Biomedical subjects

Hiromitsu Yamamoto

Publications and source records attributed to Hiromitsu Yamamoto.

At least 19 recordsLinked to original sources

PubMed2006

Runx3 expression during mouse tongue and palate development.

Studies of molecular mechanisms underlying the development of the mammalian oral mucosa have revealed a major involvement of transforming growth factor beta (TGF-beta) and bone morphologic protein (BMP) signaling pathways. Here, we examined the expression of a downstream target of TGF-beta and BMPs, Runx3, in oral mucosa. Runx3 is a runt-related transcription factor that acts as a gastric tumor suppressor and regulator of growth and differentiation in mammalian gastric epithelial cells. Another member of the Runx family in C. elegans, run, is involved in the development of a functional hypodermis and gut. In this report, we examined Runx3 expression using reverse transcription-polymerase chain reaction, immnunohistochemistry, and in situ hybridization and found that Runx3 is expressed in the tongue and palate epithelium of mouse embryos from embryonic day 12.5 to 16.5. The functional relationship between Runx3 and TGF-beta/BMPs signaling in tongue and palate development is discussed.

Animals↗

PubMed2006

Biodistribution of polysorbate 80-coated doxorubicin-loaded [14C]-poly(butyl cyanoacrylate) nanoparticles after intravenous administration to glioblastoma-bearing rats.

It was recently shown that doxorubicin (DOX) bound to polysorbate-coated nanoparticles (NP) crossed the intact blood-brain barrier (BBB), and thus reached therapeutic concentrations in the brain. Here, we investigated the biodistribution in the brain and in the body of poly(butyl-2-cyano[3-(14)C]acrylate) NP ([(14)C]-PBCA NP), polysorbate 80 (PS 80)-coated [(14)C]-PBCA NP, DOX-loaded [(14)C]-PBCA NP in glioblastoma 101/8-bearing rats after i.v. injection. The biodistribution profiles and brain concentrations of radiolabeled NP were determined by radioactivity counting after i.v. administration in rats. Changes in BBB permeability after tumour inoculation were assessed by i.v. injection of Evans Blue solution. The accumulation of NP in the tumour site and in the contralateral hemisphere in glioblastoma bearing-rats probably was augmented by the enhanced permeability and retention effect (EPR effect) that may have been becoming instrumental due to the impaired BBB on the NP delivery into the brain. The uptake of the NP by the organs of the reticuloendothelial system (RES) was reduced after PS 80-coating, but the addition of DOX increased again the concentration of NP in the RES.

Animals↗

PubMed2006

[Effects of continuous infusion of landiolol on the hemodynamic response to tracheal intubation].

BACKGROUND: The clinical effect of continuous infusion of landiolol with buprenorphine and lidocaine was evaluated for its effects an attenuating the cardiovascular responses to endotracheal intubation. METHODS: Tracheal intubation was performed by the same anesthesiologist after induction of anesthesia with propofol, ketamine, midazolam, buprenorphine and lidocaine, followed by administration of vecuronium, and continuous infusion of saline (Group C; n = 20) or landiolol 0.02 (Group L 2; n = 25) or landiolol 0.04 mg x kg(-1) x min(-1) (Group L4; n = 22). Heart rate (HR), systolic (sBP) and diastolic blood pressure (dBP) were recorded just before induction of anesthesia, just after and 10 min after tracheal intubation. RESULTS: Just after tracheal intubation, HR in the Groups C and L 2, but not in the group L 4, increased significantly from the baseline. Just after the tracheal intubation, sBP in the Group L 2 decreased from the baseline, and 10 min after intubation sBP in all groups decreased significantly from the baseline. Just after tracheal intubation, dBP in all groups was unchanged, and dBP in the Groups C and L 4 decreased from the baseline 10 min after the intubation. CONCLUSIONS: Continuous infusion of landiolol 0.04 mg x kg(-1) x h(-1) with buprenorphine and lidocaine can completely attenuate the hemodynamic response to tracheal intubation.

Adrenergic beta-Antagonists↗

PubMed2006

[Main causes of the emergence delay from balanced anesthesia].

