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Biomedical subjects

I Sugimoto

Publications and source records attributed to I Sugimoto.

At least 55 records · Page 3Linked to original sources
PubMed1989

Quantitative design for photostabilization of nifedipine by using titanium dioxide and/or tartrazine as colourants in model film coating systems.

The photostabilization of nifedipine by using film coating has been investigated in model systems in which a drug sample, dispersed on a glass plate, was covered with a free film and exposed to intensive light of mercury vapour lamp. The light transmission properties of films containing titanium dioxide or tartrazine alone as colourant were not always satisfactory. The tartrazine system exhibited superior light transmission properties to the titanium dioxide system at all additive concentrations. However, in combination both colourants gave much better light protection than did the colourants separately. The film-coated drug degraded following apparent first-order kinetics. The degradation rate constant decreased as both colourant concentration and film thickness increased; thus photostabilization was almost completely achieved by applying a film (thickness: 60 microns) of the binary mixture system containing only 0.7% of each of these colourants. The protective effectiveness of a film could be quantitatively evaluated by plotting the degradation rate constant against CL value of film formulation (C: concentration of colourant; L: film thickness). The degradation rate constant showed a good linear correlation with the average percent transmittance of a film in the wavelength range relating to the photolytic degradation of the drug. The average percent transmittance was thus proved to be an important and useful parameter for estimating the photostability of film-coated drugs.

Azo Compounds↗
PubMed1988

The effect of additives on the oral mucosal absorption of human calcitonin in rats.

The oral mucosal absorption of human calcitonin (HCT) was investigated in rats. Enhanced absorption of HCT was observed by coadministration of additives such as sodium deoxycholate, sodium tauroglycocholate, quillajasaponin (Quillayannin P-20), sodium lauryl sulfate, sodium myristate and sugar esters. The contribution of sugar esters to oral mucosal absorption of HCT was studied in some detail. The addition of a sugar ester having a hydrophilic-lipophilic balance value between 11 to 16 was found to be effective in increasing the absorption of HCT. Furthermore, it suggested that the type of constituent fatty acid of sugar ester was one of several important factors for the promotion of the oral mucosal absorption of HCT.

Absorption↗
PubMed1988

Effects of penetration enhancers on percutaneous absorption of nifedipine. Comparison between Deet and Azone.

The influence of N, N-diethyl-m-toluamide (Deet) and 1-dodecylazacycloheptan-2-one (Azone), on skin permeability was examined for nifedipine (NP), taking into account their effects on the thermodynamic activity of the drug. The percutaneous absorption efficiency of NP was determined by measuring the drug concentration in rat plasma. Comparisons were made among NP suspensions in the enhancers to ensure equal thermodynamic activity. Azone increased NP penetration over that of propylene glycol (PG), while Deet produced a similar response to that of PG. The addition of a small amount of Deet to PG or diethyl sebacate (DES) provided for a rather large increase in NP penetration compared with that from PG or DES alone. The results of this study strongly suggest that Deet and Azone have different modes of action. Azone exerted a genuine effect on the skin and produced marked improvement in the penetration of NP. The effect of Deet was interesting as it was effective only in combination with other vehicles. Deet exhibits excellent solubilizing properties and penetrates the skin easily. Accordingly, it may be concluded that Deet functions simply as a cosolvent to produce saturated or supersaturated solutions of the active ingredient by its rapid disappearance from the vehicle, and thereby maximizes the thermodynamic activity of the drug.

Animals↗
PubMed1987

Moment analysis of intravenous, intraduodenal, buccal, rectal and percutaneous nifedipine in rats.

The pharmacokinetics and bioavailability of intravenous, intraduodenal, buccal, rectal and percutaneous nifedipine were studied in rats to evaluate the influence of route of administration. Plasma concentrations of nifedipine were determined by electron capture gas-liquid chromatography with preliminary oxidation of the drug to its pyridine analog. Pharmacokinetic evaluations were carried out by noncompartmental analysis of plasma concentration-time curves based on the statistical moment theory. The moments were computed by fitting a polyexponential function to the discrete time-course data of plasma concentration using the iterative least-squares method. A good computer fit to biexponential kinetics and a short mean residence time were observed after intravenous administration (i.v.). The linear distribution and disposition of nifedipine was found within the dosing range tested (0.025-0.100 mg/kg, i.v.). The systemic availability of nifedipine after intraduodenal administration was on the average between 52% and 57%, indicating that nifedipine is extensively metabolized during first passage through the liver. Avoidance of first-pass metabolism was investigated following buccal, rectal and percutaneous administration to rats. These nonportal routes of administration gave approximately 10-30% increases in systemic availability compared to that from intraduodenal nifedipine delivery. Moment analysis revealed variations of mixing condition of nifedipine at the dosing site. It was shown that the absorption occurs in a mammillary manner after intraduodenal and rectal administration. On the other hand, there is steady-state absorption of the drug from the buccal route of administration. Following percutaneous administration, the drug seems to be absorbed catenary to some degree.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Buccal↗
PubMed1987

Enhancement of transdermal delivery by superfluous thermodynamic potential. I. Thermodynamic analysis of nifedipine transport across the lipoidal barrier.

