title: Development of novel polymer-stabilized diosmin nanosuspensions: in vitro appraisal and ex vivo permeation.
abstract: Scanty solubility and permeability of diosmin (DSN) are perpetrators for its poor oral absorption and high inter-subject variation. This article investigated the potential of novel DSN nanosuspensions to improve drug delivery characteristics. Bottom-up nanoprecipitation technique has been employed for nanosuspension development. Variables optimized encompassed polymeric stabilizer type, DSN: stabilizer ratio, excess stabilizer removal, spray drying, and mannitol incorporation. In vitro characterization included particle size (PS), infrared spectroscopy (IR), differential scanning calorimetry (DSC), X-ray powder diffraction (XRD), transmission electron microscope (TEM), scanning electron microscopy (SEM), and dissolution profile. Ex vivo permeation was assessed in rats using non-everted sac technique and HPLC. Optimal DSN nanosuspension (DSN:hydroxypropylmethyl cellulose HPMC 2:1) was prepared with acid base neutralization technique. The formula exhibited the lowest PS (336 nm) with 99.9% drug loading and enhanced reconstitution properties after mannitol incorporation. SEM and TEM revealed discrete, oval drug nanocrystals with higher surface coverage with HPMC compared to MC. DSN nanosuspension demonstrated a significant enhancement in DSN dissolution (100% dissolved) compared to crude drug (51%). Permeation studies revealed 89% DSN permeated from the nanosuspension after 120 min compared to non-detected amounts from drug suspension. Conclusively, novel DSN nanosuspension could successful improve its dissolution and permeation characteristics with promising consequences of better drug delivery.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Alexandria University, Egypt.
authors.forename: May S
authors.initials: MS
authors.lastname: Freag
authors.forename: Yosra S R
authors.initials: YS
authors.lastname: Elnaggar
authors.forename: Ossama Y
authors.initials: OY
authors.lastname: Abdallah
mesh_terms: D000818:Animals; D002152:Calorimetry, Differential Scanning; D011232:Chemical Precipitation; D002626:Chemistry, Pharmaceutical; D002851:Chromatography, High Pressure Liquid; D003460:Crystallization; D018360:Crystallography, X-Ray; D004145:Diosmin / Q000737:chemistry / Q000378:metabolism*; D004337:Drug Carriers; D004355:Drug Stability; D005079:Excipients / Q000737:chemistry*; D065347:Hypromellose Derivatives; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D008855:Microscopy, Electron, Scanning; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D036103:Nanotechnology; D010316:Particle Size; D010539:Permeability; D033362:Powder Diffraction; D051381:Rats; D017208:Rats, Wistar; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D004337:Drug Carriers; D005079:Excipients; D065347:Hypromellose Derivatives; D004145:Diosmin; D008747:Methylcellulose
keywords: DSN; Diosmin; Dissolution; HPMC; MC; Nanocrystals; Nanosuspension; Permeation; diosmin; hydroxypropylmethyl cellulose; methyl cellulose