BACKGROUND: Occasionally emergence from anesthesia is delayed. We examined the factors which exert influence on the emergence time. METHODS: The emergence time was assessed in 1133 surgical patients who received balanced anesthesia. Balanced anesthesia was maintained with infusion of propofol, ketamine, vecuronium, and buprenorphine, with nitrous oxide. OT time was defined as the time from the end of operation to extubation, TA time from extubation to leaving the operation room, and these times were examined retrospectively. RESULTS: The emergence time of OT was 3.9 +/- 2.6 min, and that of TA was 3.7 +/- 2.2 min, for all subjects who were extubated in the operating room. Factors affecting the emergence delay were ASA classification, JCS classification, ages, department of surgery, the time of anesthesia, and the anesthesiologists. CONCLUSIONS: When the anesthesiologists keep in mind early emergence and become accustomed to this balanced anesthesia, the emergence time will be shorter, and the extubated cases in the operating room will increase.

Adult↗

PubMed2005

Effectiveness of submicron-sized, chitosan-coated liposomes in oral administration of peptide drugs.

The mucoadhesive behavior of chitosan-coated liposomes in the intestinal tract of the rat was examined to elucidate their particle size effects on the absorption of an entrapped drug, calcitonin. The intestine was removed from rats after oral administration of liposomes containing a fluorescent dye, and its various parts were observed with confocal laser scanning microscopy. Penetration of submicron-sized liposomes (ssLip) or chitosan-coated ssLip (ssCS-Lip) into the mucosa was observed, while such behavior was not observed for the multilamellar liposomes, even when coated with chitosan (CS-Lip). The retentive property of ssCS-Lip was confirmed by measuring the amount of dye in each part of the intestine. The pharmacologic effects of calcitonin-loaded liposomes of different particle size were measured after oral administration in rats. The pharmacologic effect of oral administration of ssLip coated with chitosan was detected up to 120 h after administration. The extensive pharmacologic effect of ssCS-Lip was attributed to their prolonged retention in the intestinal mucosa, partly owing to their penetrative property into the intestinal mucosa. The chitosan-coated ssLip, with their higher retentive property in the intestinal tract, are much more effective than ssLip and CS-Lip in improving the enteral absorption of peptide drugs.

Adhesiveness↗

PubMed2005

Novel mucoadhesion tests for polymers and polymer-coated particles to design optimal mucoadhesive drug delivery systems.

To design an effective particulate drug delivery system having mucoadhesive function, several mucoadhesion tests for polymers and the resultant particulate systems were developed. Mucin particle method is a simple mucoadhesion test for polymers, in which the commercial mucin particles are used. By measuring the change in particle size or zeta potential of the mucin particle in a certain concentration of polymer solution, we could estimate the extent of their mucoadhesive property. BIACORE method is also a novel mucoadhesion test for polymers. On passing through the mucin suspension on the polymer-immobilized chip of BIACORE instrument, the interaction was quantitatively evaluated with the change in its response diagram. By using these mucoadhesion tests, we detected a strong mucoadhesive property of several types of chitosan and Carbopol. Evaluation of mucoadhesive property of polymer-coated particulate systems was demonstrated with the particle counting method developed by us. To detect the mucoadhesive phenomena in the intestinal tract, we observed the rat intestine with the confocal laser scanning microscope (CLSM) after oral administration of the particulate systems. The resultant photographs clearly showed a longer retention of submicron-sized chitosan-coated liposomes (ssCS-Lip) in the intestinal tract than other liposomal particles tested such as non-coated liposomes and chitosan-coated multilamellar one. These observations explained well the superiority of the ssCS-Lip as drug carrier in oral administration of calcitonin in rats than other liposomal particles.

Adhesiveness↗

PubMed2005

Nanoparticles enhance therapeutic efficiency by selectively increased local drug dose in experimental colitis in rats.

Nanoparticles (NP) are proposed for targeted drug delivery to the inflammation site in severe cases of inflammatory bowel disease where state-of-the-art delivery devices fail. FK506 (tacrolimus) entrapped into NP was administered either orally or rectally to male Wistar rats suffering from a preexisting experimental colitis. Clinical activity score, colon/body weight index, and myeloperoxidase activity were determined to assess the inflammation. Tissue penetration experiments elucidated the processes involved in the proposed new therapeutic approach. The therapeutic effects of FK506 solutions as well as FK506-NP by oral route were minor. The myeloperoxidase activity and colon/body weight ratio decreased significantly (P < 0.05) only after the rectal administration of FK506-NP, whereas treatment by free drug was not different from colitis control in both 2,4,6-trinitrobenzenesulfonic acid and oxazolone colitis model. NP allows an enhanced and selective drug penetration into the inflammation site as opposed to surrounding healthy tissue (healthy: FK506, 109 +/- 18 nmol/cm2; FK506-NP, 51 +/- 13 nmol/cm2; colitis: FK506, 79 +/- 28 nmol/cm2; FK506-NP, 105 +/- 24 nmol/cm2), presumably by protecting the encapsulated drug against influences from efflux systems and mucosal metabolism. The relative drug penetration into the inflamed tissue is about 3-fold higher compared with healthy tissue when using NP as drug carriers. The use of drug-loaded NP offers several advantages compared with standard therapeutic strategies such as a higher selectivity in adhesion to and enhanced drug penetration into the inflamed tissue.

