Supersaturatable formulations for the enhanced oral absorption of sirolimus

The purpose of this study was to develop supersaturatable formulations for the enhanced solubility and oral absorption of sirolimus. Supersaturatable formulations of hydrophilic polymers and/or surfactants were screened by formulation screening, which is based on solvent casting. The solid dispersio...

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Bibliographic Details
Published in:International journal of pharmaceutics 2013-03, Vol.445 (1-2), p.108-116
Main Authors: Kim, Min-Soo, Kim, Jeong-Soo, Cho, Wonkyung, Cha, Kwang-Ho, Park, Hee-Jun, Park, Junsung, Hwang, Sung-Joo
Format: Article
Language:English
Subjects:
Absorption
Administration, Oral
Amorphous
Animals
bioavailability
Biological Availability
cellulose
Drug Compounding
Excipients - chemistry
hydrophilic polymers
Hypromellose Derivatives
Immunosuppressive Agents - blood
Immunosuppressive Agents - chemistry
Immunosuppressive Agents - pharmacokinetics
Male
Methylcellulose - analogs & derivatives
Methylcellulose - chemistry
Pharmacokinetic
pharmacokinetics
polyethylene glycol
Polyethylene Glycols - chemistry
Rats
Rats, Sprague-Dawley
Screening
Sirolimus
Sirolimus - blood
Sirolimus - chemistry
Sirolimus - pharmacokinetics
solubility
solvents
spray drying
succinic acid
Sucrose - analogs & derivatives
Sucrose - chemistry
Supersaturation
surfactants
Vitamin E - analogs & derivatives
Vitamin E - chemistry
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Summary:The purpose of this study was to develop supersaturatable formulations for the enhanced solubility and oral absorption of sirolimus. Supersaturatable formulations of hydrophilic polymers and/or surfactants were screened by formulation screening, which is based on solvent casting. The solid dispersion particles in the optimized formulations were prepared by spray drying. The particles were characterized in vitro and in vivo. The most effective supersaturatable formulation found in the formulation screening process was hydroxypropylmethyl cellulose (HPMC)-d-α-tocopheryl polyethylene glycol 1000 succinate (TPGS), followed by HPMC–Sucroester. In addition, the supersaturated state generated from HPMC–TPGS and HPMC–Sucroester 15 particles prepared by spray drying significantly improved the oral absorption of sirolimus in rats. Based on the pharmacokinetic parameters and supporting in vitro supersaturated dissolution data, the enhanced supersaturation properties of sirolimus led to enhanced in vivo oral absorption. In addition, the experimental results from the formulation screening used in our study could be useful for enhancing the bioavailability of sirolimus in preformulation and formulation studies.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2013.01.067