Mitsuo Matsumoto

Showa Pharmaceutical University, Machida, Tōkyō, Japan

Are you Mitsuo Matsumoto?

Claim your profile

Publications (48)65.18 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The enhancing effect of p-Menthane-3,8-diol (MDO) on skin permeation of antipyrine (ANP) and indomethacin (IM) through Yucatan micropig skin in vitro was compared with 1-menthol. p-Menthane-3,8-diol is a metabolite of 1-menthol and has little odor. It is easy to combine the vehicle because of lower lipophilicity than 1-menthol. All formulations contained 40% (v/v) ethanol. The permeation of ANP increased with MDO about three times that without enhancer by increasing ANP concentration in the skin. However, the MDO effect was about a quarter that of 1-menthol. The permeation of IM with MDO was about 15 times that with no enhancer and it was almost the same as that with 1-menthol. The lag time of permeation was not significantly changed by MDO, which was not so in the case of 1-menthol. Skin concentration of IM increased about 11 times and six times with MDO and 1-menthol, respectively. MDO and 1-menthol partitioned to the skin relatively high concentrations, 5.9 and 2.5 mg/ cm3, respectively. The solubility of IM in the skin was improved by MDO, and consequently, the permeation of IM was enhanced.
    Drug Development and Industrial Pharmacy 08/2004; 30(6):673-7. DOI:10.1081/DDC-120039185 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: 3-l-Menthoxypropane-1,2-diol (MPD) is a derivative of l-menthol, which has an enhancement effect on drug permeation through skin. In this study, the effect of MPD on drug permeation through skin was compared with that of l-menthol. MPD or l-menthol at final concentrations of 3% in 40% ethanol was added to the drugs indomethacin or antipyrine and each mix then applied to Yucatan micropig skin in vitro. Drug concentrations in the skin were higher in the presence of either MPD or l-menthol, however, only l-menthol shortened the lag time of permeation. MPD enhanced the skin permeation of the drugs only by increasing the skin concentration of the drugs. In contrast, l-menthol enhanced the skin permeation of the drugs by increasing both the skin concentration and the diffusion rate in skin. The infrared (IR) spectra and X-ray diffraction patterns of stratum corneum after treatment with MPD did not differ from those of intact stratum corneum. A change in the IR spectra of stratum corneum after treatment with l-menthol was observed at the CH band, and the peaks representative of the lipid structure in the X-ray diffraction patterns decreased in intensity. These results suggest that l-menthol, but not MPD, disrupts the intercellular lipid structure of stratum corneum. Thus, MPD is expected to be a moderate skin permeation enhancer.
    International Journal of Pharmaceutics 07/2003; 258(1-2):217-23. DOI:10.1016/S0378-5173(03)00205-9 · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The effects of hydrogenated and unhydrogenated phosphatidylcholine (HPC, PC) on the permeation of indomethacin (IM) through hairless rat skin were investigated using liquid paraffin (LP) and a gel prepared with LP and hydrogenated soybean phospholipid (HSL). IM solubility at 95 degrees C increased in proportion to the concentration of HPC or PC, whereas solubility at 37 degrees C did not increase with HPC. IM showed no permeation until 10 h from LP without HPC/PC, but permeated at rates of approximately 5 and 10 microg/cm2 within 10 h from LP with HPC and PC, respectively. The permeation from the gel with various formulations (HSL, 15%; PC/HPC, 0-5%; IM, 0.5-2%) was determined. Permeation rates were 1.7-4.8 microg/cm2 per h and were proportional to the skin concentration. Skin concentration was correlated to the release rate from the gel. We concluded that IM was solubilized by phospholipids, high activity in the vehicle led to high partition of IM in skin, and permeation increased due to a high skin concentration.
    International Journal of Pharmaceutics 08/2001; 222(1):57-64. DOI:10.1016/S0378-5173(01)00695-0 · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To decrease the sensation of roughness when a tablet, which is rapidly disintegrated by saliva (rapidly disintegrating tablet), is orally taken, we prepared rapidly disintegrating tablets using microcrystalline cellulose (Avicel PH-M series), a new type of pharmaceutical excipient that is spherical and has a very small particle size (particle size, 7-32 microm), instead of conventional microcrystalline cellulose (PH-102) used in the formulation of tablets containing acetaminophen or ascorbic acid as model drugs for tableting study. Tablets (200 mg) prepared using spherical microcrystalline