• 약학회지
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• 제35권3호
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• pp.197-202
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• 1991

In order to study drug release from the suppository, three types of hollow suppositories and one conventional suppository were prepared using indomethacin(IDM) as a model drug and Witepsol H-15 as a base. The 4 types of suppository prepared are as follows: type I, conventional suppository containing 50 mg of IDM powder, type II, hollow supository containing 50 mg of IDM powder in the cavity, type III, hollow suppository containing 25 mg of IDM powder in the base and IDM microcapsules (25 mg as IDM powder) in the cavity, and type IV, hollow suppository containing IDM microcapsules (25 mg as IDM powder) in the base and 0.5 ml of 5%(w/v) IDM-PEG 300 solution in the cavity. The drug amount released(%) from type II and I within 24 hrs was 46.7% and 66.9%, respectively. Comparing with the drug amount released from four types of suppository within initial 2 hrs and 24 hrs, that of type IV was high as 32.7% and 76.6%, respectively. IDM-ethycellulose microcapsules passed through 270 mesh sieve and the IDM content was 20.95%.

• Journal of Pharmaceutical Investigation
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• 제21권2호
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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.

• Journal of Pharmaceutical Investigation
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• 제23권3호
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• pp.127-132
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• 1993

The effect of omeprazole (OPZ) suppository on rat rectal mucosa was investigated microscopically. The suppository was prepared with Witepsol H15 base by molding method. Rectal irritation was evaluated according to defined pathological features. The suppository produced a slight damage to the rectal mucosa at 1 hr after the interectal administration, which was almost completely recovered within 24 hr. The damage was not due to OPZ but due to suppository base, Witepsol H15, itself, since Witepsol H15 suppository without OPZ produced the same damage. Therefore, it was concluded that OPZ itself has no rectal mucosa-irritating effect and thus can be developed as a suppository dosage form without any further toxicity problems.

• Journal of Pharmaceutical Investigation
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• 제34권2호
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• pp.91-94
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• 2004

To develop a poloxamer-based solid suppository with poloxamer mixtures, the melting points of various formulations composed of P 124 and P 188 were investigated. To investigate the effect of poloxamer to the dissolution ad dissolution mechanism of diclofenac sodium from the suppository the dissolution of diclofenac sodium delivered by the poloxamer-based suppository was performed. Furthermore, to investigate the mucoadhesive property of the poloxamer-based sold suppository, the identification test in the rectum was carried out after its rectal administration in rats. The poloxamer mixtures composed of P 124 and P 188 were homogeneous. Ver small amounts of P 188 affected the melting points of poloxamer mixtures. In particular, the poloxamer mixture [P 124/P 188 (97/3%)] with the melting point of about $32^{\circ}C$ was a sold for at room temperature and instantly melted at physiological temperature. Furthermore, very small amounts of P 188 in the poloxamer-based suppository hardly affected the dissolution rates of diclofenac sodium from the suppository. Dissolution mechanism analysis showed the dissolution of diclofenac sodium was proportional to the time. At 4 h after administration, the blue colo of poloxamer-based suppository [diclofenac sodium/poloxamer mixture (2.5/97.5%)] with the P 124/ P 188 ratio of (97/3%) and blue lake in the rectum was faded. However, the position of suppository in the rectum did not significantly change with time. Thus, it retained in thε rectum for at least 4 h. Our results indicated that the poloxamer-based sold suppository with P 124 and P 188 would be a candidate of rectal dosage form for diclofenac sodium.

• Archives of Pharmacal Research
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• 제26권2호
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• pp.162-167
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• 2003

Liquid suppository systems composed of poloxamers and bioadhesive polymers were easy to administer to the anus and mucoadhesive to the rectal tissues without leakage after the dose. However, a liquid suppository containing diclofenac sodium could not be developed using bioadhesive polymers. since the drug was precipitated in this preparation. To develop a liquid suppository system using sodium chloride instead of bioadhesive polymers, the physicochemical properties such as gelation temperature, gel strength and bioadhesive force of various formulations composed of diclofenac sodium, poloxamers and sodium chloride were investigated. Furthermore, the pharmacokinetic study of diclofenac sodium delivered by the liquid suppository was performed. Diclofenac sodium significantly increased the gelation temperature and weakened the gel strength and bioadhesive force, while sodium chloride did the opposite. The liquid suppositories with less than 1.0％ of sodium chloride, in which the drug was not precipitated, were inserted into the rectum without difficulty and leakage. Furthermore, liquid suppository gave significantly higher initial plasma concentrations and faster Tmax of diclofenac sodium than did solid suppository, indicating that drug from liquid suppository could be absorbed faster than that from solid one in rats. Our results suggested that a thermosensitive liquid suppository system with sodium chloride and poloxamers was a more physically stable, convenient and effective rectal dosage form for diclofenac sodium.

• Journal of Pharmaceutical Investigation
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• 제38권5호
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• pp.289-293
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• 2008

To develop a poloxamer-based solid suppository with poloxamer and polyethylene glycol mixtures, the melting point of various formulations composed of P 188 and propylene glycol were investigated. The dissolution and antitumor activity of clotrimazole delivered by the poloxamer-based suppository were performed. The poloxamer mixtures composed of P 188 and propylene glycol were homogeneous phases. P 188 greatly affected the melting point of poloxamer mixtures. In particular, the poloxamer mixture [P 188/propylene glycol(70/30%)] with the melting point of about $32^{\circ}C$ was a solid form at room temperature and instantly melted at physiological temperature. Furthermore, the ratio of P 188/propylene glycol greatly affected the dissolution rates of clotrimazole from poloxamer-based suppository. It gave the more effective anti-tumor activity than conventional PEG-based suppository due to fast dissolution. Thus, the clotrimazole-Ioaded poloxamer-based solid suppository was an effective rectal dosage form with anti-tumor activity.

