Biomedical subjects

Hiromitsu Yamamoto

Publications and source records attributed to Hiromitsu Yamamoto.

36 records · Page 2Linked to original sources

PubMed2004

Die wall pressure measurement for evaluation of compaction property of pharmaceutical materials.

The aim of this study was to evaluate the compaction property of several pharmaceutical materials by measuring the die wall pressure. The profile of die wall force during tabletting process was measured with the compaction process analyzer (TabAll). Several compaction parameters such as maximum die wall pressure (MDP), residual die wall pressure (RDP) and pressure transmission ratio (PTR) from upper punch to lower punch were calculated. The ejection pressure (EP) of tablet compacted was also measured as a parameter for sticking property of the compacts. The profile of die wall force observed was classified to the typical two types, a small type and a large one. Partly pre-gelatinized starch (PCS), cornstarch and low substituted hydroxypropylcellulose (L-HPC) were the small type, while crystalline lactose, ascorbic acid and potassium chloride were the large type. The die wall force of crystalline lactose remarkably increased at the ejection of tablet and then capping was observed. RDP value of PCS, cornstarch, L-HPC was smaller than that of crystalline lactose, ascorbic acid, potassium chloride. As the higher pressure transmission ratio from upper punch to lower punch means a good compressing property of the powder, we proposed that RDP/MDP is a useful parameter for evaluating the compaction property of powders. Although potassium chloride which is strongly plastic deformable powder showed the highest RDP value among the powders tested, the RDP/MDP value was lower than that of crystalline lactose or ascorbic acid and the tensile strength of resultant tablet of potassium chloride was much higher than these powders.

Compressive Strength↗

PubMed2004

Runx2 and Runx3 are essential for chondrocyte maturation, and Runx2 regulates limb growth through induction of Indian hedgehog.

The differentiation of mesenchymal cells into chondrocytes and chondrocyte proliferation and maturation are fundamental steps in skeletal development. Runx2 is essential for osteoblast differentiation and is involved in chondrocyte maturation. Although chondrocyte maturation is delayed in Runx2-deficient (Runx2(-/-)) mice, terminal differentiation of chondrocytes does occur, indicating that additional factors are involved in chondrocyte maturation. We investigated the involvement of Runx3 in chondrocyte differentiation by generating Runx2-and-Runx3-deficient (Runx2(-/-)3(-/-)) mice. We found that chondrocyte differentiation was inhibited depending on the dosages of Runx2 and Runx3, and Runx2(-/-)3(-/-) mice showed a complete absence of chondrocyte maturation. Further, the length of the limbs was reduced depending on the dosages of Runx2 and Runx3, due to reduced and disorganized chondrocyte proliferation and reduced cell size in the diaphyses. Runx2(-/-)3(-/-) mice did not express Ihh, which regulates chondrocyte proliferation and maturation. Adenoviral introduction of Runx2 in Runx2(-/-) chondrocyte cultures strongly induced Ihh expression. Moreover, Runx2 directly bound to the promoter region of the Ihh gene and strongly induced expression of the reporter gene driven by the Ihh promoter. These findings demonstrate that Runx2 and Runx3 are essential for chondrocyte maturation and that Runx2 regulates limb growth by organizing chondrocyte maturation and proliferation through the induction of Ihh expression.

Animals↗

PubMed2004

Pharmacokinetic and immunosuppressive effects of tacrolimus-loaded biodegradable microspheres.

The objective of this study was to characterize the pharmacokinetics and immunosuppression of a tacrolimus-loaded biodegradable microsphere (TLBM) in rats. We prepared TLBM. DA/Slc rats were given TLBM at a dose of 1.6 mg/kg (n = 9), 2.4 mg/kg (n = 5), or 7.2 mg/kg (n = 7) tacrolimus contents by a single subcutaneous administration to achieve sustained release over a long period. DA/Slc rats were given TLBM by a single subcutaneous administration at a dose of 4.8 mg/kg (n = 6) tacrolimus contents to clarify the main site of TLBM uptake in the organs. In the rat liver transplantation model, the recipients were given TLBM at a dose of 0.16 mg/kg (n = 5), 2.4 mg/kg (n = 4), or 4.8 mg/kg (n = 5) tacrolimus contents by a single subcutaneous administration on the first day after operation. Overall survival days were compared. Continuous flat parallel concentration profiles were significant for 10 days from the first day after a single subcutaneous administration of TLBM (P <.01). The relationship between the dosages of TLBM administration and area under the concentration-time curve (AUC) up to 18 days demonstrated a linear regression line (P <.01). In addition, the relationship between the dose of TLBM and the survival days of the recipients in the liver transplantation model showed a positive correlation. The current pharmacokinetic study of TLBM revealed significantly increased tacrolimus levels in the regional lymph nodes compared with other organs except bone marrow (P <.01). In conclusion, TLBM allowed tacrolimus to release gradually in a very stable manner for 10 days, with dose-dependent immunosuppression after a single subcutaneous administration. The main site of TLBM uptake after subcutaneous administration was the regional lymph node of administration site.