cellulose, PH-M-06, with the smallest particle size (mean value, 7 microm) had sufficient crushing tolerance (approximately, 8 kg) and were very rapidly, disintegrated (within 15 s) when the mixing ratio of PH-M-06 to low-substituted hydroxypropylcellulose (L-HPC) was 9:1. Sensory evaluation by volunteers showed that PH-M-06 was superior to PH-102 in terms of the feeling of roughness in the mouth. Consequently, it was found that particle size is an important factor for tablet preparation using microcrystalline cellulose. It is possible to prepare drugs such as acetaminophen and ascorbic acid (concentration of approximately 50%) in the tablet form using PH-NM-06 in combination with L-HPC as a good disintegrant at a low compression force (1-6 kN). To solve the problem of poor fluidity in the preparation of these tablets, we investigated the use of spherical sugar granules (Nonpareil, NP-101 (sucrose and starch, composition ratio of 7:3), NP-103 (purified sucrose), NP-107 (purified lactose) and NP-108 (purified D-mannitol)). Rapidly disintegrating tablets can be prepared by the direct compression method when suitable excipients such as fine microcrystalline cellulose (PH-M-06) and spherical sugar granules (NP) are used.
    CHEMICAL & PHARMACEUTICAL BULLETIN 03/2001; 49(2):134-9. DOI:10.1248/cpb.49.134 · 1.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present stud,vas to evaluate the bioavailability of a drug from rapidly disintegrating tablets prepared using fine spherical crystalline cellulose (PH-M-06(R)) and spherical sugar granules (Nonpareil(R), NP). Rapidly disintegrating tablets containing acetaminophen as the model drug in combination with a mixture of NP-108 (purified D-mannitol) and PH-M-06 were prepared. Plasma concentration profiles and pharmacokinetic parameters of acetaminophen in rabbits were investigated after oral administration of the prepared tablets. No significant difference in C-max and AUC(0-infinity) of acetaminophen between rapidly disintegrating tablets and conventional tablets was observed after direct administration of these tablets into the stomach of rabbits. However, t(max) (15 min) of acetaminophen from rapidly disintegrating tablets was significantly (p<0.05) shorter than that from conventional tablets (130 min). The same t(max) was observed for rapidly disintegrating tablets and solution. When suitable excipients such as fine spherical microcrystalline cellulose (PH-M series) and spherical sugar granules (NP series) were used, rapidly disintegrating tablets could be prepared by the conventional direct compression method. According to the results of moment analysis, the mean residence time (MRT) obtained between both rapidly disintegrating and conventional tablets indicates that the mean absorption time (MAT) from these tablets is approximately 60 and 90 min, respectively. This difference in MAT between the two tablets may be caused by the difference in the sum of the mean dissolution time (MDT) and the mean disintegration time (MDIT) of these tablets. Rapidly disintegrating tablets allow rapid absorption of the drug compared with conventional tablets.
    CHEMICAL & PHARMACEUTICAL BULLETIN 02/2001; 49(2):230-232. DOI:10.1248/cpb.49.230 · 1.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In this study, a pharmacokinetic model of cibenzoline in healthy volunteers was examined in order to design a pharmacokinetic model for establishing a relevant dosage regimen for patients with arrhythmias.Seven healthy volunteers between 25 and 43 years of age participated in the study. Each volunteer received two 100-mg capsules of cibenzoline with 150mL of water at 9 am after overnight fasting. Blood samples were collected before and 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 5, 6, 7, 8, and 24 hours after the oral dose.The serum cibenzoline concentrations were measured by a high performance liquid chromatography (HPLC) with ultraviolet detection at 230nm. The pharmacokinetics of cibenzoline in the healthy volunteers could be described using the one-compartment model (ke=0.283hr-1, Vd=0.249L/kg, ka=0.953hr-1) in healthy volunteers. The means of tmax and Cmax were 1.32 hr and 631ng/mL, respectively. A significant correlation was found between the predicted concentrations using our obtained one-compartment pharmacokinetic parameters and those observed in patients treated with cibenzoline for one month or longer. These results indicate that the one-compartment model is therefore useful for studying the pharmacokinetics of cibenzoline after oral administration.
    01/2001; 27(4):375-379. DOI:10.5649/jjphcs.27.375
  • [Show abstract] [Hide abstract]
