Ex vivo mucoadhesion of different zinc-pectinate hydrogel beads

https://doi.org/10.1016/j.ijpharm.2007.06.034Get rights and content

Abstract

The objective of this study was to investigate the mucoadhesive properties of pre-swelled hydrogel beads made of six types of pectin from three manufacturers. The types of pectin differed mainly in the degree of methoxylation and degree of amidation. Zinc ions were used as cross-linking agent. The mucoadhesive properties were tested on an inverted fresh porcine small intestine attached to a rotating cylinder. Beads made of pectin with a high degree of methoxylation (70%) showed superior mucoadhesive results compared to the other formulations, which could be correlated to the lower amount of zinc in this formulation, subsequently leading to a lower amount of cross-linking and higher mobility of the polymer chains of these beads. This study therefore also indicated the importance of doing mucoadhesive measurements on relevant formulations, and not basing the understanding solely on investigating polymer solutions. Samples from different manufacturers produced the same results.

Introduction

Achieving mucoadhesion of a formulation in the gastrointestinal tract could lead to a higher bioavailability of the entrapped drug due to increased residence time and a closer contact between the absorptive membrane and the formulation (Yin et al., 2006). This could also allow drug release over sustained periods of time, reducing the need for re-administration and/or reducing the amount of drug needed.

The dominant feature of pectin ((1  4) α-d-galacturonic acid units) is shown in Fig. 1, indicating the different types of substitution investigated in this article. In a previous study, we showed that only pectin with a degree of methoxylation (DM) of about 35% showed a selective interaction with mucin (probably through hydrogen bonding), whereas the general (unspecific) adhesion of pectin generally increased with increasing degree of total substitution (Hagesaether and Sande, 2007). This work was conducted on pectin solutions versus a mucin dispersion using a tensile test. Work on free films confirmed the selective interaction of pectins with a high ability to engage in hydrogen bonds (Hagesaether and Sande, submitted for publication). But, in contrast to the findings on solutions, the general adhesion was higher for the films of pectin with a DM of about 35%. This was considered to be caused by the higher cohesion of this film. This indicated that the properties of the formulation influenced the mucoadhesive properties, and is in line with (Koffi et al., 2006), showing a correlation between the viscoelastic properties of gels and their bioadhesiveness. In addition, as pure pectin formulations dissolve too rapidly, it is important for realistic pectin formulations that the solubility of the polymer in water is reduced, by cross-linking.

Particulate systems are generally considered to be advantageous for mucoadhesive formulations, and small sized particles are often preferred, as the size enables them to make intimate contact with a larger mucosal surface area (Sudhakar et al., 2006).

It is well known that the experimental set-up could influence on the results obtained from testing of mucoadhesion (Sandri et al., 2005), and a method mimicking the in vivo situation should therefore be employed.

The aim of this study was consequently to test the mucoadhesive properties of relevant particulate pectin formulations using a set-up mimicking the environment in the small intestine. The pectin types chosen differ i.a. in functional groups and consequently the molecular weight and viscosity. All of these properties are known to affect the mucoadhesion (Dodou et al., 2005). Pectin types were obtained from several manufacturers in order to investigate if products from different manufacturers display varying mucoadhesive properties. As a reference for mucoadhesiveness, alginate was chosen. Alginate has a chemical structure similar to pectin, but is neither methoxylated nor amidated. Alginate is generally recognized as a substance possessing excellent mucoadhesive properties (Duchêne et al., 1988).

Section snippets

Materials

Alginic acid sodium salt from brown algae, low viscosity, batch 084K0005, M/G ratio of 1.56, degree of polymerization of 60–400 and a molecular weight range of 12,000–80,000 (information provided by the manufacturer), was purchased from Sigma-Aldrich (St. Louis, USA) and used as received.

Six types of citrus pectin (purified and characterized by capillary viscometry (Hagesaether and Sande, 2007)), listed in Table 1, were studied. A fractional factorial design was used. The factors varied among

Manufacturing of hydrogel beads

The acid groups of pectin are known to engage in coordination bonds with divalent cations forming the well known egg-box structure. Stability is improved when there are at least seven consecutive carboxyl groups on each participating chain. Pectin with a low DM will consequently be expected to show a more extensive bonding. Amidation of pectin is known to increase the sensitivity towards gelation by calcium (Sande, 2005), and reduced diameter has been observed for amidated pectin beads (

Acknowledgments

All the pectin types were kindly provided by the manufacturers. The authors are grateful to Torill Marie Rolfsen at Department of Molecular Biosciences, University of Oslo, for carrying out the SEM measurements, and to Mr. Scheie and coworkers from the slaughterhouse Fatland Oslo A/S for supply of porcine intestinal mucosa.

References (22)

Cited by (31)

  • Gum-based hydrogels in drug delivery

    2020, Biopolymer-Based Formulations: Biomedical and Food Applications
  • Trigonella foenum-graecum L. seed mucilage-gellan mucoadhesive beads for controlled release of metformin HCl

    2014, Carbohydrate Polymers
    Citation Excerpt :

    However, hydrophilic polymers like GG and FSM also have ability to form non-covalent bonds like van der Waals forces or ionic interactions, resulting mucoadhesion. Achieving mucoadhesion of a formulation in the G.I.T. could lead higher bioavailability of the encapsulated drug due to increased gastric residence time and a closer contact between the absorptive mucous membrane and the formulation (Hagesaether, Bye, & Sande, 2008). This could also allow drug release over sustained periods of time, reducing the need of readministration of dosage form.

  • Formulation of bioadhesive hexylaminolevulinate pellets intended for photodynamic therapy in the treatment of cervical cancer

    2013, International Journal of Pharmaceutics
    Citation Excerpt :

    Prior to testing, the tissue was defrosted in phosphate buffer pH 4 at 37 °C for 60 min using a magnetic stirrer and heated disc. The retention of pellets to vaginal tissue was tested in a modified version of the rotating cylinder method (Hagesaether et al., 2008) to provide information on the bioadhesive properties of the formulation. The tissue was fastened on a cylinder, and kept hydrated with phosphate buffer pH 4 prior to the test.

View all citing articles on Scopus
View full text