Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II): In vivo evaluation

Nobuyuki Tanaka, Keiji Imai, Kazuto Okimoto, Satoshi Ueda, Yuji Tokunaga, Rinta Ibuki, Kazutaka Higaki, Toshikiro Kimura

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

A novel sustained-release (SR) system, disintegration-controlled matrix tablet (DCMT), was developed for poorly water-soluble drugs. DCMT, consisting of wax and solid dispersion (SD) granules containing a disintegrant, could control the release of nilvadipine (NiD), a model compound, by its disintegration. In the present study, two DCMTs (DCMT-1 and DCMT-2) with different release rates of NiD were orally administered to beagle dogs, and in vivo absorption of NiD from DCMTs was compared with that from immediate-release (IR) tablets. DCMTs successfully sustained the absorption of NiD longer than IR tablets, while they did not decrease the bioavailability of NiD. DCMT-2, providing the slower release of NiD than DCMT-1, prolonged the absorption longer than DCMT-1. In vivo absorption profiles of NiD from DCMTs were significantly correlated with in vitro release profiles, suggesting that the release property from DCMTs would maintain regardless of the change in physiological condition through the gastrointestinal tract. Furthermore, the food intake did not affect the absorption of NiD after oral administration of DCMT-2. The present results strongly indicate that the DCMT system would be a promising SR system, which could improve the solubility and sustain the absorption of poorly water-soluble drugs.

Original languageEnglish
Pages (from-to)51-56
Number of pages6
JournalJournal of Controlled Release
Volume112
Issue number1
DOIs
Publication statusPublished - May 1 2006

Fingerprint

nilvadipine
Tablets

Keywords

  • Absorption
  • Disintegration
  • IVIVC
  • Nilvadipine
  • Solid dispersion
  • Sustained-release

ASJC Scopus subject areas

  • Pharmaceutical Science

Cite this

Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II) : In vivo evaluation. / Tanaka, Nobuyuki; Imai, Keiji; Okimoto, Kazuto; Ueda, Satoshi; Tokunaga, Yuji; Ibuki, Rinta; Higaki, Kazutaka; Kimura, Toshikiro.

In: Journal of Controlled Release, Vol. 112, No. 1, 01.05.2006, p. 51-56.

Research output: Contribution to journalArticle

Tanaka, Nobuyuki ; Imai, Keiji ; Okimoto, Kazuto ; Ueda, Satoshi ; Tokunaga, Yuji ; Ibuki, Rinta ; Higaki, Kazutaka ; Kimura, Toshikiro. / Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II) : In vivo evaluation. In: Journal of Controlled Release. 2006 ; Vol. 112, No. 1. pp. 51-56.
@article{5e5b78d74a094f13ad16ccf841c69a12,
title = "Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II): In vivo evaluation",
abstract = "A novel sustained-release (SR) system, disintegration-controlled matrix tablet (DCMT), was developed for poorly water-soluble drugs. DCMT, consisting of wax and solid dispersion (SD) granules containing a disintegrant, could control the release of nilvadipine (NiD), a model compound, by its disintegration. In the present study, two DCMTs (DCMT-1 and DCMT-2) with different release rates of NiD were orally administered to beagle dogs, and in vivo absorption of NiD from DCMTs was compared with that from immediate-release (IR) tablets. DCMTs successfully sustained the absorption of NiD longer than IR tablets, while they did not decrease the bioavailability of NiD. DCMT-2, providing the slower release of NiD than DCMT-1, prolonged the absorption longer than DCMT-1. In vivo absorption profiles of NiD from DCMTs were significantly correlated with in vitro release profiles, suggesting that the release property from DCMTs would maintain regardless of the change in physiological condition through the gastrointestinal tract. Furthermore, the food intake did not affect the absorption of NiD after oral administration of DCMT-2. The present results strongly indicate that the DCMT system would be a promising SR system, which could improve the solubility and sustain the absorption of poorly water-soluble drugs.",
keywords = "Absorption, Disintegration, IVIVC, Nilvadipine, Solid dispersion, Sustained-release",
author = "Nobuyuki Tanaka and Keiji Imai and Kazuto Okimoto and Satoshi Ueda and Yuji Tokunaga and Rinta Ibuki and Kazutaka Higaki and Toshikiro Kimura",
year = "2006",
month = "5",
day = "1",
doi = "10.1016/j.jconrel.2006.01.020",
language = "English",
volume = "112",
pages = "51--56",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Development of novel sustained-release system, disintegration-controlled matrix tablet (DCMT) with solid dispersion granules of nilvadipine (II)

