The feasibility of orodispersible films made of polymethylmethacrylate salts

Orodispersible films (ODFs) are fast-dissolving dosage forms intended to deliver drugs both locally and systemically after administration in the oral cavity. ODFs have gained an increased interest in the academic and industrial world because they have a huge clinical potential to legitimate expectations of special subpopulations, such as pediatric, elderly and dysphagic patients, who have difficulty in swallowing conventional tablets and capsules. The preparation of films for oromucosal drug delivery is challenging compared to other dosage forms. Indeed, depending on the physical-chemical characteristics of the ingredients loaded and their amount in the formulation, modifications of the mechanical properties can occur resulting in films too flexible or brittle to guarantee the integrity. Poly(sodium methacrylate, methyl methacrylate), NaPMM, and poly(potassium methacrylate, methyl methacrylate), KPMM, have been proposed to design drug delivery systems intended for buccal administration of active ingredients [Ciluzo et al., J Control Rel, 2003]. These materials were obtained by neutralizing with alkali two grade of pharmaceutical approved polymethyl methacrylate (HPMM) differ in the ratio of the monomers (namely methacrylate and methyl methacrylate) which form the repeating unit. In the former (HPMM1) the ratio of the monomers is 1:1 (Eudragit® L), while in the latter (HPMM2) it is equal to 1:2 (Eudragit® S). The current work aims to evaluate the suitability of NaPMM and KPMM plasticized with PEG 400 as film-forming material to design ODFs. Preliminarily, placebo ODFs containing XPMM and PEG 400 in the ratio from 90/10 to 40/60 (%, w/w) were prepared by a solvent casting technique to study the influence of formulation variables on the film dissolution time and tensile properties, which are the critical attributes of ODF according to Ph. Eur. The loading capacity of the optimal formulation was investigated by using three drugs (i.e. ketoprofen, olanzapine and diclofenac sodium) having different physico-chemical properties. XPMM resulted suitable for the preparation of ODF by casting. All formulations were homogeneously transparent in appearance, easy-to-handle -cut, and packed without any failures and disintegrated within 30s complying the Pharmacopeia requirements for orodispersible dosage forms. As expected all placebo ODFs without plasticizer resulted brittle. The tensile properties of films were modulated by changing the monomers ratio of XPMM, the alkali metal ions as well as the polymer/plasticizer ratio. XPMM plasticized with 20% w/w PEG400 appear the optimal formulations. To load all the active ingredients, the addition of Span®80 and Tween®80 was required to avoid the shrinkage of the dispersion casted on the release liner. All drug loaded ODFs maintained satisfactory ductility, flexibility and resistance to elongation for the production, packaging and handling procedures. The loading of the selected drugs did not cause any variations of the tensile properties which were superimposable to those of placebo films. Indeed, the disintegration time of films satisfied the requirement and t80 was lower of 15 min for all formulations.