Biomedical subjects

K Sugibayashi

Publications and source records attributed to K Sugibayashi.

At least 73 records · Page 4Linked to original sources

PubMed1990

A disintegration test for vaginal tablets: comparison with BP test.

To improve the disintegration test for vaginal tablets described in the British Pharmacopoeia (BP), a monitoring apparatus was added, and tested with seven effervescent and five non-effervescent tablets. A tablet was placed on the metal disc of the BP disintegration apparatus, and the guided plate was placed on the tablet. The guided plate moved downward smoothly in a cylinder as the tablet disintegrated. The movement was recorded by using a kymograph. The end-point and process of disintegration of the tablet were automatically recorded and the results obtained suggest that the modified test is a useful tool for the quality control of vaginal tablets.

Female↗

PubMed1990

Disintegration test to measure lot-to-lot variations of vaginal tablets.

Attempts were made to investigate the disintegration test for vaginal tablets. Disintegration tests were done for four different commercial vaginal tablets (three lots each) by the watch glass method and Japanese Pharmacopoeia (JP) disintegration method, and the resulting profiles were compared to those by the modified British Pharmacopoeia (BP) method on a point of lot-to-lot variation of the disintegration times. The disintegration time of every tablet by the modified BP method was longest, followed by the watch glass method, and finally by the JP disintegration method. The results for lot-to-lot differences in disintegration times by the modified BP method were similar to those by the watch glass method. However, such lot-to-lot differences as found by the modified BP method and watch glass method were not always observed by the JP disintegration method. It was concluded from these results that the modified BP method was most suitable for investigating lot-to-lot differences in the disintegration of vaginal tablets.

Administration, Intravaginal↗

PubMed1990

Enhanced transdermal delivery of zidovudine in rats and human skin.

Zidovudine (azidothymidine, AZT), a potent antiviral agent acting on acquired immunodeficiency syndrome virus, was examined with regard to permeation through rat and human skin. A steady state plasma concentration of AZT after transdermal application in rats estimated from both pharmacokinetics data after i.v. administration and penetration rate through excised rat skin from 10% oleic acid (OA) aqueous solution shows penetration about 85 times higher compared to that from 10% OA would be needed for therapeutic efficacy. A mixed-solvent system consisted of 5% Sefsol-318 (S-318), 10% OA, 10% N-methyl-2-pyrrolidone (MP), 20% propylene glycol (PG) and water showed promising characteristics as a vehicle in terms of permeability of AZT through excised rat skin. The maximum flux of 0.41 mumol/cm2/h was observed in excised human skin after application of a gel formulation including S-318, OA, MP and PG. The result suggests a possible use of the gel formulation to gain an effective plasma concentration in humans.

Administration, Cutaneous↗

PubMed1990

Prediction of skin permeability of drugs. I. Comparison with artificial membrane.

In order to measure the contribution of lipid and pore (aqueous) pathways to the total skin permeation of drugs, and to establish a predictive method for the steady state permeation rate of drugs, the relationship between permeability through excised hairless rat skin and some physicochemical properties of several drugs were compared with those through polydimethylsiloxane (silicone) and poly(2-hydroxyethyl methacrylate) (pHEMA) membranes, as typical solution-diffusion and porous membranes, respectively. A linear relationship was found between the permeability coefficients of drugs for the silicone membrane and their octanol/water partition coefficients. For the pHEMA membrane, the permeability coefficients were almost constant independent of the partition coefficient. On the other hand, the skin permeation properties could be classified into two types: one involves the case of lipophilic drugs, where the permeability coefficient is correlated to the partition coefficient, similar to the silicone membrane; and the other involves hydrophilic drugs, where the permeability coefficients were almost constant, similar to pHEMA membrane. From the above results, the stratum corneum, the main barrier in skin, could be described as a membrane having two parallel permeation pathways: lipid and pore pathways. An equation for predicting the steady state permeation rate of drugs was derived based on this skin permeation model.

Animals↗

PubMed1990

Membrane permeation-controlled transdermal delivery system design. Influence of controlling membrane and adhesive on skin permeation of isosorbide dinitrate.

