Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats
Abstract
Semisolid self-microemulsifying drug delivery system (SMEDDS) with optimized drug loading capacity, stability, dispersibility in aqueous media and in vitro drug release profile, was evaluated in vivo regarding effects on pharmacokinetics of acyclovir, an antiviral with low bioavailability (BA) and short half-life (t(1/2)). Additional goal of this study was evaluation of safety of this semisolid SMEDDS consisted of medium chain length triglycerides (oil) (10% w/w), macrogolglycerol hydroxystearate (surfactant) (56.25% w/w), polyglyceryl-3-dioleate (cosurfactant) (6.25% w/w), glycerol (cosolvent) (20% w/w), macrogol 8000 (viscosity modifier) (7.5% w/w), and acyclovir (2.5 mg/ml). The study was performed on fully mature white male Wistar rats. The pharmacokinetics of acyclovir was monitored in three groups (1-3) of animals after administration of drug solution (intravenously (IV)), drug suspension (orally) and semisolid SMEDDS (orally), respectively. The determined pharmacokinetic paramet...ers were: maximum concentration of acyclovir in serum (C-max), time taken to reach C-max (T-max), areas under time-concentration curves (AUC(0-t) and AUC(0-infinity)), terminal elimination rate constant (k(el)), t(1/2), volume of distribution (V-d), mean residence time (MRT), clearance (Cl), zero concentration (C-0), steady state volume of distribution (V-ss), and BA. Additionally, for safety evaluation, animals were treated orally with aqueous solution of acyclovir, drug-free semisolid SMEDDS and acyclovir-loaded semisolid SMEDDS, during 21 days (groups 4-7). Serum samples of sacrificed animals were used for biochemical analysis of enzymatic activity of alanine transaminase (ALT) and aspartate transaminase (AST), urea, creatinine, and uric acid. Acyclovir administered by semisolid SMEDDS reached twice higher C-max (0.92 +/- 0.21 mu g/ml) and has significantly shorter T-max (14 +/- 10.84 min) compared to the suspension of acyclovir (C-max 0.29 +/- 0.09 mu g/ml and T-max 26.00 +/- 5.48 min). BA of the drug was significantly increased by semisolid SMEDDS, while the analysis of biochemical parameters excluded damage on function of liver and kidneys caused by the investigated drug delivery system.
Keywords:
Self-microemulsifying drug delivery systems (SMEDDS) / Semisolid SMEDDS / Acyclovir / Wistar rats / Oral bioavailability / SafetySource:
European Journal of Pharmaceutical Sciences, 2018, 121, 287-292Publisher:
- Elsevier Science BV, Amsterdam
Funding / projects:
DOI: 10.1016/j.ejps.2018.06.005
ISSN: 0928-0987
PubMed: 29883728
WoS: 000437223600030
Scopus: 2-s2.0-85048641726
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Institution/Community
PharmacyTY - JOUR AU - Đekić, Ljiljana AU - Janković, Jovana AU - Rasković, Aleksandar AU - Primorac, Marija PY - 2018 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3242 AB - Semisolid self-microemulsifying drug delivery system (SMEDDS) with optimized drug loading capacity, stability, dispersibility in aqueous media and in vitro drug release profile, was evaluated in vivo regarding effects on pharmacokinetics of acyclovir, an antiviral with low bioavailability (BA) and short half-life (t(1/2)). Additional goal of this study was evaluation of safety of this semisolid SMEDDS consisted of medium chain length triglycerides (oil) (10% w/w), macrogolglycerol hydroxystearate (surfactant) (56.25% w/w), polyglyceryl-3-dioleate (cosurfactant) (6.25% w/w), glycerol (cosolvent) (20% w/w), macrogol 8000 (viscosity modifier) (7.5% w/w), and acyclovir (2.5 mg/ml). The study was performed on fully mature white male Wistar rats. The pharmacokinetics of acyclovir was monitored in three groups (1-3) of animals after administration of drug solution (intravenously (IV)), drug suspension (orally) and semisolid SMEDDS (orally), respectively. The determined pharmacokinetic parameters were: maximum concentration of acyclovir in serum (C-max), time taken to reach C-max (T-max), areas under time-concentration curves (AUC(0-t) and AUC(0-infinity)), terminal elimination rate constant (k(el)), t(1/2), volume of distribution (V-d), mean residence time (MRT), clearance (Cl), zero concentration (C-0), steady state volume of distribution (V-ss), and BA. Additionally, for safety