Discover the power of POLYOX ™ polyethylene oxide polymers for advanced oral drug delivery
Gopeshkumar Singh, Senior Applications Scientist, IFF Pharma Solutions
Elizabeth Tocce, Lead Applications Scientist, IFF Pharma Solutions
Oral dosage forms are a preferred drug delivery route due to their convenience, high patient compliance and cost-effectiveness.1 However, developing advanced oral dosage forms, such as those with modified-release profiles, requires sophisticated delivery systems. Examples include osmotic pump systems and hydrophilic matrix tablets, which use advanced technology to optimize drug delivery by controlling drug release to a specific target site. This approach maximizes therapeutic efficacy while potentially minimizing adverse events. To achieve these effects, sophisticated drug delivery systems rely on specialized excipients like polyethylene oxide (PEO). Known for its high swelling capacity and flexibility across a wide range of applications—PEO stands out as a key excipient for advanced oral dosage forms.
The first commercially available PEO excipient—POLYOX™ water soluble resin—was discovered over 70 years ago. PEO has since been used to pioneer oral drug delivery technologies like osmotic pump systems and has also been added to the National Formulary (an official publication that provides the composition, description, method of preparation and dosage for drugs), signifying its importance in the pharmaceutical industry. Today, PEO excipients still hold tremendous potential for formulators to develop innovative oral applications. Read on to explore what makes PEO special and how it can be harnessed to advance the next generation of oral drug delivery systems.
Polyethylene oxide: Not your average polymer
PEO is a versatile, water-soluble polymer with a simple linear chemistry, available at molecular weights ranging from 100,000 to 7 million daltons. So, what is the significance of this? The broad molecular weight range of PEO makes it an ideal choice for developing unique drug delivery systems. The polymer's properties, including viscosity and swelling, vary significantly with molecular weight, allowing formulators to fine-tune PEO to meet specific drug delivery needs.2 For instance, high molecular weight polymers exhibit increased viscosity and swelling compared to lower molecular weight grades.
No matter the molecular weight of PEO, protecting it from moisture and air is vital for its long-term utility. This is because, while PEO polymers demonstrate good stability once formulated into pharmaceutical systems, the polymer itself is susceptible to chain cleavage through autooxidation—a process where oxygen in the air reacts with ether units in the polymer chain, breaking it into smaller fragments. This degradation can reduce molecular weight and alter key properties of the polymer. Environmental factors, such as temperature and humidity, can influence this autooxidation process. Therefore, to minimize chain degradation and help preserve molecular weight, PEO should be stored in cool and dry conditions. PEO also exhibits thermoplastic behavior, which enables it to be processed through various manufacturing techniques. Its low toxicity, biocompatibility, rapid swelling and mucoadhesive properties further enhance its safety, tolerability and versatility in pharmaceutical applications.
How can formulators harness the power of polyethylene oxide to advance oral drug delivery?
1. Leverage the high swelling capacity of polyethylene oxide polymers for specialized oral dosage forms
PEO is one of the highest swelling polymers in the pharmaceutical industry, which makes it an ideal excipient choice for developing osmotic pumps, gastro-retentive systems and abuse-resistant tablets. Osmotic pumps are an advanced drug delivery method that uses osmosis—the spontaneous flow of solvent across a semipermeable membrane from a solution with a lower concentration of solutes to a more concentrated solution—to deliver pharmacotherapy and enable controlled drug delivery for up to 24 hours. A bilayer push-pull osmotic pump tablet consists of a drug layer, push layer and coating membrane. The enhanced swelling capacity of high molecular weight PEO polymers in the push layer exhibit good compatibility with low molecular weight PEO used to suspend active pharmaceutical ingredients (APIs) in the drug layer. The high swelling capacity of PEO, combined with its thermoplastic and inherently tough nature, makes it an optimal candidate for abuse deterrent formulations, too.
Individual tough particles of POLYOX™—IFF Pharma Solutions PEO polymer—can be fused to create large, crush-resistant tablets. PEO also works well in gastro-retentive systems. The high swelling, fast hydration, bioadhesive and buoyant features of POLYOX™ polymers enable this technology to work by keeping the dosage form in the stomach for prolonged periods of time. This can be particularly useful for drugs that are absorbed primarily in the upper gastrointestinal tract.
Top tip from IFF Pharma Solutions: To enhance gastro-retentive formulations, we recommend combining POLYOX™ PEO polymers with METHOCEL™, a hydroxypropyl methylcellulose (HPMC, also known as hypromellose) excipient. This synergistic combination maximizes both the rapid swelling properties of POLYOX™ polymers and the robust gel strength of METHOCEL™ HPMC, resulting in improved gastric retention performance.
2. Explore polyethylene oxide as an alternative polymer for optimized modified-release matrix tablets
Hydrophilic matrix tablets enable extended-release in oral drug delivery systems. By controlling how the drug is released, these tablets reduce dosing frequency and maintain more consistent drug levels in the blood, improving patient compliance.3 The non-ionic, hydrophilic nature of PEO, combined with its superior flow properties, make it ideal for matrix tablets. Within these formulations, PEO polymers can act as a rate controlling excipient by swelling upon exposure to water and slowly eroding over time.2 Modifying the molecular weight and/or amount of the polymer enables formulators to significantly change the rate of drug release in these tablets, tailoring it to their specific needs.
