ABSTRACT
The aim of this study was to compare pharmacokinetic characteristics of fixed-dose combination (FDC) of two different salt form of amlodipine, amlodipine adipate/valsartan and amlodipine besylate/ valsartan, in healthy Korean volunteers under fasting conditions. A randomized, open-label, single-dose, two-treatment, two-way crossover study with a 14-day wash-out period was conducted. Plasma samples were collected for up to 144 hours for amlodipine and 24 hours for valsartan. Plasma concentrations of amlodipine and valsartan were analyzed using a validated ultra-performance liquid chromatography tandem mass-spectrometry. A non-compartmental method was used to calculate pharmacokinetic parameters. Vital signs and adverse events were monitored and physical examinations, laboratory tests, and electrocardiograms were conducted to evaluate safety. 44 subjects completed the study. The 90% CIs for the geometric mean ratio of Cmax and the AUC0-t were 93.5 - 100.4% and 93.2 - 98.3% for amlodipine, and 92.1 - 121.3% and 94.1 - 115.2% for valsartan, respectively. 17 adverse events occurred in 15 subjects during the study; 5 and 7 adverse drug reactions from the 5 and 6 subjects were considered to probably be related to the test and reference treatments respectively. All adverse drug reactions were in line with those known for the reference drug. All subjects recovered fully with no sequelae. A FDC of amlodipine adipate/valsartan and amlodipine besylate/valsartan combination tablets met the regulatory criteria for bioequivalence. In addition, no significant difference was observed in the safety assessments between two treatments. Thus, the newly developed FDC of amlodipine adipate/valsartan seems to be interchangeable with amlodipine besylate valsartan combination.
Subject(s)
Amlodipine/pharmacokinetics , Angiotensin II Type 1 Receptor Blockers/pharmacokinetics , Antihypertensive Agents/pharmacokinetics , Calcium Channel Blockers/pharmacokinetics , Tetrazoles/pharmacokinetics , Adult , Amlodipine/administration & dosage , Amlodipine/adverse effects , Amlodipine/blood , Amlodipine, Valsartan Drug Combination , Angiotensin II Type 1 Receptor Blockers/administration & dosage , Angiotensin II Type 1 Receptor Blockers/adverse effects , Angiotensin II Type 1 Receptor Blockers/blood , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/adverse effects , Antihypertensive Agents/blood , Area Under Curve , Asian People , Calcium Channel Blockers/administration & dosage , Calcium Channel Blockers/adverse effects , Calcium Channel Blockers/blood , Chromatography, Liquid , Cross-Over Studies , Drug Combinations , Half-Life , Healthy Volunteers , Humans , Male , Metabolic Clearance Rate , Models, Cardiovascular , Republic of Korea , Tandem Mass Spectrometry , Tetrazoles/administration & dosage , Tetrazoles/adverse effects , Tetrazoles/blood , Therapeutic Equivalency , Young AdultABSTRACT
The mixture of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer (F-68) and poly vinyl alcohol (PVA) forms a polymer complex gel by intra/intermolecular interaction via hydrogen bonding in water, which is verified by differential scanning calorimetry. With 30 wt% F-68 aqueous solution and 15 wt% PVA aqueous solution, F-68/PVA complex gel was prepared and its swelling transition was observed at approximately 37 degrees C. Based on the temperature-sensitivity of hydrogen bondings in F-68/PVA complex gel, temperature sensitive drug delivery system has been designed and characterized. For the stability in the aqueous media, F-68/PVA complex gel was prepared with a form of polymeric bead, followed by the encapsulation with poly(lactide-co-glycolide) membrane. With changing the ratio of F-68/PVA, the swelling transition of polymer complex gel was manipulated and pulsatile release of acetoaminophen, used as a model drug, was demonstrated in response to pulsatile change of temperature between 35 degrees C and 40 degrees C.
Subject(s)
Acetaminophen/administration & dosage , Acetaminophen/chemistry , Drug Delivery Systems/methods , Lactic Acid/chemistry , Polyethylene Glycols/chemistry , Polyglycolic Acid/chemistry , Polymers/chemistry , Polyvinyl Alcohol/chemistry , Propylene Glycols/chemistry , Temperature , Capsules/chemistry , Coated Materials, Biocompatible/chemistry , Complex Mixtures/chemistry , Diffusion , Drug Delivery Systems/instrumentation , Gels/chemistry , Hydrogen Bonding , Materials Testing , Molecular Weight , Phase Transition , Polylactic Acid-Polyglycolic Acid Copolymer , Surface PropertiesABSTRACT
Core/shell nanoparticles with lipid core, were prepared and characterized as a sustained delivery system for protein. The lipid core is composed of protein-loaded lecithin and the polymeric shell is composed of Pluronics (poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymer, F-127). Based on the preparation method in the previous report by us, the freeze-drying of protein-loaded lecithin was performed in the F-127 aqueous solution containing trehalose used as a cryoprotectant to form stabilized core/shell nanoparticles. Cryo-TEM (transmittance electron microscopy) and a particle size analyzer were used to observe the formation of stabilized core/shell nanoparticles. For the application of core/shell nanoparticles as a protein drug carrier, lysozyme and vascular endothelial growth factor (VEGF) were loaded into the core/shell nanoparticles by electrostatic interaction, and the drug release pattern was observed by manipulating the polymeric shell.