A membrane permeation-controlled transdermal delivery system (MC-TDS) of isosorbide dinitrate (ISDN), a model drug, was prepared from polyvinyl alcohol aqueous gel containing the drug, a membrane consisting of ethylene-vinyl acetate copolymer membrane and acrylic adhesive (EV-a). The permeability of ISDN through the EV-a membrane was 2.5 times higher than that through excised hairless rat skin. The ratio of plasma concentration of ISDN after application of MC-TDS on stripped (damaged) skin relative to intact skin was lower than that after application of Frandol tape-S, a marketed ISDN TDS, which suggests that the EV-a membrane might work as a control membrane for overall delivery rate of ISDN to the body. When MC-TDS stored at 30 degrees C for 13.5-48h was applied to the damaged skin, however, the initial plasma concentration of ISDN was very much higher than the expected therapeutic level and was not controlled by the EV-a membrane. The initial high plasma concentration of ISDN after application of the stored MC-TDS on the damaged skin was due to migration of ISDN from the reservoir to the adhesive during storage at 30 degrees C. The migration of drugs into the adhesive might be an important problem in developing efficient MC-TDS.

Administration, Cutaneous↗

PubMed1990

Effect of monoglycerides on the percutaneous absorption of papaverine hydrochloride.

The skin permeation enhancement of papaverine hydrochloride by free fatty acids (C3-C12), monoglycerides (side chains C5-C12) and caprylic acid (C8) esters was evaluated using the excised hairless rat skin. Enhancement was marked in the case of glyceryl monocaprylate; the cumulative amount of papaverine that permeated through skin over 28 hours from an aqueous suspension was 29.7 mg/cm2 with, and 26.9 micrograms/cm2 without glyceryl monocaprylate. The mechanism of enhancement was studied by measuring the effect the enhancers had on the diffusion and partition parameters of papaverine. Free fatty acids mainly affected the drug's diffusion, and monoglycerides mainly affected the drug's partition. For monoglyceride enhancers, a good linear relationship between the flux of papaverine and the amount of enhancer in skin was established. n-Octanol-water partition coefficients (log Pcal) of the enhancers were selected as indicators of their physicochemical properties, and related to their penetration-enhancing abilities. A parabolic relationship was found between the log of the flux of papaverine and log Pcal, for all types of enhancers. The relationship may be a good indicator in predicting enhancing effects.

1-Octanol↗

PubMed1989

Utility of topical formulations of morphine hydrochloride containing azone and N-methyl-2-pyrrolidone.

In order to develop the transdermal formulations of morphine hydrochloride with high skin permeation rate and prolonged action, several gels and patches containing potent penetration enhancer, laurocapram (Azone), were prepared. Since there was a long lag time period for morphine permeation through the excised hairless rat skin in Azone treatment, N-methyl-2-pyrrolidone was added to the Azone gel or patch as a co-enhancer to increase the skin permeation of morphine hydrochloride, especially in the early phase. The mixed solvent of N-methyl-2-pyrrolidone and water showed cosolvency of morphine hydrochloride, and the co-enhancer could shorten the lag time period of skin permeation of morphine hydrochloride. However, the co-enhancer alone had little effect on the skin permeation of morphine hydrochloride. It was effective only when using with Azone. Coadministration of Azone with the co-enhancer showed high in vitro skin permeation and in vivo blood level of the drug. A marked analgesic effect was found after application of morphine hydrochloride patch containing Azone and N-methyl-2-pyrrolidone. The pharmacological effect was much more prolonged than that after the conventional s.c. injection. From these results, it was predicted that the topical formulations of morphine hydrochloride containing Azone and N-methyl-2-pyrrolidone might be useful for the relief of severe chronic pain in patients.

Administration, Topical↗

PubMed1989

Prediction of the in-vitro human skin permeability of nicorandil from animal data.

A method for estimating the in-vitro permeability of human skin to drugs, based on in-vitro permeation studies using animal skins, has been developed. The skins from hairless rats, guinea-pigs, dogs and pigs were used, with nicorandil and deionized water as model drug and solvent in a drug-donor compartment. Diffusion coefficients through the skin barrier, D, and partition coefficients from the drug-donor compartment to skin, K, of the drug, in each species, were calculated by curve-fitting the in-vitro permeation data to a diffusion equation describing the drug permeation through a homogeneous membrane, using a non-linear least squares method. Each barrier thickness, L, was measured microscopically from microtomed skin sections. A positive relationship was found between the skin permeability, Kp, and K value among the four species, but species differences in the D and L values were small in spite of the Kp values being different among the four species. A positive correlation was also observed between the calculated and experimental K values among the four species, and hence it was suggested that the main factor for the species difference in the skin permeability of nicorandil would be the difference in partitioning of the drug from vehicle to stratum corneum. As a result, it has become feasible to predict and estimate skin permeability of nicorandil in humans by substituting each parameter, extrapolated from the animal skin permeation data and partition experiments, in the diffusion equation.

