Comparison of three different types of cilostazol-loaded solid dispersion: Physicochemical characterization and pharmacokinetics in rats.
The aim of this research was to compare three different types of cilostazol-loaded solid dispersion system including solvent-evaporated, solvent-wetted and surface-attached solid dispersion. The effect of polymers and surfactants on the aqueous solubility of cilostazol was investigated, leading to the selection of polyvinylpyrrolidone (PVP) and sodium lauryl sulphate (SLS). Employing a spray-drying technique, numerous surface-attached, solvent-evaporated and solvent-wetted solid dispersions were prepared with various amounts PVP and SLS using water, 90% ethanol and acetone, respectively. Their physicochemical properties, solubility, dissolution and oral bioavailability in rats were assessed compared to the drug powder. Among each solid dispersion system tested, the surface-attached, solvent-evaporated and solvent-wetted solid dispersions composed of cilostazol, PVP and SLS at weight ratios of 3.0 : 0.75 : 1.5, 3.0 : 3.0 : 1.5 and 3.0 : 3.0 : 1.5, respectively, provided the highest drug solubility and dissolution. The solvent-evaporated solid dispersion gave homogeneous and very small spherical particles, in which the drug was changed to an amorphous state. In the solvent-wetted solid dispersion, the amorphous drug was attached to the polymer surface. Conversely, in the surface-attached solid dispersion, the carriers were adhered onto the surface of the unchanged crystalline drug. The solubility, dissolution and oral bioavailability were significantly increased in the order of solvent-evaporated>solvent-wetted>surface-attached>drug powder. Thus, the type of solid dispersion considerably affected the physicochemical properties, aqueous solubility and oral bioavailability. Furthermore, the cilostazol-loaded solvent-evaporated solid dispersion with the highest oral bioavailability would be actively recommended as a practical oral pharmaceutical product.
College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea; International Centre of Chemical and Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Omer
O
Mustapha
College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
Kyung Soo
KS
Kim
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Dow University of Health Sciences, Karachi, Sindh, 74200, Pakistan.
Shumaila
S
Shafique
College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea.
Dong Shik
DS
Kim
College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea; Department of Pharmaceutical Engineering, Dankook University, 119 Dandae-ro, Dongnam-gu, Cheonan, 330-714, South Korea.
Sung Giu
SG
Jin
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
Youn Gee
YG
Seo
School of Pharmacy, Sungkyunkwan University, 300 Cheoncheon-dong, Jangan-gu, Suwon 440-746, South Korea.
Yu Seok
YS
Youn
College of Pharmacy, Chung-Ang University, 221 Heuksuk-dong, Dongjak-gu, Seoul 156-756, South Korea.
Kyung Taek
KT
Oh
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea.
Chul Soon
CS
Yong
College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan 712-749, South Korea. Electronic address: jongohkim@yu.ac.kr.
Jong Oh
JO
Kim
College of Pharmacy & Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-gu, Ansan, 426-791, South Korea. Electronic address: hangon@hanyang.ac.kr.
Han-Gon
HG
Choi
D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D055598:Chemical Phenomena; D000077407:Cilostazol; D004337:Drug Carriers / Q000737:chemistry; D004339:Drug Compounding / Q000379:methods; D008297:Male; D008855:Microscopy, Electron, Scanning; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D011208:Powders; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents; D013499:Surface Properties; D013501:Surface-Active Agents; D013777:Tetrazoles / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D014867:Water
D004337:Drug Carriers; D010975:Platelet Aggregation Inhibitors; D011208:Powders; D012997:Solvents; D013501:Surface-Active Agents; D013777:Tetrazoles; D014867:Water; D000077407:Cilostazol
Cilostazol; Crystallinity; Oral bioavailability; Solubility; Solvent-evaporated solid dispersion; Solvent-wetted solid dispersion; Surface-attached solid dispersion