Quantitative Assessment of the in Vivo Dissolution Rate to Establish a Modified IVIVC for Isosorbide Mononitrate Tablets

Author(s):  
Guoqing Zhang ◽  
Li Zhang ◽  
Yuexiang Tan ◽  
Lei Wang ◽  
Zeneng Cheng
1988 ◽  
Vol 38 (1) ◽  
pp. 19-26
Author(s):  
Haruo NAKAGAKI ◽  
Nobuhiko FUJIGAKI ◽  
Taeko MURAKAMI ◽  
Kazuo KATO ◽  
Teruhisa MIZUNO ◽  
...  

1982 ◽  
Vol 10 (1) ◽  
pp. 17-24 ◽  
Author(s):  
P.B. Daly ◽  
S.S. Davis ◽  
M. Frier ◽  
J.G. Hardy ◽  
J.W. Kennerley ◽  
...  

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Dalton E Carter ◽  
Tao Peng ◽  
Melanie R Moody ◽  
Shao-Ling Huang ◽  
David D McPherson ◽  
...  

Background: We have previously demonstrated thrombolytic efficacy of tissue plasminogen activator (tPA)-loaded echogenic liposomes (TELIP), a directed therapeutic construct that features exposed tPA fibrin-binding sites, in a rabbit abdominal aorta thrombosis model. The most relevant animal model for evaluation of directed thrombolytic therapy for ischemic stroke is the rabbit thrombotic stroke model previously used to validate recombinant tPA (rtPA; Alteplase). The ability to precisely monitor tPA-mediated thrombus dissolution in vivo is important for quantitative assessment of directed TELIP efficacy. Hypothesis: A gas-free ultrasound contrast agent can be incorporated into blood clots at a concentration that does not affect the tPA-mediated clot dissolution rate, while enabling quantitative assessment of the clot dissolution rate. Methods: In 1.5-ml Eppendorf tubes, 0.2-ml clots were formed from a mixture of whole rabbit blood, 1 M calcium chloride, human thrombin and various amounts of microcrystalline cellulose. At 0-time, 50 μg rtPA in 0.5 ml porcine plasma was added to each tube. Washed clots in tubes were weighed with an analytical balance at 30, 60 and 90 minutes. Clot echogenicity at each time point was assessed with a Philips HDI 5000 ultrasound system using an L12-5 linear array probe positioned laterally to tubes placed in an anechoic chamber. Recorded Images were subjected to videodensitometric analysis that converted image reflectivity to mean gray scale values (MGSV). Results: We found that 1.12 mg/ml of microcrystalline cellulose in rabbit blood clots (0.2 ml) provided optimal echogenicity without affecting the clot dissolution rates (0.3-0.6 mg/min.) caused by 100 μg/ml of rtPA. The clot dissolution rate measured by videodensitometric analysis of serial sonograms of the echogenic clots agreed well with that determined by mass loss measurements (0.28% 0-time value/minute). Conclusions: We have developed a method for monitoring rtPA-mediated clot mass loss by ultrasound imaging techniques and validated it in vitro. This method will be important for demonstrating the enhanced efficacy and decreased hemorrhagic effects provided by directed tPA vehicles relative to systemic administration of the free thrombolytic.


1988 ◽  
Vol 38 (1) ◽  
pp. 11-18
Author(s):  
Haruo NAKAGAKI ◽  
Nobuhiko FUJIGAKI ◽  
Taeko MURAKAMI ◽  
Kazuo KATO ◽  
Yukitaro SAKAKIBARA

1988 ◽  
Vol 38 (1) ◽  
pp. 27-39 ◽  
Author(s):  
Haruo NAKAGAKI ◽  
Nobuhiko FUJIGAKI ◽  
Taeko MURAKAMI ◽  
Kazuo KATO ◽  
Teruhisa MIZUNO ◽  
...  

Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.


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