title: Controlled initial surge despite high drug fraction and high solubility.
abstract: Potential connections between release profiles and solvent evaporation rates alongside polymer chemistry were elucidated for the release of tetracycline hydrochloride from two different poly (d, l-lactide-co-glycolide) (PLGA) film matrices containing high drug fractions (50%, 30%, and 15%), and prepared at two distinct solvent evaporation rates. At highest tetracycline concentrations (50%), (i) the early release rates were ≤0.5 μg/min in all cases; (ii) release was linear from systems fabricated with lower lactic content and slower solvent evaporation rate and bimodal from systems fabricated with higher lactic content and faster evaporation rate; (iii) surface fractions covered by the drug were similar at both evaporation rates for 85:15 PLGA but very different for 50:50 PLGA, leading to unexpectedly reduced early release from 50:50 PLGA than from 85:15 PLGA when both the matrices were fabricated using a slower evaporation rate. These features remained unaffected in case of low drug concentration. Results suggested that during the formation of the drug-polymer microstructure, the combined effect of polymer chemistry and solvent evaporation rate sets apart the surface characteristics and the initial release profiles of systems containing high drug fraction, and an appropriate combination of these parameters may be utilized to control the early stage of drug release.
authors.affiliation: a Office of Science and Engineering Laboratories, Center for Devices and Radiological Health and.
authors.forename: Srilekha
authors.initials: S
authors.lastname: Sarkar Das
authors.affiliation: a Office of Science and Engineering Laboratories, Center for Devices and Radiological Health and.
authors.forename: Anne D
authors.initials: AD
authors.lastname: Lucas
authors.affiliation: b Office of Product Quality/Office of Testing and Research, Center for Drug Evaluation and Research, US Food and Drug Administration , Silver Spring , MD , USA.
authors.forename: Alan S
authors.initials: AS
authors.lastname: Carlin
authors.affiliation: a Office of Science and Engineering Laboratories, Center for Devices and Radiological Health and.
authors.forename: Jiwen
authors.initials: J
authors.lastname: Zheng
authors.affiliation: a Office of Science and Engineering Laboratories, Center for Devices and Radiological Health and.
authors.forename: Dinesh V
authors.initials: DV
authors.lastname: Patwardhan
authors.affiliation: a Office of Science and Engineering Laboratories, Center for Devices and Radiological Health and.
authors.forename: David M
authors.initials: DM
authors.lastname: Saylor
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D065546:Drug Liberation; D019344:Lactic Acid / Q000737:chemistry*; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013752:Tetracycline / Q000008:administration & dosage* / Q000737:chemistry; D014835:Volatilization
chemical_list: D000900:Anti-Bacterial Agents; D003692:Delayed-Action Preparations; D012997:Solvents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D013752:Tetracycline
keywords: Biodegradable; PLGA; controlled release; solvent casting; solvent evaporation; tetracycline