    ABSTRACT: Nitric oxide (NO) is one of the most versatile mediators in mammalian biology. In the present study, we investigated the absorption-enhancing effects of an NO donor, 3-(2-hydroxy-1-methylethyl-2-nitrosohydrazino)-N-methyl-1-propa namine (NOC7), on drugs that are poorly absorbed from the gastrointestinal tract. NOC7 significantly increased the jejunal absorption of fluorescein isothiocyanate dextrans (FDs) of different average molecular weights (4000-20,000). This enhancing effect decreased as the FD molecular weight increased. Another NO donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), also increased the absorption of FD-4 from the jejunum. The absorption enhancement effect of NOC7 significantly decreased after coadministration with an NO scavenger, 2-(4-carboxyphenyl)-4,4,5, 5-tetramethylimidazole-1-oxyl-3-oxide, sodium salt. Furthermore, the enhancement effect of NOC7 was reversed shortly after cessation of the enhancer treatment. Little damage by NOC7 to the intestinal mucosa was observed in terms of release of lactose dehydrogenase and protein from the intestinal mucosa. NOC7 also increased the absorption of FD-4 by the colon and rectum. The findings suggest that an NO donor can improve the absorption of macromolecules from all regions of the rat intestine with very little mucosal damage and that an NO donor can act as a potent absorption enhancer.
    Journal of Pharmaceutical Sciences 11/2000; 89(10):1296-304. DOI:10.1002/1520-6017(200010)89:103.0.CO;2-K · 3.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Twelve medium to long chain fatty acid Esters (Esters), the total number of carbon atoms of which ranged from 17 to 34, were used to study the effect of the vehicle on the permeation of ketoprofen, and the effect was compared with the case of indomethacin. The solubility of ketoprofen was higher in Esters with a smaller number of carbon atoms. The permeation rate of ketoprofen from the Ester suspension through excised hairless rat skin was proportional to its solubility in the suspension, which was the same in the case of indomethacin. The diffusion constant and partition coefficient were calculated using the computer program MULTI(FILT). The diffusion constant decreased with increasing number of carbon atoms, and the partition coefficient was increased with increasing number of carbon atoms, in both cases of ketoprofen and indomethacin. Esters also penetrated the skin with the concentration of about 10 mg/g, independent of the number of carbon atoms. The Esters in the skin increase the diffusion rate of the drugs, especially in the case of Esters with a small number of carbon atoms. Also the drug solubility in the skin was improved, although the effect was similar for the range of Esters investigated in the present study. Then the permeation rate of ketoprofen and indomethacin increased.
    International Journal of Pharmaceutics 10/2000; 205(1-2):117-25. DOI:10.1016/S0378-5173(00)00496-8 · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aim of the present study was to investigate the effect of hydroxypropylmethylcellulose (HPMC-2208), used as an excipient for controlled release of drug, on the release profiles and bioavailability of the poorly water-soluble nifedipine (NP) from a tablet prepared using macrogol 6000 (PEG) and HPMC. The crushing tolerance of the NP tablet prepared using PEG and HPMC (NP-PEG-HPMC tablet) was markedly increased with increasing compression force used during the preparation from 20 to 200 MPa. The values reached their maximal levels (approximately 13 kg for the NP-PEG-HPMC tablet and 8 kg for the PEG tablet) at the compression force of 100 MPa. Although NP is a poorly water-soluble drug, it was rapidly dissolved from the NP-PEG tablet (without HPMC) due to the improvement of its dissolution rate in the presence of PEG. NP dissolution was complete at the latest within 1 h. On the other hand, dissolution of NP from the NP-PEG-HPMC tablet was significantly delayed with an increase in the concentration of HPMC in the tablet. The dissolution of NP from the NP-PEG-HPMC tablet containing 50% HPMC-2208 was markedly delayed as the viscosity of HPMC also increased. Interestingly, the same peak plasma NP concentration (C(max)) and the area under the plasma NP concentration-time curve (AUC(0-10)) were observed for both the NP-PEG tablet and NP-PEG-HPMC tablets, however, the time to C(max) (t(max)) for the NP-PEG-HPMC tablet was significantly higher when the NP-PEG-HPMC tablet was orally administered to rabbits. We describe here a preparation method of a new sustained-release NP-PEG-HPMC tablet using a mixture of NP-PEG granules (prepared with PEG) and HPMC.
