title: Combined use of bile acids and aminoacids to improve permeation properties of acyclovir.
abstract: The aim of this work was to develop a topical formulation with improved permeation properties of acyclovir. Ursodeoxycholic (UDC) and dehydrocholic (DHC) acids were tested as potential enhancers, alone or in combination with different aminoacids. Equimolar binary and ternary systems of acyclovir with cholic acids and basic, hydrophilic or hydrophobic aminoacids were prepared by co-grinding in a high vibrational micromill. Differential scanning calorimetry (DSC) was used to characterize the solid state of these systems, while their permeation properties were evaluated in vitro through a lipophilic artificial membrane. UDC was more than 2 times more effective than DHC in improving drug AUC and permeation rate. As for the ternary systems drug-UDC-aminoacid, only the combined use of l-lysine with UDC acid produced an evident synergistic effect in enhancing drug permeation properties, enabling an almost 3 and 8 times AUC increase compared to the binary UDC system or the pure drug, respectively. The best systems were selected for the development of topical cream formulations, adequately characterized and tested for in vitro drug permeation properties and stability on storage. The better performance revealed by acyclovir-UDC-l-lysine was mainly attributed to the formation of a more permeable activated system induced by the multicomponent co-grinding process.
authors.affiliation: Dept. of Chemistry, School of Sciences of Human Health, University of Florence, via U. Schiff, 6 Sesto Fiorentino 50019 Florence, Italy. Electronic address: marzia.cirri@unifi.it.
authors.forename: M
authors.initials: M
authors.lastname: Cirri
authors.affiliation: Dept. of Chemistry, School of Sciences of Human Health, University of Florence, via U. Schiff, 6 Sesto Fiorentino 50019 Florence, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Maestrelli
authors.affiliation: Dept. of Chemistry, School of Sciences of Human Health, University of Florence, via U. Schiff, 6 Sesto Fiorentino 50019 Florence, Italy.
authors.forename: N
authors.initials: N
authors.lastname: Mennini
authors.affiliation: Dept. of Chemistry, School of Sciences of Human Health, University of Florence, via U. Schiff, 6 Sesto Fiorentino 50019 Florence, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Mura
mesh_terms: D000212:Acyclovir / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D001647:Bile Acids and Salts / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods; D004355:Drug Stability; D004356:Drug Storage / Q000379:methods; D008239:Lysine / Q000737:chemistry; D010539:Permeability; D014580:Ursodeoxycholic Acid / Q000737:chemistry
chemical_list: D000596:Amino Acids; D001647:Bile Acids and Salts; D014580:Ursodeoxycholic Acid; D008239:Lysine; D000212:Acyclovir
keywords: Acyclovir; Aminoacids; Bile acid; Co-grinding; Permeation enhancers; Topical formulations