Animals↗

PubMed2004

Design of pH-sensitive microspheres for the colonic delivery of the immunosuppressive drug tacrolimus.

Recently, tacrolimus was shown to be effective in mitigating inflammatory bowel disease (IBD). In the treatment of IBD, oral drug delivery using pH-dependent polymers is one of the most successful therapeutic strategies. Eudragit P-4135F, a pH-sensitive polymer for colonic delivery was used to prepare tacrolimus microparticles using an oil/oil emulsification or an oil/water emulsification technique combined with a solvent extraction or evaporation step. Although the pH-dependent drug release was similar for all types of microspheres, it was generally found that encapsulation rates of oil/water systems (extraction 38.8 +/- 9.4%; evaporation 56.3 +/- 1.9%) were superior to the oil/oil emulsification (4.8 +/- 0.4%). Eudragit P-4135F was found to limit drug leakage at pH 6.8 to levels lower than 10% within 6 h. At pH 7.4, almost immediate release (within 30 min) was observed. From differential scanning calorimetry and X-ray analyses, the drug inside the polymeric microsphere matrix was concluded to be present in a molecular dispersion. Generally, all formulations proved their applicability in vitro as a promising device for pH-dependent colonic delivery of tacrolimus, however, the oil/water technique was found to be superior to the oil/oil approach and among them solvent evaporation seemed to be more advisable, due to the higher encapsulation rate.

Colon↗

PubMed2004

In vitro evaluation of floating and drug releasing behaviors of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method.

Hollow microspheres (microballoons) floatable in JPX III No.1 solution were developed as a dosage form characterized by excellent buoyant properties in the stomach. Microballoons were prepared by the emulsion solvent diffusion method utilizing enteric acrylic polymers codissolved with drug in a mixture of dichloromethane and ethanol. The release properties of five different drugs exhibiting distinct water solubilities (aspirin, salicylic acid, ethoxybenzamide, indomethacin and riboflavin) entrapped within microballoons were investigated. Buoyancy of the microballoons decreased with increasing drug release rate. In the case of aspirin, salicylic acid and ethoxybenzamide, the drug release profiles of microballoons proved a linear relationships by Higuchi plotting. However, indomethacin and riboflavin release profiles did not follow the Higuchi equation. When the loading amount of riboflavin was higher than the solubility in the mixture of dichloromethane and ethanol, the drug release profiles of the microballoons displayed an initial burst release. The insoluble riboflavin in the mixture of dichloromethane and ethanol adsorbed on to the microballoon surface in the crystal state. Such riboflavin crystals were released preferentially at the initial stage of the release test, which was attributable to the initial burst. In addition, by incorporating a polymer such as hydroxypropylmethylcellulose within the shell of microballoons, the release rate of riboflavin from the microballoons could be controlled while maintaining high buoyancy.

Drug Evaluation, Preclinical↗

PubMed2004

A novel evaluation method of gastric mucoadhesive property in vitro and the mucoadhesive mechanism of tetracycline-sucralfate acidic complex for eradication of Helicobacter pylori.

PURPOSE: The gastric mucoadhesive property of tetracycline-sucralfate acidic complex (CO) was evaluated by using a novel method in vitro to compare with the in vivo test. The mucoadhesive mechanism of the acidic complex was also studied. METHODS: The gastric mucosa removed from a rat was placed covering the end of a plunger and secured in a disposable syringe. The acidic test medium was gradually infused in and then flowed out. Two different kinds of CO, tetracycline, or a physical mixture (PM) were introduced into the device to compare their mucoadhesive properties. The tetracycline content in the residue on the mucosa was measured. The results were compared with those of the in vivo test. The acidic response of CO and the protein binding capacity of a sucrose octasulfate group (SOS) in sucralfate or CO were evaluated. RESULTS: The mucoadhesive properties of CO were clearly superior to those of PM. The remaining amounts of tetracycline in each test sample, determined by the in vitro test, were in agreement with those of the in vivo test. The excellent mucoadhesive property of CO appeared to be caused by the rapid response to the acid and resulting mucoadhesive gel formation. Furthermore, the binding capacity of SOS to the protein was clearly greater than that of PM. The excessive acid treatment during the preparation of CO tended to decrease the mucoadhesive property. CONCLUSIONS: CO appeared to be potentially useful for the eradication of Helicobacter pylori because of the direct delivery of tetracycline to the gastric mucosa for an extended period of time.

