Peer-Reviewed Journal Details
Mandatory Fields
Ilie, Alexandra-Roxana; Griffin, Brendan T.; Vertzoni, Maria; Kuentz, Martin; Cuyckens, Filip; Wuyts, Koen; Kolakovic, Ruzica; Holm, RenÚ
2020
November
Drug Development and Industrial Pharmacy
Toward simplified oral lipid-based drug delivery using mono-/di-glycerides as single component excipients
Published
Optional Fields
Lipid-based drug delivery systems Long versus medium chain lipid excipients Biorelevant media Dilution and dispersion testing In vivo pharmacokinetics
1
10
Objective This study aimed to systematically explore compositional effects for a series of lipid systems, on the inávitro drug solubilization and inávivo bioavailability of three poorly water-soluble drugs with different physico-chemical properties. Significance While many lipid-based drug products have successfully reached the market, there is still a level of uncertainty on the design guidelines for such drug products with limited understanding on the influence of composition on inávitro and inávivo performance. Methods and Results Lipid-based drug delivery systems were prepared using either single excipient systems based on partially digested triglycerides (i.e. mono- and/or di-glycerides) or increasingly complex systems by incorporating surfactants and/or triglycerides. These lipid systems were evaluated for both inávitro and inávivo behavior. Results indicated that simple single component long chain lipid systems are more beneficial for the absorption of the weak acid celecoxib and the weak base cinnarizine compared to equivalent single component medium chain lipid systems. Similarly, a two-component system produced by incorporating small amount of hydrophilic surfactant yields similar overall pharmacokinetic effects. The lipid drug delivery systems based on medium chain lipid excipients improved the inávivo exposure of the neutral drug JNJ-2A. The higher inávivo bioavailability of long chain lipid systems compared to medium chain lipid systems was in agreement with inávitro dilution and dispersion studies for celecoxib and cinnarizine. Conclusions The present study demonstrated the benefits of using mono-/di-glycerides as single component excipients in LBDDS to streamline formulation screening and improve oral bioavailability for the three tested poorly water-soluble drugs.
0363-9045
10.1080/03639045.2020.1843475
Grant Details
Horizon 2020
PEARRL European Training network, which has received funding from the Horizon 2020 Marie Sklodowska-Curie Innovative Training Networks programme under [grant agreement No. 674909]