• Journal of Pharmaceutical Investigation
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• 제28권4호
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• pp.275-282
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• 1998

In order to develop a desirable in vitro release which correlates well with in vivo bioavailability, hollow type suppository containing Propranolol HCl(PPH) powder in the cavity and conventional type suppository with dispersed PPH in the base were prepared. Polyvinyl alcohol (PVA) hydrogel as a base and PPH as a model drug were used for the preparation of suppository. The rates of drug release from the suppositories were studied by Paddle method, Muranish method, Dialysis tubing method and Rotating dialysis cell method. The release profiles from suppositories using the four different release tests were compared. After a rectal administration in rat, the mean $C_{max}$ of hollow type suppository was significantly lower than that of conventional type, but $T_{max}$, $AUC_{0{\to}12}$ and MRT of hollow type were significantly higher 1.6 times, 1.2 times and 1.9 times than those of conventional type, respectively. The computer program was used to simulate plasma concentration from in vitro released amounts of drug and in vivo pharmacokinetic parameters. Based on comparison of the simulated bioavailability from computer program with experimental bioavailability in rat we have found out in vitro release test which correlates well with in vivo bioavailability. Our results have shown the best correlation between in vitro release and in vivo bioavailability in PPH-PVA hydrogel hollow type suppository for the paddle method and conventional type suppository for the rotating dialysis cell method. In this work we propose that PPH-PVA hydrogel suppository shows in vitro-in vivo correlation. This data should help to optimize the formulation of the drug and provide a basis for quality control procedures.

• 한국임상약학회지
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• 제8권2호
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• pp.143-146
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• 1998

Acetaminophen (APAP) suppositories with active ingredients, i.e., polyethylene glycol (PEG), Witepsol H-15 (WH), were prepared for hospital use and investigated on their drug release characteristics and pharmacokinetics. WH was employed as oil-soluble base with an aim of reducing fragility and mucosa irritancy that are common drawbacks found in PEG suppositories. Also hollow type suppository was tried as compared with conventional type suppository. Drug release tests revealed that in most formulations, more than $80\%$ of loaded APAP were released within 20 minutes, except for APAP-WH hollow type suppositories. Significant differences in the plasma concentration profile were observed among four type suppositories. $T_{max}$ of APAP-PEG and APAP-WH suppositories were 90 and 60 minutes, respectively, in hollow types. APAP-WH hollow type suppositories demonstrated fast absorption rates of APAP as compared with those of APAP-PEG suppositories. No burst effect was observed from APAP-WH suppository in contrast to APAP conventional type suppository, whereas AUCs of all the suppositories were similar. APAP-WH hollow type suppository may be an useful dosage form for hospital use.

• Journal of Pharmaceutical Investigation
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• 제27권3호
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• pp.165-171
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• 1997

Ibuprofen, a nonsteroidal antiinflammatory, analgesic and antipyretic drug, has several limitations in clinical application because of low solubility in water and gastrointestinal irritation. Effect of ibuprofen/$2-Hydroxypropyl-{\beta}-cyclodextrin\;(HP{\beta}CD)$ inclusion compound on release of suppository was investigated. Complex formation was confirmed by $^{1}H-\;and\;^{13}C-NMR$ spectroscopy. The release of ibuprofen from suppository base in vitro was significantly increased by the complexation with $HP{\beta}CD$. The release of ibuprofen from hydrophilic base was faster than that from hydrophobic base. In vivo studies, the release rate of ibuprofen from suppository was accelerated after rectal administration in complex form. This results suggested that ibuprofen/$HP{\beta}CD$ complex can be practically used for suppository to have faster effect of ibuprofen with reduced side effect.

• Journal of Pharmaceutical Investigation
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• 제30권3호
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• pp.167-172
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• 2000

The purpose of this study is to develop a transurethral liquid suppository containing prostaglandin $E_1\;(PGE_1)-loaded$ microemulsion, which undergoes a phase transition to gels at body temperature. The effects of oils, ethanol as solvent and HCl as pH-controlling agent on the physicochemical properties of liquid suppositories composed of poloxamer P 407, P 188 and carbopol was investigated. The stability of $PGE_1$ and release of $PGE_1$ from liquid suppository were evaluated. Oils such as Neobee and soybean oil significantly decreased the gelation temperature but increased the gel strength of liquid suppository due to their strongly binding with the components of liquid suppository base. However, ethanol slightly did the opposite. The pH of liquid suppositories hardly affected the gelation temperature and gel strength due to addition of very small HCl (0.005-0.01%). A liquid suppository [$PGE_1/P$ 407/P 188/carbopol/Neobee/ethanol/HCl (0.2/14/14/0.4/7/2/0.005%)], which had the gelation temperature $(34.2{\pm}0.6^{\circ}C)$ and gel strength $(31.35{\pm}4.37\;sec)$ suitable for liquid suppository system, was easily administered and not leak out from the body. About 60% of $PGE_1$ was released out within 2 h from this formulation. It was shown that the release of $PGE_1$ was proportional to the square root of time, indicating that $PGE_1$ might be released from the suppository by Fickian diffusion. It was stable at $4^{\circ}C$ for at least 2 months. The results suggest that transurethral liquid suppository containing prostaglandin $E_1-loaded$ microemulsion is thought to be a convenient, safe and effective dosage form for $PGE_1$. However, it should be further developed as a more convenient and stable dosage form for $PGE_1$.