Astrogliosis has a unique reaction during spinal cord damage, with helpful or adverse impacts on recovery. There is consequently a pressing need for treatment to target activated astrocytes and their unsafe response after injury to ensure some preservative effect during the progressive damage. We specifically developed and characterized a functionalized nanogel-based nanovector in vitro and in vivo, demonstrating its selectivity towards astrocytes, and limited uptake by macrophages when functionalized with both NH2 and Cy5 groups. In vitro experiments showed that the internalization was mediated by a clathrin-dependent endocytic pathway. After internalization into the cytoplasm of astrocytes, nanogels undergo lysosomal degradation and release compounds with potential therapeutic efficacy.New drugs are frequently found with poor water-solubility in recent pharmaceutical projects, which brings difficulties of bioavailability for the clinical development of new drugs. When these drug compounds in a crystalline state are absorbed by gastrointestinal tract, their dissolution rates and absorption rates are very limited. Nowadays, various methods have been developed to improve the solubility, dissolution and bioavailability of drugs. According to the characteristics of drugs, this work suggests the use of spray drying technology to amorphize APIs (active pharmaceutical ingredients) to improve their bioavailability. This work reviews the properties of the spray-dried amorphous drugs, the progress made in drug synthesis and application, and the existing problems.The purpose of this study was to optimize the melt granulation process of fenofibrate using twin-screw granulator. Initial screening was performed to select the excipients required for melt granulation process. A 3 × 3 factorial design was used to optimize the processing conditions using the % drug loading (X1) and screw speed (X2) as the independent parameters and granule friability (Y1) % yield (Y2) as the dependent parameters. The effect of the independent parameters on the dependent parameters was determined using response surface plots and contour plots. A linear relationship was observed between % drug loading (X1) and % friability (Y1) and a quadratic relationship was observed between the independent parameters (X1 and X2) and % yield (Y2). The processing conditions for optimum granules were determined using numerical and graphical optimization and it was found that 15% drug loading at 50 rpm results in maximum % yield of 82.38% and minimum friability of 7.88%. The solid-state characterization of the optimized granules showed that the drug turned from crystalline state to amorphous state during melt granulation process. The optimized granules were compressed into tablets using Purolite® as the super disintegrating agent. The optimized formulation showed >85% drug release in 0.75% SLS solution within 60 min.Therapeutic monoclonal antibodies and related products have steadily grown to become the dominant product class within the biopharmaceutical market. Production of antibodies requires special precautions to ensure safety and efficacy of the product. In particular, minimizing antibody product heterogeneity is crucial as drug substance variants may impair the activity, efficacy, safety, and pharmacokinetic properties of an antibody, consequently resulting in the failure of a product in pre-clinical and clinical development. This review will cover the manufacturing and formulation challenges and advances of therapeutic monoclonal antibodies, focusing on improved processes to minimize variants and ensure batch-to-batch consistency. Processes put in place by regulatory agencies, such as Quality-by-Design (QbD) and current Good Manufacturing Practices (cGMP), and how their implementation has aided drug development in pharmaceutical companies will be reviewed. Advances in formulation and considerations on the intended use of a therapeutic antibody, including the route of administration and patient compliance, will be discussed.Acetaminophen, a central antipyretic and analgesic drug, is one of the most commonly used drugs among individuals of all ages throughout the world. This study pharmacokinetically and pharmacodynamically investigated the transport of acetaminophen to the central nervous system and systemic circulation after intranasal (i.n.) administration, and evaluated the potential of a transnasal acetaminophen formulation in comparison to other routes of administration. Direct transport to the brain and the pharmacological effect after the i.n. administration of acetaminophen with polyvinylpyrrolidone (PVP; a mucoadhesive agent) and poly-l-arginine (PLA; an absorption enhancer) were investigated to improve retention of the dosage solution in the olfactory epithelium region and enhance the transfer of acetaminophen to the brain. The transport of acetaminophen to the brain was rapid, and the concentration in the brain, especially the olfactory bulb, was higher after i.n. administration, resulting in a greater antipyretic effect in comparison to other routes of administration. The delivery system using PVP and PLA produced a high and prolonged antipyretic effect by enhancing the transfer of acetaminophen to the brain through suppression of the transfer to systemic circulation. Thus, this transnasal drug delivery system using PVP and PLA may be a promising method for transporting acetaminophen to the brain.In an attempt to optimize the anti- hyperlipidemic effect and reduce statins induced hepatotoxicity, Atorvastatin Calcium (ATC) transdermal proniosomal gel (PNG) was developed. Different non-ionic surfactants (NISs) (Spans, Tweens, Cremophor RH 40 and Brij 52) were incorporated in the vesicle's lipid bilayer, in combination with lecithin. PNG formulae were characterized for encapsulation efficiency percent (% EE), vesicle size, polydispersity index (PDI) and zeta potential (ZP). Ex-vivo permeation study was performed using full thickness rat skin measuring drug flux and skin permeability coefficients. The pharmacodynamic performance of optimized transdermal ATC- PNG on both lipid profile and liver biomarkers was assessed and compared to oral ATC administration in poloxamer 407-induced hyperlipidemic rats. https://www.selleckchem.com/products/pf-00835231.html The liver tissues were subjected to histological examination as well. The results revealed nano-size range vesicles with relatively high ATC entrapment efficiency. Ex-vivo results demonstrated the permeation superiority of ATC proniosomes over free drug.
