Biomedical subjects

Riichi Tawa

Publications and source records attributed to Riichi Tawa.

3 recordsLinked to original sources

PubMed2005

Oral solid gentamicin preparation using emulsifier and adsorbent.

Oral gentamicin (GM) therapy has been challenged by formulating GM in oral solid preparation. GM was dispersed with a surfactant used for the self-microemulsifying drug delivery system (SMEDDS), PEG-8 caprylic/capric glycerides (Labrasol), and the mixture was solidified with several kinds of adsorbents. The used adsorbents were microporous calcium silicate (Florite RE), magnesium alminometa silicate (Neusilin US2), and silicon dioxide (Sylysia 320). In vitro release study showed that the percentage released of GM from each preparation per 2 h was 99.8+/-0.06% for Florite RE 10 mg, 96.7+/-1.16% for Florite RE 20 mg, 98.3+/-0.32% for Neusilin US2, and 94.4+/-0.23% for Sylysia 320. The T50% values were 0.35+/-0.05 h for Florite RE 10 mg, 0.34+/-0.03 h for Florite RE 20 mg, 0.26+/-0.03 h for Neusilin US2, and 0.15+/-0.01 h for Sylysia 320. The in vivo rat absorption study showed that Florite RE 10 mg preparation had the highest C(max) (2.14+/-0.67 microg/ml) and AUC (4.74+/-1.21 microg h/ml). Other preparations had C(max) and AUC of 0.69+/-0.10 microg/ml and 1.56+/-0.43 microg h/ml for Florite RE 20 mg, 1.07+/-0.31 microg/ml and 1.80+/-0.33 microg h/ml for Neusilin US2, and 0.99+/-0.21 microg/ml and 1.77+/-0.50 micorg h/ml for Sylysia 320, respectively. The bioavailability (BA) of GM from the microporous calcium silicate preparation, Florite RE 10 mg, was 14.1% in rats, derived by comparing the AUC obtained after intravenous injection of GM, 1.0 mg/kg, to another group of rats. The microporous calcium silicate preparation using Florite RE 10 mg was evaluated in dogs after oral administration in an enteric capsule, Eudragit S100 (50 mg/dog). High plasma GM levels were obtained (i.e., the C(max) was 1.26+/-0.20 microg/ml and the AUC was 2.59+/-0.33 microg h/ml). These results suggest that an adsorbent system is useful as an oral solid delivery system of poorly absorbable drugs such as GM.

Adsorption↗

PubMed2003

Evaluation of oral formulations of gentamicin containing labrasol in beagle dogs.

Gentamicin (GM) is a polarized water-soluble compound having very poor intestinal membrane permeability resulting in low oral bioavailability. Labrasol was found to improve the intestinal absorption of GM in rats. In the present study, GM formulations containing labrasol were evaluated in beagle dogs after filling into hydroxypropylmethyl cellulose (HPMC) capsules wrapped with Eudragit L100 (Eud L) and Eudragit S100 (Eud S) films. The results of the in vitro drug release studies could not differentiate between two kinds of enteric capsules and among the three kinds of GM formulations. Oral administration of GM solution at a dose of 50.0 mg per dog of GM and 0.60 ml per dog of labrasol has resulted in Cmax values of 2.38 +/- 0.50 microg/ml and 2.30 +/- 0.42 microg/ml with Eud L and Eud S capsules, respectively. The AUC values obtained were also higher at 4.35 +/- 1.31 microg h/ml and 5.34 +/- 0.95 microg h/ml with Eud L and Eud S capsules, respectively. Formulation of GM as a suspension in labrasol has resulted in the decrease of Cmax values by two to four times and AUC values by > 2.5 times compared to the solution formulation. The above results indicate that solution formulation was better over the suspension. An absorbent, synthetic sponge was used to absorb GM solution formulation and encapsulated with Eud L and Eud S capsules. The Cmax and AUC values obtained with sponge formulation were higher than those of suspension formulations but were lower than solution formulations. There was no significant difference in the extent of GM absorption between Eud L and Eud S capsules used for encapsulating GM formulations.

Administration, Oral↗

PubMed2002

Diethyl ether fraction of Labrasol having a stronger absorption enhancing effect on gentamicin than Labrasol itself.

In our previous study, we had reported that Labrasol has a good gastrointestinal (GI) absorption enhancing effect on poorly absorbable drugs. In order to improve further absorption enhancing effect of Labrasol on gentamicin (GM), which is a representative water-soluble, poorly absorbable drug, Labrasol was fractionated with hexane, diethyl ether, ethyl acetate and water. The absorption enhancing effect of each fraction of Labrasol and Labrasol alone were evaluated in vivo using rats. Each test formulation of GM was administered into the rat colon at a dose of 5.0 mg/kg and plasma GM concentrations were measured by a HPLC method. Among the four fractions of Labrasol and Labrasol, diethyl ether fraction showed the strongest absorption enhancing effect on GM. When the doses of diethyl ether fraction were 1.0, 0.5 and 0.1 ml/kg, the Cmax values were 8.95 +/- 1.46, 8.02 +/- 2.14 and 7.41 +/- 1.25 microg/ml, respectively. Moreover, AUC(0-6) values were also maintained at high level, i.e. 27.28 +/- 5.90, 20.32 +/- 3.79 and 19.61 +/- 2.09 microg h/ml. Based on the AUC(0-6) values obtained with each fraction, the rank order of absorption enhancing effect on GM was diethyl ether > ethyl acetate=hexane > aqueous fraction.

Animals↗