ArticleDrug design, development and therapy2022
Reduced the Food Effect and Enhanced the Oral Bioavailability of Ivacaftor by Self-Nanoemulsifying Drug Delivery System (SNEDDS) Using a New Oil Phase.
Article in Drug design, development and therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 11 citations in OpenAlex.
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- Enhancing Drug Solubility, Bioavailability, and Targeted Therapeutic Applications through Magnetic Nanoparticles.Molecules (Basel, Switzerland) · 2024Review
- Ivacaftor pharmacokinetics and lymphatic transport after enteral administration in rats.Frontiers in pharmacology · 2024Article
- Preparation and Characterization of Pazopanib Hydrochloride-Loaded Four-Component Self-Nanoemulsifying Drug Delivery Systems Preconcentrate for Enhanced Solubility and Dissolution.Pharmaceutics · 2022Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Purpose: The purpose of this work was to develop an ivacaftor self-nanoemulsion drug delivery system (IVA-SNEDDS) using the newly developed double headed miscellaneous lipid (DHML) as oil phase to reduce the food effect and inter-individual absorption variability of IVA. Methods: The lipids with the greatest solubility to IVA were selected as the oil phase of IVA-SNEDDS by saturation solubility method. Then, among different surfactants and co-surfactants, those with good emulsifying ability for the selected oil phase were selected, and the proportion of surfactant and co-surfactant was further selected by pseudo-ternary phase diagram. The prepared IVA-SNEDDS were screened and evaluated in vitro and in beagle dogs. Results: The optimized IVA-SNEDDS formulation consisting of DHML, Tween 80, and Transcutol HP with the weight ratio of 2:2:1 was physically stable and it was easy to disperse in water, pH 1.2 hydrochloric acid and pH 6.8 phosphate buffer solution, and generated a fine homogeneous nanoemulsion, with mean globule size less than 75 nm regardless of dilution ratio. In vitro drug release studies showed that the drug in IVA-SNEDDS could be completely released in a short time, while the drug release in IVA-suspension was less than 1% at 60 min. In vivo, using IVA-suspension (Fed) as a reference, the relative oral bioavailability of IVA-suspension (Fasted), IVA-SNEDDS (Fasted), and IVA-SNEDDS (Fed) were 23.35%, 153.63%, and 149.89%, respectively. This showed that IVA-SNEDDS could eliminate the positive food effect, improve the oral bioavailability, and reduce the IVA absorption difference between individuals. Conclusion: As the oil phase of SNEDDS, DHML can significantly improve the drug solubility and drug loading of IVA-SNEDDS. Moreover, DHML was easily emulsified and can effectively form a nanoemulsion in vivo and in vitro. The prepared IVA-SNEDDS can reduce the inter-individual absorption variability of IVA, eliminate its food effect and improve its oral bioavailability.
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