Determination of Mucoadhesion of Polyvinyl Alcohol Films to Human Intestinal Tissue

Abstract

The absorption of drugs with narrow absorption windows in the upper small intestine can be improved with a mucoadhesive drug delivery system such as enteric films. To predict the mucoadhesive behaviour in vivo, suitable in vitro or ex vivo methods can be performed. In this study, the influence of tissue storage and sampling site on the mucoadhesion of polyvinyl alcohol film to human small intestinal mucosa was investigated. Tissue from twelve human subjects was used to determine adhesion using a tensile strength method. Thawing of tissue frozen at -20 °C resulted in a significantly higher work of adhesion (p = 0.0005) when a low contact force was applied for one minute, whereas the maximum detachment force was not affected. When the contact force and time were increased, no differences were found for thawed tissue compared to fresh tissue. No change in adhesion was observed depending on the sampling location. Initial results from a comparison of adhesion to porcine and human mucosa suggest that the tissues are equivalent.

Keywords: ex vivo measurements; human intestinal mucosa; intestinal application; mucoadhesion; site-specific application.

Figure 1

Results for Setting A. (A): Individual data of the calculated WoA (Nm × mm) with median (n = 12); black: fresh tissue; red: thawed tissue; (B): pooled medians of all subjects with median line; (C): Individual data of the calculated F_max (N) with median (n = 12); black: fresh tissue; red: thawed tissue; (D): pooled medians of all subjects with median line. Significant difference of WoA and F_max was checked by using a Wilcoxon signed rank test: *** (p < 0.001).

Figure 2

Results for Setting B. (A): Individual data of the calculated WoA (Nm × mm) with median (n = 8); black: fresh tissue; red: thawed tissue; (B): pooled medians of all subjects with median line; (C): Individual data of the calculated F_max (N) with median (n = 8); black: fresh tissue; red: thawed tissue; (D): pooled medians of all subjects with median line. Significant difference of WoA and F_max was checked by using a Wilcoxon signed rank test.

Figure 3

Comparison of the results for Setting A and B on fresh tissue. (A): Individual data of the calculated WoA (Nm × mm) with median (n = 8); black: Setting A; red: Setting B; (B): pooled medians of all subjects with median line; (C): Individual data of the calculated F_max (N) with median (n = 8); black: Setting A; red: Setting B; (D): pooled medians of all subjects with median line. Significant difference of WoA and F_max was checked by using a Wilcoxon signed rank test: ** (p < 0.01).

Figure 4

Comparison of the results for Setting A and B on thawed tissue. (A): Individual data of the calculated WoA (Nm × mm) with median (n = 8); black: Setting A; red: Setting B; (B): pooled medians of all subjects with median line; (C): Individual data of the calculated F_max (N) with median (n = 8); black: Setting A; red: Setting B; (D): pooled medians of all subjects with median line. Significant difference of WoA and F_max was checked by using a Wilcoxon signed rank test: ** (p < 0.01).

Figure 5

Comparison of the results for Setting A on fresh tissue of pigs (n = 3) and humans (n = 12). (A): Pooled medians of the calculated WoA (Nm × mm) with median line; red: pig; black: human; (B): Pooled medians of the calculated F_max (N) with median line; red: pig; black: human. Significant difference of WoA and F_max was checked by using a Mann-Whitney U test.

Figure 6

(A): Fresh tissue; (B): thawed tissue after a storage time of 7 days at T = −20 °C in a freezer.