Ammonium methacrylate units polymer content and their effect on acyclovir colloidal nanoparticles properties and bioavailability in human volunteers.
Acyclovir (ACV)-Eudragit (EUD) nanoparticles (NPs) were prepared using both EUD RS 100 and RL 100 with different charge density. The effect of charge intensity on particle size, encapsulation efficiency, and in vitro dissolution was assessed. The bioavailability of ACV NP colloids were evaluated in human volunteers, compared with commercial product using a validated LC-MS/MS method with a lower limit of quantification (LLOQ) of 0.02 microg/ml. EUD RL 100 with higher ammonium groups gave smaller NPs than EUD RS 100. The surface charge of the polymer did not affect encapsulation efficiency and in vitro dissolution. In human volunteers, both F2 and F5 colloidal nanosuspensions prepared with EUD RS and RL respectively in drug to polymer ratio 1:3 sustained the oral absorption of ACV, expressed by the significant lower C(max), significant delayed T(max) and the significant higher HVD(t 50%C(max)). The mean C(max) of F2, F5, and Zovirax were 0.61+/-0.06, 0.73+/-0.07 and 0.92+/-0.21 microg/ml respectively. Furthermore, the AUC(0-12) of F2 and F5 was significantly higher than that of Zovirax((R)) with values of 4.37+/-0.88, 5.14+/-0.87 and 3.21+/-0.53 microg/ml h respectively. The higher AUC(0-12) for both F2 and F5 reflected high relative bioavailability of 136.2% and 159.9% respectively compared to commercial ACV tablets.
Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo, Egypt. ah_elshafeey@hotmail.com
Ahmed H
AH
Elshafeey
Amany O
AO
Kamel
Gehanne A S
GA
Awad
D000212:Acyclovir / Q000008:administration & dosage / Q000493:pharmacokinetics*; D000284:Administration, Oral; D000328:Adult; D001682:Biological Availability; D002021:Buffers; D002152:Calorimetry, Differential Scanning; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid; D003102:Colloids; D005464:Fluorobenzenes / Q000097:blood; D006801:Humans; D006863:Hydrogen-Ion Concentration / Q000187:drug effects; D007700:Kinetics; D008297:Male; D013058:Mass Spectrometry; D008689:Methacrylates / Q000494:pharmacology*; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D011108:Polymers / Q000494:pharmacology*; D011743:Pyrimidines / Q000097:blood; D012015:Reference Standards; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000097:blood; D013997:Time Factors
D002021:Buffers; D003102:Colloids; D005464:Fluorobenzenes; D008689:Methacrylates; D011108:Polymers; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000212:Acyclovir