• Journal of Pharmaceutical Investigation
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• v.16 no.4
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• pp.148-151
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• 1986

This paper was designed to investigate the influence of different suppository bases on both the rectal absorption and dissolution rate of lithium carbonate, and to compare bioavailability from rectal administration with that from oral administration. The dissolution rates were in such order as PEG 4000, surfactant A (Witepsol 15+sodium lauryl sulfate), surfactant B (Witepsol 15+cholic acid), Witepsol 15 and cacao butter. Among various suppository bases, the blood level of lithium carbonate after rectal administration was increased in the following order: surfactant A>surfactant B>PEG 4000>Witepsol 15>cacao butter. When it comes to compare oral with rectal administration in AUC values, surfactants and PEG 4000 showed similar blood levels to oral administration, but lipophilic bases such as Witepsol 15 and cacao butter showed far lower blood level than oral administration. Peak time in oral administration was 2 hrs, but those in rectal administration using various suppository bases were $6{\sim}8$ hrs.

• Journal of Pharmaceutical Investigation
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• v.18 no.1
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• pp.15-21
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• 1988

An inclusion complex of phenytoin (PT) with ${\beta}-cyclodextrin\;({\beta}-CyD)$ in molar ratio of 1 : 1 was prepared, and the interaction between host and guest molecules was confirmed by infrared spectrometry, differential scanning calorimetry and X-ray diffractometry. Suppositories were prepared by the fusion method. PT and $PT-{\beta}-CyD$ complex were added to PEG 1540 and Witepsol H-15 under the vigorous stirring at $40^{\circ}C$. Content uniformity was tested for different formulations of the PT suppositories. The release rates were dependent on the K.P. V dissolution apparatus and the dialyzing tubing method. Then, the release rates were increased in the following order: $PT-{\beta}-CyD$ complex in PEG 1540>PT in PEG 1540>$PT-{\beta}-CyD$ complex in Witepsol H-15>PT in Witepsol H-15. The area under the curve and maximum blood concentration after rectal administration were increased in the following order: $PT-{\beta}-CyD$ complex in PEG 1540>PT in PEG 1540>$PT-{\beta}-CyD$ complex in Witepsol H-15>PT in Witepsol-15.

• Journal of Pharmaceutical Investigation
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• v.23 no.3
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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.

• YAKHAK HOEJI
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• v.35 no.3
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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%.

• YAKHAK HOEJI
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• v.37 no.4
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• pp.370-382
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• 1993

In order for formulation of rectal containing OMZ, the OMZ suppositories were prepared using water-soluble base, PEG 4000 base and oil-soluble base, Witepsol H 15. Chemical stability of OMZ in suppositories was increased when Witepsol H 15 was used as a suppository base and arginine was added as a stabilizer. The decomposition of OMZ in suppository bases followed the first-order kinetics and their rate constants were 0.11 day $^{1}(t_{1/2}$=/6.25 days) for Witepsol H 15 suppository and 0.48 day $^{1}(t_{1/2}$=/1.43 days) for PEG 4000 suppository, respectively. On the other hand, the decomposition rate constants of Witepsol suppository and PEG suppository stabilized with arginine were 3.89$\times$10$^{-3}$(t$_{1/2}$=171.1 days) and 8.76$\times$10$^{-3}$ day $^{1}(t_{1/2}=79.9 days), respectively. Shelf-lives of the Witepsol and PEG suppositories stabilized with arginine were t$_{90%}$=291.8 days and t$_{90%}$=282.1 days at $35^{\circ}C$ and 75% RH, respectively. The dissolution test of OMZ suppositories was performed by rotating dialysis cell(RDC) method and the release rate constant was calculated by the simplified Higuchi's equation, Q'=K' t$^{1/2}$. Dissolution of OMZ from suppositories was augmented as arginine was added, particle size of OMZ was reduced and a suitable surfactant such as SLS was added. RDC method was more appropriate and available than Paddle method to evaluate the dissolution rate of lipophilic-base suppositoies. Arginine was found to be a very useful exipient for the enhancement of stability and dissolution of OMZ in suppositories.

