title: Study of sodium hyaluronate-based intranasal formulations containing micro- or nanosized meloxicam particles.
abstract: This article reports on the micro- and nanonization of meloxicam (MEL) with the aim of developing pre-dispersions as intermediates for the design of intranasal formulations. As a new approach, combined wet milling technology was developed in order to reduce the particle size of the MEL. Different milling times resulted in micro- or nanosized MEL in the pre-dispersions with polyvinyl alcohol as stabilizer agent, which were directly used for preparing intranasal liquid formulations with the addition of sodium hyaluronate as mucoadhesive agent. Reduction of the MEL particle size into the nano range led to increased saturation solubility and dissolution velocities, and increased adhesiveness to surfaces as compared with microsized MEL particles. A linear correlation was demonstrated between the specific surface area of MEL and the AUC. The in vitro and in vivo studies indicated that the longer residence time and the uniform distribution of nano MEL spray throughout an artificial membrane and the nasal mucosa resulted in better diffusion and a higher AUC. Nanosized MEL may be suggested for the development of an innovative dosage form with a different dose of the drug, as a possible administration route for pain management.
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary; Richter Gedeon Nyrt., Budapest, Hungary.
authors.forename: Csilla
authors.initials: C
authors.lastname: Bartos
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Rita
authors.initials: R
authors.lastname: Ambrus
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Péter
authors.initials: P
authors.lastname: Sipos
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Mária
authors.initials: M
authors.lastname: Budai-Szűcs
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Erzsébet
authors.initials: E
authors.lastname: Csányi
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: Róbert
authors.initials: R
authors.lastname: Gáspár
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: Árpád
authors.initials: Á
authors.lastname: Márki
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: Adrienn B
authors.initials: AB
authors.lastname: Seres
authors.affiliation: Department of Pharmacodynamics and Biopharmacy, University of Szeged, Szeged, Hungary.
authors.forename: Anita
authors.initials: A
authors.lastname: Sztojkov-Ivanov
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary.
authors.forename: Tamás
authors.initials: T
authors.lastname: Horváth
authors.affiliation: Department of Pharmaceutical Technology, University of Szeged, Szeged, Hungary. Electronic address: revesz@pharm.u-szeged.hu.
authors.forename: Piroska
authors.initials: P
authors.lastname: Szabó-Révész
mesh_terms: D000268:Adhesiveness; D000281:Administration, Intranasal; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical; D004339:Drug Compounding; D005079:Excipients / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D008297:Male; D000077239:Meloxicam; D008567:Membranes, Artificial; D053758:Nanoparticles; D009297:Nasal Mucosa / Q000378:metabolism; D010316:Particle Size; D011142:Polyvinyl Alcohol; D051381:Rats; D017207:Rats, Sprague-Dawley; D012212:Rheology; D012995:Solubility; D013843:Thiazines / Q000008:administration & dosage* / Q000493:pharmacokinetics; D013844:Thiazoles / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D008567:Membranes, Artificial; D013843:Thiazines; D013844:Thiazoles; D011142:Polyvinyl Alcohol; D006820:Hyaluronic Acid; D000077239:Meloxicam
keywords: AUC; Combined wet milling; Intranasal formulation; Meloxicam; Mucoadhesivity; Permeability