Table 1.
FDA-approved drugs utilizing lipid systems.
| Molecule (trade name) | New drug application year | Biopharmaceutic classification system | Type of lipid-based formulation | Oil | Surfactant (HLB <12) | Surfactant (HLB >12) | Hydrophilic cosolvent |
|---|---|---|---|---|---|---|---|
| Ergocalciferol (Drisdol®) | 1941 | 3 | I | Soybean oil | ‒ | ‒ | ‒ |
| Calcitriol (Rocaltrol®) | 1978 | 2/4 | I | Fractionated triglycerides of coconut oil | ‒ | ‒ | ‒ |
| Valproic acid (Depakene®) | 1978 | 1 | I | Corn oil | ‒ | ‒ | ‒ |
| Isotretinoin (Accutane®) Discontinued | 1982 | 2 | I | Beeswax, hydrogenated soybean oil flakes, hydrogenated vegetable oil, soybean oil | ‒ | ‒ | ‒ |
| Cyclosporin A (Sandimmune®) | 1983 | 2 | II | Olive oil | ‒ | Polyoxyethylated oleic glycerides | Ethanol 12.5% |
| Dronabinol (Marinol®) | 1985 | 2/4 | I | Sesame oil | ‒ | ‒ | ‒ |
| Clofazimine (Lamprene®) Discontinued | 1986 | 2 | I | Beeswax | ‒ | ‒ | ‒ |
| Cyclosporin A (Sandimmune®) | 1990 | 2 | II | Corn oil | Linoleic macroglycerides | ‒ | Ethanol 12.7% |
| Ranitidine (Zantac®) Discontinued | 1994 | 3 | ‒ | Medium-chain triglycerides | Gelucire 33/01 | ‒ | ‒ |
| Cyclosporin A (Neoral®) | 1995 | 2 | III A/III B | Corn oil mono-di-triglycerides | ‒ | Polyoxyl 40 hydrogenated castor oil | Ethanol 11.9%, glycerol, propylene glycol |
| Tretinoin (Vesanoid®) Discontinued | 1995 | ‒ | I | Beeswax, hydrogenated soybean oil flakes, hydrogenated vegetable oil, soybean oil | ‒ | ‒ | ‒ |
| Ritonavir (Norvir®) | 1996 | 4 | III A | ‒ | Oleic acid | Polyoxyl 35 castor oil | Ethanol |
| Saquinavir (Fortovase®) Discontinued | 1997 | 4 | ‒ | Medium-chain mono- and di-glycerides | ‒ | ‒ | ‒ |
| Progesterone (Prometrium®) | 1998 | 2 | I | Peanut oil | ‒ | ‒ | ‒ |
| Amprenavir (Agenerase®) Discontinued | 1999 | 2 | IV | ‒ | ‒ | Vitamin E TPGS | PEG400, propylene glycol |
| Bexarotene (Targretin®) | 1999 | ‒ | IV | ‒ | ‒ | Polysorbate 20 | PEG400 |
| Doxercalciferol (Hectorol®) | 1999 | 2/4 | I | Coconut oil | ‒ | ‒ | Alcohol |
| Sirolimus (Rapamune®) | 1999 | ‒ | III | Phosphatidylcholine, mono- and di-glycerides, soy fatty acids, ascorbyl palmitate | ‒ | Polysorbate 80 | 1.5%–2.5% ethanol, propylene glycol |
| Cyclosporin A (Gengraf®) | 2000 | 2 | IV | ‒ | ‒ | Polysorbate 80, Polyoxyl 35 castor oil | Propylene glycol, alcohol 12.8% v/v |
| Cyclosporin A (Gengraf®) | 2000 | 2 | IV | ‒ | ‒ | Polyoxyl 40 hydrogenated castor oil, polysorbate 80 | Propylene glycol |
| Ritonavir/lopinavir (Kaletra®) Discontinued | 2000 | 4 | III | ‒ | Oleic acid | Polyoxyl 35 castor oil | Propylene glycol |
| Dutasteride (Avodart®) | 2001 | 2/4 | I | Mono-di-glycerides of caprylic/capric acid | ‒ | ‒ | ‒ |
| Isotretinoin (Claravis®) | 2003 (ANDA) | 2 | ‒ | Hydrogenated vegetable oil, soybean oil, white wax | ‒ | Polysorbate 80 | ‒ |
| Omega-3-acid ethyl esters (Lovaza®) | 2004 | ‒ | I | Soybean oil | ‒ | ‒ | ‒ |
| Tipranavir (Aptivus®) | 2005 | 4 | III A | Mono-/di-glycerides of caprylic/capric acids | ‒ | Polyoxyl 35 castor oil | Ethanol, propylene glycol |
| Tipranavir (Aptivus®) | 2005 | 4 | IV | ‒ | ‒ | Vitamin E TPGS | PEG 400, propylene glycol, water |
| Paricalcitol (Zemplar®) | 2005 | 4 | I | Medium-chain triglycerides fractionated from coconut oil or palm kernel oil | ‒ | ‒ | Alcohol |
| Lubiprostone (Amitiza®) | 2006 | 2/4 | I | Medium-chain triglycerides | ‒ | ‒ | ‒ |
| Fenofibrate (Lipofen®) | 2006 | 2 | III | ‒ | ‒ | Gelucire 44/14 (lauroyl macrogol glyceride type 1500) | ‒ |
| Topotecan HCl (Hycamtin®) | 2007 | 1 | I | Hydrogenated vegetable oil | Glyceryl monostearate | ‒ | ‒ |
| Loratadine (Claritin®) | 2008 | 2 | ‒ | Caprylic/capric glycerides | ‒ | Polysorbate 80 | ‒ |
| Isotretinoin (Absorica®) | 2012 | 2 | ‒ | Soybean oil, stearoyl polyoxylglycerides | Sorbitan monooleate | ‒ | ‒ |
| Enzalutamide (Xtandi®) | 2012 | 2 | I | Caprylocaproyl polyoxyglycerides | ‒ | ‒ | ‒ |
| Nintedanib (Ofev®) | 2014 | 2/4 | II | Medium-chain triglycerides, hard fat | Lecithin | ‒ | ‒ |
| Calcifediol (Rayaldee®) | 2016 | 2/4 | II/III | Mixture of lipophilic emulsifier with a HLB <7 and an absorption enhancer with HLB of 13–18 Oily vehicle-mineral oil, liquid paraffins, or squalene |
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‒, not applicable; HLB, hydrophilic–lipophilic balance.
The table is adapted from Ref. 26 complying with the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).