Animals↗

PubMed2004

The acidic complexation of tetracycline with sucralfate for its mucoadhesive preparation.

The complex of antibiotics with sucralfate (SF) was prepared with acid. The mechanism of the complexation and some factors concerning the preparation, which influence the mucoadhering property, were studied. The complexation was confirmed by the change in color and instrumental analysis. The acidic complex appeared to be produced by reagglomeration of SF preliminary particles. It was suggested that the amide or amine groups of tetracycline (TC) and aluminum moieties of SF serve as the binding sites. The potential of multiple binding sites and a priority in them were suggested by the Scatchard plot analysis. The additional amounts of acid and the increase in the surface area increased the number of sites. The amount of the additional acid appeared to be the most important factor during the preparation of the acidic complex. The appropriate amount of acid added appeared to produce a complex rich in TC. However, an excess amount might cause the excess dissociation of aluminum moieties, which destroys the mucoadhesive paste-forming property.

Acids↗

PubMed2004

Biodegradable microsphere-loaded tacrolimus enhanced the effect on mice islet allograft and reduced the adverse effect on insulin secretion.

The adverse effects of tacrolimus have limited the use of this potent immunosuppressive drug in clinical transplantation. To improve the therapeutic effects, we developed a new type of tacrolimus with biodegradable microsphere technology and examined the immunosuppressive effects on allogeneic islet transplantation and the side-effects on insulin secretion in vivo. With a single subcutaneous injection, mouse blood concentrations of tacrolimus (M-FK) carried in biodegradable microspheres remained flat for 2 weeks (only 10 h for conventional tacrolimus). A single subcutaneous administration of 20 mg/kg of M-FK significantly prolonged the survival of islet allografts (MST = 28 days) compared with the control group (MST = 10 days). Series administration of 10 mg/kg of M-FK at 7-day intervals markedly prolonged the survival of islet grafts, and resulted in 60% allograft acceptance. In mice with syngeneic islet transplantations, a single administration of 30 mg/kg of tacrolimus inhibited insulin secretion, whereas a single administration of an equal dosage of M-FK did not. The results suggested that M-FK enhanced the immunosuppressive effects on islet allograft rejection more effectively with reduced side-effects on insulin secretion.

Animals↗

PubMed2004

[Comparison of analgesics used during balanced anesthesia on the incidence of PONV].

BACKGROUND: When we make reference to the quality of anesthesia, we consider three points, early emergence, postoperative pain relief, and postoperative nausea and vomiting (PONV). Among these, PONV is comparatively neglected. Many analgesics used during anesthesia may cause PONV. METHODS: The incidence of PONV was assessed in 100 surgical patients who had received balanced anesthesia. Anesthesia was induced with propofol, ketamine, midazolam and buprenorphine (Group P), or butorphanol (Group T), and vecuronium was given to facilitate tracheal intubation. The patients received balanced anesthesia with infusion of propofol, ketamine, vecuronium, and either buprenorphine (Group P) or butorphanol (Group T), with nitrous oxide. PONV was recorded for 24 hours postoperatively. RESULTS: Incidences of nausea were 27.1% in Group P and 15.8% in Group T (NS). Incidences of vomiting were 12.5% in Group P and 5.3% in Group T (NS). However, a high incidence of PONV was found in female (42.2%) vs. male (6.2%) (P < 0.01) and in over 25 BMI group (34.5%) vs. under 25 BMI group (15.5%) (P < 0.05). CONCLUSIONS: The type of analgesics used during balanced anesthesia is not important for development of PONV, but patient's factors, such as gender and BMI, are more closely associated with PONV.

Aged↗

PubMed2003

In vivo evaluation of riboflavin-containing microballoons for floating controlled drug delivery system in healthy human volunteers.