Animals↗

PubMed2005

A pH-sensitive microsphere system for the colon delivery of tacrolimus containing nanoparticles.

Nanoparticles (NP) are known to accumulate at the site of inflammation in inflammatory bowel disease. In order to avoid premature uptake or degradation of NP during their passage through the small intestine, it appeared necessary to devise a form of local delivery system for NP. Tacrolimus (FK506) loaded poly(lactic-co-glycolic acid) NP entrapped into pH-sensitive microspheres (NPMS) were designed to achieve greater selectivity to their site of action when administered orally. The therapeutic efficacy of this drug delivery system was tested in an experimental colitis in rats. The in vitro characterization showed a successful incorporation of FK506-NP and strongly pH-sensitive release kinetics of both NP and drug. During the in vivo studies, clinical activity, colon/body weight index, and myeloperoxidase activity were determined to assess the severity of inflammation. Systemic availability of a fluorescent dye entrapped in the microspheres was measured in order to determine possible adverse effects. The NPMS as well as the controls of NP and MS formulations exhibited significant mitigating effects in the clinical activity index after 3 days of treatment with similar levels for the various therapies. When observing colon/body weight index and myeloperoxidase activity, only the NPMS group reached statistically significant differences (P<0.05) compared to the colitis control group while other groups did not (colitis control: 21.94+/-4.97; FK506 solution: 15.81+/-3.42; FK506-NP: 17.03+/-5.52; FK506-MS: 15.17+/-7.81; and FK-NPMS: 10.26+/-7.76 U/mg tissue). Moreover, the NPMS system reduced the systemic absorption of the entrapped dye compared to the dye solution or simple NP formulation (relative biovailability-solution: 100+/-14.9%; NP: 46.8+/-8.6%; and NPMS: 29.4+/-3.3%). The results suggest that the NPMS system can provide selective delivery of NP in the colon and develop a significant mitigating effect, while the control group treatments appeared to be insufficient.

Colon↗

PubMed2005

Solid dispersion particles of amorphous indomethacin with fine porous silica particles by using spray-drying method.

The solid dispersion particles of indomethacin (IMC) were prepared with different types of silica, non-porous (Aerosil 200) or porous silica (Sylysia 350) by using spray-drying method. Powder X-ray diffraction analysis showed that IMC in solid dispersion particles is in amorphous state irrespective of the type of silica formulated. In DSC analysis, the melting peak of IMC in solid dispersion particles with Sylysia 350 shifted to lower temperature than that in solid dispersion particles with Aerosil 200 although the peak of each solid dispersion particles was much smaller than that of original IMC crystals. Dissolution property of IMC was remarkably improved by formulating the silica particles to the solid dispersion particles. In comparing the effect of the type of the silica particles, the dissolution rate of solid dispersion particles with Sylysia 350 was faster than that with Aerosil 200. The formulation amount of IMC did not affect on the amorphous state of IMC in the resultant solid dispersion particles in powder X-ray diffraction patterns. However, the area of the melting peak of IMC in the solid dispersion particles increased and an exothermic peak owing to recrystallization was observed with increasing the IMC content in the DSC patterns. The dissolution rate of IMC from the solid dispersion particles with Sylysia 350 was faster than that of Aerosil 200 irrespective of IMC content. In stability test, amorphous IMC in the solid dispersion particles with each silica particles did not crystallize under storing at severe storage conditions (40 degrees C, 75% RH) for 2 months, while amorphous IMC without silica easily crystallized under same conditions.

Indomethacin↗

PubMed2005

Surface-modified PLGA nanosphere with chitosan improved pulmonary delivery of calcitonin by mucoadhesion and opening of the intercellular tight junctions.

