TABLE 4.
Doxorubicin formulations
| Formulations | Manufacturer | Composition/Strength | Regulatory status |
|---|---|---|---|
| Adriamycin PFS™ (Doxorubicin HCl Injection, USP; 2 mg/ml sterile, isotonic solution) Adriamycin RDF™ (Powder for Injection; doxorubicin hydrochloride for injection, USP; Sterile red-orange lyophilized powder) |
Pharmacia & Upjohn S.p.A (Now Pfizer) | Each ml contains doxorubicin HCI 2 mg, USP, and the following inactive ingredients: sodium chloride 0.9% and water for injection q.s. Hydrochloric acid is used to adjust the pH to a target pH of 3.0. | Received FDA approval in July 1993 Discontinued in the US |
| Nanoformulations | |||
| Doxil® Caelyx® (PEGylated liposomes) |
Janssen Pharmaceuticals Janssen-Cilag International NV |
2 mg/ml of doxorubicin, 3.19 mg/ml of N-(carbonyl-methoxypolyethylene glycol 2000)-1,2-distearoyl-sn-glycero-3-phosphoethanolamine sodium salt (DSPE-PEG 2000), 9.58 mg/ml of fully hydrogenated soy phosphatidylcholine (HSPC), and 3.19 mg/ml of cholesterol. Mean particle size: 87.3 ± 8.5 nm |
FDA approval of Doxil® in 1995 EMEA approval of Caelyx® in 1996 |
| MYOCET™ (non-PEGylated liposomes) | Zeneus Teva BV | Single lamellar liposomes (approximately 150 nm) composed of egg phosphatidylcholine: cholesterol (55:45 mole percent) containing 300 mM citrate at pH 4.5. Encapsulation efficiency >95% After encapsulation of doxorubicin, the drug-to-lipid ratio of Myocet is approximately 0.25:1 (wt:wt) and the pH is 6.5–8.5. Encapsulation is achieved via an active loading process, which utilizes an acidic (pH 4.5) proton concentration gradient. The internal complex is a flexible assembly of doxorubicin monomers stacked into fibers that are cross-linked by citrate into a hexagonal array with a 35 Å lattice repeat. Supplied as a three-vial system: doxorubicin HCl, liposomes and buffer, 0.9% (w/v) sodium chloride solution for injection |
Myocet was approved in Europe and Canada in 2000 and is currently undergoing a Phase 3 global trial. |
| LIPODOX (SPIL DXR HCl liposome injection) generic version of Doxil®/Caelyx®) | Sun Pharmaceutical Industries Ltd. | Available as 2 mg/ml (20 mg/10 ml and 50 mg/25 ml) Doxorubicin hydrochloride liposome injection. The drug product appears as a translucent, red liposomal dispersion. | Due to shortage of Doxil® in 2011, FDA allowed temporary import of Lipo-DOX for the treatment of epithelial ovarian cancer (EOC) FDA approved the generic version of Doxil® in 2013 |
| Lipodox® (second-generation PEGylated liposomal doxorubicin) | TTY Biopharm Company Ltd, Taipei, Taiwan | Distearoylphosphatidylcholine (DSPC)/PEG-DSPE liposome with a slightly higher phase transition temperature than HSPC, distearoylphosphatidylcholine (DSPC), and cholesterol with a surface coating of PEG. | Commercially available in Taiwan since 1998 |
| Thermodox® (thermally sensitive liposomal doxorubicin) | Celsion Corporation | DPPC, MSPC, and PEG 2000-DSPE (90:10:4 molar ratio) | Phase III trial (OPTIMA study) for treatment of nonresectable hepatocellular carcinoma (HCC), in conjunction with standardized radiofrequency ablation (sRFA ≥ 45). |
| TLD1/TaliDox® (glycan targeted liposomal Xdoxorubicin) | InnoMedica | Comprises of 1,2-distearoyl-snglycero-3-phosphocholine (DSPC), cholesterol, and DSPE-MPEG 2000 Particle size: approximately 60 nm with a PDI < 0.01 |
Phase I/IIa in Switzerland (NCT03387917) in patients with advanced solid tumors. InnoMedica has decided to submit the dossier for marketing authorization to Swissmedic in the first half of 2021. |
| EGFR(V)-EDV-Dox™ | EnGeneIC Ltd. | EGFR (vectibix sequence)-targeted EnGeneIC delivery vehicle (EDV) containing doxorubicin. Bacterially derived nanocell packages Doxorubicin, into a 400 nm particle which targets specific cancer cells using bispecific antibodies (BsAb) | Phase I ACTRN12609000672257 Phase I NCT02766699 |