Beads made of α-cyclodextrin and soybean oil: the drying method influences bead properties and drug release.
Freeze-dried beads made of α-cyclodextrin and soybean oil were reported previously as an efficient system for the oral delivery of lipophilic drugs. In the present study, oven-drying was evaluated as another method for drying beads. Oven-drying was optimised and the properties of the resulting beads were assessed. The behavior of oven-dried beads and the release of indomethacin from these beads were evaluated in vitro in simulated gastrointestinal fluids and compared with those of freeze-dried beads. The stability of freeze-dried and oven-dried unloaded beads stored at 25°C for 12 months and at 40°C for 6 months in closed and open vials was also studied by different techniques. An oven-drying time of 6 hours at 25°C was chosen as optimal conditions. Oven-dried beads exhibited a sticky texture making them difficult to handle. They were harder, less fragile and smaller than the freeze-dried ones. The characteristics of oven-dried beads make them more resistant in vitro even in media containing bile salt. The rate of indomethacin release from oven-dried beads was much slower than that from the freeze-dried ones. Whatever the drying method, beads must be stored at room temperature protected from humidity. However, no products of oil degradation were detected with both kinds of beads. This work clearly emphasized that the drying method of the beads had a strong influence on their properties, behavior in simulated gastrointestinal fluids and drug release.
Univ Paris-Sud, CNRS UMR 8612, Physico-chimie - Pharmacotechnie - Biopharmacie, IFR 141, Faculté de Pharmacie, Châtenay-Malabry, France.
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Hamoudi
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Saunier
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Gueutin
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Fattal
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Bochot
D000284:Administration, Oral; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry*; D055598:Chemical Phenomena; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry*; D004339:Drug Compounding; D004349:Drug Packaging; D004355:Drug Stability; D005230:Fatty Acids, Nonesterified / Q000032:analysis; D005612:Freeze Drying; D005750:Gastric Juice / Q000737:chemistry; D005766:Gastrointestinal Contents / Q000737:chemistry; D006358:Hot Temperature / Q000009:adverse effects; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage / Q000737:chemistry*; D007700:Kinetics; D008054:Lipid Peroxides / Q000032:analysis; D010189:Pancreatic Juice / Q000737:chemistry; D012995:Solubility; D013024:Soybean Oil / Q000737:chemistry*; D047391:alpha-Cyclodextrins / Q000737:chemistry*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004337:Drug Carriers; D005230:Fatty Acids, Nonesterified; D008054:Lipid Peroxides; D047391:alpha-Cyclodextrins; D013024:Soybean Oil; D007213:Indomethacin; C032613:alpha-cyclodextrin