Isosorbide Dinitrate Orally Disintegrating Films Cyclodextrins/HPMC Based: Mechanical, Optical, and Physicochemical Studies

Abstract

Orally disintegrating films (ODFs) were prepared from hydroxypropyl methylcellulose (HPMC E6 1.5%, 2.0%, and 2.5%), plasticizers ((glycerin (Gly), propylene glycol (PP), or polyethylene glycol (PEG)), and isosorbide dinitrate using the solvent casting method. Design of experiments (DoE) was used considering the amount of film-forming agent (HPMC) and the nature of the plasticizers as independent variables and thickness, mechanical properties, disintegration time, and dissolution efficiency as dependent variables. The best formulation was selected based on the desirability function ($f_D$). Color analysis was performed using CIE-$Lab$ coordinates. DSC curves and XRPD diffractograms showed ISDN amorphization, probably due to complexation with polymers (HPMC E6 and HPβCD). The polymer (HPMC E6) and plasticizer played a critical role in the mechanical and optical properties of the films; however, these factors had no significant effect on the dissolution efficiency of ISDN. Principal component analysis revealed a more defined distinction of the ODFs according to their chromatic characteristics. ODFs prepared with Gly and PEG 400 were translucent, whereas the other films were transparent. The dissolution efficiency values of the ODFs (F1-9) were higher than those observed for the reference product (88.35(0.01%), indicating increased solubility of ISDN, probably due to complexation with polymers (HPMC E6 and HPβCD). The maximum value obtained for desirability function ($f_D)$ was 0.86, which corresponded to the use of 1.5% to 2.0% polymer (HPMC E6) and Gly or PP as plasticizers. The F5 formulation showed adequate thickness (85.00(6.38 (m), elongation at break (4.82(0.01%), adhesiveness (0.23(0.09 mJ), dissolution efficiency (95.97(0.01%), and high transparency.

Keywords:
isosorbide dinitrate; cyclodextrins; orally disintegrating films; mechanical properties; desirability function

HIGHLIGHTS

• Orally films Cyclodextrins/HPMC based films were prepared by solvent casting.

• Films for oral delivery of ISDN were prepared by 3² factorial designs.

• Mechanical, optical, and dissolution properties were evaluated.

• The experimental design allowed to optimize the formulations.

• The best formulation was obtained by means of the desirability function.