Preparation of sustained-release coated particles by novel microencapsulation method using three-fluid nozzle spray drying technique.

We prepared sustained-release microcapsules using a three-fluid nozzle (3N) spray drying technique. The 3N has a unique, three-layered concentric structure composed of inner and outer liquid nozzles, and an outermost gas nozzle. Composite particles were prepared by spraying a drug suspension and an ethylcellulose solution via the inner and outer nozzles, respectively, and mixed at the nozzle tip (3N-PostMix).

Design of self-dispersible dry nanosuspension through wet milling and spray freeze-drying for poorly water-soluble drugs.

The purpose of the present research is to establish a novel nanosizing technique starting from wet nano-milling, named "dry nanosuspension" technique for poorly water-soluble drugs. The spray freeze-drying (SFD) method was applied instead of the spray-drying one previously developed. Drug particles were milled in the aqueous solution of dispersing agents using an oscillating beads-milling apparatus.

Design of sustained release fine particles using two-step mechanical powder processing: particle shape modification of drug crystals and dry particle coating with polymer nanoparticle agglomerate.

We attempted to prepare sustained release fine particles using a two-step mechanical powder processing method; particle-shape modification and dry particle coating. First, particle shape of bulk drug was modified by mechanical treatment to yield drug crystals suitable for the coating process. Drug crystals became more rounded with increasing rotation speed, which demonstrates that powerful mechanical stress yields spherical drug crystals with narrow size distribution.

[Effect of concomitant use of dental drug on the properties of recombinant human basic fibroblast growth factor formulation for periodontal disease].

We have discussed the essential property for periodontal disease medication using protein, such as recombinant human basic fibroblast growth factor (rhbFGF). In our previous study, the criteria of thickener for the medication, viscosity, flowability etc., were set.

[Effect of crystalline metastasis of lactose on hardness of compressed baby milk powder].

The purpose of this study was to examine the relationship between the crystalline metastasis of lactose, which is a main component baby milk powder, and the hardness of baby milk powder compressed by humidification followed by drying. Because baby milk powder is manufactured using a spray dryer, lactose in compressed baby milk powder exists in an amorphous (solid dispersion) form. X-ray diffraction measurement showed that this amorphous lactose metastasized to β-form crystalline lactose, and thereafter metastasized to the α-form during the humidification-drying process.

Evaluation of disintegration properties of orally rapidly disintegrating tablets using a novel disintegration tester.

This report describes a new disintegration tester that can determine not only the disintegration time of orally rapidly disintegrating tablets (ODT), but also the disintegration behavior and mechanism. Using the tester, the disintegration properties of the tablets prepared in a previous study were examined. The purpose of this study is to confirm the utility of the tester as an instrument for evaluating the disintegration properties of ODT and determine relations among time, behavior and mechanism of the disintegration.

Investigation of surfactants suitable for stabilizing of latanoprost.

The content of latanoprost, a therapeutic drug for glaucoma, is likely to decrease in solution. In a previous study, we confirmed that this was associated with latanoprost adsorption to the container and hydrolysis of latanoprost, and established a formulation of latanoprost eye drop solution that can be stored at room temperature. In addition, we clarified that a surfactant added to the formulation stabilized latanoprost by forming complex micelle.

Spray freeze-dried porous microparticles of a poorly water-soluble drug for respiratory delivery.

Particles of poorly water-soluble drugs were prepared to develop a dry powder inhaler (DPI). Spray freeze-drying (SFD) technique using a four-fluid nozzle (4N), which has been developed by authors, was applied in this research. Ciclosporin and mannitol were used as a poorly water-soluble model drug and a dissolution-enhanced carrier, respectively.

Novel ultra-cryo milling and co-grinding technique in liquid nitrogen to produce dissolution-enhanced nanoparticles for poorly water-soluble drugs.

A novel ultra-cryo milling micronization technique for pharmaceutical powders using liquid nitrogen (LN2 milling) was used to grind phenytoin, a poorly water-soluble drug, to improve its dissolution rate. LN2 milling produced particles that were much finer and more uniform in size and shape than particles produced by jet milling. However, the dissolution rate of LN2-milled phenytoin was the same as that of unground phenytoin due to agglomeration of the submicron particles.

