• Archives of Pharmacal Research
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• v.18 no.4
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• pp.219-223
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• 1995

Rectal absorption of opeprazole, a proton pump inhibitor, from suppositories was studied in rabbits. The suppositories were prepared by the conventional melting method with two types of bases, water-soluble polyethylene glycol (PEG) 4000 and oil-soluble Witepsol H15 bases, and administered intractally (ir) to rabbits at a dose of 10 mg omeprazole/kg. The plasma omeprazole concentration-time profiles of the two suppositories were compared with those following intravenous 9iv) administration of the same dose. There were no significant differences between the two suppositories in bioabailabilities and peak plasma concentrations $(C_{max})$. Bioavaiabilities and $C_{max}$ of PEG- and Witpsol suppositories were 30.3 and 33.9%, and 7.0 and $5.6\mug/ml$, resepectively. However, PEG suppository showed significantly (p<0.05) shorter time to reach peak plasma concentration $(T_{max})$ mean absorption time (MAT) and mean residence time in the plasma (MRT) than Witepsol suppository. The $T_{max}$ MRT nad MAT were 25.0, 83.0 and 38.5 min for PEG syppository, but were 90.0, 122.5 and 78.0 min for Wiepsol supposiotory, respectively. These differences between thw two suppositories could be explanined by the difference in the in vitro dissolution rates between the suppositories. The dissolution of omeprazole form PEG suppository was reportedly much faster than that from Witepsol suppository. It suggests that plasma profiles of omeprazole, especially $C_{max}$ MAT and MRT, could be controlled by modifying the in vitro dissolution rate of the drug from the suppositories. Above results suggest that rectal suppository is worth developing as an alternative dosage form of omeprazole to the conventional oral preparations which need sophisticated treatments, such as enterix coating, to prevent acid degradation of the drug in the stomach fluid.

• Journal of Pharmaceutical Investigation
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• v.14 no.2
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• pp.55-61
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• 1984

This investigation was designed to determine the release of fenbufen from suppositories and their bioavailability in rabbits. Suppositories containing fenbufen were made by the fusion method with Witepsol H-15, Wecobee and PEG 1540 base. Displacement value, weight variation, content uniformity, melting point and melting time were determined for preformulation of the fenbufen suppositories. The release rates were determined with the KP dissolution apparatus and with cellophane tube dialysis device and were increased in order of PEG 1540, Witespol H-15 and Wecobee. The bioavailabilities of fenbufen after rectal administration were also increased in order of PEG 1540, Witespol H-15 and Wecobee.

• Journal of Pharmaceutical Investigation
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• v.21 no.2
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• pp.73-78
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• 1991

The influence of different suppository bases on the rectal absorption and the dissolution rate of propranolol was investigated. The bioavailability of propranolol in rectal suppository was determined by comparing the area under the concentration-time curves(AUC) for oral administration with rectal suppositories in rabbits. The dissolution $rates(D_{20min})$ were higher in such order as tween (TWE), witepsol H-15(WIT), polyethylene glycol(PEG) suppository. The maximum blood concentrations $(C_{max})$ were 803.9 ng/ml for TWE suppository, 770.2 ng/ml for WIT suppository, 281.2 ng/ml for PEG suppository and 177.1 ng/ml for oral administration. The relative bioavailabilities were 233.5% for TWE suppository, 218.1% for TWE suppository, 191.3% for PEG suppository. The correlation between $D_{20min}$ and AUC, the time for dissolution in 75% and $C_{max}$, the mean dissolution time and the mean residence time showed significant linear relationship respectively.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.11a
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• pp.21-24
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• 1993

Many attempts have been made to use hydrogel as del ivory systems for various drug and vioactive materials to prolong and control their pharmacological activities. Rectal administration of drugs by using hydrogel bases, such as poloxamer ABA block copolymer (Pluronic F-127) gels, polyacrylic acid (Carbomer 934, 940, or 941) aqueous gels, and polyvilyl alcohol gels, have been reported on the preparation and potential suppository use of new gels(Eudragit L, Eudragit S, and Eudispert) that are block copolymers of methacrylic acid and methyl methacrylate. If) These hydrogel and xerogel preparations, especially Eudispert hv gels, show excellent staying and bioadhesive effects in the lower part of the rectum in rats and rabbits compared with those of polyethylene glycol (PEG)2000 and Witepsol H-15(or S-55) suppositories. Visual and optical microscopic observation of rectal membrances indicated no irritation or abnormality after administration of Eudispert hv tydrogel and xerogel.

• Journal of Pharmaceutical Investigation
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• v.25 no.3
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• pp.227-237
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• 1995