Animals↗

PubMed1989

Effect of several enhancers on the skin permeation of water-soluble drugs.

Since the percutaneous absorption rates of water-soluble drugs are low in general, an enhancing system is needed when using the skin as an administration site for the drugs. We have investigated the effect of various penetration enhancers on the in vitro and in vivo percutaneous absorptions of catecholamine analogs, i.e. levodopa (LD), dopamine hydrochloride (DPH) and isoproterenol hydrochloride (IPH), as model water-soluble drugs. It was found that medium-chain glycerides (Sefsol 318) markedly enhanced the in vitro permeation of the drugs through excised hairless rat skin among the enhancers tested in the present experiments; the permeation rates with 5% Sefsol 318 in water were about 65, 34 and 53 times higher than the corresponding control (without enhancer) for LD, DPH and IPH, respectively. In addition, the in vivo percutaneous absorption experiments showed that the blood levels of these drugs after application of aqueous gels containing 5% Sefsol 318 on rat skin were higher than those in the absence of enhancer. Drug levels in the liver and kidney were also higher than without Sefsol 318. Percutaneous administration of DPH with Sefsol 318 to hairless rats resulted in lower diastolic blood pressure and a slightly higher heart rate with as compared to administration without the enhancer. These results suggest that Sefsol 318 is a potential candidate to enhance the transdermal absorption of water-soluble drugs.

Animals↗

PubMed1989

Skin permeability of water-soluble drugs.

The permeabilities of several water-soluble drugs through excised hairless rat skin from their aqueous suspensions were investigated by using newly designed two-chamber diffusion cells. Disodium cromoglycate, diclofenac sodium, dopamine hydrochloride, isoproterenol hydrochloride, diltiazem hydrochloride and papaverine hydrochloride were selected as water-soluble drugs. Indomethacin, a lipophilic drug, and deuterium oxide (D2O) were used for comparison. The skin permeability coefficients of these water-soluble drugs were 100--1000 times lower than that of indomethacin. Since these drugs have high solubility in the donor solution (distilled water or lactate buffer), however, the skin permeation rates, which are in general proportional to the product of skin permeability coefficient and solubility of drugs in the drug-donor compartment, were comparable to or higher than that of indomethacin (1.7 micrograms/cm2/h): the skin permeation rate of dopamine hydrochloride (458 micrograms/cm2/h) was about 300 times higher than that of indomethacin. The water-soluble drugs with lower molecular weight and higher solubility in water showed higher skin permeation rates. These results suggest that some water-soluble drugs with low molecular weight and high solubility in water might be good candidates for transdermal drug delivery.

Animals↗

PubMed1989

[Study on transdermal absorption of borneol-salicylic acid eutectic mixture].

Borneol is an organic drug having property to form eutectic mixture with salicylic acid. We compared the transdermal absorption rate of borneol alone with that of borneol-salicylic acid eutectic mixture in hairless rats. The results showed that the borneol-salicylic acid eutectic mixture can evidently increase the absorption rate of borneol and provided a method for manufacturing borneol preparation which can easily be absorbed transdermally.

Animals↗

PubMed1989

Percutaneous absorption enhancer applied to membrane permeation-controlled transdermal delivery of nicardipine hydrochloride.

In the design of nicardipine hydrochloride-transdermal delivery systems (NC-TDS), the enhancing and regulating effects of penetration-enhancers and permeation controlling membranes were evaluated. Laurocapram (Azone) was selected as a model enhancer. Since its enhancing effect is considered to occur in the stratum corneum, its release from ethylene-vinyl acetate copolymers (EVAc), ethylene-vinyl alcohol copolymers (EVAl) or poly(2-hydroxyethylmethacrylate) (pHEMA) membranes was used as a criterion for membrane selection. The release rate was highest from pHEMA. Accordingly, a TDS consisting of a NC reservoir containing 1 w/v% Azone and a pHEMA membrane was prepared, and the effect of skin stripping on the plasma concentration of NC after NC-TDS administration was evaluated in rats. The increased ratio in drug plasma concentration caused by skin stripping was lower when the NC-TDS treatment was compared with a non-regulating NC-gel treatment. Our results suggest that the membrane permeation-controlled TDS of NC may be useful for long-term constant drug delivery with minimum dependence on skin conditions.

Administration, Cutaneous↗

PubMed1988