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Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method.
J Pharm Pharmacol. 2016 Mar; 68(3):316-23.JP

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.

Authors+Show Affiliations

Pharmaceutical Research and Technology Labs., Astellas Pharma Inc., Yaizu, Shizuoka, Japan. Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.Pharmaceutical Research and Technology Labs., Astellas Pharma Inc., Yaizu, Shizuoka, Japan.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.Astellas Ireland Co., Ltd., Mulhuddart, Dublin 15, Ireland.Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, Kita-ku, Okayama, Japan.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26773717

Citation

Tsunashima, Daisuke, et al. "Preparation of Extended Release Solid Dispersion Formulations of Tacrolimus Using Ethylcellulose and Hydroxypropylmethylcellulose By Solvent Evaporation Method." The Journal of Pharmacy and Pharmacology, vol. 68, no. 3, 2016, pp. 316-23.
Tsunashima D, Yamashita K, Ogawara K, et al. Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method. J Pharm Pharmacol. 2016;68(3):316-23.
Tsunashima, D., Yamashita, K., Ogawara, K., Sako, K., & Higaki, K. (2016). Preparation of extended release solid dispersion formulations of tacrolimus using ethylcellulose and hydroxypropylmethylcellulose by solvent evaporation method. The Journal of Pharmacy and Pharmacology, 68(3), 316-23. https://doi.org/10.1111/jphp.12515
Tsunashima D, et al. Preparation of Extended Release Solid Dispersion Formulations of Tacrolimus Using Ethylcellulose and Hydroxypropylmethylcellulose By Solvent Evaporation Method. J Pharm Pharmacol. 2016;68(3):316-23. PubMed PMID: 26773717.
* Article titles in AMA citation format should be in sentence-case
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, Y1 - 2016/01/15/ PY - 2015/08/26/received PY - 2015/12/13/accepted PY - 2016/1/17/entrez PY - 2016/1/17/pubmed PY - 2017/1/4/medline KW - controlled release KW - dissolution KW - oral absorption KW - pharmacokinetics KW - solid dispersion SP - 316 EP - 23 JF - The Journal of pharmacy and pharmacology JO - J Pharm Pharmacol VL - 68 IS - 3 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. SN - 2042-7158 UR - https://www.unboundmedicine.com/medline/citation/26773717/Preparation_of_extended_release_solid_dispersion_formulations_of_tacrolimus_using_ethylcellulose_and_hydroxypropylmethylcellulose_by_solvent_evaporation_method_ L2 - https://doi.org/10.1111/jphp.12515 DB - PRIME DP - Unbound Medicine ER -