• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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• pp.177-177
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• 1994

좌제중에서 OMZ의 분해는 1차 반응적이었으며, 안정화제로서는 arginine이 가장 좋아서 arginine을 10 mg 첨가한 Witepsol H15 좌약과 PEG 4000좌약의 분해속도 상수는 각각. 3.89$\times$10-3day$^{-1}$, 8.67$\times$$10^{-3}$ day$^{-1}$이어서, arginine 비첨가 Witepsol Hl5기제 (k = 00.11 day$^{-1}$, PEG 4000기제( k = 0.48 day$^{-1}$)의 경우보다 훨씬 양호하였으며, 35$^{\circ}C$, 75%RH에서 장기보존시험 결과 Witepsol H15 좌제와 PEG 4000 기제는 각각 k = 3.63$\times$$10^{-4}$ day$^{-1}$, t190% = 291 8 days와 k = 3.69$\times$$10^{-4}$ day$^{-1}$ 및 t90% = 282.1 days이었으며, 좌제로부터 약물의 용출에 미치는 영향은 arginine의 첨가, 원료약품 입자의 미세화, 적절한 계면활성제의 첨가 그리고 지용성 기제량의 감소등으로서 이들은 약물의 용출을 증가시켰다. 실험한 좌약의 bioavailability는 경구용 캅셀이 17%, 지용성좌제 44.9%, 수용성좌제 41.0%로서 좌제가 유의성 있게 높았으며(p<0.01), 지용성좌제에 SLS나 EDTA를 첨가하였을 때에는 각각 29.7%, 32.7%로서 이들을 첨가하지 않았을 때 보다 유의성 있게 낮았다(p<0.01). 또한 직장점막 자극시험결과 부작용을 관찰할 수 없었으며 간초회통과 회피율은 수용좌제에서 28.9%, 지용성좌제에서 33.6%로 나타나서 OMZ의 투여경로는 직장좌제가 유용한 한가지 투여방법이 될 것임을 시사하였다.

• YAKHAK HOEJI
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• v.43 no.2
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• pp.150-159
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• 1999

Hollow type suppositories inserted polyvinyl alcohol (PVA) hydrogel capsule containing propranolol·HCI (PPH) were prepared using different bases, polyethylene glycol (PEG), Witepsol H-15 (WH-15) and Witepsol W-35 (WW-35) to improve the controlled release of PPH. The release of PPH from the hollow type suppository inserted PVA hydrogel capsule was retarded than that from PEG, WH-15, or WW-35 hollow type suppositories in rat rectal cavity. When the suppositories were administered to rats, the controlled release of PPH was proved by the plasma concentration-time-profiles of PPH. No significant difference (p〈0.05) among the three different hollow type suppositories was observed in terms of AUC and MRT of PPH. WH-15 hollow type suppository inserted 12% of PVA hydrogel capsule caused irritation to rat rectal mucosa. However, the WH-15 hollow type suppository inserted PVA hydrogel capsule caused no severe irritation on rectal mucosa. The application of the hollow type suppositories using PVA in sustained rectal delivery of drugs might be feasible.

• YAKHAK HOEJI
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• v.37 no.5
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• pp.427-436
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• 1993

The pharmacokinetics and relationship between in vitro dissolution and in vivo fraction absorbed were investigated after intravenous(iv) injection of omeprazole(OMZ), oral administration of OMZ capsules and rectal administration of 8 types of suppositories. The plasma concentration of OMZ (C$_{p}$)-time (t) curve after iv. administration fitted a two-compartment open model and the equation which best fitted the pharmacokinetics of OMZ was $C_{p}$ = 13.936 $e^{-8.78t}$+2.973 $e^{-0.716t}$. The bioavailabilities of OMZ in Witepsol H15 base (Supp-2) and PEG 4000 base (Supp-6) suppositories were 40.7% and 33.4%, respectively, which are higher(p<0.001) than 13% of oral administration of capsule. The avoidance fractions of the first-pass metabolism for Supp-2 and Supp-6 suppositiories were 31.8% and 23.4%, respectively, suggesting that the rectal application of OMZ may be a more adequate route of administration than oral one.

• YAKHAK HOEJI
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• v.49 no.4
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• pp.260-267
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• 2005

[ $PGE_1$ ] is an endogenous substance of potent vasodialator as well as inhibitor of platelet aggregation. It has been used therapeutically in peripheral arterial occlusive disease and impotence. Intracavernous injection of $PGE_1$ for erectile dysfunction has been established for several years as a treatment option for erectile dysfunction of diverse etiologies, but this mode of administration is limited by penile discomfort, pain at the injection site, inconvenience and noncompliance. As the matter of worse, the $\beta-hydroxy$ moiety of $PGE_1$ is extremely susceptible to dehydration in solution to give inactive $PGA_1$ and $PGB_1$. For the improvement of stability, rapid absorption at action site and the convenience of application, $PGE_1$ was formulated as urethral suppositories of three types of formulations, such as PEG, witepsol, and the mixture of PEG and witepsol. The stability test of $PGE_1$ and the release test in urinary suppositories were performed. Futhermore, the effect of enhancers and vehicle composition on the penetration of $PGE_1$ through excised rat skin was evaluated by permeability coefficient and enhancement ratio.

• Journal of Pharmaceutical Investigation
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• v.24 no.3
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• pp.145-153
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• 1994

Ibuprofen is an effective non-steroidal anti-inflammatory drug (NSAID), but it has several limitations in clinical application because of low solubility in water and gastrointestinal irritation. A water-soluble salt of ibuprofen, ibuprofen Iysinate, has been synthesized to overcome these shortcomings, and it was formulated as suppository for rectal administration. Witepsol and polyethylene glycols were employed as suppository bases for either ibuprofen or ibuprofen Iysinate, in order to compare the bioavailability in rabbits. The plasma concentrations of ibuprofen were assayed by HPLC after a rectal administration of ibuprofen and ibuprofen Iysinate, respectively. In addition to the comparison of two suppository bases, the other factors which affect on rectal absorption were also evaluated, especially in the point of not only particle size and shape of ibuprofen Iysinate but also effects of additives such as stearic acid, cetyl alcohol and capric acid. And pharmacokinetic parameters such as AUC, $C_{max}$, and $T_{max}$ were also compared. In conclusion, spray-dried ibuprofen Iysinate which was polyporous and spherical shape gave an increased absorption from the rectal formulations with Witepsol Hl5 and stearic acid.

• 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.

• 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.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.