Development of a novel ultra cryo-milling technique for a poorly water-soluble drug using dry ice beads and liquid nitrogen.

A novel ultra cryo-milling micronization technique has been established using dry ice beads and liquid nitrogen (LN2). Drug particles were co-suspended with dry ice beads in LN2 and ground by stirring. Dry ice beads were prepared by storing dry ice pellets in LN2.

Development of formulation device for periodontal disease.

In addition to providing standard surgical treatment that removes the plaque and infected tissues, medications that can regenerate periodontal tissue are also required in the treatment of periodontal disease. As a form of regenerative medication, various growth factors are expected to be used while treating periodontal disease. A protein-like growth factor is often developed as a lyophilized product with dissolution liquid, considering its instability in the solution state.

[Making tablets of powdered milk and the physical properties].

Compressed baby milk powder has proven to be very convenient for parents due to the ease with which it can be handled, and the fact that use of a measuring scoop is not necessary. The purpose of this study was to develop a compressed baby milk powder and analyze the resulting physical properties. The basic production process consisted of the following steps: 1) molding milk powder by low compression pressure, 2) humidification at 25°C·97%RH and 3) drying with use of a desiccant.

Preparation and evaluation of orally rapidly disintegrating tablets containing taste-masked particles using one-step dry-coated tablets technology.

In this study, in order to address the problems with manufacturing orally rapidly disintegrating tablets (ODT) containing functional (taste masking or controlled release) coated particles, such as the low compactability of coated particles and the rupture of coated membrane during compression, a novel ODT containing taste-masked coated particles (TMP) in the center of the tablets were prepared using one-step dry-coated tablets (OSDrC) technology. As a reference, physical-mixture tablets (PM) were prepared by a conventional tableting method, and the properties of the tablets and the effect of compression on the characteristics of TMP were evaluated. OSDrC was found to have higher tensile strength and far lower friability than PM, but the oral disintegration time of OSDrC is slightly longer than that of PM following high compression pressure.

Sugar ester J-1216 enhances percutaneous permeation of ionized lidocaine.

Percutaneous absorption enhancers affect not only the permeability of skin but also the thermodynamic properties of active ingredients in the vehicle. The present study examined the effect of J-1216, a sucrose laurate with hydrophilic-lipophilic balance = 16, on the percutaneous permeation of lidocaine (LC) from this point of view. The percutaneous permeation of LC from aqueous vehicles (pH 6.

Design of dry nanosuspension with highly spontaneous dispersible characteristics to develop solubilized formulation for poorly water-soluble drugs.

Purpose: The powderization of the aqueous nanosuspension of a poorly water-soluble drug, which was prepared by wet-milling technique developed by authors, was investigated to apply to the development of solid dosage forms.

Methods: Drug particles were suspended and milled in the aqueous medium using the oscillating beads-milling apparatus. The recovered nanosuspension was spray-dried 1) with no additive or 2) with co-dissolving mannitol as a nanoparticle carrier.

[Dissolution characteristics of composite particles using a spray freeze drying].

A spray freeze drying (SFD) method, using a spray nozzle, liquid N(2) and a lyophilizer, was developed to prepare composite particles of a poorly water-soluble drug. The resultant particles were found to have a porous structure. The purpose of the present research was to prepare a sustained release formulation using the SFD technique.

[Influence of compression pressure and die-wall pressure on tablet sticking].

An eccentric-type tablet machine fitted with 8-mm-diameter flat-faced punches was used to measure the forces of upper and lower punches, die-wall pressure, tablet ejection force, and scraper pressure (SCR), a type of shear stress, to evaluate sticking behavior. The shear stress between the surfaces of the tablet and lower punch was determined using an SCR detection system. Mean surface roughness (R(a)) of tablets, measured by laser scanning microscopy, was used to estimate the magnitude of sticking.

The stabilization mechanism of latanoprost.

