The impact of polymers on 3D microstructure and controlled release of sildenafil citrate from hydrophilic matrices
Authors:
- Anna Krupa,
- Zbisław Tabor,
- Jacek Tarasiuk,
- Beata Strach,
- Krzysztof Pociecha,
- Elżbieta Wyska,
- Sebastian Wroński,
- Ewelina Łyszczarz,
- Renata Jachowicz
Abstract
Sildenafil citrate has short biological half-life in humans. Thus, matrix tablets of controlled release were designed and prepared by compaction on the basis of hydrophilic polymers, i.e. HPMC, sodium alginate, carbomer, poloxamer and their mixtures. The impact of these polymers on sildenafil release in vitro and its pharmacokinetics in vivo was evaluated. Since drug release rate from hydrophilic matrices can be govern by the porosity of the matrix, the microstructure of tablets was studied using X-ray microcomputed tomography. 3D network of either open (percolating) or closed (non-percolating) pores was reconstructed. The tortuosity and the diameter of both kinds of pores were determined. Their spatial distribution within the matrix was analyzed in linear and radial direction. Polymer-dependent characteristics of the open pores (Ø > 2 μm) architecture was shown. The release profiles of sildenafil from matrix tablets fitted to Korsmeyer-Peppas model (r2: 0.9331–0.9993) with either Fickian diffusion or anomalous transport involved. Mean dissolution time (MDT) from tablets made of HPMC, carbomer or a mixture of HPMC and sodium alginate (2:1) was ca. 100 min, which was more than twelve times longer as compared to matrices prepared of silicified microcrystalline cellulose (MDT = 8 min). MDT correlated with the number of the open pores (Pearson's r = 0.94). Sustained release of sildenafil from ground carbomer tablets reflected in the slow absorption of the drug (tmax = 5.0 ± 1.2 h) in vivo and the relative bioavailability of 151%. Interestingly, the relative bioavailability of sildenafil from binary matrices composed of HPMC and sodium alginate (2:1) was almost four times higher than that of sildenafil alone.
- Record ID
- CUTdf9163c0c3f9416988ad089763171612
- Publication categories
- ;
- Author
- Journal series
- European Journal of Pharmaceutical Sciences, ISSN 0928-0987, e-ISSN 1879-0720
- Issue year
- 2018
- Vol
- 119
- Pages
- 234-243
- Other elements of collation
- fot.; tab.; wykr.; Bibliografia (na s.) - 243; Oznaczenie streszczenia - Abstr.; Numeracja w czasopiśmie - Vol. 119
- Substantive notes
- Supplementary data to this article can be found online at https:// doi.org/10.1016/j.ejps.2018.04.023
- Keywords in English
- carbomer, controlled releasec HPMC, MicroCT, microstructure, sildenafil citrate, sodium alginate
- DOI
- DOI:10.1016/j.ejps.2018.04.023 Opening in a new tab
- URL
- https://www.sciencedirect.com/science/article/abs/pii/S092809871830188X Opening in a new tab
- Related project
- Charakterystyka matryc hydrofilowych zawierających inhibitory fosfodiesterazy-5 w warunkach in vitro/in vivo. . Project leader at PK: , ,
- Language
- eng (en) English
- License
- Score (nominal)
- 35
- Additional fields
- Indeksowana w: Web of Science, Scopus
- Uniform Resource Identifier
- https://cris.pk.edu.pl/info/article/CUTdf9163c0c3f9416988ad089763171612/
- URN
urn:pkr-prod:CUTdf9163c0c3f9416988ad089763171612
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