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@#In order to evaluate the consistency of the release behavior between the self-made saxagliptin and metformin hydrochloride sustained-release tablets and the reference preparations in vitro, the similarity of the dissolution curves between the self-made preparations and the reference preparations in four dissolution mediums: HCl (pH 1.0), acetate buffer saline (pH 4.5), phosphate buffer saline (pH 6.8) and pure water, and the gel morphology and strength of the self-made preparations and the reference preparations in the HCl (pH 1.0) solution medium were compared.Results showed that in four dissolution mediums, the dissolution rates of saxagliptin in the self-made preparations and the reference preparations at 15 min were greater than 85%, and the ?2 similarity factors of metformin hydrochloride were 89, 83, 80, 86, all greater than 50, so the dissolution of the self-made preparations was consistent with those of the reference preparations.The volume expansion rate, water absorption rate and erosion rate were consistent with those of the reference preparations, and the gel strength of the self-made preparations was the same as that of the reference preparations.The in vitro release behaviors of the self-made preparations and the reference preparations are consistent, which provide a good guarantee for bioequivalence.
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Objective:To evaluate the efficacy of bupivacaine pamoate for sciatic nerve block in rats.Methods:Forty-eight SPF healthy male Sprague-Dawley rats, weighing 300-400 g, were divided into 6 groups using a random number table method: bupivacaine pamoate vehicle group (group VE), bupivacaine HCl group (group BH), liposomal bupivacaine group (group BL), low-dose bupivacaine pamoate group (group HL), moderate-dose bupivacaine pamoate group (group HM) and high-dose bupivacaine pamoate group (group HH), with 8 animals in each group.In VE, BH, BL, HL, HM and HH groups, bupivacaine pamoate vehicle 0.4 ml, bupivacaine HCl solution 0.4 ml, liposomal bupivacaine suspension 0.4 ml, and 1, 3 and 10 mg/ml bupivacaine pamoate suspension 0.4 ml were injected around the left sciatic nerve, respectively.The thermal paw withdrawal latency were measured before administration (T 0) and at 0.5, 1.5, 3, 5, 8, 12, 16, 24 and 48 h after injection (T 1-9). The percentage of maximum possible effect (MPE) of thermal paw withdrawal latency was calculated, and motor function score was simultaneously performed to evaluate the efficacy of sensory and motor block.Five and three rats in each group were sacrificed at 2 and 7 days after administration (T 9, 10), respectively, and the sciatic nerve at the injection site and the surrounding muscle tissues were harvested for microscopic examination (with a light microscope) after Luxol fast blue and HE staining.Nerve damage and inflammatory responses were assessed and scored to evaluate neurotoxicity. Results:Compared with group VE, the MPE was significantly increased at T 1-4 in group HL, at T 1-8 in group HM and at T 1-8 in group HH, the motor function scores were decreased at T 1-4 in group HL, at T 1-5 in group HM and at T 1-7 in group HH ( P<0.05), and no significant change was found in inflammatory response scores for the sciatic nerve and surrounding muscles at each time point in HL, HM and HH groups ( P>0.05). Compared with group BH, the MPE was significantly increased at T 3-8, motor function scores were decreased at T 3-5, and inflammatory response scores for the muscles around the sciatic nerve were decreased at T 9 in group HM ( P<0.05). Compared with group BL, the MPE was significantly increased at T 3-7, motor function scores were decreased at T 4, 5, and inflammatory response scores for the sciatic nerve and surrounding muscles were decreased at T 9 in group HM ( P<0.05). The nerve damage score was 0 in the six groups. Conclusion:Bupivacaine pamoate can block the sciatic nerve of rats, the duration of block is prolonged with the increase in the concentration, and the duration of motor block is not longer than that of sensory block; compared with the same concentration and equal volume of bupivacaine HCl and liposomal bupivacaine, bupivacaine pamoate produces longer duration of sciatic nerve block and less neurotoxicity.
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@#Solid dispersions of the insoluble compound CHMFL-KIT-110 were prepared by solvent method with polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer (Soluplus),Poloxamer 407,PEG 6000,Copovidone (Kollidon VA64) as carriers and SLS,Tween 80,Cremophor RH40 as solubilizers. The optimal formulation was screened and obtained with dynamic solubilities and supersaturation performances as indexes. The final product was characterized by Fourier transform infrared (FT-IR),differential thermal analysis (DTA) and X-ray powder diffraction (XRPD). The stability and pharmacokinetic behavior in rats were also investigated. Results suggested that when the weight ratio of CHMFL-KIT-110/Soluplus/SLS was 1∶4∶0.5,dynamic solubility of the solid dispersions was significantly improved with no recrystallization. In the accelerated condition (40 °C,75% RH) for 30 days,CHMFL-KIT-110 in the solid dispersions was still amorphous with no crystal observed. The results of pharmacokinetics in rats showed that the cmax and AUC0→t of CHMFL-KIT-110 solid dispersions were 373.1 times and 358.7 times higher than those of free drugs,respectively. These results help to understand the formulation development and clinical practice of CHMFL-KIT-110.
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Objective To evaluate the application value of Microendoscopic Discectomy (MED) in the treatment of lumbar disc herniation and lumbar spinal stenosis. Methods 188 cases of lumbar disc herniation and lumbar spinal stenosis were treated by MED, 38 cases of them performed lateral recess decompression. Results The mean follow-up period was 6.9 months. excellent and good therapeutic result rate was 97.4% (Macnab's standard). Conclusions MED in the treatment of lumbar disc herniation and lumbar spinal stenosis has short-term satisfactory therapeutic efficacy.