Solubilizing excipients in oral and injectable formulations.
A review of commercially available oral and injectable solution formulations reveals that the solubilizing excipients include water-soluble organic solvents (polyethylene glycol 300, polyethylene glycol 400, ethanol, propylene glycol, glycerin, N-methyl-2-pyrrolidone, dimethylacetamide, and dimethylsulfoxide), non-ionic surfactants (Cremophor EL, Cremophor RH 40, Cremophor RH 60, d-alpha-tocopherol polyethylene glycol 1000 succinate, polysorbate 20, polysorbate 80, Solutol HS 15, sorbitan monooleate, poloxamer 407, Labrafil M-1944CS, Labrafil M-2125CS, Labrasol, Gellucire 44/14, Softigen 767, and mono- and di-fatty acid esters of PEG 300, 400, or 1750), water-insoluble lipids (castor oil, corn oil, cottonseed oil, olive oil, peanut oil, peppermint oil, safflower oil, sesame oil, soybean oil, hydrogenated vegetable oils, hydrogenated soybean oil, and medium-chain triglycerides of coconut oil and palm seed oil), organic liquids/semi-solids (beeswax, d-alpha-tocopherol, oleic acid, medium-chain mono- and diglycerides), various cyclodextrins (alpha-cyclodextrin, beta-cyclodextrin, hydroxypropyl-beta-cyclodextrin, and sulfobutylether-beta-cyclodextrin), and phospholipids (hydrogenated soy phosphatidylcholine, distearoylphosphatidylglycerol, L-alpha-dimyristoylphosphatidylcholine, L-alpha-dimyristoylphosphatidylglycerol). The chemical techniques to solubilize water-insoluble drugs for oral and injection administration include pH adjustment, cosolvents, complexation, microemulsions, self-emulsifying drug delivery systems, micelles, liposomes, and emulsions.
Strickley
Robert G
RG
Formulation & Process Development, Gilead Sciences Inc., Foster City, California 94404, USA. rstrickley@gilead.com
D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D003505:Cyclodextrins / Q000737:chemistry; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007275:Injections, Intravenous; D004364:Pharmaceutical Preparations / Q000008:administration & dosage / Q000737:chemistry*; D010743:Phospholipids / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D013501:Surface-Active Agents / Q000737:chemistry; D013678:Technology, Pharmaceutical
D003505:Cyclodextrins; D004337:Drug Carriers; D004655:Emulsions; D005079:Excipients; D004364:Pharmaceutical Preparations; D010743:Phospholipids; D012997:Solvents; D013501:Surface-Active Agents