Development of novel polymer-stabilized diosmin nanosuspensions: In vitro appraisal and ex vivo permeation

• Published in: International journal of pharmaceutics Vol. 454; no. 1; pp. 462 - 471
• Main Authors: Freag, May S., Elnaggar, Yosra S.R., Abdallah, Ossama Y.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.09.2013
• Subjects: absorption; Animals; Calorimetry, Differential Scanning; cellulose; Chemical Precipitation; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Crystallization; Crystallography, X-Ray; differential scanning calorimetry; Diosmin; Diosmin - chemistry; Diosmin - metabolism; Dissolution; Drug Carriers; Drug Stability; drugs; Excipients - chemistry; high performance liquid chromatography; Hypromellose Derivatives; infrared spectroscopy; Intestinal Absorption; Intestines - metabolism; Kinetics; Male; mannitol; Methylcellulose - analogs & derivatives; Methylcellulose - chemistry; Microscopy, Electron, Scanning; Microscopy, Electron, Transmission; Nanocrystals; Nanoparticles; Nanosuspension; Nanotechnology; neutralization; Particle Size; Permeability; Permeation; Powder Diffraction; Rats; Rats, Wistar; scanning electron microscopy; Solubility; Spectroscopy, Fourier Transform Infrared; spray drying; Technology, Pharmaceutical - methods; transmission electron microscopes; transmission electron microscopy; X-radiation; X-ray diffraction; Nanocrystals; MC; Permeation; Nanosuspension; Dissolution; DSN; HPMC; Diosmin; methyl cellulose; hydroxypropylmethyl cellulose
• ISSN: 0378-5173; 1873-3476; 1873-3476
• DOI: 10.1016/j.ijpharm.2013.06.039

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 (336nm) 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 120min 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.