evaluation, animals were treated orally with aqueous solution of acyclovir, drug-free semisolid SMEDDS and acyclovir-loaded semisolid SMEDDS, during 21 days (groups 4-7). Serum samples of sacrificed animals were used for biochemical analysis of enzymatic activity of alanine transaminase (ALT) and aspartate transaminase (AST), urea, creatinine, and uric acid. Acyclovir administered by semisolid SMEDDS reached twice higher C-max (0.92 +/- 0.21 mu g/ml) and has significantly shorter T-max (14 +/- 10.84 min) compared to the suspension of acyclovir (C-max 0.29 +/- 0.09 mu g/ml and T-max 26.00 +/- 5.48 min). BA of the drug was significantly increased by semisolid SMEDDS, while the analysis of biochemical parameters excluded damage on function of liver and kidneys caused by the investigated drug delivery system. PB - Elsevier Science BV, Amsterdam T2 - European Journal of Pharmaceutical Sciences T1 - Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats VL - 121 SP - 287 EP - 292 DO - 10.1016/j.ejps.2018.06.005 ER -
@article{ author = "Đekić, Ljiljana and Janković, Jovana and Rasković, Aleksandar and Primorac, Marija", year = "2018", abstract = "Semisolid self-microemulsifying drug delivery system (SMEDDS) with optimized drug loading capacity, stability, dispersibility in aqueous media and in vitro drug release profile, was evaluated in vivo regarding effects on pharmacokinetics of acyclovir, an antiviral with low bioavailability (BA) and short half-life (t(1/2)). Additional goal of this study was evaluation of safety of this semisolid SMEDDS consisted of medium chain length triglycerides (oil) (10% w/w), macrogolglycerol hydroxystearate (surfactant) (56.25% w/w), polyglyceryl-3-dioleate (cosurfactant) (6.25% w/w), glycerol (cosolvent) (20% w/w), macrogol 8000 (viscosity modifier) (7.5% w/w), and acyclovir (2.5 mg/ml). The study was performed on fully mature white male Wistar rats. The pharmacokinetics of acyclovir was monitored in three groups (1-3) of animals after administration of drug solution (intravenously (IV)), drug suspension (orally) and semisolid SMEDDS (orally), respectively. The determined pharmacokinetic parameters were: maximum concentration of acyclovir in serum (C-max), time taken to reach C-max (T-max), areas under time-concentration curves (AUC(0-t) and AUC(0-infinity)), terminal elimination rate constant (k(el)), t(1/2), volume of distribution (V-d), mean residence time (MRT), clearance (Cl), zero concentration (C-0), steady state volume of distribution (V-ss), and BA. Additionally, for safety evaluation, animals were treated orally with aqueous solution of acyclovir, drug-free semisolid SMEDDS and acyclovir-loaded semisolid SMEDDS, during 21 days (groups 4-7). Serum samples of sacrificed animals were used for biochemical analysis of enzymatic activity of alanine transaminase (ALT) and aspartate transaminase (AST), urea, creatinine, and uric acid. Acyclovir administered by semisolid SMEDDS reached twice higher C-max (0.92 +/- 0.21 mu g/ml) and has significantly shorter T-max (14 +/- 10.84 min) compared to the suspension of acyclovir (C-max 0.29 +/- 0.09 mu g/ml and T-max 26.00 +/- 5.48 min). BA of the drug was significantly increased by semisolid SMEDDS, while the analysis of biochemical parameters excluded damage on function of liver and kidneys caused by the investigated drug delivery system.", publisher = "Elsevier Science BV, Amsterdam", journal = "European Journal of Pharmaceutical Sciences", title = "Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats", volume = "121", pages = "287-292", doi = "10.1016/j.ejps.2018.06.005" }
Đekić, L., Janković, J., Rasković, A.,& Primorac, M.. (2018). Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats. in European Journal of Pharmaceutical Sciences Elsevier Science BV, Amsterdam., 121, 287-292. https://doi.org/10.1016/j.ejps.2018.06.005
Đekić L, Janković J, Rasković A, Primorac M. Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats. in European Journal of Pharmaceutical Sciences. 2018;121:287-292. doi:10.1016/j.ejps.2018.06.005 .
Đekić, Ljiljana, Janković, Jovana, Rasković, Aleksandar, Primorac, Marija, "Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats" in European Journal of Pharmaceutical Sciences, 121 (2018):287-292, https://doi.org/10.1016/j.ejps.2018.06.005 . .