Hollow microspheres (microballoons) floatable in JPXIII no. 1 solution were developed as a floating controlled drug delivery system. Microballoons (MB) were prepared by the emulsion solvent diffusion method utilizing enteric acrylic polymers dissolved in a mixture of dichloromethane and ethanol. To assess the usefulness of the intragastric floating properties of MB in sustained pharmacological action, nonfloating microspheres (NF) possessing riboflavin release profiles equivalent to those of MB were prepared. Riboflavin powder, riboflavin-containing MB, and riboflavin-containing NF were administrated orally to each of three healthy volunteers. Riboflavin pharmacokinetics was investigated via analysis of urinary excretion of riboflavin. As a result, although urinary excretion of riboflavin following administration of MB was not sustained in the fasted state, urinary excretion of MB was significantly sustained in comparison to riboflavin powder and NF in the fed condition. Additionally, the excretion half-life time (t(1/2)) of MB was prolonged significantly by feeding. Furthermore, MB provided significantly high total urinary excretion (%) of riboflavin compared to NF in the fasted and the fed conditions. In view of the finding regarding similar riboflavin release profiles of MB and NF in JP XIII no. 1 solution (pH 1.2) and no. 2 solution (pH 6.8), the intragastric floating properties of MB appeared to be beneficial with respect to sustained pharmacological action.

Administration, Oral↗

PubMed2003

Microsphere design for the colonic delivery of 5-fluorouracil.

The treatment of colon cancer has been aimed by approaches of oral drug administration. 5-Fluorouracil is the standard treatment still nowadays and would be a candidate to be delivered orally to the colon. A pH-sensitive polymer Eudragit P-4135F was used to prepare microspheres by a simple oil/water emulsification process. Process parameters were analyzed in order to optimize the drug loading and release profiles. In further attempts mixtures with Eudragit RS100 were prepared to prolong drug release. Scanning electron microscopy and confocal laser scanning microscopy permitted a structural analysis. The solvent extraction was preferable over solvent evaporation with a view to the encapsulation rate (extraction: 37%; evaporation: 19%) due to the hydrophilic character of the drug while release pattern were nearly unchanged. Eudragit P-4135F, pure or in mixture, was found to retain drug release at pH 6.8 lower than 35% within 6 h. At pH 7.4, nearly immediate release (within 30 min) was observed for pure P-4135F, while mixtures enabled to prolong the release slightly. Analysis of the morphology led to an inhomogeneous polymer distribution of P-4135F and RS100 throughout the particle core. A capsule-like structure was concluded which allowed only slight changes of the release kinetics by the addition of RS100. However, the formulation proved its applicability in-vitro as a promising device for pH-dependent colon delivery of 5-fluorouracil.

Acrylic Resins↗

PubMed2003

A new agglomerated KSR-592 beta-form crystal system for dry powder inhalation formulation to improve inhalation performance in vitro and in vivo.

A new agglomerated KSR-592 (steroid) beta-form needle-like crystals with lactose system for dry powder inhalation (DPI) was developed to improve inhalation performance with Jethaler. The drug agglomerates were prepared by the method of spherical agglomeration in liquid so as to control the particle size and the mechanical strength of agglomerates by changing the agitation speed of the agglomeration system. The agglomerates mixed with lactose particles for the DPI formulation were effectively disintegrated into respirable fine particle in the milling chamber of the device (Jethaler) when inhaled. The DPI formulation with these agglomerates exhibited ideal fluidity and provided a larger fine particle fraction (FPF: 29.7%) than the formulation with agglomerates consisting of alpha-form (plate-like) crystals (24.5%). The air-flow rate of inhalation had no effect on the disintegration properties of these agglomerates, suggesting a reliable inhalation performance in vivo. Further, an in vivo test of the aerosolized KSR-592 (beta-form) crystals having the same particle size distribution as those in the aerosol produced by Jethaler was conducted by means of a dry powder inhalation testing system using Brown Norway rats. Inhaled KSR-592 (beta-form) crystals were found to be uniformly deposited in the lungs of Brown Norway rat sensitized by ovalbumin (OA) and suppressed the increase in eosinophil number in the lungs after OA challenge.

Administration, Inhalation↗

PubMed2003

Physicochemical properties to determine the buoyancy of hollow microspheres (microballoons) prepared by the emulsion solvent diffusion method.

