Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method

Daisuke Tsunashima, Kazunari Yamashita, Ken Ichi Ogawara, Kazuhiro Sako, Kazutaka Higaki

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Objectives Tacrolimus is a poorly water-soluble compound that is used to prevent allograft rejection. We aimed to prepare an extended release formulation of tacrolimus to achieve both an extended release profile and improved solubility of tacrolimus. Methods Extended release granules (ERG) of tacrolimus were prepared with lactose, ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) via the solvent evaporation method. Key findings In an in vitro release study, ERG had an extended release profile, and the release rate of tacrolimus was regulated by the quantity of lactose, EC and HPMC in the formulation. HPMC-containing ERG successfully enhanced and maintained supersaturation of tacrolimus even after 24 h in a supersaturated release study. In contrast, the extent of supersaturation rapidly decreased after 4 h and the concentration nearly reached the same level as that of crystalline tacrolimus at 24 h for ERG without HPMC. In vivo absorption characteristics were compared between ERGs and immediate release (IR) formulation of tacrolimus. Successful and sustained absorption of tacrolimus without reducing bioavailability compared with IR formulation was observed for ERG. Conclusions These results suggest the feasibility of combining an EC-based formulation with solid dispersion utilizing HPMC for the extended release of oral formulations and sustained absorption of tacrolimus.

Original languageEnglish
Pages (from-to)316-323
Number of pages8
JournalJournal of Pharmacy and Pharmacology
Volume68
Issue number3
DOIs
Publication statusPublished - Mar 1 2016

Fingerprint

Tacrolimus
Lactose
ethyl cellulose
Hypromellose Derivatives
Solubility
Biological Availability
Allografts
Water

Keywords

  • controlled release
  • dissolution
  • oral absorption
  • pharmacokinetics
  • solid dispersion

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method. / Tsunashima, Daisuke; Yamashita, Kazunari; Ogawara, Ken Ichi; Sako, Kazuhiro; Higaki, Kazutaka.

In: Journal of Pharmacy and Pharmacology, Vol. 68, No. 3, 01.03.2016, p. 316-323.

Research output: Contribution to journalArticle

@article{5daf68dd93234e9f9050c348b38f7614,
title = "Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method",
abstract = "Objectives Tacrolimus is a poorly water-soluble compound that is used to prevent allograft rejection. We aimed to prepare an extended release formulation of tacrolimus to achieve both an extended release profile and improved solubility of tacrolimus. Methods Extended release granules (ERG) of tacrolimus were prepared with lactose, ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) via the solvent evaporation method. Key findings In an in vitro release study, ERG had an extended release profile, and the release rate of tacrolimus was regulated by the quantity of lactose, EC and HPMC in the formulation. HPMC-containing ERG successfully enhanced and maintained supersaturation of tacrolimus even after 24 h in a supersaturated release study. In contrast, the extent of supersaturation rapidly decreased after 4 h and the concentration nearly reached the same level as that of crystalline tacrolimus at 24 h for ERG without HPMC. In vivo absorption characteristics were compared between ERGs and immediate release (IR) formulation of tacrolimus. Successful and sustained absorption of tacrolimus without reducing bioavailability compared with IR formulation was observed for ERG. Conclusions These results suggest the feasibility of combining an EC-based formulation with solid dispersion utilizing HPMC for the extended release of oral formulations and sustained absorption of tacrolimus.",
keywords = "controlled release, dissolution, oral absorption, pharmacokinetics, solid dispersion",
author = "Daisuke Tsunashima and Kazunari Yamashita and Ogawara, {Ken Ichi} and Kazuhiro Sako and Kazutaka Higaki",
year = "2016",
month = "3",
day = "1",
doi = "10.1111/jphp.12515",
language = "English",
volume = "68",
pages = "316--323",
journal = "Journal of Pharmacy and Pharmacology",
issn = "0022-3573",
publisher = "Pharmaceutical Press",
number = "3",

}

TY - JOUR

T1 - Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method

AU - Tsunashima, Daisuke

AU - Yamashita, Kazunari

AU - Ogawara, Ken Ichi

AU - Sako, Kazuhiro

AU - Higaki, Kazutaka

PY - 2016/3/1

Y1 - 2016/3/1

N2 - Objectives Tacrolimus is a poorly water-soluble compound that is used to prevent allograft rejection. We aimed to prepare an extended release formulation of tacrolimus to achieve both an extended release profile and improved solubility of tacrolimus. Methods Extended release granules (ERG) of tacrolimus were prepared with lactose, ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) via the solvent evaporation method. Key findings In an in vitro release study, ERG had an extended release profile, and the release rate of tacrolimus was regulated by the quantity of lactose, EC and HPMC in the formulation. HPMC-containing ERG successfully enhanced and maintained supersaturation of tacrolimus even after 24 h in a supersaturated release study. In contrast, the extent of supersaturation rapidly decreased after 4 h and the concentration nearly reached the same level as that of crystalline tacrolimus at 24 h for ERG without HPMC. In vivo absorption characteristics were compared between ERGs and immediate release (IR) formulation of tacrolimus. Successful and sustained absorption of tacrolimus without reducing bioavailability compared with IR formulation was observed for ERG. Conclusions These results suggest the feasibility of combining an EC-based formulation with solid dispersion utilizing HPMC for the extended release of oral formulations and sustained absorption of tacrolimus.

AB - Objectives Tacrolimus is a poorly water-soluble compound that is used to prevent allograft rejection. We aimed to prepare an extended release formulation of tacrolimus to achieve both an extended release profile and improved solubility of tacrolimus. Methods Extended release granules (ERG) of tacrolimus were prepared with lactose, ethylcellulose (EC) and hydroxypropylmethylcellulose (HPMC) via the solvent evaporation method. Key findings In an in vitro release study, ERG had an extended release profile, and the release rate of tacrolimus was regulated by the quantity of lactose, EC and HPMC in the formulation. HPMC-containing ERG successfully enhanced and maintained supersaturation of tacrolimus even after 24 h in a supersaturated release study. In contrast, the extent of supersaturation rapidly decreased after 4 h and the concentration nearly reached the same level as that of crystalline tacrolimus at 24 h for ERG without HPMC. In vivo absorption characteristics were compared between ERGs and immediate release (IR) formulation of tacrolimus. Successful and sustained absorption of tacrolimus without reducing bioavailability compared with IR formulation was observed for ERG. Conclusions These results suggest the feasibility of combining an EC-based formulation with solid dispersion utilizing HPMC for the extended release of oral formulations and sustained absorption of tacrolimus.

KW - controlled release

KW - dissolution

KW - oral absorption

KW - pharmacokinetics

KW - solid dispersion

UR - http://www.scopus.com/inward/record.url?scp=84963579080&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84963579080&partnerID=8YFLogxK

U2 - 10.1111/jphp.12515

DO - 10.1111/jphp.12515

M3 - Article

C2 - 26773717

AN - SCOPUS:84963579080

VL - 68

SP - 316

EP - 323

JO - Journal of Pharmacy and Pharmacology

JF - Journal of Pharmacy and Pharmacology

SN - 0022-3573

IS - 3

ER -