In vitro techniques were used to test certain concepts regarding the enhancement of the transdermal delivery of nifedipine from topical vehicles. Tested vehicles include the volatile solvent acetone, nonvolatile solvents such as propylene glycol and isopropyl myristate, volatile/nonvolatile mixtures, and those mixtures with a polymer additive. An ethylene-vinyl acetate (EVA) copolymer membrane was used as the lipoidal barrier for the diffusing drug. Not merely the rate of transport per unit area, but the activity coefficient and the diffusion coefficient of the penetrating agent in the barrier were obtained. Despite the 10,000-fold difference in the vehicle concentration, water and several hydrophilic vehicles containing finely ground suspensions of the drug produced nearly the same rate of penetration. Some lipophilic solvents affected the barrier function of the EVA membrane to promote penetration of the drug. It has been found that the activity coefficient in the EVA membrane is very susceptible to wide variations by imbibition of such solvents. From volatile/nonvolatile mixtures, a transient enhancement in the transport of nifedipine across the membrane was observed. The increase in the flux was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The eventual decrease in penetration was the result of the drug precipitation from the supersaturated solution. The precipitation was inhibited and/or retarded during the entire time course of the experiments when a polymer additive was present. The steady-state fluxes from mixtures with a polymer additive were higher by about 3 to 5 times than that of the control experiment.

Biological Transport↗
PubMed1987

Enhancement of transdermal delivery by superfluous thermodynamic potential. II. In vitro-in vivo correlation of percutaneous nifedipine transport.

Nifedipine was selected as a representative compound to investigate a method for improving transdermal bioavailability. The general strategy explored to improve the percutaneous transport of nifedipine was the manipulation of thermodynamics of the drug substance by the use of volatile/nonvolatile systems as vehicles. To investigate the potential of the strategy, diffusion studies were conducted using an ethylene-vinyl acetate copolymer (EVA) membrane and full-thickness excised abdominal skin of rats. Little penetration through EVA membrane or rat skin was found either from the volatile solvent ethanol (EtOH) or from the nonvolatile solvent diethyl sebacate (DES). When the vehicle was changed to a mixed solvent containing both EtOH and DES in a volume ratio of 75:25, penetration through EVA membrane or rat skin was increased up to 3 to 4 times, compared with those values for DES. The increase in the penetration was accounted for by the increase in the thermodynamic activity of the drug in the nonvolatile vehicle caused by the evaporation of the volatile component. The bioavailability of percutaneous nifedipine in rats was determined from the drug solutions containing different proportions of EtOH and DES. Once again, the highest bioavailability was achieved from the mixed solvent containing EtOH and DES in a volume ratio of 75:25. The area under the plasma nifedipine concentration-time curve for the mixed solvent was higher by about 4 times than that for DES.

Administration, Cutaneous↗
PubMed1987

Enhancement of transdermal delivery by superfluous thermodynamic potential. III. Percutaneous absorption of nifedipine in rats.

The bioavailability of percutaneous nifedipine was studied in rats. To improve the transdermal delivery of nifedipine, concentration changes due to loss of a volatile component in the vehicle were utilized. The percutaneous absorption of nifedipine was enhanced from binary solvent systems of acetone and propylene glycol (PG) or isopropyl myristate (IPM), compared with the results from simple PG or IPM saturated with the drug. In contrast, no appreciable increases in the percutaneous absorption of nifedipine from PG or IPM above controls were observed for pretreatment of the dosing site with acetone. From a ternary vehicle of volatile/nonvolatile-hydrophile/nonvolatile-lipophile solvent system, i.e., acetone-PG-IPM, a very dramatic enhancement in the bioavailability of nifedipine was noted. In addition, a marked increase in the penetration of PG from the ternary solvent system was found, compared with the result from the binary solvent system of acetone and PG. Nifedipine solutions with the volatile component eventually caused precipitation at the dosing site and so reduced the plasma nifedipine concentration. The precipitation was inhibited or retarded when polymer additives were incorporated in the ternary solvent system, and the high plasma nifedipine concentrations were maintained. This effect was not diminished when the formulation was administered immediately after the evaporation of acetone. The area under the plasma nifedipine concentration-time curve from the ternary solvent system with a polymer additive was higher by about 75 times than that from PG saturated with the drug.(ABSTRACT TRUNCATED AT 250 WORDS)

Acrylic Resins↗
PubMed1985

Determination of nifedipine in human plasma by high-performance liquid chromatography with electrochemical detection.

A rapid, accurate and sensitive high-performance liquid chromatographic assay was developed for the determination of nifedipine in human plasma. A toluene extract of an alkalinized plasma sample was chromatographed on a reversed-phase column with electrochemical detection at +0.95 V. The recovery of nifedipine from plasma was about 100%. The detection limit for nifedipine in plasma was 2 ng/ml using 0.5 ml of sample. The assay gave a linear response over the concentration range 5-400 ng/ml in plasma. The coefficients of variation from 9.6 to 191.0 ng/ml varied between 5.2 to 1.0% and the accuracy did not exceed 3.0%. Photodegradation products and metabolites of nifedipine did not interfere in the analysis. This method allowed the behaviour of nifedipine in humans to be studied.

Administration, Oral↗