Biodegradable Injectable In Situ Implants and Microparticles for Sustained Release of Montelukast: In Vitro Release, Pharmacokinetics, and Stability
Journal Title: AAPS PharmSciTech - Year 2014, Vol 15, Issue 3
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 and Affiliations
Tarek A. Ahmed, Hany M. Ibrahim, Ahmed M. Samy, Alaa Kaseem, Mohammad T. H. Nutan, Muhammad Delwar Hussain
Keywords
Related Articles
- EP ID EP682402
- DOI 10.1208/s12249-014-0101-3
- Views 75
- Downloads 0
Whey Protein/Polysaccharide-Stabilized Emulsions: Effect of Polymer Type and pH on Release and Topical Delivery of Salicylic Acid
Emulsions are widely used as topical formulations in the pharmaceutical and cosmetic industries. They are thermodynamically unstable and require emulsifiers for stabilization. Studies have indicated that emulsifiers coul...
Conjugation of Hot-Melt Extrusion with High-Pressure Homogenization: a Novel Method of Continuously Preparing Nanocrystal Solid Dispersions
Over the past few decades, nanocrystal formulations have evolved as promising drug delivery systems owing to their ability to enhance the bioavailability and maintain the stability of poorly water-soluble drugs. However,...
Relaxation Kinetic Study of Eudragit® NM30D Film Based on Complex Modulus Formalism
This study is aimed at resolving and characterizing the primary (α) and secondary relaxations (β) in Eudragit® NM30D film based on apparent activation energies derived from complex modulus formali...
A Novel Oral Preparation of Hydroxysafflor Yellow A Base on a Chitosan Complex: A Strategy to Enhance the Oral Bioavailability
Hydroxysafflor yellow A (HSYA), the main active pharmaceutical ingredient of the safflower plant (Carthamus tinctorius L.), is a hydrophilic drug with low oral bioavailability (BA). The objective of the present study was...
Chaperone Potential of Pulicaria undulata Extract in Preventing Aggregation of Stressed Proteins
This study examined the effect of an aqueous extract of Pulicaria undulata on the 1,4-dithiothreitol (DTT)-induced aggregation of proteins. The effects of the chaperone properties of P. undulata extract on protein aggreg...