title: 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.
authors.affiliation: Amity Institute of Pharmacy, Amity University, Lucknow, 226028, Uttar Pradesh, India. mvramana@lko.amity.edu.
authors.forename: Venkata Ramana
authors.initials: VR
authors.lastname: Malipeddi
authors.affiliation: School of Pharmacy and Biomedical Sciences, The University of Newcastle, Newcastle, Callaghan NSW, 2308, Australia.
authors.forename: Kamal
authors.initials: K
authors.lastname: Dua
authors.affiliation: Laureate Institute of Pharmacy, Jawalamukhi, Kangra, 176031, Himachal Pradesh, India.
authors.forename: Rajendra
authors.identifier: 0000-0002-1286-1874
authors.initials: R
authors.lastname: Awasthi
mesh_terms: D000284:Administration, Oral; D000818:Animals; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry*; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry; D065546:Drug Liberation; D005480:Flurbiprofen / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D057927:Hydrophobic and Hydrophilic Interactions; D007249:Inflammation / Q000517:prevention & control; D008297:Male; D008353:Mannitol / Q000737:chemistry; D008863:Microspheres; D010316:Particle Size; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry*; D011109:Polymethacrylic Acids / Q000737:chemistry; D051381:Rats; D012995:Solubility; D014508:Urea / Q000737:chemistry
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; C496966:Eudragit RSPO; D011108:Polymers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D008353:Mannitol; D005480:Flurbiprofen; D014508:Urea
keywords: Controlled release; Flurbiprofen; Fusion method; Microspheres; Rat paw edema; Solid dispersions; Solvent evaporation method