The content of latanoprost is likely to decrease in solution because of the adsorption to eye drop containers and hydrolysis. We reduced these problems and established a formulation of latanoprost eye drops which is stable at room temperature. We assume that the additive surfactants form micelles and stabilize latanoprost in this formulation.

Chitosan-interferon-β gene complex powder for inhalation treatment of lung metastasis in mice.

We prepared gene powders with chitosan as a non-viral vector and mannitol as a dry powder carrier to compare their gene expression and therapeutic efficacy to intravenous or intratracheal gene solutions using mice burdened with pulmonary metastasis prepared by injecting CT26 cells. The expression of a luciferase expression plasmid driven by the cytomegalovirus promoter (pCMV-Luc) and plasmid DNA encoding farnesylated enhanced green fluorescent protein (pEGFP-F) suggested that the genes expressed in both normal and tumorous tissues and the intratracheal powder resulted in higher expression than the intravenous or intratracheal solution. The intravenous and intratracheal solutions and the intratracheal powder of pCMV-Muβ encoding murine interferon-β were administered the day after the inoculation of mice with CT26 cells.

Universal wet-milling technique to prepare oral nanosuspension focused on discovery and preclinical animal studies - Development of particle design method.

Simple and easy methods to prepare oral nanosuspension of a poorly water-soluble pharmaceutical candidate compound, called a candidate, have been developed to support the discovery and preclinical studies using animals. The different wet-milling processes in miniature, middle and large preparation scales have been established in order to cover the various types of studies with wide scale. The powder of phenytoin, a poorly water-soluble model drug candidate, was suspended in the aqueous medium, in which the appropriate dispersing agents were dissolved, and milled by agitating together with small hard beads made of zirconia.

Evaluation of additives required for periodontal disease formulation using basic fibroblast growth factor.

To design a suitable periodontal disease formulation using basic fibroblast growth factor (bFGF), legally available thickeners were evaluated focusing on their viscosity, extrusive force from a syringe, flow property and inertness to bFGF. Thirteen candidate thickeners showed appropriate viscosity (about 1×10⁴ mPa·s), and further evaluations were conducted on them. Flow property was evaluated by the tilting test tube method.

Influence of compression pressure and velocity on tablet sticking.

A rotary tablet machine fitted with 8-mm diameter flat-faced punches was used to measure scraper pressure (SCR), a type of shear stress, to evaluate sticking behavior. The shear stress between the surfaces of the tablet and lower punch was determined using an SCR detection system. Mean surface roughness (R(a)) of tablets, measured by a scanning laser-microscope, was used to estimate the magnitude of sticking.

One-step preparation of pharmaceutical nanocrystals using ultra cryo-milling technique in liquid nitrogen.

A novel micronization technique for pharmaceutical powders has been established using liquid nitrogen (LN2). Different from the conventional dry milling while cooling the milling pot by LN2, the materials were directly suspended in LN2 together with hard small spherical balls, called beads, and broken down by agitating intensively. The present beads milling in LN2 was named "ultra cryo-milling" in this paper.

Optimized pulmonary gene transfection in mice by spray-freeze dried powder inhalation.

Spray-freeze drying (SFD) is an attractive technique to prepare highly porous dry powders for inhalation. However, there have been few reports of its application to dry powder inhalers (DPIs). Therefore, in this study, we prepared dry plasmid DNA (pDNA) powders with different molecular ratios of chitosan to pDNA (N/P ratios) by SFD.

Novel spray freeze-drying technique using four-fluid nozzle-development of organic solvent system to expand its application to poorly water soluble drugs.

Spray freeze-drying (SFD) technique using four-fluid nozzle (4N), which is a novel particle design technique previously developed by authors, has been further developed to expand its application in pharmaceutical industry. The organic solvent was utilized as a spray solvent to dissolve the poorly soluble drug instead of conventional aqueous solution. Acetonitrile solution of the drug and aqueous solution of the polymeric carrier were separately and simultaneously atomized through 4N, and collided each other at the tip of nozzle edge.