title: Controlled-release triple anti-inflammatory therapy based on novel gastroretentive sponges: characterization and magnetic resonance imaging in healthy volunteers.
abstract: The current work aimed to develop novel composite sponges of chitosan (CH)-chondroitin sulfate (CS) as a low-density gastroretentive delivery system for lornoxicam (LOR). This triple anti-inflammatory therapy-loaded matrices are expected to expand and float upon contact with gastric fluids for prolonged times. CH and CS solutions (3%, w/w) were prepared, mixed in different ratios, lyophilized, coated with magnesium stearate and compressed. The CH:CS interpolymer complex (IPC) was evaluated via FT-IR, DSC, and XRD. The compressed-sponges were evaluated for appearance, structure, porosity, pore diameter, density, wetting-time, floating characteristics, adhesion-retention, and LOR-release. The gastroretentivity of the best achieved magnetite-loaded sponges was monitored in healthy volunteers via MRI. The interaction between CH (protonated amino groups) and CS (anionic carboxylate/sulfate groups) proved IPC formation. DSC and XRD studies confirmed loss of LOR crystallinity. The sponges possessed interconnecting porous-network structures. The porosity, mean pore diameter, and bulk density of CH:CS (10:3) IPC sponges were 11.779%, 25.4 nm, and 0.670 g/mL, respectively. They showed complete wetting within seconds, gradual size-expansion within minutes and prolonged adhesion for hours. Controlled LOR-release profiles were tailored over 12h to satisfy individual patient needs. Monitoring of sponges via MRI proved their gastroretentivity for at least 5h.
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt. Electronic address: mina_ebrahim@yahoo.com.
authors.forename: Mina Ibrahim
authors.initials: MI
authors.lastname: Tadros
authors.affiliation: Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
authors.forename: Rania Hassan
authors.initials: RH
authors.lastname: Fahmy
mesh_terms: D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000737:chemistry; D002152:Calorimetry, Differential Scanning; D048271:Chitosan / Q000737:chemistry; D002809:Chondroitin Sulfates / Q000737:chemistry; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage; D016503:Drug Delivery Systems; D052203:Ferrosoferric Oxide / Q000008:administration & dosage / Q000737:chemistry; D005753:Gastric Mucosa / Q000378:metabolism; D064368:Healthy Volunteers; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D010894:Piroxicam / Q000008:administration & dosage / Q000031:analogs & derivatives*; D016062:Porosity; D017550:Spectroscopy, Fourier Transform Infrared; D013229:Stearic Acids / Q000737:chemistry; D014961:X-Ray Diffraction
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003287:Contrast Media; D003692:Delayed-Action Preparations; D013229:Stearic Acids; D010894:Piroxicam; C031183:stearic acid; D002809:Chondroitin Sulfates; D048271:Chitosan; C059451:lornoxicam; D052203:Ferrosoferric Oxide
keywords: Chitosan–chondroitin sulfate interpolymer complex; Gastroretentive sponges; Lornoxicam; Magnetic resonance imaging; Triple anti-inflammatory therapy