• Korean Journal of Clinical Pharmacy
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• v.8 no.2
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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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• v.24 no.3
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• pp.115-129
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• 1994

In the present study, quantitative and qualitative histology was used to assess the effects of ibuprofen suppositories with various treatments on the rectal mucosa of rats. Two suppositories were prepared with Witepsol W35 and compared with two commercial ibuprofen suppositories Reference I (Showa Pharm.ind., Tokyo, Japan), Reference II (P.Pharm., Seoul, Korea). Single and multiple dose(dosing interval 4 hr, n=4) studies were conducted. All suppositories significantly increased epithelial cell loss, but the extent of rectal irritation was variable. These studies showed that the incorporation of ibuprofen into the suppository bases increases the morphological change in rectal tissue both for the single and multiple administrations of suppositories, but which was significantly recovered within 24 hr although the interanimal variability in scores was very substantial. Multiple administration of ibuprofen suppositories caused significant damage to rectal mucosa, but it must be considered that these were under the severe condition, that is, interval of administration (4 hr) was three times shorter than normal interval of administration and dose was fifteen times larger than usual human dose. Aluminum oxide $(Al_2O_3)$, a dispersing agent, slightly increased the irritation of rectal mucosa in rats at 5 hr and 24 hr after multiple administration, but it was possible to ignore the difference of irritation in the data at 5hr and 24hr after single administration. Finally, it was concluded that Witepsol W35 and ibuprofen had a slight rectal mucosa-irritating effect on the usual human dose, and ibuprofen suppositories prepared with Witepsol W35 or Witepsol W35, $Al_2O_3$ showed almost similar extent of rectal irritation with commercial ibuprofen products.

• YAKHAK HOEJI
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• v.40 no.4
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• pp.400-410
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• 1996

In oder to develop the controlled release of drugs from the suppositories, in vitro drug release and in vivo absorption in rabbits were investigated. Various suppo sitory forms with hollow cavities, into which drugs in the form of fine powder or solid dispersion system(SDS) could be placed, were utilized. The oleaginous Witepsol H-15 (WH-15) as a base, and indomethacin (IDM) of a very slightly soluble drug and propranolol-HCL (PPH) of a very soluble drug were employed as model drugs. The in vitro drug release showed that the cumulative release amount of PPH from PPH-(methylcellulose) MC-SDS and PPH-(ethylcellulose) EC-SDS hollow type suppositories reached 40% and 12% in 6 hrs,respectively. On the other hand, the drug release for a conventional suppository was 80% in 6 hrs. For the IDM suppositories,the cumulative drug release from IDM-(polyvinylpyrrolidone) PVP-SDS hollow type suppositories reached 99% in 24 hrs, whereas that from a conventional suppository reached 85%. An in vivo experiment with rabbits showed that IDM-PVP-SDS hollow type suppository delayed the absorption of IDM, significantly. The $t_{max},\;C_{max}\;and\;AUC_{0{\to}8}$ of IDM-PVP-SDS suppository were 60 min, 12.12${\mu}g$/ml and 2657${\mu}g$/ml/min, respectively. The $t_{max},\;C_{max}\;and\;AUC_{0{\to}8}$ of controlled group were 20 min, 15.49${\mu}g$/ml and 2190${\mu}g$/ml/min, respectively.

• 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.20 no.3
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• pp.153-159
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• 1990

To increase the solubility of fentiazac which is used widely as a non-steroidal antiinflammatory drug, its inclusion complex and suppositories were prepared and studied. Inclusion complexes of fentiazac with ${\beta}-cyclodertin$ $({\beta}-CyD)$ were prepared by four diffrent methods; coprecipitation method, kneading method, solvent evaporation method, freeze drying method. Suppositories of $fentiazac/{\beta}-CyD$ with PEG 1500 and Witepsol H-15 were prepared by solvent evaporation method and freeze drying method. Inclusion complex formation of fentiazac with ${\beta}-CyD$ was ascertained by powder X-ray diffractometry, differential scanning calorimetry and IR spectroscopy. The dissolution rate of fentiazac from the inclusion complex increased in distilled water and KP 2nd disintegration test fluids (pH 6.8) but extemly decreased in KP 1st disintegration test fluid (pH 1.2). Inclusion complexes prepared by freeze drying method and solvent evaporation method were similar. Freeze drying method seemed to be suitable for preparation of complex with most higher dissolution rate but coprecipitation method seemed not to be suitable. The dissolution rate of fentiazac increased markedly by ${\beta}-CyD$ complexation. The release rates of suppositories increased in the following order. Complex prepared by freeze dying method in PEG 1500 > complex prepared by solvent evaporation method in PEG 1500 > fentiazac in PEG 1500 > complex prepared by freeze dying method in Witepsol H-15 > complex prepared by solvent evaporation method in Witepsol H-15 > fentiazac in Witepsol H-15.