Surface-modified DL-lactide/glycolide copolymer (PLGA) nanospheres with chitosan (CS) were prepared by the emulsion solvent diffusion method for pulmonary delivery of peptide, i.e., elcatonin. The nanosphere suspension was successfully aerosolized with a nebulizer similar to the drug solution, whereas the microsphere suspensions could not be aerosolized. After pulmonary administration, CS-modified PLGA nanospheres were more slowly eliminated from the lungs than unmodified PLGA nanospheres. CS-modified PLGA nanospheres loaded with elcatonin reduced blood calcium levels to 80% of the initial calcium concentration and prolonged the pharmacological action to 24 h, which was a significantly longer duration of action than that by CS-unmodified nanospheres. These results were attributed to the retention of nanospheres adhered to the bronchial mucus and lung tissue and sustained drug release at the adherence site. In addition, CS and CS on the surface of the nanospheres enhanced the absorption of drug. The rank order of the absorption of the model drugs with CS solution was carboxyfluorescein>FITC-dextran-4 (FD-4; Mw. 4000)>FD-21 (Mw. 21,000)>FD70 (Mw. 70,000), which corresponded to the molecular weights ([Mw.] given in parentheses). The absorption-enhancing effect may have been caused by opening the intercellular tight junctions.

Absorption↗

PubMed2005

FK506 microparticles mitigate experimental colitis with minor renal calcineurin suppression.

PURPOSE: FK506 microparticles providing selective colonic drug delivery were tested for their efficiency in a local treatment to the inflamed gut tissue in inflammatory bowel disease (IBD). Because FK506 proved its distinct mitigating potential in the treatment of IBD, risking, however, severe adverse effects, a more selective delivery to the site of inflammation may further improve efficiency and tolerability. METHODS: A model colitis was induced to male Wistar rats by trinitrobenzenesulfonic acid. FK506 was entrapped into microspheres (MS) prepared with the pH-sensitive polymer Eudragit P-4135F in order to allow drug delivery to the colon. Clinical activity score, colon/body weight index, and myeloperoxidase activity were determined to assess the inflammation, and adverse effects of FK506 resulting from its systemic absorption were quantified as well. RESULTS: The clinical activity score and myeloperoxidase activity decreased after the administration of all FK506-containing formulations. The MS formulations proved to be as efficient in mitigating the experimental colitis as the subcutaneous drug solution (myeloperoxidase activity, MS: 9.64+/-6.6 U/mg tissue; subcutaneous: 7.48+/-6.96 U/mg) and to be superior to drug solution given by oral route (oral: 12.66+/-5.46 U/mg; untreated colitis control: 21.88+/-4.12 U/mg). The FK506 subcutaneous group exhibited increased levels of adverse effects, whereas the FK506-MS group proved its potential to retain the drug from systemic absorption as evidenced by reduced nephrotoxicity. CONCLUSIONS: The development of this selective delivery system for FK506 should be given particular consideration in the treatment of IBD, as it allows therapy that profits from FK506's high immune suppressive effect with a simultaneously reduced nephrotoxicity.

Animals↗

PubMed2005

Observations in simultaneous microencapsulation of 5-fluorouracil and leucovorin for combined pH-dependent release.

5-Fluorouracil (5-FU) in combination with leucovorin (LV) is nowadays the standard treatment in colon cancer and would be a candidate to be delivered orally to the colon. Eudragit P-4135F or Eudragit RS100 were used separately to prepare microspheres by an oil/oil emulsification process trapping 5-FU and LV simultaneously. Scanning electron microscopy permitted a structural analysis, process parameters were analyzed and drug loading and release profiles were recorded. Particle size varied between 123 (RS100) and 146 microm (P-4135F). Generally, higher encapsulation rates were found with RS100 (5-FU, 60.3+/-9.7%; LV, 81.4+/-8.6%) compared to P-4135F (5-FU, 48.3+/-2.0%; LV, 55.4+/-2.7%). Microparticles made from Eudragit RS100 released the incorporated drug combination within 8 h not exhibiting general differences between the kinetics of both drugs. P-4135F was found to maintain the undesired 5-FU release at pH 6.8 lower than 25% within 4 h while at pH 7.4, a nearly immediate release (within 15 min) was observed. Although the release was similar at pH 7.4, at pH 6.8 LV showed a distinct initial drug loss of about 60% and a complete release within 2 h. SEM analyses revealed a substantial presence of LV crystals on the particle surface provoking a distinct burst effect of LV. These observations were concluded to be related to the high lipophilicity of P-4135F provoking a separation between P-4135F and LV during the preparation process.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed2005

Body distribution of polysorbate-80 and doxorubicin-loaded [14C]poly(butyl cyanoacrylate) nanoparticles after i.v. administration in rats.

