Embedding of Poorly Water-Soluble Drugs in Orodispersible Films—Comparison of Five Formulation Strategies

Abstract

The poor bioavailability of many newly developed active pharmaceutical ingredients (APIs) poses a major challenge in formulation development. To overcome this issue, strategies such as the preparation of amorphous solid dispersions (ASDs), and the application of the APIs in lipid nanocarriers or the wet-milling of the substances into nanoparticles have been introduced. In addition to an efficient formulation strategy, a dosage form that is accepted by all patients is also of great importance. To enable a simple application of the oral dosage form for all patients, orodispersible films (ODFs) are a very promising delivery platform for the APIs because the films directly disintegrate in the mouth. In this study, two poorly water-soluble APIs, fenofibrate and naproxen, were formulated using five different formulation strategies and then embedded in ODFs. It was found that the deliverable amount of API with one ODF highly depends on the formulation strategy as well as the physicochemical properties of the formulated API. The most promising film formulations were ASD-ODFs as well as films with API-loaded lipid nanoemulsions. Both showed a reduction of the dissolution time of the APIs from the ODF compared to an ODF with unformulated API micro particles. In addition, short disintegration times were achieved, although the mechanical film properties were slightly worse compared to the API-free film formulation.

Orodispersible Films—Current State of the Art, Limitations, Advances and Future Perspectives

“…The surface area may be increased by micronisation made by ultrasonication which finally leads to greater dissolution behaviour [ 42 ]. Interesting studies were performed by Steiner et al Five different formulation strategies were closely investigated regarding their impact on API bioavailability: the preparation of amorphous solid dispersions, embedding of the APIs in a lipid nanosuspension and a lipid nanoemulsion, and the embedding of API nanoparticles or micronized API particles in the film-forming matrix [ 43 ].…”

Recent progress in orodispersible films‐mediated therapeutic applications: A review

“…However, different solubility‐enhancing formulation strategy has its pros and cons. The suitable formulation method should be considered according to the lipophilicity of APIs as well 21 . Additionally, thiolation of polymeric excipients enables to improve the solubility of less water‐soluble drugs as well.…”

Orodispersible Films: Current Innovations and Emerging Trends

“…The simplification of the formulation process and the enhancements in drug solubility and bioavailability have positioned the ODF as a promising drug delivery method for loratadine. In another interesting investigation, poorly aqueous soluble drugs such as fenofibrate and naproxen were formulated as nanoparticles using various strategies and were incorporated into ODFs [ 146 ]. The research findings revealed that the dose of API that can be administered in a single ODF significantly relies on the chosen formulation approach and the physicochemical characteristics of the API.…”