Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability
Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoa...
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| Format: | Article |
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MDPI AG
2017-06-01
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| Series: | Pharmaceutics |
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| Online Access: | http://www.mdpi.com/1999-4923/9/3/22 |
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| author | Viviana De Caro Alessia Ajovalasit Flavia Maria Sutera Denise Murgia Maria Antonietta Sabatino Clelia Dispenza |
| author_facet | Viviana De Caro Alessia Ajovalasit Flavia Maria Sutera Denise Murgia Maria Antonietta Sabatino Clelia Dispenza |
| author_sort | Viviana De Caro |
| collection | DOAJ |
| description | Administered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m2. FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application. |
| first_indexed | 2024-04-13T06:17:21Z |
| format | Article |
| id | doaj.art-8d5cb2b07e794f5aa3c50887921ce218 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-04-13T06:17:21Z |
| publishDate | 2017-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-8d5cb2b07e794f5aa3c50887921ce2182022-12-22T02:58:46ZengMDPI AGPharmaceutics1999-49232017-06-01932210.3390/pharmaceutics9030022pharmaceutics9030022Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance BioavailabilityViviana De Caro0Alessia Ajovalasit1Flavia Maria Sutera2Denise Murgia3Maria Antonietta Sabatino4Clelia Dispenza5Dipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, PA 90123, ItalyDipartimento dell'Innovazione Industriale e Digitale, Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Palermo, PA 90128, ItalySiSaf Ltd, Innovation Centre, Northern Ireland Science Park, Queen’s Island, Belfast BT3 9DT, UKDipartimento di Scienze e Tecnologie Biologiche Chimiche e Farmaceutiche (STEBICEF), Università degli Studi di Palermo, Palermo, PA 90123, ItalyDipartimento dell'Innovazione Industriale e Digitale, Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Palermo, PA 90128, ItalyDipartimento dell'Innovazione Industriale e Digitale, Ingegneria Chimica, Gestionale, Informatica, Meccanica, Università degli Studi di Palermo, Palermo, PA 90128, ItalyAdministered by an oral route, Furosemide (FUR), a diuretic used in several edematous states and hypertension, presents bioavailability problems, reported as a consequence of an erratic gastrointestinal absorption due to various existing polymorphic forms and low and pH-dependent solubility. A mucoadhesive sublingual fast-dissolving FUR based film has been developed and evaluated in order to optimize the bioavailability of FUR by increasing solubility and guaranteeing a good dissolution reproducibility. The Differential Scanning Calorimetry (DSC) analyses confirmed that the film prepared using the solvent casting method entrapped FUR in the amorphous state. As a solid dispersion, FUR increases its solubility up to 28.36 mg/mL. Drug content, thickness, and weight uniformity of film were also evaluated. The measured Young’s Modulus, yield strength, and relative elongation of break percentage (EB%) allowed for the classification of the drug-loaded film as an elastomer. Mucoadhesive strength tests showed that the force to detach film from mucosa grew exponentially with increasing contact time up to 7667 N/m2. FUR was quickly discharged from the film following a trend well fitted with the Weibull kinetic model. When applied on sublingual mucosa, the new formulation produced a massive drug flux in the systemic compartment. Overall, the proposed sublingual film enhances drug solubility and absorption, allowing for the prediction of a rapid onset of action and reproducible bioavailability in its clinical application.http://www.mdpi.com/1999-4923/9/3/22mucoadhesive filmsublingual absorptionamorphous solid dispersionfurosemide bioavailabilitytransmucosal delivery |
| spellingShingle | Viviana De Caro Alessia Ajovalasit Flavia Maria Sutera Denise Murgia Maria Antonietta Sabatino Clelia Dispenza Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability Pharmaceutics mucoadhesive film sublingual absorption amorphous solid dispersion furosemide bioavailability transmucosal delivery |
| title | Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability |
| title_full | Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability |
| title_fullStr | Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability |
| title_full_unstemmed | Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability |
| title_short | Development and Characterization of an Amorphous Solid Dispersion of Furosemide in the Form of a Sublingual Bioadhesive Film to Enhance Bioavailability |
| title_sort | development and characterization of an amorphous solid dispersion of furosemide in the form of a sublingual bioadhesive film to enhance bioavailability |
| topic | mucoadhesive film sublingual absorption amorphous solid dispersion furosemide bioavailability transmucosal delivery |
| url | http://www.mdpi.com/1999-4923/9/3/22 |
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