ABSTRACT
Background@#Hydrogen bonding interaction was considered to play a critical role in controlling drug release from transdermal patch. However, the quantitative evaluation of hydrogen bonding strength between drug and polar functional group was rarely reported, and the relationship between hydrogen bonding strength and controlled release capacity of pressure sensitive adhesive (PSA) was not well understood. The present study shed light on this relationship.@*Methods@#Acrylate PSAs with amide group were synthesized by a free radical-initiated solution polymerization. Six drugs, , etodolac, ketoprofen, gemfibrozil, zolmitriptan, propranolol and lidocaine, were selected as model drugs. drug release and skin permeation experiments and pharmacokinetic experiment were performed. Partial correlation analysis, fourier-transform infrared spectroscopy and molecular simulation were conducted to provide molecular details of drug-PSA interactions. Mechanical test, rheology study, and modulated differential scanning calorimetry study were performed to scrutinize the free volume and molecular mobility of PSAs.@*Results@#Release rate of all six drugs from amide PSAs decreased with the increase of amide group concentrations; however, only zolmitriptan and propranolol showed decreased skin permeation rate. It was found that drug release was controlled by amide group through hydrogen bonding, and controlled release extent was positively correlated with hydrogen bonding strength.@*Conclusion@#From these results, we concluded that drugs with strong hydrogen bond forming ability and high skin permeation were suitable to use amide PSAs to regulate their release rate from patch.
ABSTRACT
@#To evaluate pharmacokinetic and metabolic characteristics of clevidipine butyrate lipid microspheres(CDB-LM)injection in mice, a novel HPLC-FLD method was developed for simultaneous measurement of clevidipine butyrate(CDB)and its metabolites clevidipine acid(MI)in whole blood samples. The chromatographic column was Waters C18(4. 6 mm×150 mm, 5 μm)and the mobile phase is consisted of acetonitrile-methanol-phosphate(2 ∶1 ∶2). The detection wavelength of FLD included excitation wavelength at 358 nm and emission wavelength at 440 nm. The pharmacokinetic parameters of CDB and MI were calculated by using DAS 2. 0. Then obtained parameters were statisticaly analyzed using PASW Statistics 18. The results showed that the half-life of CDB and MI were about 4 min and 20 min, respectively. Pharmacokinetic parameters of the low- and high-dose groups were as follows: CL of CDB were 4. 21 and 2. 72 L ·min-1 ·kg-1; AUC0-t were 3. 86 and 6. 43 mg/L ·min; MRT0-t were 7. 09 and 6. 17 min. CL of MI were 0. 34 and 0. 22 L ·min-1 ·kg-1; AUC0-t were 52. 23 and 74. 90 mg/L ·min; MRT0-t were 201. 24 and 217. 33 min. A method of protein precipitation was established, and acetonitrile was used to deal with whole blood samples. This method was simple, fast, with no interference with endogenous impurities. The results showed that the established HPLC-FLD method was simple and sensitive. It can be used to determine CDB and MI simultaneously. Comparing the low-dose group with the high-dose group, it was found that the plasma concentration-time curve of the two groups revealed the same tendency, which confirms that CDB has a short half-life and that it metabolizes to MI quickly.