title: Novel montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats.
abstract: To develop a montelukast sodium-loaded stable oral suspension bioequivalent to the commercial granules in rats, several montelukast sodium-loaded suspensions were prepared with a suspending agent, stabilizers and anti-aggregation agents, and their stabilities were investigated by visually observing the sedimentation phenomenon and determining the concentration of the degradation product. Moreover, dissolution and pharmacokinetic studies of the optimized formulation were examined in rats compared to commercial montelukast sodium-loaded granules. Avicel RC-591 (Avicel), a suspending agent, prevented the sedimentation of these suspensions at >2.496 (w/v) per cent composition. Amongst the stabilizers tested, fumaric acid provided the lowest concentration of montelukast sulphoxide (a degradation product) in these suspensions at 40 °C, demonstrating its excellent stabilizing activity. Furthermore, as an anti-aggregation agent, glycerin gave lower amounts of degradation product than those with poloxamer 407 and Tween 80. In particular, montelukast-loaded oral suspension, an aqueous suspension containing montelukast sodium/Avicel/fumaric acid/glycerin at a concentration of 312/2496/15.6/62.4 (mg/100 ml), and the commercial granules exhibited similar dissolution profiles in 0.5% (w/v) aqueous solution of sodium lauryl sulphate. Moreover, the pharmacokinetics in rats provided by this suspension was comparable to that of the commercial granules, suggesting that they were bioequivalent. In addition, it was physically and chemically stable at 40 °C for at least 6 months. Thus, this montelukast sodium-loaded oral suspension, with bioequivalence to the commercial granules and excellent stability, could be a prospective dosage form for the treatment of asthma.
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea.
authors.forename: Dong Wuk
authors.initials: DW
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea.|Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-Myeon, 893-5, Hwaseong, Gyeonggi-Do, 445-913, South Korea.
authors.forename: Young Hun
authors.initials: YH
authors.lastname: Kim
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea.
authors.forename: Abid Mehmood
authors.initials: AM
authors.lastname: Yousaf
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea.
authors.forename: Dong Shik
authors.initials: DS
authors.lastname: Kim
authors.affiliation: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-Myeon, 893-5, Hwaseong, Gyeonggi-Do, 445-913, South Korea.
authors.forename: Taek Kwan
authors.initials: TK
authors.lastname: Kwon
authors.affiliation: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-Myeon, 893-5, Hwaseong, Gyeonggi-Do, 445-913, South Korea.
authors.forename: Jung Hee
authors.initials: JH
authors.lastname: Park
authors.affiliation: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-Myeon, 893-5, Hwaseong, Gyeonggi-Do, 445-913, South Korea.
authors.forename: Yong Il
authors.initials: YI
authors.lastname: Kim
authors.affiliation: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-Myeon, 893-5, Hwaseong, Gyeonggi-Do, 445-913, South Korea.
authors.forename: Jae-Hyun
authors.initials: JH
authors.lastname: Park
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea.
authors.forename: Sung Giu
authors.initials: SG
authors.lastname: Jin
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea.
authors.forename: Kyung Soo
authors.initials: KS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.|College of Pharmacy, Inje University, Inje-ro 197, Gimhae, 621-749, South Korea.
authors.forename: Kwan Hyung
authors.initials: KH
authors.lastname: Cho
authors.affiliation: National Pharmaceutical Engineering Centre for Solid Preparation in Chinese Herbal Medicine, Jiangxi University of Traditional Chinese Medicine, 56 Yangming Road, Nanchang, Jiangxi, 330006, China.
authors.forename: Dong Xun
authors.initials: DX
authors.lastname: Li
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Yeungnam University, 214-1, Dae-Dong, Gyongsan, 712-749, South Korea.
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.affiliation: Pharmaceutical Research Centre, Hanmi Pharm. Co., Paltan-Myeon, 893-5, Hwaseong, Gyeonggi-Do, 445-913, South Korea. jswoo@hanmi.co.kr.
authors.forename: Jong Soo
authors.initials: JS
authors.lastname: Woo
authors.affiliation: College of Pharmacy and Institute of Pharmaceutical Science and Technology, Hanyang University, 55 Hanyangdaehak-ro, Sangnok-Gu, Ansan, 426-791, South Korea. hangon@hanyang.ac.kr.
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
mesh_terms: D000085:Acetates / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000592:standards; D000284:Administration, Oral; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000592:standards; D002482:Cellulose / Q000737:chemistry; D003521:Cyclopropanes; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D005650:Fumarates / Q000737:chemistry; D005990:Glycerol / Q000737:chemistry; D008297:Male; D011804:Quinolines / Q000008:administration & dosage / Q000737:chemistry* / Q000493:pharmacokinetics / Q000592:standards; D017207:Rats, Sprague-Dawley; D012995:Solubility; D013440:Sulfides; D013535:Suspensions; D013678:Technology, Pharmaceutical / Q000379:methods*; D013810:Therapeutic Equivalency
chemical_list: D000085:Acetates; D018927:Anti-Asthmatic Agents; D003521:Cyclopropanes; D005079:Excipients; D005650:Fumarates; D011804:Quinolines; D013440:Sulfides; D013535:Suspensions; C032005:fumaric acid; D002482:Cellulose; C093875:montelukast; D005990:Glycerol
keywords: Bioavailability; Dissolution; Montelukast sodium; Oral suspension; Stability