Enhance the dissolution rate and oral bioavailability of pranlukast by preparing nanosuspensions with high-pressure homogenizing method.
OBJECTIVE
Pranlukast, one of the potential therapeutic tools in the treatment of asthma, has limited clinical applications due to its poor water solubility. The study is aimed to provide a platform for better utilizing pranlukast with enhancement of the dissolution rate and, thus, the oral bioavailability of pranluka'st by preparing nanosuspensions through high-pressure homogenization method.


METHODS
Poloxamer407 and PEG200 were chosen as stabilizer and surfactant. The formulation was investigated systematically with the dissolution tests as predominant method. Nanosuspensions were prepared by programmed high-pressure homogenization method. The product was characterized by particle size analysis, TEM and XRD are evaluated by in vitro dissolution tests and in vivo absorption examination. In addition, nanosuspensions with only pranlukast were prepared and compared with formulated nanosuspensions.


RESULTS
The optimal values of formulation were 0.5% (w/v) pranlukast with 0.375% (w/v) Poloxamer407, 0.375% (w/v) PEG200 and the screened programming homogenizing procedure parameters were 680 bar for the first 15 circles, 1048 bar for the next 9 circles and 1500 bar for the last 9 circles. Nanosuspensions of 318.2 ± 7.3 nm, -29.3 ± 0.8 mV were obtained. The XRD analysis indicated no change of crystalline occurred in the process of homogenization. The in vitro dissolution behavior of nanosuspensions exhibited complete release in 30 min with a remarkable fast dissolution rate. The in vivo bioavailability of formulated pranlukast nanosuspensions demonstrated its enhancement of fast onset of therapeutic drug effects with 4.38-fold improved compared to that of raw crystals.


CONCLUSIONS
The study provides a feasible, practical thinking of industry development in the clinical use of pranlukast.
Laboratory of Pharmaceutics, School of Medicine, Tsinghua University, Beijing, China.
Lan
L
Wang
Yanli
Y
Hao
Nan
N
Liu
Mingshu
M
Ma
Zhe
Z
Yin
Xiaoning
X
Zhang
D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D001682:Biological Availability; D002867:Chromones / Q000008:administration & dosage / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics*; D003460:Crystallization; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry; D008297:Male; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles / Q000737:chemistry*; D010316:Particle Size; D020442:Poloxamer / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013499:Surface Properties; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
D018927:Anti-Asthmatic Agents; D002867:Chromones; D005079:Excipients; D020442:Poloxamer; D011092:Polyethylene Glycols; C047681:pranlukast