(M1430-02-08) Quantitating Swelling Pressure Generated by the Push Layer of an Osmotic Pump Tablet

Purpose: Push-Pull Osmotic Pump (PPOP) tablets can deliver zero-order controlled release. The push layer consists of swelling polymer, typically polyethylene oxide (PEO), and osmogen, and the pull layer contains active pharmaceutical ingredient (API) and carrier excipient. The bilayer tablet is coated with a selectively permeable barrier membrane, and one or more holes are laser-drilled through the barrier membrane on the pull layer side. Upon oral administration, aqueous media permeates through the barrier membrane into the bilayer core, triggering the push layer to swell. The resulting swelling pressure drives the pull layer through the laser-drilled hole(s), illustrated in Figure 1. The 4, 5, and 7 million molecular weight (MW) grades of polyethylene oxide (PEO) are typically used in the push layer [1], but no previous studies were found documenting quantification of swelling pressure imparted by these PEO grades. Thus, characterization methodology was developed to quantitate swelling pressure generated by PEO in the push layer and hence gain mechanistic insight into PPOP tablet functionality.

Methods: Recently published texture analysis methodology [2] was adapted using a configuration similar to that in Figure 2, but probe setup and push layer compact treatment were adapted to optimize swelling pressure measurement. The push layer components, 79.5% PEO, 19.5% micronized sodium chloride, and 1% red iron oxide, were compacted at 17.8 kN to a single layer tablet using round flat-face beveled-edge (FFBE) tooling of 10.3 mm diameter. Tablet weight was targeted at 400 mg, and PEO MW grade was varied. Three texture analysis configurations were investigated (Figure 2): 1) conical cup geometry with volume capacity for ~5 mL of aqueous media, 2) stainless steel strainer cup set in a 250 mL beaker, 3) fabricated cylinder fitted in a 500 mL measuring cup.

Results: With setup 3, swelling was forced within confined space to occur in the vertical (axial) direction rather than in the radial direction, similar to what occurs in the PPOP tablet (Figure 1). Furthermore, there was sufficient clearance to secure the push layer tablet at the bottom of the fabricated cylinder and to position the texture analyzer probe down to the tablet without contacting the cylinder wall. It was important that there was also a small gap between the probe and the cylinder wall to allow continuous access of aqueous media to the tablet for initiation and sustenance of push layer swelling. The swelling pressure vs. time profiles measured using setup 3 are shown in Figure 3, and quantifiable parameters were mathematically determined from the profiles. Areas under the swelling pressure vs. time curves over 24 h (AUC_{P, 0-24h}) from push layer tablets containing the 4, 5, and 7 million MW grades of PEO were 32.4 ± 3.8, 32.2 ± 7.0, and 30.7 ± 4.1 kg-h, respectively. Swelling pressures at 15 h (P_15h) from the three high MW PEO grades were 1.28 ± 0.21, 1.26 ± 0.34, and 1.23 ± 0.19 kg, respectively, and maximum swelling pressures (P_max) were 2.06 ± 0.12, 1.94 ± 0.28, and 1.76 ± 0.22 kg. Exploring more broadly the range of PEO MW grades, the 2 million MW grade imparted lower AUC_{P, 0-24h}, P_15h, and P_max of  25.5 ± 4.6 kg-h, 0.94 ± 0.24 kg, and 1.74 ± 0.21 kg, respectively, and the 1 million MW grade delivered even lower corresponding attribute values of 22.0 ± 3.1 kg-h, 0.81 ± 0.17 kg, and 1.56 ± 0.18 kg. The 0.2 and 0.1 million MW grades delivered the lowest corresponding attribute values of 10.1 ± 1.7 kg-h, 0.23 ± 0.15 kg, and 0.96 ± 0.16 kg and 5.0 ± 0.7 kg-h, 0.13 ± 0.09 kg, and 0.46 ± 0.02 kg, respectively.

Conclusion: The 4, 5, and 7 million MW PEO grades delivered comparable swelling pressure over 24 h, supporting aforementioned literature recommendations for use in the push layer [1]. The 2, 1, 0.2, and 0.1 million MW PEO grades imparted ~75%, ~65%, ~30%, and ~15%, respectively, of the swelling pressure generated by the three high MW PEO grades, indicating that the measurement methodology was sufficiently discriminatory to differentiate swelling pressure imparted across the range of PEO MW grades. With this quantitative understanding, the formulator now has mechanistic insight of functionality that PEO imparts on swelling pressure in the PPOP tablet and why the three high MW PEO grades are recommended in the push layer.

References: W. Lin, Y. Li, Q. Shi, X. Liao, Y. Zeng, W. Tian, X. Xie and H. Liu, "Preparation and evaluation of bilayer-core osmotic pump tablets containing topiramate," PLoS ONE, vol. 17, no. 2, p. e0264457, 2022.
M. Knarr, "Advanced analysis of alginate for treatment of gastroesophageal reflux disease," Gastroenterol Hepatol Open Access, vol. 16, no. 1, pp. 46-49, 2025.

Acknowledgements: The authors gratefully acknowledge Matthias Knarr, Ken Penkala, Kerstin Schmidt, Rhea Wang, Sophie Zhai, Ian Gillespie, Richard Olszowy, Kevin O’Donnell, Paula Garcia Todd, Gopesh Singh, Elizabeth Tocce, and Tom Gilbert. The authors have no conflicts of interest.

Figure 1. PPOP tablet cross-sectional appearance and mechanistic illustration of functionality.

Figure 2. Texture analysis illustration published by Knarr [1], but showing that probe setup and push layer compact treatment were varied to optimize swelling pressure measurement.

Figure 3. Swelling pressure vs. time profiles over 24 h. Profiles from the three high MW PEO grades in blue. Profiles from lower MW PEO grades in pink.