title: Naproxen Microparticulate Systems Prepared Using In Situ Crystallisation and Freeze-Drying Techniques.
abstract: Poor drug solubility and dissolution rate remain to be one of the major problems facing pharmaceutical scientists, with approximately 40% of drugs in the industry categorised as practically insoluble or poorly water soluble. This in turn can lead to serious delivery challenges and poor bioavailability. The aim of this research was to investigate the effects of the surfactants, poloxamer 407 (P407) and caprol® PGE 860 (CAP), at various concentrations (0.1, 0.5, 1 and 3% w/v) on the enhancement of the dissolution properties of poorly water-soluble drug, naproxen, using in situ micronisation by solvent change method and freeze-drying. The extent at which freeze-drying influences the dissolution rate of naproxen microcrystals is investigated in this study by comparison with desiccant-drying. All formulations were evaluated and characterised using particle size analysis and morphology, in vitro dissolution studies, differential scanning calorimetry (DSC), and Fourier transform infra-red (FT-IR) spectroscopy. An increase in poloxamer 407 concentration in freeze-dried formulations led to enhancement of drug dissolution compared to desiccator-dried formulations, naproxen/caprol® PGE 860 formulations and untreated drug. DSC and FT-IR results show no significant chemical interactions between drug and poloxamer 407, with only very small changes to drug crystallinity. On the other hand, caprol® PGE 860 showed some interactions with drug components, alterations to the crystal lattice of naproxen, and poor dissolution profiles using both drying methods, making it a poor choice of excipient.
authors.affiliation: Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, SR1 3SD, UK.
authors.forename: Amanda
authors.initials: A
authors.lastname: Solaiman
authors.affiliation: Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, SR1 3SD, UK.
authors.forename: Adam Keenan
authors.initials: AK
authors.lastname: Tatari
authors.affiliation: Department of Pharmacy, Health and Well-being, University of Sunderland, Sunderland, SR1 3SD, UK. amal.elkordy@sunderland.ac.uk.
authors.forename: Amal Ali
authors.initials: AA
authors.lastname: Elkordy
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000493:pharmacokinetics; D001682:Biological Availability; D002152:Calorimetry, Differential Scanning / Q000379:methods; D003460:Crystallization / Q000379:methods*; D003890:Desiccation / Q000379:methods; D005079:Excipients / Q000737:chemistry / Q000493:pharmacokinetics; D005612:Freeze Drying / Q000379:methods*; D005990:Glycerol / Q000031:analogs & derivatives; D009288:Naproxen / Q000737:chemistry / Q000493:pharmacokinetics; D020442:Poloxamer / Q000737:chemistry / Q000493:pharmacokinetics; D012995:Solubility; D012997:Solvents / Q000737:chemistry / Q000493:pharmacokinetics; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013501:Surface-Active Agents / Q000737:chemistry / Q000493:pharmacokinetics; D014961:X-Ray Diffraction / Q000379:methods
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005079:Excipients; D012997:Solvents; D013501:Surface-Active Agents; D020442:Poloxamer; D009288:Naproxen; D005990:Glycerol
keywords: caprol® PGE 860; dissolution enhancement; freeze-drying; in situ micronisation; naproxen; poloxamer 407