Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therape...Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.展开更多
Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepato...Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.展开更多
Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability). Its bioavailability is limited by the dissolution rate. This study was aimed to enhance the rate of disso...Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability). Its bioavailability is limited by the dissolution rate. This study was aimed to enhance the rate of dissolution of poorly water soluble drug, FF. Initially, solid dispersions of fenofibrate (SDFs) were formulated with Carplex-80 or PEG-4000 or in combination at various weight ratios and were subjected to dissolution study. On the basis of drug release at various time intervals, the formulation producing maximum drug concentration was evaluated physicochemically using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). It was observed that the peak drug concentration was obtained at 120 min of dissolution by formulation SDF-7, which contains a mixture of Carplex-80 and PEG-4000 at weight ratio 1:5:6 of FF:PEG-4000:Carplex-80, respectively. Thus, the extent of drug release by SDF-7 was maximized by 2.5-fold than that of pure FF. Physicochemical characterization revealed the reason for this increased drug release as a conversion of crystalline FF to amorphous form and ensured the chemical compatibility among FF and carriers. The results specified the significant improvement of FF release using solid dispersion technique.展开更多
文摘Cefuroxime Axetil (CA) a widely used cephalosporin antibiotic displays low aqueous solubility and high membrane penetrability. This results in its solubility driven variable and/or low oral bioavailability and therapeutic efficacy as a major drawback. Thus, most of the goal of our study was to increase the solubility as well as dissolution rate of CA using the simple and cost-effective solid dispersion (SD) method. At first, the SD formulations of CA were prepared at various weight ratios of Carplex-67 and PEG-4000 by solvent evaporation technique. These new formulations were then subjected to an in-vitro drug release performance study and tested for physicochemical characterization to distinguish the thermal behavior, crystallinity, interactions phenomena, and surface morphology. Among the formulated Cefuroxime Axetil Solid Dispersion (CSD), CSD-8 which contained CA, Carplex-67, and PEG-4000 at the weight ratio 1:3:2, respectively showed the most significant (p in-vitro dissolution in water, Gastric Simulated Fluid (GSF), and Intestinal Simulated Fluid (ISF). This study also showed a significant (p < 0.001) increase in drug release compared to the marketed product. Therefore, it is supposed to be a promising alternative to conventional antimicrobial therapy.
文摘Paracetamol (PCM) is enlisted in the WHO model list as an essential medicine for pain and palliative care, but at overdose, it causes hepatic damage. This study was designed to assess the analgesic efficacy and hepatoprotective property of a solid dispersion (SD) loaded with PCM. A number of PCM loaded formulations (PSDs) were fabricated using silica alone or in combination with polyethylene glycol and/or Na-citrate followed by in-vitro dissolution profiling. Selected PSDs with improved dissolution profile were subjected to solid-state characterization (DSC, PXRD, FTIR, and SEM), stability study along with investigation of in-vivo analgesic efficacy and effect on hepatocytes. Among these, PSD10 showed a rapid and significantly higher in-vitro drug release than pure PCM. This improvement was distinct to other PSDs also. Solid-state characterization of PSD10 authenticated the conversion of crystalline PCM to amorphous form upon formulation. Subsequent oral administration of PSD10 in Swiss albino mice showed 1.44-fold greater analgesic efficacy than pure PCM at dose 30 mg/kg. Besides, at acute toxic dose, liver histology of PSD10 mice was comparable with NC mice indicating hepatic protection upon formulation, whereas the PCM mice showed extensive hepatic necrosis which was also endorsed by significantly higher values of SGPT, SGOT, and ALP than PSD10 mice. Finally, an accelerated stability study of PSD10 performed according to the guideline of ICH noticed no remarkable deviation in its dissolution performance as well as crystalline nature. Thus, this newly developed PSD10 may be a safe and promising alternative for pain management and palliative care.
文摘Fenofibrate (FF) is an anti-hyperlipidaemic drug belonging to BCS class-II (low solubility, high permeability). Its bioavailability is limited by the dissolution rate. This study was aimed to enhance the rate of dissolution of poorly water soluble drug, FF. Initially, solid dispersions of fenofibrate (SDFs) were formulated with Carplex-80 or PEG-4000 or in combination at various weight ratios and were subjected to dissolution study. On the basis of drug release at various time intervals, the formulation producing maximum drug concentration was evaluated physicochemically using differential scanning calorimetry (DSC), powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). It was observed that the peak drug concentration was obtained at 120 min of dissolution by formulation SDF-7, which contains a mixture of Carplex-80 and PEG-4000 at weight ratio 1:5:6 of FF:PEG-4000:Carplex-80, respectively. Thus, the extent of drug release by SDF-7 was maximized by 2.5-fold than that of pure FF. Physicochemical characterization revealed the reason for this increased drug release as a conversion of crystalline FF to amorphous form and ensured the chemical compatibility among FF and carriers. The results specified the significant improvement of FF release using solid dispersion technique.
