Table 2.
Bioavailability enhancement by lipid based formulations.
| Drug/BCS class | Formulation (Excipients) | Test system | Results | Mechanism |
|---|---|---|---|---|
| Acyclovir (III)35 | Microemulsion (Labrafac, Labrasol, Plurol oleique, water) | Sprague-Dawley rats | Relative bioavailability enhanced by 12.78 times when compared with tablet | Enhanced solubilization in microemulsion |
| Atorvastatin (II)36 | SMEDDS | Beagle dogs | Significant increase in relative bioavailability (about 1.5 times) for all three formulations when compared with tablet | Enhanced intestinal solubility and mucosal permeability |
| (a) Labrafil, Cremophor RH40, propylene glycol | ||||
| (b) Estol, Cremophor RH40, propylene glycol | ||||
| (c) Labrafac, Cremophor RH40, propylene glycol | ||||
| Carvedilol (II)37 | SEDDS (Labrfil M1944CS, Tween 80, Transcutol) | Beagle dogs | Relative bioavailability enhanced by 4.1 times when compared with tablet | Enhanced solubility and dissolution rate |
| Coenzyme Q10 (II)38 | SEDDS (Myvacet 9-45, Labrafac CM-10, Lauroglycol) | Coonhound dogs | Relative bioavailability enhanced by 2 times when compared with powder | Enhanced aqueous solubilization |
| Cyclosporin (II)22 | SEDDS-Sandimmune (corn oil, ethanol) | Humans | Increased relative bioavailability and Cmax in humans. Neoral superior to Sandimmune in terms of reduced food effect, dose linearity and reduced interindividual variability | Due to formation of microemulsion after aqueous dilution for Neoral when compared with Sandimmune |
| SMEDDS-Neoral (corm oil glycerides, Cremophor RH40, ethanol) | ||||
| Danazol (II)25 | LCT solution (soyabean oil) | Beagle dogs | Relative bioavailability in the order of LCT solution>LCT-SMEDDS>MCT-SMEDDS>micronized powder. | Enhanced intestinal solubilization resulted in increased relative bioavailability. Significant drug precipitation in MCT-SMEDDS |
| LCT-SMEDDS (soyabean oil, Maisine 35-1, Cremophor EL, ethanol) | ||||
| MCT-SMEDDS (Captex 355, Capmul MCM, Cremophor EL) | ||||
| Griseofluvin (II)39 | Corn oil emulsion, corn oil suspension | Rats | Relative bioavailability in the order of corn oil emulsion>corn oil suspension>aqueous suspension | Enhanced solubilization in emulsion resulted in more relative bioavailability |
| Halofantrine (II)23 | MCT-SEDDS (Captex 355, Capmul MCM, Cremophor EL, ethanol) | Beagle dogs | Higher relative bioavailability from LCT SMEDDS compared with other formulations. All formulations enhanced bioavailability by 6–8 times when compared with solid tablet formulation | Enhanced solubilization and prevention of precipitation after aqueous dispersion |
| MCT-SMEDDS (Captex 355, Capmul MCM, Cremophor EL, ethanol) | ||||
| LCT-SMEDDS (soyabean oil, Maisine 35-1, Cremophor EL, ethanol) | ||||
| Ibuprofen (II)40 | Microemulsion (MCT oil, DGMO-C, HCO-40) | Rats | Bioavailability in microemulsion comparable with organic solution and higher than aqueous suspension | Enhanced solubility of compound in oil |
| Indomethacin (II)41 | SEDDS (Tween 85, ethyl oleate) | Sprague-Dawley rats | Relative bioavailability of SEDDS 1.57 times higher when compared with aqueous suspension | Improvement in the solubility and dissolution |
| Itraconazole (II)42 | SEDDS (Transcutol, Pluronic L64, tocopherol acetate) | Sprague-Dawley rats | Relative bioavailability of SEDDS was significantly higher than marketed capsule and reduced food effect when administered in SEDDS | Enhanced dissolution by incorporation in SEDDS |
| Ontazolast (II)26 | SEDDS (Gelucire 44/14, Peceol) | Charles River CD rats | Absolute bioavailability increased atleast by 10 times from SEDDS formulations. SEDDS formulations enhanced lymphatic transport | SEDDS formulation improved dissolution and solubility, and also enhanced bioavailability through lymphatic absorption thereby bypassing extensive hepatic metabolism |
| Penclomedine (Not available)43 | LCT (soyabean oil, Triolein), MCT (Trioctanoin), SCT (Tributyrin), liquid paraffin emulsion | Rats | Bioavailability is in the order of MCT>LCT>paraffin emulsion>SCT>aqueous suspension | Higher bioavailability in MCT is due to reduced drug precipitation during lipid digestion |
| Phenytoin (II)44 | Corn oil emulsion, corn oil suspension | Rats | Relative bioavailability in rats is in the order of emulsion>oil suspension>aqueous suspension | Enhanced solubility in lipid emulsion |
| Progesterone (IV)45 | SEDDS (mono-di-glycerides, Polysorbate 80) | Beagle dogs | Relative bioavailability of SEDDS is 9 times higher than the aqueous suspension | Enhancement of solubility and permeability when administered in SEDDS |
| Seocalcitol (Not available)46 | LCT-SMEDDS (sesame oil, Peceol, Cremophor RH40) | Sprague-Dawley rats | Absolute bioavailability LCT-SMEDDS is equal to MCT-SMEDDS | Similar solubility values of drug in SIF may have resulted in similar bioavailability |
| MCT-SMEDDS (Vicscoleo, Akoline, Cremophor RH40) | ||||
| Silymarin (Not available)47 | SMEDDS (Tween 80, ethyl alcohol, ethyl linoleate) | Rabbits | Relative bioavailability of SMEDDS is 1.88 and 48.82 times higher than PEG solution and suspension respectively | Alternative pathways such as lymphatic transport contribution to enhanced bioavailability |
| Simvastatin (II)48 | SMEDDS (Caproyl 90, Cremophor EL, Carbitol) | Beagle dogs | Relative bioavailability is 1.5 times higher in SMEDDS compared with conventional tablet | Enhanced solubility in lipid excipients |
| Tocotrienols (II)49 | Two SEDDS (Tween 80 and Labrasol) | Humans | Relative bioavailability enhanced by 2–3 times when compared with non-self-emulsifying formulation | Enhanced solubility and finer dispersion properties |
| Vitamin E (II)21 | SEDDS (Tween 80, Span 80 and palm oil) | Humans | Relative bioavailability of SEDDS is 2-folds higher than oil solution | Presence of surfactant in SEDDS led to higher bioavailability when compared with oil solution |