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Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats.
Eur J Pharm Sci. 2018 08 30; 121:287-292.EJ

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 (t1/2). 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 (Cmax), time taken to reach Cmax (Tmax), areas under time-concentration curves (AUC0-t and AUC0-∞), terminal elimination rate constant (kel), t1/2, volume of distribution (Vd), mean residence time (MRT), clearance (Cl), zero concentration (C0), steady state volume of distribution (Vss), 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 Cmax (0.92 ± 0.21 μg/ml) and has significantly shorter Tmax (14 ± 10.84 min) compared to the suspension of acyclovir (Cmax 0.29 ± 0.09 μg/ml and Tmax 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.

Authors+Show Affiliations

University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Vojvode Stepe 450, 11221 Belgrade, Serbia. Electronic address: ljiljanadjek@gmail.com.Pharmacy Janković, Miloša Bajića 13, 21000 Novi Sad, Serbia.University of Novi Sad, Faculty of Medicine, Department of Pharmacology, Toxicology and Clinical Pharmacology, Hajduk Veljkova 3, 21000 Novi Sad, Serbia.University of Belgrade, Faculty of Pharmacy, Department of Pharmaceutical Technology and Cosmetology, Vojvode Stepe 450, 11221 Belgrade, Serbia.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

29883728

Citation

Djekic, Ljiljana, et al. "Semisolid Self-microemulsifying Drug Delivery Systems (SMEDDSs): Effects On Pharmacokinetics of Acyclovir in Rats." European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, vol. 121, 2018, pp. 287-292.
Djekic L, Janković J, Rašković A, et al. Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats. Eur J Pharm Sci. 2018;121:287-292.
Djekic, L., Janković, J., Rašković, A., & Primorac, M. (2018). Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats. European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences, 121, 287-292. https://doi.org/10.1016/j.ejps.2018.06.005
Djekic L, et al. Semisolid Self-microemulsifying Drug Delivery Systems (SMEDDSs): Effects On Pharmacokinetics of Acyclovir in Rats. Eur J Pharm Sci. 2018 08 30;121:287-292. PubMed PMID: 29883728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Semisolid self-microemulsifying drug delivery systems (SMEDDSs): Effects on pharmacokinetics of acyclovir in rats. AU - Djekic,Ljiljana, AU - Janković,Jovana, AU - Rašković,Aleksandar, AU - Primorac,Marija, Y1 - 2018/06/06/ PY - 2018/02/17/received PY - 2018/04/18/revised PY - 2018/06/05/accepted PY - 2018/6/9/pubmed PY - 2019/8/29/medline PY - 2018/6/9/entrez KW - Acyclovir KW - Oral bioavailability KW - Safety KW - Self-microemulsifying drug delivery systems (SMEDDSs) KW - Semisolid SMEDDS KW - Wistar rats SP - 287 EP - 292 JF - European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences JO - Eur J Pharm Sci VL - 121 N2 - 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 (t1/2). 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 (Cmax), time taken to reach Cmax (Tmax), areas under time-concentration curves (AUC0-t and AUC0-∞), terminal elimination rate constant (kel), t1/2, volume of distribution (Vd), mean residence time (MRT), clearance (Cl), zero concentration (C0), steady state volume of distribution (Vss), 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 Cmax (0.92 ± 0.21 μg/ml) and has significantly shorter Tmax (14 ± 10.84 min) compared to the suspension of acyclovir (Cmax 0.29 ± 0.09 μg/ml and Tmax 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. SN - 1879-0720 UR - https://www.unboundmedicine.com/medline/citation/29883728/Semisolid_self_microemulsifying_drug_delivery_systems__SMEDDSs_:_Effects_on_pharmacokinetics_of_acyclovir_in_rats_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0928-0987(18)30261-6 DB - PRIME DP - Unbound Medicine ER -