Design and characterization of double layered mucoadhesive system containing bisphosphonate derivative

Abstract

The objective of this study is to evaluate the effect of formulation variables on different evaluation properties such as cumulative percentage release and swelling index in development of two layered buccal mucoadhesive system consisting of a highly water soluble drug risedronate sodium. The mucoadhesive systems were developed with varied concentrations of the polymers (1-2%) using plasticizer/permeation enhancer (25-50% w/w of polymer). Two layered films comprised of risedronate sodium with chitosan (85% deacetylated) and hydroxypropylmethyl cellulose (HPMC 4KM) interpolymer complex of different ratios were prepared by solvent casting method. An impermeable backing membrane of ethyl cellulose was incorporated into the films. The study shows the effect of multipolymeric films on the release of a bisphosphonates derivative. The optimized formulations showed films with uniform drug content (90.91 ± 0.17-105.53% ± 2.15), thickness (0.22 ± 0.01 mm to 0.31 ± 0.06 mm), mucoadhesivity (26 ± 3.61-42.33 ± 2.82 g), and controlled drug release profile up to a period of 10 hours. The films were also studied for swelling index, moisture uptake, viscosity, folding endurance, water vapor transmission rate, and mucoadhesive time.

Figure 1

Mucoadhesive strength test apparatus.

Figure 2

FTIR spectra of (a) pure drug, (b) pure chitosan, and (c) pure HPMC 4KM. (d) physical mixture (1 : 1) HPMC 4KM and chitosan and (e) physical mixture of drug : polymer (1 : 1) [Drug + HPMC4KM + chitosan].

Figure 3

Swelling degree of the bilayered mucoadhesive films.

Figure 4

Ex vivo drug release profile of formulations A1, A2, and A3.

Figure 5

Ex vivo drug release profile of formulations A4, A5, and A6.

Figure 6

Ex vivo drug release profile of formulations A7, A8, and A9.

Figure 7

Ex vivo drug release profile of formulations A10, A11, and A12.

Figure 8

Ex vivo drug release profile of formulations A13 and A14.