Previously it was shown that poly(butyl cyanoacrylate) (PBCA) nanoparticles coated with polysorbate 80 are able to cross the blood-brain barrier (BBB) after i.v. administration. The objective of the present study was to investigate the influence of polysorbate 80 and doxorubicin-loading on the body distribution in rats. The biodistribution profile and brain concentration of (14)C-radiolabeled PBCA nanoparticles, polysorbate 80 coated (14)C-PBCA nanoparticles, and doxorubicin-loaded (14)C-PBCA nanoparticles were determined by radioactivity counting after i.v. administration in rats. The (14)C-PBCA nanoparticles showed a significant accumulation in the organs of the reticuloendothelial system (RES). Polysorbate 80 coating of the (14)C-PBCA nanoparticles decreased this accumulation to about 40% after 1 h post injection. The brain concentration was increased about 2-fold after polysorbate 80-coating at this time point. The presence of doxorubicin in this preparation, however, decreased the brain concentration to levels similar to uncoated particles, probably caused by the positive charge of this compound. After longer time periods after injection the differences between the three preparations decreased.

Animals↗

PubMed2005

Tabletting of solid dispersion particles consisting of indomethacin and porous silica particles.

We attempted to make the rapidly dissolving tablet (Tab) containing solid dispersion particles (SD) with indomethacin (IMC) and porous silica (Sylysia350) as carrier prepared by using spray-drying technique. Rapidly dissolving tablet was formulated with mannitol as a diluent and low substituted hydroxypropylcellulose (L-HPC) or partly pre-gelatinized starch (PCS) as a disintegrant. The percent dissolved from Tab (SD) was higher than that of tablet containing physical mixture (PM) at 20 min. Nearly 100% of drug in Tab (SD) was dissolved within 60 min, while the drug dissolution of Tab (PM) was not completed at the same time period. In addition, the tensile strength of Tab (SD) was much higher than that of Tab (PM). Adding L-HPC in Tab (SD) (Tab (SD-L-HPC)), the percent dissolved from Tab (SD-L-HPC) at 5 min became much higher than that from Tab (SD). The dissolution profile of IMC from Tab (SD-L-HPC) was almost the same irrespective of the compression pressure, while the tensile strength of tablet increased with increasing the compression pressure. In comparing the compaction property of these tablets by observing the ratio of residual die wall pressure (RDP) to maximum die wall pressure (MDP) (RDP/MDP), it was found that addition of L-HPC in the tablet formulation improved compactibility. In case that PCS was formulated as disintegrant, Tab (SD-PCS), similar improvement in the dissolution profile and tensile strength was observed, though the dissolution rate of IMC from Tab (SD-PCS) was slightly lower than that from Tab (SD-L-HPC) irrespective of the compression pressure.

Compressive Strength↗

PubMed2005

[Clinical study of vecuronium maintenance speed in trigeminal microvascular decompression surgery].

BACKGROUND: Patients receiving chronic carbamazepine therapy may be resistant to vecuronium. The purpose of this study was to determine maintenance speed of vecuronium in trigeminal microvascular decompression surgery. METHODS: The vecuronium maintenance speed of the patient for microvascular decompression diagnosed as trigeminal neuralgia (group T: n=18) or hemi-facial spasm (group C: n=18) was examined retrospectively. Anesthesia was induced with propofol, ketamine, midazolam and buprenorphine. Vecuronium was given to facilitate tracheal intubation. The patients received balanced anesthesia with infusion of propofol, ketamine, buprenorphine and vecuronium (60-80 microg x kg(-1) x h(-1)), with nitrous oxide. In both groups the scheduled vecuronium maintenance speed was increased if needed, using the TOF-Watch, at the time of body movement or with more than four TOF count. RESULTS: All patients of group T were medicated with carbamazepine before operation. None of C received carbamazepine. With C, vecuronium maintenance speed was as scheduled. With T, however, scheduled vecuronium speed increased in most of the cases. Actual vecuronium speed was significantly faster with T, compared with C. Although actual speed divided by scheduled speed was 1 in group C, it was 1.4 in T. CONCLUSIONS: Vecuronium maintenance speed is 1.4 times of scheduled speed in patients medicated with carbamazepine.

