Improved oral bioavailability of repaglinide, a typical BCS Class II drug, with a chitosan‐coated nanoemulsion

Abstract

The aim of the present study was to develop modified nanoemulsions to improve the oral bioavailability and pharmacokinetics of a poor water‐soluble drug, repaglinide (RPG). The repaglinide‐loaded nanoemulsions (RPG‐NEs) were prepared from olive oil as internal phase, span 80, tween 80, and poloxamer 188 as emulsifiers, using homogenization technique. The mean droplet size, zeta potential, and entrapment efficiency of RPG‐NEs were 86.5 ± 3.4 nm, −33.8 ± 2.1 mV, and 96.3 ± 2.3%, respectively. The chitosan‐coated RPG‐NEs (Cs‐RPG‐NEs) showed an average droplet size of 149.3 ± 3.9 nm and a positive zeta‐potential of +31.5 ± 2.8 mV. Drug release profile of RPG‐NEs was significantly higher than free drug in the simulated gastrointestinal fluids (p < .005). The in vivo study revealed 3.51‐ and 1.78‐fold increase in the AUC0‐12h and Cmax of the drug, respectively, in RPG‐NEs‐receiving animals in comparison to the free drug. The pharmacokinetic analysis confirmed that Cs‐RPG‐NEs were more efficient than uncoated ones for the oral delivery of RPG. Cs‐RPG‐NEs showed a longer t1/2 and higher AUC0‐∞ compared to control group. The relative bioavailability of Cs‐RPG‐NEs was higher than that of uncoated RPG‐NEs and free drug. Collectively, these findings suggest that chitosan‐coated nanoemulsions are promising carrier for improving the oral bioavailability of RPG.

Predictive Study of the Active Ingredients and Potential Targets of Codonopsis pilosula for the Treatment of Osteosarcoma via Network Pharmacology

“…TCMSP provides comprehensive information about components in Chinese herbs, while TCMID provides information on all aspects of traditional Chinese medicines, including herbs and herbal ingredients. Oral bioavailability (OB), which is the percentage of an orally administered drug that reaches the systemic circulation, reflects the degree of absorption and utilization of drugs in the body [ 23 ]. The drug-likeness (DL) value reflects the structural similarity between the compound and drug molecule, so the DL compounds are more likely to display suitable pharmacodynamic and pharmacokinetic properties [ 24 ].…”

“…TCMSP provides comprehensive information about components in Chinese herbs, while TCMID provides information on all aspects of traditional Chinese medicines, including herbs and herbal ingredients. Oral bioavailability (OB), which is the percentage of an orally administered drug that reaches the systemic circulation, reflects the degree of absorption and utilization of drugs in the body [23].…”

Snedds as Lipid-Based Nanocarrier Systems: Concepts and Formulation Insights

“…The oral route is commonly used for drug delivery because of its safety [1], comfort [2], minimum effort [3], and greater patient compliance [4]. However, many drugs have difficulty in developing as oral dosage forms because of their low solubility, low permeability [6], poor bioavailability, delayed onset of action, high inter/intra subject variability [5], and lack of dose linearity [6].…”

“…Low solubility-high permeability [3]; Class III. High solubility-low permeability [4]; Class IV. Low solubility low permeability [10].…”

“…The conventional techniques are salt forms, solid dispersions [16], use of co-solvents [12], hydrotropy, micronization, change in dielectric constant of solvent, amorphous forms [7], chemical modification of drug, use of surfactants, inclusion complex [3], alteration of pH of solvent, use of hydrates or solvates [6], use of soluble prodrugs [8], application of ultrasonic waves [9], functional polymer technology, controlled precipitation technology [12], evaporative precipitation in aqueous solution [18], use of precipitation inhibitors, solvent deposition [4], precipitation [2], selective adsorption on insoluble carriers [9]. However, conventional approaches have many limitations like for example salt formation [12] of drugs is commonly used but always unattainable.…”