design approaches. Waste can also present itself as unused excipient material. Excipient material may need to be landfilled for various reasons including expired or non-conforming material. Polyethylene oxide (PEO) is a material that undergoes auto-oxidation that results in decreased molecular weight (MW), and thus decreased aqueous viscosity, over time. Very high MW PEO can quickly lose viscosity at ambient storage conditions which requires testing at regular intervals to confirm material meets specification. The current retest period for the two highest MW POLYOX™ PEO products, Coagulant (nominal 5MM MW) and 303 (nominal 7 MM MW), is 6 months. Although material can be still used after 6 months, testing must be performed to ensure the material meets critical property requirements for use in each drug product. If material does not meet these requirements, pharmaceutical companies may dispose of the PEO in landfills or incinerate it, contributing to waste and/or CO₂ emissions. Extending the retest period by reducing the auto-oxidation of PEO can prevent additional waste of unusable PEO material. One method to reduce the auto-oxidation of PEO is to use packaging that has a low oxygen transmission (OTR) rate. This study evaluated a foil-lined pouch with reduced OTR compared to standard fiber drums. In addition to reducing the auto-oxidation (and thus viscosity loss rate) of PEO, the foil packaging allows for less physical waste going to the landfills, providing a more sustainable packaging option.

Methods: Proprietary foil-lined pouches placed in a cardboard box (Figure 1a) and standard fiber drums (Figure 1b) were filled with POLYOX™ WSR Coagulant NF (PEO 5MM Da), 3 lots each. The containers were put into ambient storage (Temp 10 °C to 35 °C Humidity 25% to 85% ) for up to 2 years. Individual containers were pulled at pre-determined time intervals and evaluated for 1% aqueous viscosity per specification testing (Method 101962). Percent viscosity (v) retained were calculated as v_retained =  v_final/v_initial*100. To compare waste generated in fiber drums vs foil-lined pouches in boxes, the weight of each packaging type is reported and divided by the amount of PEO within a given packaging type (63.5 kg PEO in a fiber drum and 20 kg PEO in a foil-lined pouch). The fiber drums, polyethylene liners, tamper seals, foil-lined pouches are assumed to be sent to a landfill, while the polyethylene lids and cardboard boxes are assumed to be recycled.

Results: The material stored in the foil-lined pouch-in-cardboard box system had slower viscosity loss rates compared to material stored in fiber drums (Figure 2). The three batches stored in the foil-lined pouches lost about 10-15% of their initial viscosities over a 2-year period and all batches were above the minimum viscosity specification of 5500 cP. In contrast, the material stored in fiber drums lost 10-15% of their initial viscosity by 6-9 months and fell below the minimum viscosity specification by 18 months. The foil-lined pouch generates less waste than the fiber drum on a per kilogram of PEO basis. The fiber drum mass that is assumed to be landfilled (drum, liner and seals) is 0.086 kg per kg of PEO compared to 0.0075 kg per kg PEO for the foil-lined pouch (pouch), a >90% reduction in landfill and incineration waste.  It is assumed that the cardboard box that the foil-lined pouch is put into will be recycled. In addition to less landfill waste, the lighter foil-lined packaging is more energy efficient in ocean and air freight transportation, leading to fewer CO₂ emissions per kg of PEO. Improved stability and smaller packaging size enable more energy efficient ocean transport instead of airfreight. Ocean transport emits about 50-fold less CO₂ emissions compared to airfreight, making it a more sustainable option [2]. More PEO material can be packed onto a pallet using the pouch-in-a-box packaging (320 kg of PEO) versus a fiber drum packaging (254 kg of PEO), a 26% increase, further reducing CO₂ emissions associated with transporting PEO around the world.

Conclusion: Using cardboard and minimalist design, the foil-lined pouch-in-a-box packaging system can contribute to sustainability initiatives in pharmaceutical production by reducing the potential landfill contributions from both unusable PEO material and non-recyclable packaging. The minimalist packaging also improves the transportation efficiency per kg of PEO, resulting in fewer CO₂ emissions. By embracing these practices, the pharmaceutical industry can contribute to a more sustainable future while maintaining product safety and efficacy.

References: [1] D. Flack, "Sustainability in Pharmaceutical Packaging," American Pharmaceutical Review, vol. 26, no. 8, pp. 78-79, 1 December 2023.

[2] European Chemical Transport Association, "Europen Chemical Industry Counsil: Guidelines for Measuring and Managing CO2 emission from Freight Transport Options," 2011.

Figure 1: Image of foil-lined pouch in a box packaging (a) and fiber drums (b)

Figure 2: Viscosity retained of PEO 5MM MW after storage in ambient conditions in foil-lined pouches (ES packaging, 3 batches in diamonds, blue circles and squares) and multiple batches in fiber drums (red circles). The dark grey region indicates viscosity below specification (5500-7500 cP). Light grey region indicates possible viscosity below specification, depending on the starting value.

Figure 3: Weight of packaging components of a fiber drum (a) and the foil-lined pouch-in-a-box (b). For each, the landfill waste generated per kg of PEO is calculated.