Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats
Sildenafil citrate, an oral drug used to treat erectile dysfunction, has low water solubility and oral bioavailability. The solubility is greatly influenced by the pH, changing from 37.25 mg/mL to 0.22 mg/mL with a change in pH from 1.2 to 8.0. This indicates that the absorption may decrease in pati...
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MDPI AG
2023-10-01
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| Series: | Life |
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| Online Access: | https://www.mdpi.com/2075-1729/13/11/2126 |
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| author | Chin-Yu Shih Chao-Yi Chen Hsien-Te Lin Ying-Ju Liao Yao-Jen Liang |
| author_facet | Chin-Yu Shih Chao-Yi Chen Hsien-Te Lin Ying-Ju Liao Yao-Jen Liang |
| author_sort | Chin-Yu Shih |
| collection | DOAJ |
| description | Sildenafil citrate, an oral drug used to treat erectile dysfunction, has low water solubility and oral bioavailability. The solubility is greatly influenced by the pH, changing from 37.25 mg/mL to 0.22 mg/mL with a change in pH from 1.2 to 8.0. This indicates that the absorption may decrease in patients who use drugs, such as proton pump inhibitors (PPIs), for gastroesophageal reflux disease. To improve the absorption of sildenafil citrate at various gastric pH levels, a sildenafil citrate orally disintegrating tablet (ODT), which has a rapid disintegration feature, was produced by a 3D printing technique. Our study investigated the pharmacokinetic parameters of the sildenafil citrate ODT in rats after oral administration and compared the absorption of the sildenafil citrate ODT and sildenafil citrate commercial tablet (RLD), with and without PPI treatment. The LC/MS/MS analysis of the plasma sildenafil concentration revealed that the area under curve from time 0 to infinity (AUC<sub>0–∞</sub>) of sildenafil in the sildenafil citrate ODT group was significantly higher than in the sildenafil citrate RLD group whether it was in combination with the PPI or not (274.8% and 144%, respectively; <i>p</i> < 0.05). The relative systemic bioavailability of sildenafil citrate RLD significantly decreased with the PPI, but that of sildenafil citrate ODT was not affected by the PPI. These results indicate that the relative systemic bioavailability of sildenafil citrate ODT was increased when it was prepared using the 3D printing technique and the absorption of this formulation was not affected by the PPI. |
| first_indexed | 2024-03-09T16:40:28Z |
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| language | English |
| last_indexed | 2024-03-09T16:40:28Z |
| publishDate | 2023-10-01 |
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| series | Life |
| spelling | doaj.art-c664e7ae81064a4d88cfc7cbf98208ac2023-11-24T14:52:17ZengMDPI AGLife2075-17292023-10-011311212610.3390/life13112126Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in RatsChin-Yu Shih0Chao-Yi Chen1Hsien-Te Lin2Ying-Ju Liao3Yao-Jen Liang4Graduate Institute of Applied Science and Engineering, Fu-Jen Catholic University, New Taipei City 242062, TaiwanMerdury Biopharmaceutical Corporation, New Taipei City 235030, TaiwanMerdury Biopharmaceutical Corporation, New Taipei City 235030, TaiwanMerdury Biopharmaceutical Corporation, New Taipei City 235030, TaiwanGraduate Institute of Applied Science and Engineering, Fu-Jen Catholic University, New Taipei City 242062, TaiwanSildenafil citrate, an oral drug used to treat erectile dysfunction, has low water solubility and oral bioavailability. The solubility is greatly influenced by the pH, changing from 37.25 mg/mL to 0.22 mg/mL with a change in pH from 1.2 to 8.0. This indicates that the absorption may decrease in patients who use drugs, such as proton pump inhibitors (PPIs), for gastroesophageal reflux disease. To improve the absorption of sildenafil citrate at various gastric pH levels, a sildenafil citrate orally disintegrating tablet (ODT), which has a rapid disintegration feature, was produced by a 3D printing technique. Our study investigated the pharmacokinetic parameters of the sildenafil citrate ODT in rats after oral administration and compared the absorption of the sildenafil citrate ODT and sildenafil citrate commercial tablet (RLD), with and without PPI treatment. The LC/MS/MS analysis of the plasma sildenafil concentration revealed that the area under curve from time 0 to infinity (AUC<sub>0–∞</sub>) of sildenafil in the sildenafil citrate ODT group was significantly higher than in the sildenafil citrate RLD group whether it was in combination with the PPI or not (274.8% and 144%, respectively; <i>p</i> < 0.05). The relative systemic bioavailability of sildenafil citrate RLD significantly decreased with the PPI, but that of sildenafil citrate ODT was not affected by the PPI. These results indicate that the relative systemic bioavailability of sildenafil citrate ODT was increased when it was prepared using the 3D printing technique and the absorption of this formulation was not affected by the PPI.https://www.mdpi.com/2075-1729/13/11/2126bioavailabilitypharmacokineticsorally disintegrating tablets3D printing technique |
| spellingShingle | Chin-Yu Shih Chao-Yi Chen Hsien-Te Lin Ying-Ju Liao Yao-Jen Liang Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats Life bioavailability pharmacokinetics orally disintegrating tablets 3D printing technique |
| title | Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats |
| title_full | Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats |
| title_fullStr | Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats |
| title_full_unstemmed | Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats |
| title_short | Oral Bioavailability and Pharmacokinetics of Sildenafil Orally Disintegrating Tablets under Various Gastric pH Levels Following Administration of Omeprazole in Rats |
| title_sort | oral bioavailability and pharmacokinetics of sildenafil orally disintegrating tablets under various gastric ph levels following administration of omeprazole in rats |
| topic | bioavailability pharmacokinetics orally disintegrating tablets 3D printing technique |
| url | https://www.mdpi.com/2075-1729/13/11/2126 |
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