(W1030-09-50) Development of Colon-Targeting UniORV Containing Salazosulfapyridine Composed of Chitosan/Alginate-Based Matrix

Purpose: The development of colon-specific drug delivery systems has gained importance in the context of increasingly sophisticated demands for targeted therapeutic delivery, particularly for the treatment of localized gastrointestinal disorders, such as ulcerative colitis. The UniORV system serves as a pioneering platform for the synthesis of polymer-based amorphous solid dispersions. The colon, characterized by lower proteolytic enzyme activity than that in the stomach and small intestine, offers a unique environment that potentially enhances the local availability of active compounds by mitigating decomposition. This targeted delivery is particularly advantageous for treating localized diseases, significantly amplifying therapeutic effects and minimizing systemic side effects. This study introduces an advanced formulation of the UniORV system.

Methods: The colon-targeting UniORV was manufactured as previously reported with slight modifications. Briefly, chitosan, sodium alginate, and salazosulfapyridine were uniformly dissolved or dispersed and dropped intermittently, followed by subsequent UniORV cross-linking with glutaraldehyde or cinnamaldehyde. Figure 1 depicts a schematic illustration of colon-targeting UniORV, a novel granular formulation that employs a chitosan/alginate matrix specifically designed to enhance the delivery and efficacy of salazosulfapyridine (SASP). The SASP dissolution rate was evaluated by performing a dissolution test using the paddle method. We optimized the chitosan/sodium alginate ratio and utilized specific crosslinking agents, namely, glutaraldehyde and cinnamaldehyde, to improve the release profile of the SASP and ensure maximal direct therapeutic action at the colonic site.

Results: The optimized formulations demonstrated a significant reduction in premature release and ensured minimal dissolution in the stomach (pH 1.2) and the small intestine (pH 6.8). Table 1 lists the UniORV formulations, all of which were produced as spherical particles with a particle size of 100–500 µm. Table 2 summarizes the results of the dissolution tests. The dissolution rate at pH 1.2 after 2 hours was 20% or less for all the formulations. The UniORV formulations 1, 3, and 5 (without crosslinking), and UniORV formulation 2 with chitosan/sodium alginate (ratio of 0.2) demonstrated considerable dissolution of SASP at pH 6.8 after 2 hours. In contrast, the UniORV formulations 4 and 7, showed a dissolution rate of approximately 70%, and the UniORV formulations 6 and 8 of approximately 50% after 24 h under colonic conditions (pH 7.4). The dissolution rate at pH 7.4 was found to decrease with an increase in the chitosan to sodium alginate ratio. Additionally, similar dissolution rates were evident in the formulations crosslinked with either glutaraldehyde or cinnamaldehyde.

Conclusion: UniORV does not elute in the stomach or small intestine and is thus expected to release drugs in the large intestine. The study results provide a safer formulation for the colorectal delivery of UniORV.

References: [1] Yamada, K. et al., J. Drug. Deliv. Sci. Technol., 95, 105624 (2024)

Acknowledgements: The authors declare that they have no competing interests.

Figure 1. Schematic illustration of colon-targeting UniORV.

Table 1. Formulation of UniORV. N: without crosslinking, G: crosslinking with Glutaraldehyde, and C: crosslinking with Cinnamaldehyde.

Table 2. Dissolution rate of UniORV.