    International Journal of Pharmaceutics 08/2000; 202(1-2):173-8. DOI:10.1016/S0378-5173(00)00426-9 · 3.79 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A computer program is described for maximum likelihood estimation within the gamma or normal distribution which can be used to estimate pharmacokinetic parameters. Pharmacokinetic analysis using this proposed program was investigated by the Monte Carlo method. The assumed pharmacokinetic models were a one-compartment intravenous model and an oral model. The simulated drug concentrations were generated using a 10% S.D. based on the gamma or normal distribution. The gamma or normal distribution was adopted as the probability density function (p.d.f.) to estimate model parameters. The Powell method was used to maximize the logarithmic likelihood. There were no differences in the estimated parameters in terms of statistical and frequency distributions between the gamma and normal distributions using the generated data and the p.d.f. distributions. However, the number of failures to calculate the parameters using the p.d.f. with the normal distribution was more than five times that using the gamma distribution. This result suggests that it may be necessary to evaluate the validity of results computed using the maximum likelihood estimation based on a normal distribution as a data error distribution and p.d.f.
    Biological & Pharmaceutical Bulletin 03/2000; 23(2):235-9. DOI:10.1248/bpb.23.235 · 1.78 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The objective of this study was to evaluate the effect of a nitric oxide (NO) donor, S-nitroso-N-acetyl-DL-penicillamine (SNAP), on the nasal absorption of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in rabbits and to evaluate the irritation (cytotoxicity) potential of the NO donor on the mucosal membrane using a cultured cell system (strain KB, human epidermoid carcinoma of the floor of the mouth). Significantly higher serum G-CSF concentration and increased total leukocyte count in the peripheral blood were observed after coadministration of rhG-CSF (100 microg/kg) with SNAP at various doses (0.3-3.3 mg/kg). The serum G-CSF concentration and the increased total leukocyte count were markedly decreased by the presence of the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5-tetramethyl-imidazole-1-oxyl 3-oxide sodium salt (carboxy-PTIO), in combination with rhG-CSF and SNAP. However, no significant inhibitory effect of glutathione (peroxynitrite scavenger) on the absorption-enhancing effect of SNAP was observed. These results suggest that carboxy-PTIO inhibits the absorption-enhancing effect of NO released from SNAP. We found that SNAP has a very low potential for cytotoxicity, as evaluated by the cell detachment assay, release of lactate dehydrogenase (LDH) from cultured cells and morphological observations of nasal tissue of rabbits. It is concluded that a NO donor such as SNAP is a promising absorption enhancer for nasal protein-drug delivery.
    Journal of Drug Targeting 02/2000; 8(3):185-94. DOI:10.3109/10611860008996864 · 2.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Tranilast (TL) oily gels containing UV-absorbing agents (UV absorber) were prepared, and the effect of the agents against photodegradation of TL was investigated. When 0.1% TL oily gel without UV absorber was exposed to light, TL was photochemically decomposed to the extent of 74.1% of its initial content at the end of the first hour. Although there were differences in the preventive effect on photodegradation of TL depending on the UV absorbers employed, 2-(2-benzotriazolyl)-p-cresol (BTPC) was the most effective absorber. The addition of UV absorbers to the oily gel did not affect the release of TL from the gel, the skin permeation, or the skin concentration of TL following topical application. UV absorbers added to TL oily gel penetrated into skin; however, their concentration in skin was similar to that following application of commercial sunscreen. These results suggest that the addition of UV absorbers to the oily gel of TL may be useful in preventing photodegradation of TL in the gel.
    CHEMICAL & PHARMACEUTICAL BULLETIN 01/2000; 47(12):1713-6. DOI:10.1248/cpb.47.1713 · 1.38 Impact Factor
  • 01/2000; 26(1):52-60. DOI:10.5649/jjphcs1975.26.52