Hollow microspheres (microballoons) floatable on JPXIII No.1 solution were developed as a dosage form capable of floating in the stomach. Hollow microspheres were prepared by the emulsion solvent diffusion method using enteric acrylic polymers with drug in a mixture of dichloromethane and ethanol. It was found that preparation temperature determined the formation of cavity inside the microsphere and the surface smoothness, determining the floatability and the drug release rate of the microballoon. The correlation between the buoyancy of microballoons and their physical properties, e.g. apparent density and roundness of microballoons were elucidated. The drug loading efficiency of microballoons with various types of drug was investigated and correlated to the distribution coefficient of drug between dichloromethane and water. The optimum loading amount of riboflavin in the microballoon was found to impart ideal floatable properties to the microballoons. On the other hand, little entrapment was observed for aspirin due to the low distribution coefficient; however, entrapment improved to some extent upon reduction of the pH of the process.

Chemical Phenomena↗

PubMed2002

Causal relationship between the loss of RUNX3 expression and gastric cancer.

Runx3/Pebp2alphaC null mouse gastric mucosa exhibits hyperplasias due to stimulated proliferation and suppressed apoptosis in epithelial cells, and the cells are resistant to growth-inhibitory and apoptosis-inducing action of TGF-beta, indicating that Runx3 is a major growth regulator of gastric epithelial cells. Between 45% and 60% of human gastric cancer cells do not significantly express RUNX3 due to hemizygous deletion and hypermethylation of the RUNX3 promoter region. Tumorigenicity of human gastric cancer cell lines in nude mice was inversely related to their level of RUNX3 expression, and a mutation (R122C) occurring within the conserved Runt domain abolished the tumor-suppressive effect of RUNX3, suggesting that a lack of RUNX3 function is causally related to the genesis and progression of human gastric cancer.

Animals↗

PubMed2002

Transcardiac gradient of soluble adhesion molecules predicts progression of coronary artery disease.

BACKGROUND: During the development of atherosclerotic lesion, several types of cellular adhesion molecules (CAMs) are overexpressed on the surface of vascular endothelium. Some parts of these membrane proteins are proteolysed and are detected in blood as soluble forms. AIMS: The purpose of this study is to investigate the relationship between the transcardiac gradient of soluble cellular adhesion molecules (sCAMs) and the clinical characteristics of coronary artery disease (CAD). METHODS: We studied 46 patients with clinically stable CAD. Serum sCAM levels in both aortic sinus and coronary sinus were measured using enzyme-linked immunosorbent assay, and the transcardiac gradient of sCAMs was calculated. We also evaluated the angiographic severity of CAD, response of coronary artery to acetylcholine (Ach), as well as progression of coronary atherosclerosis over a 6-month period. RESULTS: The transcardiac gradient of sCAMs did not correlate to the angiographic severity of coronary atherosclerosis. The transcardiac gradient of sVCAM-1 was significantly higher in patients with vasoconstrictive response to Ach than patients without vasoconstrictive response to Ach (191.5+/-98.2 vs. -9.2+/-14.1 ng/ml, P<0.05). Furthermore, patients who exhibited progression of coronary atherosclerosis had a higher transcardiac gradient of sVCAM-1 at the initial study than patients without progression (47.8+/-24.5 vs. -6.4+/-12.3 ng/ml, P<0.05). CONCLUSIONS: An elevated transcardiac gradient of sVCAM-1 may represent the persistent activation of coronary artery that is accompanied by endothelial dysfunction, and may be a predictive index of progression of coronary atherosclerosis. Measurement of coronary circulating sVCAM-1 could provide important functional and predictive information about atherosclerosis.

Biomarkers↗

PubMed2002

Size-dependency of DL-lactide/glycolide copolymer particulates for intra-articular delivery system on phagocytosis in rat synovium.

PURPOSE: The present study evaluated the size-dependency of DL lactide/glycolide copolymer (PLGA) particulates for an intra articular delivery system on phagocytosis in the rat synovium after administering directly into the joint cavity. We also investigated the biocompatibility of PLGA particulate systems administered directly into the joint cavity of the rat. METHODS: Fluoresceinamine bound PLGA (FA-PLGA) nanospheres and microspheres were prepared by the modified emulsion solven diffusion method. The suspension of these particulate systems was administered into the rat-joint cavity and the biological action of the synovium was evaluated by histological inspection and fluorescence microscopy. RESULTS: A colloidal suspension of the FA-PLGA nanospheres, with a mean diameter of 265 nm, was phagocytosed in the synovium by the macrophages infiltrated through the synovial tissues. The phagocytosed nanospheres were delivered to the deep underlying tissues. An aqueous suspension of the FA-PLGA microspheres, with a mean diameter of 26.5 microm, was not phagocytosed in the macrophages. The macrophages slightly proliferated in the epithelial lining synovial-cells and the microspheres were covered with a granulation of multinucleated giant cells. The molecular weights of the polymer in these particulate systems were slowly reduced in the synovium. Localize inflammatory responses were almost undetected. CONCLUSIONS: PLGA nanospheres should be more suitable for delivery to inflamed synovial tissue than microspheres due to their ability to penetrate the synovium. PLGA particulate systems with biocompatibility in the joint can provide local-therapy action in joint disease in a different manner depending on the size of the system.