Aged↗

PubMed2004

pH-sensitive microsphere delivery increases oral bioavailability of calcitonin.

Oral calcitonin (CT) administration is aimed in the treatment of calcemia in order to circumvent the required regular injections. CT containing microspheres (MS) were designed for colonic delivery by applying a pH-sensitive polymer Eudragit P-4135F for a double emulsion [water/oil/water (w/o/w)] microsphere preparation technique. CT was incorporated in the internal aqueous phase and carboxyfluorescein was encapsulated similarly to allow the characterization of the MS dissolution behavior. Eudragit P-4135F was found to keep the leakage of CT and carboxyfluorescein in vitro at pH 6.8 below 20% within 4 h while at pH 7.4, a fast release was observed for both, dye and peptide. Plasma levels of carboxyfluorescein after oral MS administration proved a sustained release in a rat model, where Cmax of carboxyfluorescein solution was found at around 60 min while for MS formulations it was detected after 4 h. At a dose of 20 microg CT/kg, no significant calcemic effects were found by MS formulations. However, increasing the dose to 100 microg CT/kg resulted in a distinct calcemia and revealed the sustained release properties of the MS. The relative pharmacological effect became most intense after 8-12 h based on the selective pH-dependent delivery. MS showed a fourfold increase of the area above the curve of calcium blood level compared to levels reached after CT solution. The coencapsulation of chitosan in the MS as absorption enhancer did not show any additional effect. The MS formulations proved their applicability as a promising device for pH-dependent colonic CT delivery and might be useful for other peptides.

Administration, Oral↗

PubMed2004

Pharmacoscintigraphic evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans.

Hollow microspheres (microballoons) floating on artificial gastric juice were developed as a floating controlled drug delivery system in the stomach. The intragastric behavior of 99mTc labelled microballoons (MB) and nonfloating microspheres (NF) (control) following oral administration in fasted and fed humans was investigated by gamma scintigraphy. Simultaneously, pharmacokinetic examination of riboflavin released from MB and NF was conducted in fasted and fed human subjects. In the fed state, MB were dispersed in the upper portion of the stomach; moreover, MB were retained in the stomach up to 300 min compared with NF, which descended gradually into the lower part of stomach within 90 min. In the fasted state, MB floated for approximately 60 min, after which it was removed rapidly via the cyclic activity referred to as the interdigestive migrating motor complex (IMMC). NF were removed more rapidly, i.e., within 60 min. Pharmacokinetic parameters, e.g., excretion half-life time (t1/2) and total urinary excretion, were well correlated with the gastric residence time (GRT) determined by the gamma scintigraphy analysis. The present investigation suggests that MB are very useful for improving drug bioavailability, resulting in a more sustained pharmacological action.

Adult↗

PubMed2004

In vitro and in vivo evaluation of riboflavin-containing microballoons for a floating controlled drug delivery system in healthy humans.

Microballoons (MB) possessing a spherical cavity enclosed within a hard polymer shell have been developed as a dosage form characterized by excellent buoyancy in the stomach. MB were prepared by the emulsion solvent diffusion method using enteric acrylic polymers dissolved in a mixture of dichloromethane and ethanol. Riboflavin-containing MB were administered orally to each of three healthy volunteers. The pharmacokinetics of riboflavin was investigated by analysis of the urinary excretion. Prolongation of the urinary excretion of riboflavin could be obtained by ingestion of water as well as "fed" conditions. This phenomenon was attributable to the buoyancy properties of MB in the stomach and an increase in the gastric residence time (GRT). The excretion half-life time (t(1/2)) following administration of MB (particle size: 500-1000 microm) exhibiting high buoyancy was longer than that of MB (particle size: <500 microm) displaying low buoyancy. Therefore, the intragastric floating properties of MB are potentially beneficial as far as a sustained pharmacological action is concerned. MB prepared by mixing it with hydroxypropylmethylcellulose (HPMC) in different ratio, results in improved riboflavin-release properties. These MB were evaluated in vivo by analysis of the urinary excretion of riboflavin. As a result, strong correlations were observed between the buoyancy and excretion half-life (t(1/2)) and between the riboflavin release from the MB and total urinary excretion.

Administration, Oral↗