Recent research by Dr. Manish Rane and colleagues, using POLYOX™ polymers, provides important insights into how PEO affects drug release from hydrophilic matrix tablets.2 The data demonstrates that higher molecular weight POLYOX™ polymers lead to slower drug release. Moreover, the effect of PEO concentration varies depending on the drug type. For instance, highly soluble drugs show a slight decrease in release rate as the concentration of PEO increases within the matrix formulation.2 Whereas poorly soluble drugs have a more nuanced effect. Here, the drug release profiles of formulations with low amounts of POLYOX™ polymers (<25% PEO) using a water insoluble binder, like microcrystalline cellulose (MCC), demonstrate slower release profiles than formulations with high amounts of POLYOX™ polymers (>30%).2 The release rates for poorly water-soluble active pharmaceutical ingredients (APIs) are dependent on the erosion rate of the matrix tablet. So, when the PEO concentration is too low, the release rate will be dominated by the erosion of the insoluble binder, like MCC, rather than the swelling and erosion of the PEO matrix.2,4,5.
Case study: POLYOX™ PEO vs HPMC in controlled-release tablets
To investigate the potential advantages of using POLYOX™ polymers for controlled-release in matrix tablets, two 400 mg propranolol hydrochloride formulations containing either POLYOX™ or METHOCEL™ excipients were compared.6 The results revealed that high molecular weight POLYOX™ excipients demonstrated a similar drug release profile to METHOCEL™ excipients when using a direct compression manufacturing process. However, the POLYOX™ PEO-based formulation exhibited superior flow properties in an unconstrained environment, which could make it easier to process during manufacturing. It also showed enhanced permeability compared to the METHOCEL™-containing tablet, meaning it may lead to faster or more consistent drug delivery. As such, POLYOX™ polymers may offer advantages over METHOCEL™ HPMC-based matrices, while still achieving comparable drug release profiles.
Figure 1. Direct compression of 400 mg matrix tablet formulations using POLYOX™ or METHOCEL™ excipients.
Top tip from IFF Pharma Solutions:When formulating POLYOX™ matrix tablets, the choice of binder is crucial, as it can significantly impact tablet hardness and stability. For instance, certain sugar-based binders like lactose and mannitol can negatively impact the stability of a formulated product containing POLYOX™ polymers. Binders such as MCC, dicalcium phosphate and starch are better options for both stability and tablet toughness.
3. Develop patient-centric formulations using the thermoplastic and mucoadhesive properties of polyethylene oxide
PEO is a thermoplastic and mucoadhesive polymer with a low melting point (~65-70°c), making it a great choice for buccal tablets and films, as it can penetrate mucus membranes. It can also be used in orally dissolving film formulations. These drug delivery systems are becoming increasingly popular for certain patient groups, like pediatrics, due to their ease of delivery and reduced risk of choking.
Top tip from IFF Pharma Solutions: For those looking to develop tablets, including buccal, with POLYOX™ polymers, it’s important not to over compress formulations during manufacturing because the heat generated in small areas like the tips of the tooling can cause the polymer to melt and crown. Using light roller compaction pressure is also the best way to get the components to stick together, as over compaction can make it very difficult to grind the ribbon down into granules. Ensure areas and equipment exposed to POLYOX™ polymers are cleaned with dry techniques like sweeping and vacuuming too, as contact with water can make the polymer extremely difficult to clean up. It’s also important to note that cryomilling can make the polymer brittle and more easily milled.
Harness the power of POLYOX™ polymers for advanced oral drug delivery
At IFF Pharma Solutions, we can help formulators harness the power of POLYOX™ water soluble resins to facilitate the development of advanced drug delivery solutions. Our POLYOX™ portfolio includes free-flowing hydrophilic powders supplied in a variety of viscosity grades to suit a broad array of pharmaceutical applications—including controlled-release matrix tablets, osmotic pump technologies, gastro retentive systems, and more.
Ready to turn the unique properties of POLYOX™ polymers into advanced oral drug delivery solutions?
Explore more here: IFF Pharma Solutions
[1] Alqahtani et al (2021) Advances in Oral Drug Delivery. Frontiers in pharmacology, 12, 618411.
[2] Rane et al (2024) Application of Polyethylene Oxide in Hydrophilic Matrix Tablets. Pharma Times, 45(3):41-48.
[3] Rane et al (2010) Hydrophilic matrices for oral extended release: Influence of fillers on drug release from HPMC matrices. Pharma Times, 42.
[4] Poster: The Influence of Polymer Concentration on Release of Poorly Soluble Drugs from Polyethylene Oxide Extended Release Matrices. By Dasha Palmer, Marina Levina, Thomas P. Farrell and Ali Rajabi-Siahboomi. Colorcon Inc., Global Headquarters, 275 Ruth Road, Harleysville, PA 19438 USA.
[5] Poster: Prediction of Tablet Dissolution from API and Poly(Ethylene Oxide) Properties. By Elizabeth J. Tocce, Jaime L. Curtis-Fisk, Karen M. Balwinski, Nick Grasman, True L. Rogers. The Dow Chemical Company, Midland, MI USA
[6] Poster: Influence of polymer chemistry in drug release of propranolol HCl controlled release tablets manufactured via a direct compression method (2020). By Mahmoudi, N., McIntyre, K., Lee, J., Bertrand, H., Zhang, Y., Onofre, F., & Faham, A. AAPS PharmSci 360.