Animals↗

PubMed2002

Prolonged anti-inflammatory action of DL-lactide/glycolide copolymer nanospheres containing betamethasone sodium phosphate for an intra-articular delivery system in antigen-induced arthritic rabbit.

PURPOSE: The objective of the present study was to develop prolonged anti-inflammatory action of DL-lactide/glycolide copolymer (PLGA) nanosphere incorporating a water-soluble corticosteroid (betamethasone sodium phosphate; BSP). Another aim was to demonstrate the biocompatibility and biologic efficacy of these BSP-loaded nanospheres directly administered into ovalbumin-induced chronic synovitis in the rabbit. METHODS: BSP-loaded nanospheres were prepared by an emulsion solvent diffusion method in oil (caprylate and caprate triglyceride). The drug releasing properties of the nanospheres were measured in vitro in phosphate buffer saline (PBS: pH7.4), and in vivo in rat air-pouch (pseudo synovial fluid). The BSP-loaded nanosphere suspensions were administered into the joint cavity in a model of antigen-induced arthritic rabbit and evaluated by measuring the joint swelling, and the biocompatibility was appraised by histologic microscopy. RESULTS: The BSP-nanospheres were a unimodally-dispersed particulate system with a mean diameter ranging from 300 to 490 nm, and BSP was efficiently entrapped in the lipophilic copolymer (PLGA), although its hydrophilic properties. The drug release-rate from the nanospheres in PBS was controlled by the molecular weight and the lactic/glycolic acid (LA/GA) ratio of the polymers. The in vitro releasing study demonstrated that sustained drug release occurred for over three weeks. In the antigen-induced arthritic rabbit, the joint swelling decreased significantly by administering BSP-loaded nanospheres during a 21-day period after intra-articular challenge. With regards to the prolonged anti-inflammatory efficacy, serum antibody to ovalbumin showed a sustained reduction during the period, and the steroidal effect appeared by the degradation of the polymer in the synovium. The BSP-nanosphere administered was phagocytosed by the synovial activated-cells and the cartilage degradation was almost prevented. CONCLUSIONS: Direct intra-articular injection of a PLGA nanosphere system with a water-soluble steroid provided a prolonged pharmacological efficacy in the joints of arthritic rabbits. The local anesthetic in the knee-joints was evaluated to be safe and without biologic damage.

Animals↗

PubMed2002

Improved inhalation behavior of steroid KSR-592 in vitro with Jethaler by polymorphic transformation to needle-like crystals (beta-form).

PURPOSE: The aim of the present study was to improve the dry powder inhalation behavior of steroid KSR-592 with lactose by altering the crystal shape and the particle size of the drug for use in a newly designed inhalation device, Jethaler. METHOD: The shape of the crystals was changed by polymorphic transformation of original crystal (alpha-form) to beta-form by agitating alpha-form crystals in hexane containing 5% ethanol. The inhalation properties of the resultant crystals in vitro were evaluated with a twin impinger and cascade impactor. RESULTS: Needle-like crystals (beta-form) with dimensions of 1.8 microm in width x 41 microm in length were obtained by the polymorphic transformation, the kinetics of which was described by the Avrami equation. The beta-form crystals loaded on lactose particles were easily separated and crushed into fine particles in the airstream produced in the Jethaler, which increased dramatically the respirable fraction (RF) deposited in the twin impinger (43.8%) and the fine particle fraction (FPF) of the cascade impactor (FPF = 39.3%) compared with their values for the original crystals (RF = 5.8%, FPF = 4.7%). CONCLUSION: The dry powder inhalation properties of steroid KSR-592 (platelike crystal, alpha-form) were improved dramatically by changing the crystal shape to a needle-like shape by the polymorphic transformation to the beta-form.

Administration, Inhalation↗