We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles(NPs). Surface-modified PLGA NPs w...We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles(NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan(CS) and glycol chitosan(GCS), which are mucoadhesive polymers, and polysorbate 80(P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells.Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal,non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.展开更多
We previously determined 'Tableting properties' by using a multi-functional single-punch tablet press(GTP-1). We proposed plotting 'Compactability' on the x-axis against'Manufacturability' on t...We previously determined 'Tableting properties' by using a multi-functional single-punch tablet press(GTP-1). We proposed plotting 'Compactability' on the x-axis against'Manufacturability' on the y-axis to allow visual evaluation of 'Tableting properties'. Various types of tableting failure occur in commercial drug production and are influenced by the amount of lubricant used and the shape of the punch. We used the GTP-1 to measure'Tableting properties' with different amounts of lubricant and compared the results with those of tableting on a commercial rotary tableting machine. Tablets compressed with a small amount of lubricant showed bad 'Manufacturability', leading to sticking of powder on punches.We also tested various punch shapes. The GTP-1 correctly predicted the actual tableting results for all punch shapes. With punches that were more likely to cause tableting failure, our system predicted the effects of lubricant quantity in the tablet formulation and the occurrence of sticking in the rotary tableting machine.展开更多
The purpose of this study was to design a submicron-sized liposomal non-steroidal antiinflammatory drug(NSAID)preparation that targets the retina via topical instillation of eye drops.Bromfenac(BRF)-loaded liposomes w...The purpose of this study was to design a submicron-sized liposomal non-steroidal antiinflammatory drug(NSAID)preparation that targets the retina via topical instillation of eye drops.Bromfenac(BRF)-loaded liposomes were prepared using the calcium acetate gradient method.Liposome sizes and encapsulation efficiencies were optimized by screening several liposome formulations of lipid,drug concentration,and buffer solution.BRF entrapment efficiency was greater than 90%using this method,and was low using conventional hydration methods.High initial BRF loading using the pH gradient method caused aggregation of liposomes.To circumvent aggregation,the negatively charged lipid dicetylphosphate was incorporated into liposomes,which formed anion layer preventing coalescence.Release of BRF from liposomes was sustained for several hours depending on lipid concentration,inner water phase,initial drug amounts,and surface properties.Surface modification with chitosan(CS),a mucoadhesive cationic polymer,was achieved using electrostatic interactions of negatively charged liposomes.The optimal concentration of CS for evasion of liposome aggregation was 0.15%.展开更多
The leading causes of vision impairment and blindness are posterior segment-related diseases including age-related macular degeneration,diabetic macular edema and endophthalmitis.Recently,pharmaceutical approaches to ...The leading causes of vision impairment and blindness are posterior segment-related diseases including age-related macular degeneration,diabetic macular edema and endophthalmitis.Recently,pharmaceutical approaches to these diseases have used steroids and oligonucleotides.These drugs are usually administered via invasive injection because noninvasive delivery method such as eye drop administration of drugs is not available.However,repeated injections are associated with potential risks of complications.Moreover,patients may not comply with such regimens.展开更多
We previously determined "Tableting properties" by using a multi-functional single-punch tablet press(GTP-1). We plotted "Compactability" on the x-axis against "Manufacturability"on the y...We previously determined "Tableting properties" by using a multi-functional single-punch tablet press(GTP-1). We plotted "Compactability" on the x-axis against "Manufacturability"on the y-axis to allow visual evaluation of "Tableting properties". Here, we examined whether this evaluation method can be used in the formulation design of tablets prepared by wet granulation. We used the GTP-1 to measure "Tableting properties" with different amounts of binder, disintegrant, and lubricant, and compared the results with those of tableting on a commercial rotary tableting machine. Tableting failures(capping and binding in particular) occurred when samples that had been evaluated as having poor "Compactability" or"Manufacturability" on the GTP-1 were compressed on the rotary tableting machine. Thus,our evaluation method predicted tableting failure at the commercial scale. The method will prove useful for scaling up production.展开更多
Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design do...Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design dosage forms to complete effective drug delivery.A variety of investigations have been carried out toward the design of an optimal particulate system.展开更多
The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug deliv...The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug delivery systems,because such carriers could control drug release and selective drug targeting when the carriers reach the target site in the lung.The prevention of local irritation,reduced drug toxicity,and improved drug stability are also preferable results of utilizing such carrier systems.Among a number of particulate carriers,liposomes have an advantage in safety,because they consist of phospholipids,which are bio-components.展开更多
Oral bioavailability of drug is limited by the factors such as the membrane permeability, the solubility, the dissolution rate and so on (1)In case of a poorly water-soluble drug, its solubility and dissolution rate i...Oral bioavailability of drug is limited by the factors such as the membrane permeability, the solubility, the dissolution rate and so on (1)In case of a poorly water-soluble drug, its solubility and dissolution rate is a critical factor for its oral bioavailability.Among various techniques for enhancing solubility or dissolution properties, physical modification of drug products such as reducing the particle size is one of common approaches [2].展开更多
基金supported by JSPS KAKENHI Grant Number JP16K18948
文摘We investigated the delivery of drugs to the posterior segment of the eye by non-invasive topical instillation using submicron-sized poly(D,L-lactide-co-glycolide)(PLGA) nanoparticles(NPs). Surface-modified PLGA NPs were developed to improve the drug delivery efficiency to the retina and were administered as topical eye drops to mice. Chitosan(CS) and glycol chitosan(GCS), which are mucoadhesive polymers, and polysorbate 80(P80) were used as surface modifiers, and have been reported to increase the association of NPs with cells.Coumarin-6 was used as a model drug and fluorescent marker, and after ocular administration of PLGA NP eye drops, the fluorescence intensity of coumarin-6 was observed in the retina. The fluorescence image analysis indicated that there are several possible routes to the retina and fates of PLGA NPs in ocular tissue, and that these pathways involved the corneal,non-corneal, or uveal routes. Delivery to the mouse retina segments after topical administration was increased by surface modification with CS, GCS, or P80. Surface-modified PLGA NPs are a promising method for retinal drug delivery via topical instillation.
