title: Biodegradable injectable in situ implants and microparticles for sustained release of montelukast: in vitro release, pharmacokinetics, and stability.
abstract: The objective of this study was to investigate the sustained release of a hydrophilic drug, montelukast (MK), from two biodegradable polymeric drug delivery systems, in situ implant (ISI) and in situ microparticles (ISM). N-Methyl pyrrolidone (NMP), dimethyl sulfoxide (DMSO), triacetin, and ethyl acetate were selected as solvents. The release of 10% (w/v) MK from both systems containing poly-lactic-co-glycolic acid (PLGA) as the biodegradable polymer was compared. Upon contact with the aqueous medium, the PLGA in ISI and ISM systems solidified resulting in implants and microparticles, respectively. The in vitro drug release from the ISI system showed marked difference from miscible solvents (NMP and DMSO) than the partially miscible ones (triacetin and ethyl acetate), and the drug release decreased with increased PLGA concentration. In the ISM system, the initial in vitro drug release decreased with decreased ratio of polymer phase to external oil phase. In vivo studies in rats showed that ISM had slower drug release than the drug release from ISI. Also, the ISM system when compared to ISI system had significantly reduced initial burst effect. In vitro as well as the in vivo studies for both ISI and ISM systems showed sustained release of MK. The ISM system is suitable for sustained release of MK over 4-week period with a lower initial burst compared to the ISI system. Stability studies of the ISI and ISM formulations showed that MK is stable in the formulations stored at 4°C for more than 2 years.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia.
authors.forename: Tarek A
authors.initials: TA
authors.lastname: Ahmed
authors.forename: Hany M
authors.initials: HM
authors.lastname: Ibrahim
authors.forename: Ahmed M
authors.initials: AM
authors.lastname: Samy
authors.forename: Alaa
authors.initials: A
authors.lastname: Kaseem
authors.forename: Mohammad T H
authors.initials: MT
authors.lastname: Nutan
authors.forename: Muhammad Delwar
authors.initials: MD
authors.lastname: Hussain
mesh_terms: D020341:Absorbable Implants; D000085:Acetates / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D002626:Chemistry, Pharmaceutical; D003521:Cyclopropanes; D004121:Dimethyl Sulfoxide / Q000737:chemistry; D004343:Drug Implants; D004355:Drug Stability; D007273:Injections, Intramuscular; D019344:Lactic Acid / Q000737:chemistry*; D020024:Leukotriene Antagonists / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D010316:Particle Size; D011100:Polyglycolic Acid / Q000737:chemistry*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011760:Pyrrolidinones / Q000737:chemistry; D011804:Quinolines / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D017207:Rats, Sprague-Dawley; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013440:Sulfides; D013678:Technology, Pharmaceutical / Q000379:methods; D013696:Temperature; D014215:Triacetin / Q000737:chemistry
chemical_list: D000085:Acetates; D003521:Cyclopropanes; D004343:Drug Implants; D020024:Leukotriene Antagonists; D011760:Pyrrolidinones; D011804:Quinolines; D012997:Solvents; D013440:Sulfides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; C007650:ethyl acetate; C038678:N-methylpyrrolidone; C093875:montelukast; D014215:Triacetin; D004121:Dimethyl Sulfoxide