ABSTRACT
Objective To investigate the influences of polyethylene glycol on the solubility and in vitro dissolution of m-nisoldipine,which could provide guidance for chosing formulations of m-nisoldipine. Methods Solid dispersions of m-nisoldipine were prepared by solvent-melting method with polyethylene glycol6000 matrix. DSC and XRD spectroscopy were applied to identify the solid dispersions. The solubility and in vitro dissolution were detected by UV spectroscopy. Results The DSC and XRD map were different from the crude drug and their physical mixtures. The dissolution rates(13,15,17) were faster(35. 31%,38. 71%,41. 48%) than that of the crude drug(26. 80%),and the dissolution rates of the solid dispersions in the same ratio were higher than the physical mixtures. Conclusion DSC analysis indicated that eutectic compounds were produced by the m-nisoldipine and polyethylene glycol,in which polyethylene glycol6000 acts as a carrier. The solubility and in vitro dissolution of m-nisoldipine can be increased.
ABSTRACT
This study is to explore the activation of the Ca2+/CaM/CaN signal pathway in 5-HT-induced proliferation of rat pulmonary artery smooth muscle cells (PASMCs) and the inhibitory effect of m-nisoldipine (m-Nis) on this pathway. PASMCs were cultured with the explant technique. The proliferation of PASMCs was evaluated by MTT assay. Confocal microscopy was used to measure the change of [Ca2+]i. The mRNA expression of CaM and CaN was evaluated by RT-PCR and the activity of CaN was measured according to the instruction of kits. The results of MTT assay suggested that 5-HT (1 ?mol?L-1) significantly induced the proliferation of rat PASMCs (P
ABSTRACT
Aim To explore the effect of m-Nisoldipine(m-Nis) on 5-HT-induced proliferation,migration of rat PASMCs and to study the mechanisms.Methods PASMCs were cultured with the explant technique,and were divided into 6 groups:control group,5-HT(1 μmol·L~(-1)) group and m-Nis(10~(-5),10~(-6),10~(-7),10~(-8) mol·L~(-1))group.MTT assay was used to evaluate the proliferation of PASMCs,and transwell chambers were used to detect the migration of PASMCs.In addition,the expression of PCNA and the phosphorylation of ERK1/2 were evaluated by Western blot analysis.Results m-Nis inhibited the proliferation(P<0.05 or P<0.01)and migration(P<0.01)of rat PASMCs induced by 5-HT obviously.Similarly,Western blot analysis of PCNA indicated that the expression of PCNA was significantly higher in 5-HT group than that in control group(P<0.01).Whereas,in four m-Nis treated groups,the level of PCNA was markedly decreased(P<0.05 or P<0.01).Meanwhile,m-Nis 10~(-5),10~(-6) and 10~(-7) mol·L~(-1) pretreatment also reduced 5-HT-induced phosphorylation of ERK1/2 obviously(P<0.05 or P<0.01).Conclusion m-Nis inhibits 5-HT-induced proliferation and migration of rat PASMCs obviously,which may be related to the inhibition of PCNA expression and the blockage of ERK1/2/MAPK signal pathway.
ABSTRACT
OBJECTIVE:To prepare m-nisoldipine solid dispersion from poorly-soluble m-nisoldipine so as to improve its solubility and dissolution rate in vitro. METHODS: Solid dispersions of m-nisoldipine were prepared by coprecipitation method with poloxamer as carrier; Differential scanning calorimetry (DSC) was used to determine the status of nimodipine in carrier. The solubility and the dissolution rate of the solid dispersion in vitro were studied. RESULTS: DSC analysis indicated that eutectic mixture was formed from m-nisoldipine and poloxamer. The solubility of m-nisoldipine and the its solid dispersions prepared from m-nisoldipine and poloxamer at different ratio (1∶3, 1∶5, 1∶7) were 0.89, 4.50, 15.35, and 23.03 mg?L-1, respectively, and their 120 min dissolution rates were 26.80%, 38.57%, 41.38%, and 45.92%, respectively. In the same ratio, the dissolution rates of the solid dispersions were higher than those of their physics mixtures. CONCLUSIONS: The solid dispersion of m-nisoldipine prepared with poloxamer as carrier can increase the solubility and dissolution rate in vitro.
ABSTRACT
m-Nisoldipine ( m-Nis ) , isobutyl methyl 1 , 4-dihydro - 2, 6-dimethyl-4-( 3-nitrophenyl )-3 , 5-pyridine dicarboxylate, is a new calcium antagonist. Its effects on hemodynamics and regional blood flow as well as the distribution of cardiac output were evaluated in comparison with Nis with radio-biomicrospheres in conscious rabbits. ( 1 ) m-Nis ( 1 ?g/kg ? min-1 ? 10 min, iv ) increased cardiac output and cardiac index significantly (P0.05) ; ( 2 ) m-Nis increased stroke volume and left ventricular systolic work ( per beat ) while Nis slightly increased the former and decreased the later, and these differences were statistically significant (P