Pharmaceutical Formulation Design (Yuji KUROSAKI)

Pharmaceutical Formulation Design Yuji KUROSAKI, PhD

Scientific Focus and Research Projects

The focus of scientific research projects in the Laboratory of Clinical Pharmaceutics and Pharmacokinetics is “optimization of drug therapy”. The optimized pharmacotherapy will be based on both the development of well-designed pharmaceutics (Drug Delivery System, DDS) and the precise application of these pharmaceutics to individual patient to guarantee efficacy and safety. We have applied microdialysis (MD) technique to monitor unbound drug concentration profiles of drugs, which relate directly to both the efficacy and the safety, in topically applied local acting DDSs. A modified MD technique, Lipo-MD, which we have reported, overcomes the inadequacy of conventional MD such as low recovery and delay in monitoring, especially in lipophilic drugs. We have also tried to apply this Lipo-MD technique to monitoring the local diffusion profiles of drugs based on its improved monitoring characteristics. We have prepared a hydro gel-sheet of L-HPC. This gel-sheet exhibits well-designed hydration and perspiration characteristics. Hydro gel-sheet prepared by bio-inert L-HPC will be a promising dressing material for accomplishing moist wound healing. Thus we have been investigating the following research projects by integrating physical- and bio-pharmaceutics together with theoretical pharmacokinetics.

1. Development of novel evaluation system for topical pharmacokinetic studya) Application of Lipo-Microdialysis (Lipo-MD), which has newly designed by our laboratory to topical pharmacokinetic studyb) Evaluation of dynamic diffusion process of drugs in muscle and the factors contributing to topical pharmacokinetics
2. Development of newly designed Drug Delivery Systems (DDS)c) New dermal DDS prepared with hydro-gel sheet exhibiting improved moisture controlling functions to the injured skin surfaced) Pharmacokinetic assessment of peritoneal dialysis and the application of controlled release concept to peritoneal drug dosing to improve the efficacy and safety e) Optimization of dosage formulation for improving oral bioavailability of low water-soluble drug

Topics in Our Research

1. Topical pharmacokinetic study for clarifying concentration-time profiles of drugs in the muscle of rats has been investigated by the application of in vivo microdialysis (MD) and the distance-depended concentration-time profiles have been analyzed by diffusion model incorporated with clearance to the systemic circulation.
2. Increased localization of drugs by cooling of the applied site has been demonstrated by the topical pharmacokinetic study in rat abdominal muscle (Fig. 1). This approach would enable significant improvement of local bioavailability of drugs.
3. Well-designed hydration and perspiration characteristics of L-HPC hydro-gel sheet has been clarified by physical pharmaceutical study. L-HPC hydro-gel sheet is expected to be a dressing material for accomplishing moist wound healing.
4. Changes in pharmacokinetics of drugs in peritoneal dialysis using lipid emulsions have been clarified. The utility of intraperitoneal application of lipid emulsions as a sustained release dosage form has been newly suggested.

Selected Recent Publications

1. Shinnsuke Inoue, Tetsuya Aiba, Yasuyuki Masaoka, Keiko Shimizu, Yukiko Komori, Mitsunobu Mio, Shingo Takatori, Hiromu Kawasaki and Yuji Kurosaki:Pharmacodynamic characterization of nitric oxide-mediated vasodilatory activity in isolated perfused rat mesenteric artery bed.Biol. Pharm. Bull., 34 (9), 1487-1492 (2011).
2. Takashi Makita, Tetsuya Aiba, Yuki Izuwa, Yukiko Komori, Hiromu Kawasaki and Yuji Kurosaki:Efficacy of peritoneal dialysis of tolbutamide in rats under conditions of the plasma unbound fraction being increased.Biopharm. Drug Dispos., 30 (1), 1-8 (2009).
3. Yuji Kurosaki, Masahiro Tagawa, Akiho Omoto, Hiroshi Suito, Yukiko Komori, Hiromu Kawasaki and Tetsuya Aiba:Evaluation of intramuscular lateral distribution profile of topically administered acetaminophen in rats.Int. J. Pharm., 343 (1-2), 190-195 (2007).
4. Yukiko Komori, Tetsuya Aiba, Miki Kushima, Hiromu Kawasaki and Yuji Kurosaki:Alteration of therapeutic efficacy of lipid microspheres incorporating prostaglandin E1 by mixing with aqueous solution.J. Pharm. Sci., 96 (4), 935-943 (2007).