(M1030-03-21) In Vitro Evaluation of the Effect of Polymer Concentration on the Mechanical Properties and Drug Release of Dextromethorphan Hydrobromide from Polyvinyl Alcohol Cryogels

Purpose: Cryogels have gained considerable attention in pharmaceutical and biomedical research due to their distinctive macroporous structure, high mechanical strength, and tunable drug release profiles [1]. Synthesized via cyclic freezing and thawing, this physical sol–gel transition, termed cryogelation results in a stable, chemically crosslinker-free hydrogel matrix [2–4]. Polyvinyl alcohol (PVA), a water-soluble, non-toxic, and biocompatible synthetic polymer, has been extensively utilized in drug delivery, regenerative medicine, and tissue engineering [1,2]. PVA cryogels offer unique potential as drug delivery vehicles because their porosity, mechanical properties, and release kinetics that can be modulated by varying formulation parameters such as polymer concentration and crosslinking cycles [3,5,6]. Higher concentrations of PVA are known to decrease porosity and swelling, thereby reducing drug diffusion and mechanical flexibility [7–13]. The increased density of hydroxyl groups promotes physical crosslinking, resulting in a more compact and stable network structure [10–13]. This study explores how varying PVA concentrations influence the mechanical integrity and release behavior of cryogels loaded with dextromethorphan hydrobromide (DXM), a commonly used antitussive agent.

Objective: To investigate the influence of polymer concentration and drug loading on the mechanical properties and in vitro drug release profile of DXM-loaded PVA cryogels, and to assess their potential as controlled-release drug delivery systems.

Methods: Cryogel Preparation: PVA (MW 146,000–186,000 Da, ≥99% hydrolyzed) was prepared at 5% and 10% w/w concentrations in distilled water. Four formulations were prepared: 5% PVA (unloaded), 10% PVA (unloaded), 5% PVA + 125 mg DXM and 10% PVA + 125 mg DXM. Each formulation was magnetically stirred until fully dissolved, then stored at room temperature overnight. Aliquots (0.3 mL) were dispensed into plastic molds and subjected to freeze–thaw cycles: 24 hours at −20°C, thawed at 10°C, refrozen for 2 hours at −20°C and thawed at thawed at 10°C. Mechanical Testing: A Brookfield CT3-1000 texture analyzer (Brookfield, MA, USA) was used to assess cryogel mechanical properties: cylindrical probe, target force 0.05 N, trigger load 0.067 N and test speed 0.05 mm/s. The parameters measured included: hardness (cycles 1 and 2), adhesive Force (N) and adhesiveness (mJ). Each formulation was tested in triplicate. Drug Release Assay: Drug release studies were performed in 900ml simulated gastric fluid (SGF) (pH 1.2), prepared with distilled water and 6N HCl in accordance with USP standards. The cryogels were placed in USP Apparatus II (paddle) and stirred at 50 rpm at 37 ± 0.5°C for 24 hours. Samples (1 mL) were collected at predefined intervals and analyzed using UV-Vis spectrophotometry at wavelength 278nm. A DXM calibration curve was constructed to quantify release concentrations.

Results: DXM incorporation reduced both hardness and adhesive force across formulations, indicating matrix softening. The most rigid formulation was 10% PVA (no drug), while 10% PVA + DXM was the softest. The 10% PVA cryogel without DXM exhibited the highest hardness (0.24N), while the 10% PVA cryogel with DXM showed the lowest (0.13N and 0.11N for cycles 1 and 2, respectively). These results indicate the incorporation of DXM reduces the structural rigidity of the cryogels. A similar trend was observed in the 5% formulations, with lower hardness values for the DXM-loaded cryogels compared to those without the drug. In terms of adhesive force, drug-loaded cryogels consistently demonstrated lower values, with both 5% and 10% PVA DXM cryogels showing an adhesive force of 0.12N, compared to significantly higher values in non-drug-loaded cryogels (0.37N for 5% and 0.18N for 10%). Adhesiveness showed an inconsistent pattern, increasing slightly in 5% DXM cryogels but decreasing significantly in 10% DXM cryogels. The 5% PVA cryogels consistently released more DXM than the 10% formulation over 24 hours. The drug release from the 5% PVA cryogel exhibited a significantly higher release of DXM (20.28%) compared to the 10% PVA cryogel (13.71%). The denser 10% PVA matrix likely restricted diffusion due to reduced porosity, while the more open 5% matrix facilitated higher drug mobility. Both polymer concentration and drug loading significantly influence cryogel behavior. Increasing PVA concentration enhances structural rigidity and adhesiveness but reduces drug diffusion likely due to increased hydrogen bonding and reduced porosity [10–13].

Conclusion: This study demonstrates that both polymer concentration and drug loading are critical design parameters for PVA-based cryogel. The results indicated that the mechanical strength of cryogels increases with PVA concentration but decreases upon drug loading. The adhesive properties varied depending on the cryogel formulation, with potential application-specific tuning. The drug release of DXM was inversely proportional to polymer concentration with a higher release achieved from the 5% PVA cryogel, due to a more porous and less dense matrix. These findings provide a foundation for optimizing PVA cryogels in controlled drug delivery systems tailored for specific therapeutic requirements.

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Acknowledgements: Affiliation: All authors are associated with the College of Pharmacy at Nova Southeastern University in Fort Lauderdale, Florida. We acknowledge Nova Southeastern University facilities for the implementation of the research. RLW designed, analyzed, wrote the manuscript, and conducted experiments. RLW and HO reviewed, revised and edited the content. Disclaimer: The statements, opinions and data contained in this abstract are solely those of the individual author(s) and contributor(s) and not of the AAPS, or the reviewer/editor. AAPS and/or the reviewer/editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Funding: - This research received no external funding. Disclosure or conflict of interest statements: - The authors declare no conflicts of interest.

Figure 1. Showing the PVA cryogel formulations and mechanical properties test set-up using the texture analyzer (TA) CT3-1000 (Brookfield, MA, USA). (A) i) 5% PVA Cryogel (unloaded) ii) 10% PVA Cryogel (unloaded) iii) 5% PVA Cryogel + 125mg Dextromethorphan Hydrobromide iv) 10% PVA Cryogel + 125mg Dextromethorphan Hydrobromide. (B) Represents PVA Cryogel on TA plate being assessed.

A graph showing the mean ± SD (n=3) hardness cycles 1 & 2 of 5% and 10% PVA cryogels unloaded and loaded with DXM.

A graph showing the mean (n=3) Hardness Cycles 1 & 2 & Adhesive Force of 5% and 10% PVA Cryogels Unloaded and Loaded with DXM