Development and characterization of solid dispersion-microsphere controlled release system for poorly water-soluble drug

Abstract

The present study aimed to improve solubility and prolong the release duration of a poorly soluble drug using a combination of two different types of formulations (solid dispersion and microspheres). The solid dispersions were prepared by fusion method using urea and mannitol as hydrophilic carriers. Microspheres were prepared by solvent evaporation method using Eudragit L-100 (EL100) and Eudragit RS PO (ERS) as rate-controlling polymers. Flurbiprofen (FBP)-urea (1:2) solid dispersion and microspheres of FBP-EL-100-ERS (1:0.25:0.75) were used for the development of controlled release formulation by mixing them in different proportions. The FBP-containing formulations were evaluated for percentage yield, drug content, morphology, in vitro release, and in vivo anti-inflammatory activity. The best selected formulation was further evaluated for the controlled and improved effects. SEM photomicrograph confirmed the spherical shape of microspheres and with particle size in the range of 73.5-85.4 μm. In vitro release of FBP from controlled release formulations indicated that the formulation containing solid dispersion:microspheres (1:0.5) yielded prolonged effect up to 10 h. The release kinetics followed zero-order, and the mechanism of drug release was found to be diffusion rate controlled. This formulation had shown better inhibition of edema of rat paw up to 16 h and identified as a suitable product for controlled delivery of FBP. In conclusion, the concept of using a binary mixture of solid dispersion and microspheres can be used for other drugs that exhibit a poor solubility in stomach pH and a faster release in intestinal pH.

Therapeutic Applications of Solid Dispersions for Drugs and New Molecules: In Vitro and In Vivo Activities

“…To understand and improve the dissolution behavior of poorly water-soluble drugs from SDs, flurbiprofen, a phenylalkanoic acid derivative belonging to the non-steroidal anti-inflammatory drugs, was used as a model [ 67 ]. SDs were prepared by the fusion method using urea and mannitol as hydrophilic carriers.…”

Dual crosslinked pectin–alginate network as sustained release hydrophilic matrix for repaglinide

“…Hydrated beads were removed at different time intervals and weighed after removing excess water using filter paper. The swelling ratio was determined using equation 3 [26]:…”

“…The drug release rate from crosslinked beads was ascertained using USP type II dissolution apparatus (TDT-08L, Electrolab, Mumbai, India) in 900 ml of dissolution medium at sampling was carried out in triplicate [26]. For the comparative study, the release profile of a marketed conventional tablet of repaglinide (Prandin ® tablets 2 mg, Novo Nordisk) was determined by the same procedure as followed for beads.…”

Systematic Review: The Enhancement of Anti-Inflammation Activity of Non Steroidal Anti-Inflammatory Drug (Nsaid) by Solid Dispersion Modifications

“…The percentage of drug release on flurbiprofen NSD is 11% after 60 min. While the best percentage of drug release of ratio 1:2, in the flurbiprofen-urea SD is 42% while in the flurbiprofen-mannitol SD is 35% after 60 min [18]. This is due to the high wetting effect of urea and urea have high solubility in water and other organic solvents [19].…”