Abstract
Controlled-release morphine suppositories were prepared by utilizing polyglycerol ester of fatty acid (PGEF). The addition of PGEF to fatty suppository base Witepsol H15 resulted in a decrease of morphine release rate from suppositories. Among PGEFs examined, decaglycerol heptabehenate (HB750) was the most effective additive for the controlled-release of morphine from fatty suppositories. The apparent viscosity of suppository bases increased with the increase in HB750 content, and good correlation was observed between the apparent viscosity of suppository bases at 37° C and the amount of HB750 added in the mixed base. The in vitro release rate of morphine was decreased by the addition of HB750 and the release rate constant (Higuchi's rate constant) for morphine release was significantly correlated with the HB750 content in the mixed bases as well as the apparent viscosity of mixed bases, indicating that the release of morphine from the mixed bases could be regulated by the HB750 content in the mixed bases. After rectal administration of Witepsol H-15-HB750 mixed suppositories to dogs, plasma concentrations of morphine did not increase rapidly at early time periods, but relatively high levels of morphine in plasma were sustained for longer time periods. Mean residence time of morphine was considerably prolonged without changing relative bioavailability in the case of the mixed base suppositories containing 15-17% HB750, compared with the Witepsol H15 suppository, clearly indicating that the mixed bases containing HB750 are expected to be useful for the design of controlled-release morphine suppositories.
| Original language | English |
|---|---|
| Pages (from-to) | 1480-1484 |
| Number of pages | 5 |
| Journal | Biological and Pharmaceutical Bulletin |
| Volume | 28 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Aug 2005 |
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Keywords
- Fatty suppository
- Morphine suppository
- Polyglycerol ester of fatty acid
- Release control
- Viscosity
ASJC Scopus subject areas
- Molecular Medicine
- Pharmacology, Toxicology and Pharmaceutics(all)
Cite this
Design of controlled-release morphine suppositories containing polyglycerol ester of fatty acid. / Takatori, Toshihito; Yamamoto, Kazumitsu; Yamaguchi, Toshikazu; Higaki, Kazutaka; Kimura, Toshikiro.
In: Biological and Pharmaceutical Bulletin, Vol. 28, No. 8, 08.2005, p. 1480-1484.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Design of controlled-release morphine suppositories containing polyglycerol ester of fatty acid
AU - Takatori, Toshihito
AU - Yamamoto, Kazumitsu
AU - Yamaguchi, Toshikazu
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
PY - 2005/8
Y1 - 2005/8
N2 - Controlled-release morphine suppositories were prepared by utilizing polyglycerol ester of fatty acid (PGEF). The addition of PGEF to fatty suppository base Witepsol H15 resulted in a decrease of morphine release rate from suppositories. Among PGEFs examined, decaglycerol heptabehenate (HB750) was the most effective additive for the controlled-release of morphine from fatty suppositories. The apparent viscosity of suppository bases increased with the increase in HB750 content, and good correlation was observed between the apparent viscosity of suppository bases at 37° C and the amount of HB750 added in the mixed base. The in vitro release rate of morphine was decreased by the addition of HB750 and the release rate constant (Higuchi's rate constant) for morphine release was significantly correlated with the HB750 content in the mixed bases as well as the apparent viscosity of mixed bases, indicating that the release of morphine from the mixed bases could be regulated by the HB750 content in the mixed bases. After rectal administration of Witepsol H-15-HB750 mixed suppositories to dogs, plasma concentrations of morphine did not increase rapidly at early time periods, but relatively high levels of morphine in plasma were sustained for longer time periods. Mean residence time of morphine was considerably prolonged without changing relative bioavailability in the case of the mixed base suppositories containing 15-17% HB750, compared with the Witepsol H15 suppository, clearly indicating that the mixed bases containing HB750 are expected to be useful for the design of controlled-release morphine suppositories.
AB - Controlled-release morphine suppositories were prepared by utilizing polyglycerol ester of fatty acid (PGEF). The addition of PGEF to fatty suppository base Witepsol H15 resulted in a decrease of morphine release rate from suppositories. Among PGEFs examined, decaglycerol heptabehenate (HB750) was the most effective additive for the controlled-release of morphine from fatty suppositories. The apparent viscosity of suppository bases increased with the increase in HB750 content, and good correlation was observed between the apparent viscosity of suppository bases at 37° C and the amount of HB750 added in the mixed base. The in vitro release rate of morphine was decreased by the addition of HB750 and the release rate constant (Higuchi's rate constant) for morphine release was significantly correlated with the HB750 content in the mixed bases as well as the apparent viscosity of mixed bases, indicating that the release of morphine from the mixed bases could be regulated by the HB750 content in the mixed bases. After rectal administration of Witepsol H-15-HB750 mixed suppositories to dogs, plasma concentrations of morphine did not increase rapidly at early time periods, but relatively high levels of morphine in plasma were sustained for longer time periods. Mean residence time of morphine was considerably prolonged without changing relative bioavailability in the case of the mixed base suppositories containing 15-17% HB750, compared with the Witepsol H15 suppository, clearly indicating that the mixed bases containing HB750 are expected to be useful for the design of controlled-release morphine suppositories.
KW - Fatty suppository
KW - Morphine suppository
KW - Polyglycerol ester of fatty acid
KW - Release control
KW - Viscosity
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UR - http://www.scopus.com/inward/citedby.url?scp=25644434759&partnerID=8YFLogxK
U2 - 10.1248/bpb.28.1480
DO - 10.1248/bpb.28.1480
M3 - Article
VL - 28
SP - 1480
EP - 1484
JO - Biological and Pharmaceutical Bulletin
JF - Biological and Pharmaceutical Bulletin
SN - 0918-6158
IS - 8
ER -