Omeprazole(OMP) complexes such as inclusion complexes of OMP with $hydroxypropyl-{\beta}-cyclodextrin$(HPCD) and ${\beta}-cyclodextrin({\beta}-CD)$, OMP-cholestyramine(CHL) and OMP-ethylenediamine(OMP-ED) were prepared, respectively. The partition coefficients in Witepsol H-15 /pH 7.4 phosphate buffer solution of OMP complexes$(OMP-HPCD;\;3.69{\pm}0.26,\;OMP-{\beta}-CD;\;4.08{\pm}0.21,\;OMP-CHL;\;4.36{\pm}0.25\;and\;omeprazole\;sodium(OMP-Na);\;3.64{\pm}0.37)$ were higher than that of OMP $(2.66{\pm}0.47)$. OMP was not completely dissolved until even 3 hrs, but all the OMP complexes studied were released about 100% in 20 min. The rectal suppositories containing OMP or each above OMP complex were prepared using Witepsol H-15 base, and their dissolution and stability were examined, and pharmacokinetic study were investigated after their rectal administrations to the rabbits. While the suppository containing OMP was released only less than 60% in 150 min, $OMP-{\beta}-CD$, OMP-CHL, OMP-Na and OMP-ED suppositories were all released about 65% in 20 min. Especially, OMP-HPCD suppository released OMP about 70% in 10 min. All the additives such as sodium laurylsulfate, eglumine, arginine and PVP increased drug release from OMP-HPCD suppository to some extent. The decomposition rate constants of OMP in the suppositories were $9.117{\times}10^{-3}\;day^{-l}$ for OMP suppository, $2.121{\times}10^{-2}$ for OMP-HPCD, $1.607{\times}10^{-2}$ for $OMP-{\beta}-CD$, $9.26{\times}10^{-3}$ for OMP-Na, $6.769{\times}10^{-3}$ for OMP-CHL and $5.58{\times}10^{-3}\;day^{-l}$ for OMP-ED suppository, respectively. Additives such as arginine, eglumine and ED had some stabilizing effect for OMP-HPCD, OMP-CHL and OMP-Na suppositories, respectively. After 6 month-storage at $30^{\circ}C$, 75% RH, OMP-CHL suppository was most stable. The values of Tmax for OMP-HPCD and OMP-Na suppositories were $11.7{\pm}2.36\;and\;11.4{\pm}2.56\;min$, respectively. The values of Cmax for OMP-HPCD and OMP-CHL suppository were $2.31\;{\mu}g/ml\;(p<0.01)\;and\;1.89\;{\mu}g/ml\;p<0.01)$, respectively. The values of AUC for OMP and $OMP-{\beta}-CD$ suppository were $61.9{\pm}25.79\;and\;68.6{\pm}29.48\;{\mu}g\;{\cdot}\;min/ml$, and the corresponding values for OMP-HPCD and OMP-CHL were $106.1{\pm}43.16\;(p<0.05)\;and\;127.3{\pm}42.52\;{\mu}g\;{\cdot}\;min/ml(p<0.01)$, respectively. The above results indicate the OMP-HPCD and OMP-CHL suppositories have the excellent bioavailabilties in vivo study.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1995.04a
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• pp.132-132
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• 1995

OMPED의 결합비는 1:1 몰비로 복합체가 형성됨을 확인하였다. 수용액중(pH 7.0)에서 OMP는 분해속도 k=1.542$\times$$10^{-2}$$hr^{-1}$, shelf life=6.81hr 이었고 OMPED는 k=2.088$\times$$10^{-4}$$hr^{-1}$, shelf life=502.8hr이며 중성은 물론 약산성에서 안정하였다. HPMCP로 장용피한 OMPED pellet은 산저항성이 완벽하고 용출속도가 양호하였으며, OMPED 정제에서는 CAP로 코팅한 정제가 가장 큰 AUC값을 나타내었다. Witepsol H-15 기제를 사용한 각 좌제의 생체이용율은 OMPED 좌제가 86.53 $\mu\textrm{g}$ㆍmin/$m\ell$ 로서 OMP 좌제 61.9 $\mu\textrm{g}$ㆍmin/$m\ell$ 및 OMP-$\beta$-CD 좌제 68.8 $\mu\textrm{g}$ㆍmin/$m\ell$이다.

• Journal of Pharmaceutical Investigation
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• v.18 no.2
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• pp.61-67
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• 1988

The influence of different suppository bases on the dissolution, and the bioavailability of aspirin suppositories in rabbits and humans was investigated using Witepsol H15 (WIT), WIT-Tween 80 (TWE), WIT-sodium lauryl sulfate (SLS), polyethylene glycol (PEG), hollow WIT (WIT-HOLL) and capsule incorporated into WIT (WIT-CAP). The results obtained were as follows: 1) Dissolution rates of aspirin suppositories with different bases in distilled water were faster in the order of WIT-TWE >WIT-SLS >PEG >WIT-HOLL >WIT >WIT-CAP. 2) The maximum blood levels $(C_{max})$ of aspirin in rabbits and humans were highest in WIT-TWE and WIT-SLS bases, but $C_{max}$ from WIT base was lower than that in oral administration of aspirin suspension. 3) The times reaching the maximum blood levels $(T_{max})$ in rabbits were 1 hr for oral administration, 1.5-2.5 hr for WIT-TWE, WIT-SLS, PEG, and WIT bases, and 2.5-4.0 hr for WIT-HOLL and WIT-CAP bases, but $T_{max}$ in humans were 1 hr for oral administration and WIT-TWE base, and 2-4 hr for WIT and WIT-HOLL bases. 4) Relative bioavailability (RBA) of aspirin suppositories in rabbits was higher in WIT-SLS, WIT-TWE and PEG bases than that in oral administration, and RBA of aspirin suppositories in humans was higher in the order of WIT-TWE >PEG >WIT-HOLL >oral >WIT bases tested. 5) Good correlation between dissolution rates and $C_{max}$ was obtained: y = 0.60x+32.23 (r = 0.96) for rabbits, and y = 0.60x+35.74 (r = 0.97) for humans.