T2 - In vivo evaluation

AU - Tanaka, Nobuyuki

AU - Imai, Keiji

AU - Okimoto, Kazuto

AU - Ueda, Satoshi

AU - Tokunaga, Yuji

AU - Ibuki, Rinta

AU - Higaki, Kazutaka

AU - Kimura, Toshikiro

PY - 2006/5/1

Y1 - 2006/5/1

N2 - A novel sustained-release (SR) system, disintegration-controlled matrix tablet (DCMT), was developed for poorly water-soluble drugs. DCMT, consisting of wax and solid dispersion (SD) granules containing a disintegrant, could control the release of nilvadipine (NiD), a model compound, by its disintegration. In the present study, two DCMTs (DCMT-1 and DCMT-2) with different release rates of NiD were orally administered to beagle dogs, and in vivo absorption of NiD from DCMTs was compared with that from immediate-release (IR) tablets. DCMTs successfully sustained the absorption of NiD longer than IR tablets, while they did not decrease the bioavailability of NiD. DCMT-2, providing the slower release of NiD than DCMT-1, prolonged the absorption longer than DCMT-1. In vivo absorption profiles of NiD from DCMTs were significantly correlated with in vitro release profiles, suggesting that the release property from DCMTs would maintain regardless of the change in physiological condition through the gastrointestinal tract. Furthermore, the food intake did not affect the absorption of NiD after oral administration of DCMT-2. The present results strongly indicate that the DCMT system would be a promising SR system, which could improve the solubility and sustain the absorption of poorly water-soluble drugs.

AB - A novel sustained-release (SR) system, disintegration-controlled matrix tablet (DCMT), was developed for poorly water-soluble drugs. DCMT, consisting of wax and solid dispersion (SD) granules containing a disintegrant, could control the release of nilvadipine (NiD), a model compound, by its disintegration. In the present study, two DCMTs (DCMT-1 and DCMT-2) with different release rates of NiD were orally administered to beagle dogs, and in vivo absorption of NiD from DCMTs was compared with that from immediate-release (IR) tablets. DCMTs successfully sustained the absorption of NiD longer than IR tablets, while they did not decrease the bioavailability of NiD. DCMT-2, providing the slower release of NiD than DCMT-1, prolonged the absorption longer than DCMT-1. In vivo absorption profiles of NiD from DCMTs were significantly correlated with in vitro release profiles, suggesting that the release property from DCMTs would maintain regardless of the change in physiological condition through the gastrointestinal tract. Furthermore, the food intake did not affect the absorption of NiD after oral administration of DCMT-2. The present results strongly indicate that the DCMT system would be a promising SR system, which could improve the solubility and sustain the absorption of poorly water-soluble drugs.

KW - Absorption

KW - Disintegration

KW - IVIVC

KW - Nilvadipine

KW - Solid dispersion

KW - Sustained-release

UR - http://www.scopus.com/inward/record.url?scp=33645758286&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33645758286&partnerID=8YFLogxK

U2 - 10.1016/j.jconrel.2006.01.020

DO - 10.1016/j.jconrel.2006.01.020

M3 - Article

C2 - 16545477

AN - SCOPUS:33645758286

VL - 112

SP - 51

EP - 56

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

IS - 1

ER -