ABSTRACT
Objective To design and synthesize a different molecular mass block copolymer of poly(L-phenylalanine)-b-poly (L-aspartic acid)(PPA-PAA). Methods The L-phenylalanine and L-aspartic acid were used as raw materials to synthesize L-phenyl?alanine N-carboxy-ɑ-amino acid anhydride and L-aspartic acid-β-benzylester N-carboxy-ɑ-amino acid anhydride. The target com?pounds of amphiphilic block copolymer of PPA-PAA were synthesized by ring-opening polymerization. The critical micelle concentra?tion of the amphiphilic polymer was determined by pyrene fluorescence probe method. Results The copolymers of hydrophobic chain segment 500,2000,and 4000 were synthesized and the structures were confirmed by hydrogen nuclear magnetic resonance and Fouri?er transformed infrared. The critical micelle concentration of polymers changed with adjusting the feed ratio of PPA to PAA. Conclu?sion The results show that the longer the hydrophobic chain segment of PPA is,the smaller the critical micelle concentration of poly?mers. The results lay the groundwork for further studying the stabilizing effect of the drug polymer nanoparticles with different proper?ties.
ABSTRACT
Oral hydroxycamptothecin nanosuspension (HCPT-Nano) with high supersaturated dissolution level, high permeation and well physical stability, was manufactured by microprecipitation-high press homogenization method. Its pharmaceutical properties were investigated, such as size and distribution, zeta potential, particle shape, physical existence condition, supersaturated dissolution level and so on. Particle size was measured by laser diffraction, and the mean diameters before and after lyophilization were 138 +/- 11.72 nm and 175 +/- 12.74 nm, respectively, for HCPT-Nano. Zeta potentials of HCPT-Nano was over -20 mV. The nanoparticles, being observed by transmission electron microscopy (TEM), were claviform or column in shape. DSC and X-ray diffraction revealed that HCPT existed in the form of crystal for HCPT-Nano. And HCPT-Nano could maintain higher supersaturated dissolution level for long time. So it supplied the possibility of improving oral bioavailability of HCPT when combining together admoveatur of P-gp inhibitor, CsA.
ABSTRACT
<p><b>OBJECTIVE</b>To study on pharmacokinetics of hydroxycamptothecine (HCPT) nanosuspensions in rats after oral administration.</p><p><b>METHOD</b>The plasma concentrations of HCPT were determined by HPLC-FD. The analysis was performed on a diamonsil C18 column (4.6 mm x 200 mm, 5 microm) with 0.3% acetic acid-triethylamine buffer (pH 5.0) and methanol (57: 43) as mobile phase. The flow rate was 1.0 mL x min(-1); the excitation wave was set at 363 nm, and emission wave was set at 550 nm; the temperature was 35 degrees C. All data of concentration-time of HCPT were treated with pharmacokinetics program DAS 2.0.</p><p><b>RESULT</b>The concentration-peak area of this assay had a good linear relation in the range from 1 to 50 microg x L(-1), and the minimum limit of quantitation was 1 microg x L(-1). The inter- and intra-day precisions of HCPT were smaller than 4.3%, and the accuracy were between -5.59% and 5.59%. The recoveries of HCPT in three plasma concentrations including high, medial, low concentration were 98.94%, 95.88% and 102.69%, respectively, which was in line with the request of biopharmaceutical analysis. The plasma concentration time profiles of HCPT fitted in two-compartment models well, and the main pharmacokinetic parameters found for HCPT after oral administration were as follows: Cmax 13.10 microg x L(-1), Tmax 0.75 h, t(1/2alpha) 8.242 h, t(1/2beta) 136.122 h, AUC(0-t) 116.77 microg x h x L(-1), AUC(0-infinity) 161.93 microg x h x L(-1).</p><p><b>CONCLUSION</b>The HPLC-FD method was simple, with good specificity, reproducibility, and could be used to investigate the pharmacokinetics and determinate the concentration of hydroxycamptothecin. The nanosuspension in this study could accelerate the oral absorption rate of HCPT, and make improving bioavailability of HCPT possible.</p>
Subject(s)
Animals , Male , Rats , ATP Binding Cassette Transporter, Subfamily B, Member 1 , Administration, Oral , Calibration , Camptothecin , Chemistry , Pharmacokinetics , Pharmacology , Linear Models , Nanostructures , Rats, Wistar , SuspensionsABSTRACT
OBJECTIVE: To establish methods for the identification of Rhizoma Chuanxiong and determination of Ferulic acid( FA) in Ganning granula. METHODS: The identification of Rhizoma Chuanxiong was carried out by TLC and the determination of FA was by performed by HPLC. FA was separated on Kromasil ODS-1 C18 column with water-methanol-acetic acid ( 30∶ 69. 5∶ 0. 5) as mobile phase. The detection wavelength was 322nm, the column temperature was set at room temperature and the flow rate was 1. 0mL? min-1. RESULTS: The TLC spots of the sample presented the same color as its counterparts of Rhizoma Chuanxiong standard and FA reference substance at the corresponding sites. The linear range of FA was 0. 010 12 ～ 0. 151 80? g( r=0. 999 9, n=8) . The average recovery was 97. 39% ( RSD=1. 97% ) . CONCLUSION: The methods of identification and content determination were rapid, accurate, specific and reproducible, and which are suitable for the quality control of Ganning granula.