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this study was to prepare, using taste-masked granules, tablets which can rapidly disintegrate in saliva (rapidly disintegrating tablet), of drugs with bitter taste (pirenzepine HCl or oxybutynin HCl). The taste-masked granules were prepared using aminoalkyl methacrylate copolymers (Eudragit E-100) by the extrusion method. None of the drugs dissolved from the granules (% of dissolved, < 5%) even at 480 min at pH 6.8 in the dissolution test. However, the drugs dissolved rapidly in the medium at pH 1.2 in the dissolution test. Rapidly disintegrating tablets were prepared using the prepared taste-masked granules, and a mixture of excipients consisting of crystalline cellulose (Avicel PH-102) and low-substituted hydroxypropylcellulose (L-HPC, LH-11). The granules and excipients were mixed well (mixing ratio by weight, crystalline cellulose: L-HPC = 8:2) with 1% magnesium stearate, and subsequently compressed at 500-1500 kgf in a single-punch tableting machine. The prepared tablets (compressed at 500 kgf) containing the taste-masked granules have sufficient strength (the crushing strength: oxybutynin tablet, 3.5 kg; pirenzepine tablet, 2.2 kg), and a rapid disintegration time (within 20 s) was observed in the saliva of healthy volunteers. None of the volunteers felt any bitter taste after the disintegration of the tablet which contained the taste-masked granules. We confirmed that the rapidly disintegrating tablets can be prepared using these taste-masked granules and excipients which are commonly used in tablet preparation.
    CHEMICAL & PHARMACEUTICAL BULLETIN 10/1999; 47(10):1451-4. · 1.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: An optimized method for the determination of flecainide in serum is presented. Extraction using a solid-phase C18 column and chromatography on a stabilized fluorocarbon-bonded silica gel column effectively separate flecainide from an internal standard (a positional isomer of flecainide). The HPLC apparatus and conditions were as follows: analytical column, Fluofix 120N; sample solvent, 20 microl; column temperature, 40 degrees C; detector, Shimadzu RF-5000 fluorescence spectrophotometer (excitation wavelength = 300 nm, emission wavelength = 370 nm); mobile phase, 0.06% phosphoric acid containing 0.1% tetra-n-butyl ammonium bromide-acetonitrile (75:25, v/v); flow-rate, 1.0 ml/min. The standard curves for flecainide were linear in the concentration range examined (10-2000 ng/ml). The regression equation was y = 0.08+0.0078x (r = 0.9998). The minimum detectable amount of flecainide was approximately 5 ng/ml. In the within-day study, the precision coefficients of variation were 2.66, 2.18, 2.54, 2.72, 2.88, 2.24, and 3.29% for the 10, 50, 100, 200, 500, 1000, and 1500 ng/ml standards, respectively. The absolute recovery rates of flecainide at each concentrations were 94-100%. The method described provides analytical sensitivity, specificity and reproducibility suitable for both biomedical research and therapeutic drug monitoring.
    Journal of chromatography. B, Biomedical sciences and applications 05/1999; 726(1-2):219-23. DOI:10.1016/S0378-4347(98)00578-7
  • [Show abstract] [Hide abstract]
    ABSTRACT: Previously, we found that monocarboxylic acids undergo carrier-mediated transport in primary cultures of oral mucosal epithelial cells.1 In this study, we investigated whether carrier-mediated absorption of a monocarboxylic acid from the oral mucosa occurs in vivo. Salicylic acid was administered to hamster cheek pouch. At predetermined intervals, the concentration of salicylic acid in the fluid remaining in the cheek pouch lumen and the blood salicylic acid concentration were determined. The absorption of salicylic acid was saturable at high salicylic acid concentrations. Sodium azide, a metabolic inhibitor, and carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP), a protonophore, significantly inhibited the absorption of salicylic acid but not the absorption of salicylamide from the oral mucosa. Various monocarboxylic acids inhibited the absorption of salicylic acid, whereas dicarboxylic acids had no such effect. Transfer of [14C]salicylic acid from the cheek pouch mucosa to the systemic circulation was observed, and the blood [14C]salicylic acid concentration in the case of coadministration with propionic acid was significantly lower than that in the case of no propionic acid coadministration. These results show that monocarboxylic acids undergo carrier-mediated absorption from the hamster cheek pouch mucosa.
    Journal of Pharmaceutical Sciences 02/1999; 88(1):142-6. DOI:10.1021/js970412e · 3.01 Impact Factor
  • Drug Delivery System 01/1999; 14(1):51-57. DOI:10.2745/dds.14.51
  • 01/1999; 25(6):627-633. DOI:10.5649/jjphcs1975.25.627
  • 01/1999; 25(6):634-642. DOI:10.5649/jjphcs1975.25.634
  • Nihon Kyukyu Igakukai Zasshi 01/1999; 10(11):657-666. DOI:10.3893/jjaam.10.657

Publication Stats

360 Citations
65.18 Total Impact Points

Institutions

  • 1994–2004
    • Showa Pharmaceutical University
      Machida, Tōkyō, Japan
  • 2001
    • Showa University
      Shinagawa, Tōkyō, Japan
  • 1999
    • Toho University
      Edo, Tōkyō, Japan

Disciplines