ABSTRACT
Preparation and in vitro/in vivo evaluation of gestodene [GEST] intravaginal ring [IVR] formulations which can release a constant dose of GEST during 3 weeks were investigated. In present study a reservoir gestodene intravaginal ring, including a gestodene silicone elastomer core and the non-active silicone layer, was reported, which was manufactured by reaction injection moulding at 80[degree]C for 20 min. The raw materials compatibility experiments showed that the silicone elastomer core carrier wouldn't interact with drugs. In vitro release samples were determined by HPLC and the experiment was performed under sink conditions. The equation of cumulative release verse time was Y=64.76x+5.44 [r=0.9998], performing zero-order release at about the target dose of 60 [micro]g/day over 21 days. Drug release increased with temperature elevating from 45 to 55[degree]C, which could be attributed to optimizing the prescription. In addition, the pharmacokinetic and safety studies of gestodene intravaginal ring were evaluated in female New Zealand White rabbits. The GEST in plasma was analyzed by LC-MS/MS and the results proved that the correlation between in vitro and in vivo was relatively well
ABSTRACT
This study taking gestodene (GEST) as a model, investigated the factors affecting reservoir-type intravaginal ring (IVR)'s drug release. This paper reported a gestodene intravaginal ring of reservoir design, comprising a gestodene silicone elastomer core encased in a non-medicated silicone sheath, separately manufactured by reaction injection moulding at 80 degrees C and heating vulcanization at 130 degrees C is reported. The test investigated the factors affecting drug release through a single variable method, taking the drug release rates of 21 days as standards. When changing the thickness of the controlling sheath outside, the ratio of the first day of drug release and mean daily release (MDR), named the relatively burst effect, is closing to 1 with the thickness of controlling sheath increasing, while the 1.25 mm sheath corresponding to 1.04 controlled the burst release effectively; a positive correlation (r = 0.992 2) existed between the average drug release (Q/t) and drug loading (A) within a certain range. The C6-165 controlling sheath with high solubility of GEST is easier to achieve controlled release of the drug; GEST crystalline power is more effective to implement controlled release of drugs among difficent states of the drug. A 1/4 fractional segment core gives a relatively burst effect of 1.76, while the 1/1 and 1/2 are 1.93 and 1.87 separately, at the same drug loading, concluding that use of a fractional segment core would allow development of a suitable GEST reservoir IVR. In summary, GEST reservoir-type IVR could be adjusted by the thickness of controlling sheath, the loading of drug, the material properties of controlling sheath, the dispersion state of drug, the additive composition and structure of intravaginal ring, to control the drug release behavior and achieve the desired drug release rate.
ABSTRACT
Objective To investigate the differences in the safety of the operation of different hepatic vascular exclusion for liver surgery. Methods Sixty patients with liver resection were grouped by different hepatic blood flow blocking methods, and given pre-operative assessment prior to surgery. Results On the first day after surgery, the average levels of ALT and AST were (395.0 ± 220.2) U/L and (415.3±311.0) U/L in patients who received Pringle’s method (110.2±53.0) U/L and (125.6±78.5) U/L in patients who received regional hepatic vascular exclusion, (98.9±32.2) U/L and (96.2 ±66.5) U/L in patients who didn't receive hepatic vascular exclusion, respectively. Postoperative liver function damage was more serious in patients who received Pringle's method than patients who received regional hepatic vascular exclusion or patients who didn't receive hepatic vascular exclusion, the difference was statistically significant (P<0.05) .Conclusion Regional hepatic vascular exclusion or not can not only reduce the incidence of postoperative complications, but also expand the indications for liver resection.