文摘We previously determined 'Tableting properties' by using a multi-functional single-punch tablet press(GTP-1). We proposed plotting 'Compactability' on the x-axis against'Manufacturability' on the y-axis to allow visual evaluation of 'Tableting properties'. Various types of tableting failure occur in commercial drug production and are influenced by the amount of lubricant used and the shape of the punch. We used the GTP-1 to measure'Tableting properties' with different amounts of lubricant and compared the results with those of tableting on a commercial rotary tableting machine. Tablets compressed with a small amount of lubricant showed bad 'Manufacturability', leading to sticking of powder on punches.We also tested various punch shapes. The GTP-1 correctly predicted the actual tableting results for all punch shapes. With punches that were more likely to cause tableting failure, our system predicted the effects of lubricant quantity in the tablet formulation and the occurrence of sticking in the rotary tableting machine.
文摘The purpose of this study was to design a submicron-sized liposomal non-steroidal antiinflammatory drug(NSAID)preparation that targets the retina via topical instillation of eye drops.Bromfenac(BRF)-loaded liposomes were prepared using the calcium acetate gradient method.Liposome sizes and encapsulation efficiencies were optimized by screening several liposome formulations of lipid,drug concentration,and buffer solution.BRF entrapment efficiency was greater than 90%using this method,and was low using conventional hydration methods.High initial BRF loading using the pH gradient method caused aggregation of liposomes.To circumvent aggregation,the negatively charged lipid dicetylphosphate was incorporated into liposomes,which formed anion layer preventing coalescence.Release of BRF from liposomes was sustained for several hours depending on lipid concentration,inner water phase,initial drug amounts,and surface properties.Surface modification with chitosan(CS),a mucoadhesive cationic polymer,was achieved using electrostatic interactions of negatively charged liposomes.The optimal concentration of CS for evasion of liposome aggregation was 0.15%.
文摘The leading causes of vision impairment and blindness are posterior segment-related diseases including age-related macular degeneration,diabetic macular edema and endophthalmitis.Recently,pharmaceutical approaches to these diseases have used steroids and oligonucleotides.These drugs are usually administered via invasive injection because noninvasive delivery method such as eye drop administration of drugs is not available.However,repeated injections are associated with potential risks of complications.Moreover,patients may not comply with such regimens.
文摘We previously determined "Tableting properties" by using a multi-functional single-punch tablet press(GTP-1). We plotted "Compactability" on the x-axis against "Manufacturability"on the y-axis to allow visual evaluation of "Tableting properties". Here, we examined whether this evaluation method can be used in the formulation design of tablets prepared by wet granulation. We used the GTP-1 to measure "Tableting properties" with different amounts of binder, disintegrant, and lubricant, and compared the results with those of tableting on a commercial rotary tableting machine. Tableting failures(capping and binding in particular) occurred when samples that had been evaluated as having poor "Compactability" or"Manufacturability" on the GTP-1 were compressed on the rotary tableting machine. Thus,our evaluation method predicted tableting failure at the commercial scale. The method will prove useful for scaling up production.
文摘Colloidal drug carriers such as liposomes,lipid emulsions,and polymeric nanoparticles have great potential to deliver drugs effectively.Preparation of nano-crystals of API has also received much attention to design dosage forms to complete effective drug delivery.A variety of investigations have been carried out toward the design of an optimal particulate system.
文摘The pulmonary route presents several advantages in designing drug delivery systems in both systemic and topical administration.The use of particulate carriers is an attractive method for designing pulmonary drug delivery systems,because such carriers could control drug release and selective drug targeting when the carriers reach the target site in the lung.The prevention of local irritation,reduced drug toxicity,and improved drug stability are also preferable results of utilizing such carrier systems.Among a number of particulate carriers,liposomes have an advantage in safety,because they consist of phospholipids,which are bio-components.
文摘Oral bioavailability of drug is limited by the factors such as the membrane permeability, the solubility, the dissolution rate and so on (1)In case of a poorly water-soluble drug, its solubility and dissolution rate is a critical factor for its oral bioavailability.Among various techniques for enhancing solubility or dissolution properties, physical modification of drug products such as reducing the particle size is one of common approaches [2].