Astrogliosis has a unique reaction during spinal cord damage, with helpful or adverse impacts on recovery. There is consequently a pressing need for treatment to target activated astrocytes and their unsafe response after injury to ensure some preservative effect during the progressive damage. We specifically developed and characterized a functionalized nanogel-based nanovector in vitro and in vivo, demonstrating its selectivity towards astrocytes, and limited uptake by macrophages when functionalized with both NH2 and Cy5 groups. In vitro experiments showed that the internalization was mediated by a clathrin-dependent endocytic pathway. After internalization into the cytoplasm of astrocytes, nanogels undergo lysosomal degradation and release compounds with potential therapeutic efficacy.New drugs are frequently found with poor water-solubility in recent pharmaceutical projects, which brings difficulties of bioavailability for the clinical development of new drugs. When these drug compounds in a crystalline state are absorbed by gastrointestinal tract, their dissolution rates and absorption rates are very limited. Nowadays, various methods have been developed to improve the solubility, dissolution and bioavailability of drugs. According to the characteristics of drugs, this work suggests the use of spray drying technology to amorphize APIs (active pharmaceutical ingredients) to improve their bioavailability. This work reviews the properties of the spray-dried amorphous drugs, the progress made in drug synthesis and application, and the existing problems.The purpose of this study was to optimize the melt granulation process of fenofibrate using twin-screw granulator. Initial screening was performed to select the excipients required for melt granulation process. A 3 × 3 factorial design was used to optimize the processing conditions using the % drug loading (X1) and screw speed (X2) as the independent parameters and granule friability (Y1) % yield (Y2) as the dependent parameters. The effect of the independent parameters on the dependent parameters was determined using response surface plots and contour plots. A linear relationship was observed between % drug loading (X1) and % friability (Y1) and a quadratic relationship was observed between the independent parameters (X1 and X2) and % yield (Y2). The processing conditions for optimum granules were determined using numerical and graphical optimization and it was found that 15% drug loading at 50 rpm results in maximum % yield of 82.38% and minimum friability of 7.88%. The solid-state characterization of the optimized granules showed that the drug turned from crystalline state to amorphous state during melt granulation process. The optimized granules were compressed into tablets using Purolite® as the super disintegrating agent. The optimized formulation showed >85% drug release in 0.75% SLS solution within 60 min.Therapeutic monoclonal antibodies and related products have steadily grown to become the dominant product class within the biopharmaceutical market. Production of antibodies requires special precautions to ensure safety and efficacy of the product. In particular, minimizing antibody product heterogeneity is crucial as drug substance variants may impair the activity, efficacy, safety, and pharmacokinetic properties of an antibody, consequently resulting in the failure of a product in pre-clinical and clinical development. This review will cover the manufacturing and formulation challenges and advances of therapeutic monoclonal antibodies, focusing on improved processes to minimize variants and ensure batch-to-batch consistency. Processes put in place by regulatory agencies, such as Quality-by-Design (QbD) and current Good Manufacturing Practices (cGMP), and how their implementation has aided drug development in pharmaceutical companies will be reviewed. Advances in formulation and considerations on the intended use of a therapeutic antibody, including the route of administration and patient compliance, will be discussed.Acetaminophen, a central antipyretic and analgesic drug, is one of the most commonly used drugs among individuals of all ages throughout the world. This study pharmacokinetically and pharmacodynamically investigated the transport of acetaminophen to the central nervous system and systemic circulation after intranasal (i.n.) administration, and evaluated the potential of a transnasal acetaminophen formulation in comparison to other routes of administration. Direct transport to the brain and the pharmacological effect after the i.n. administration of acetaminophen with polyvinylpyrrolidone (PVP; a mucoadhesive agent) and poly-l-arginine (PLA; an absorption enhancer) were investigated to improve retention of the dosage solution in the olfactory epithelium region and enhance the transfer of acetaminophen to the brain. The transport of acetaminophen to the brain was rapid, and the concentration in the brain, especially the olfactory bulb, was higher after i.n. administration, resulting in a greater antipyretic effect in comparison to other routes of administration. The delivery system using PVP and PLA produced a high and prolonged antipyretic effect by enhancing the transfer of acetaminophen to the brain through suppression of the transfer to systemic circulation. Thus, this transnasal drug delivery system using PVP and PLA may be a promising method for transporting acetaminophen to the brain.In an attempt to optimize the anti- hyperlipidemic effect and reduce statins induced hepatotoxicity, Atorvastatin Calcium (ATC) transdermal proniosomal gel (PNG) was developed. Different non-ionic surfactants (NISs) (Spans, Tweens, Cremophor RH 40 and Brij 52) were incorporated in the vesicle's lipid bilayer, in combination with lecithin. PNG formulae were characterized for encapsulation efficiency percent (% EE), vesicle size, polydispersity index (PDI) and zeta potential (ZP). Ex-vivo permeation study was performed using full thickness rat skin measuring drug flux and skin permeability coefficients. The pharmacodynamic performance of optimized transdermal ATC- PNG on both lipid profile and liver biomarkers was assessed and compared to oral ATC administration in poloxamer 407-induced hyperlipidemic rats. https://www.selleckchem.com/products/pf-00835231.html The liver tissues were subjected to histological examination as well. The results revealed nano-size range vesicles with relatively high ATC entrapment efficiency. Ex-vivo results demonstrated the permeation superiority of ATC proniosomes over free drug.
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