AbstractDrugs, especially low aqueous solubility drugs, are provided in a porous matrix form, preferably microparticles, which enhances dissolution of the drug in aqueous media. The drug matrices preferably are made using a process that includes (i) dissolving a drug, preferably a drug having low aqueous solubility, in a volatile solvent to form a drug solution, (ii) combining at least one pore forming agent with the drug solution to form an emulsion, suspension, or second solution, and (iii) removing the volatile solvent and pore forming agent from the emulsion, suspension, or second solution to yield the porous matrix of drug. The pore forming agent can be either a volatile liquid that is immiscible with the drug solvent or a volatile solid compound, preferably a volatile salt. In a preferred embodiment, spray drying is used to remove the solvents and the pore forming agent. The resulting porous matrix has a faster rate of dissolution following administration to a patient, as compared to non-porous matrix forms of the drug. In a preferred embodiment, microparticles of the porous drug matrix are reconstituted with an aqueous medium and administered parenterally, or processed using standard techniques into tablets or capsules for oral administration. Other References- Adeyeye & Price, “Chemical, dissolution stability and microscopic evaluation of suspensions of ibuprofen and sustained release ibuprofen-wax microspheres,” J. Microencapsul. 14(3):357-77 (1997).
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| InventorsAssigneeApplication No. 09706045 filed on 11/03/2000 US Classes:424/489, Particulate form (e.g., powders, granules, beads, microcapsules, and pellets)424/400PREPARATIONS CHARACTERIZED BY SPECIAL PHYSICAL FORMField of Search424/489, Particulate form (e.g., powders, granules, beads, microcapsules, and pellets)424/400, PREPARATIONS CHARACTERIZED BY SPECIAL PHYSICAL FORM424/405, Biocides; animal or insect repellents or attractants (e.g., disinfectants, pesticides, etc.)424/484, Matrices428/402Particulate matter (e.g., sphere, flake, etc.)Examiners Primary: Webman, Edward J.Attorney, Agent or FirmUS Patent References4818542, Porous microspheres for drug delivery and methods for making same Issued on: 04/04/1989 Inventor: DeLuca , et al.5382437, Frozen liquified gas composition and method for oral administration of drugs, biologicals, nutrients and foodstuffs Issued on: 01/17/1995 Inventor: Ecanow5468598, Solid particle dispersions for imaging systems Issued on: 11/21/1995 Inventor: Miller, et al.5470583, Method of preparing nanoparticle compositions containing charged phospholipids to reduce aggregation Issued on: 11/28/1995 Inventor: Na, et al.5500331, Comminution with small particle milling media Issued on: 03/19/1996 Inventor: Czekai, et al.5510118, Process for preparing therapeutic compositions containing nanoparticles Issued on: 04/23/1996 Inventor: Bosch, et al.5513803, Continuous media recirculation milling process Issued on: 05/07/1996 Inventor: Czekai, et al.5518187, Method of grinding pharmaceutical substances Issued on: 05/21/1996 Inventor: Bruno, et al.5518738, Nanoparticulate nsaid compositions Issued on: 05/21/1996 Inventor: Eickhoff, et al.5534270, Method of preparing stable drug nanoparticles Issued on: 07/09/1996 Inventor: De Castro5552160, Surface modified NSAID nanoparticles Issued on: 09/03/1996 Inventor: Liversidge, et al.5560932, Microprecipitation of nanoparticulate pharmaceutical agents Issued on: 10/01/1996 Inventor: Bagchi, et al.5565188, Polyalkylene block copolymers as surface modifiers for nanoparticles Issued on: 10/15/1996 Inventor: Wong, et al.5569448, Sulfated nonionic block copolymer surfactants as stabilizer coatings for nanoparticle compositions Issued on: 10/29/1996 Inventor: Wong, et al.5571536, Formulations of compounds as nanoparticulate dispersions in digestible oils or fatty acids Issued on: 11/05/1996 Inventor: Eickhoff, et al.5580579, Site-specific adhesion within the GI tract using nanoparticles stabilized by high molecular weight, linear poly (ethylene oxide) polymers Issued on: 12/03/1996 Inventor: Ruddy, et al.5587143, Butylene oxide-ethylene oxide block copolymer surfactants as stabilizer coatings for nanoparticle compositions Issued on: 12/24/1996 Inventor: Wong5591456, Milled naproxen with hydroxypropyl cellulose as a dispersion stabilizer Issued on: 01/07/1997 Inventor: Franson, et al.5609998, Process for dispersing concentrated aqueous slurries Issued on: 03/11/1997 Inventor: Texter, et al.5622938, Sugar base surfactant for nanocrystals Issued on: 04/22/1997 Inventor: Wong5657931, Stable aqueous solid particle dispersions Issued on: 08/19/1997 Inventor: Nair, et al.5662279, Process for milling and media separation Issued on: 09/02/1997 Inventor: Czekai, et al.5662883, Microprecipitation of micro-nanoparticulate pharmaceutical agents Issued on: 09/02/1997 Inventor: Bagchi, et al.5665331, Co-microprecipitation of nanoparticulate pharmaceutical agents with crystal growth modifiers Issued on: 09/09/1997 Inventor: Bagchi, et al.5716642, Microprecipitation of nanoparticulate pharmaceutical agents using surface active material derived from similar pharmaceutical agents Issued on: 02/10/1998 Inventor: Bagchi, et al.5718919, Nanoparticles containing the R(-)enantiomer of ibuprofen Issued on: 02/17/1998 Inventor: Ruddy, et al.5747001, Aerosols containing beclomethazone nanoparticle dispersions Issued on: 05/05/1998 Inventor: Wiedmann, et al.5762961, Rapidly soluble oral solid dosage forms, methods of making same, and compositions thereof Issued on: 06/09/1998 Inventor: Roser, et al.5919434, Polymeric surfactant-encapsulated microbubbles and their use in ultrasound imaging Issued on: 07/06/1999 Inventor: Dugstad, et al.5942253, Prolonged release of GM-CSF Issued on: 08/24/1999 Inventor: Gombotz, et al.5976574, Processes for spray drying hydrophobic drugs in organic solvent suspensions Issued on: 11/02/1999 Inventor: Gordon5985285, Vaccines for plague Issued on: 11/16/1999 Inventor: Titball, et al.6001336, Processes for spray drying aqueous suspensions of hydrophobic drugs and compositions thereof Issued on: 12/14/1999 Inventor: Gordon6423345, Matrices formed of polymer and hydrophobic compounds for use in drug delivery Issued on: 07/23/2002 Inventor: Bernstein, et al.6565885Methods of spray drying pharmaceutical compositions Issued on: 05/20/2003 Inventor: Tarara, et al.Foreign Patent References- 2 136 704 CA 05/01/1995
- 37 13 326 DE 10/01/1987
- 0 655 237 EP 05/01/1995
- 1 265 615 GB 03/01/1972
- 98/31346 WO 07/01/1998
- WO 98/51282 WO 11/01/1998
- 99/56731 WO 11/01/1999
International Class A61K009/16
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