Table II.
Profiling of Reactive Impurities in Selected Lots of Pharmaceutical Excipients
| Excipients | Sources/lot | Impurity (ppm) | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Glucose | HCHO | Hydrogen peroxide | NO2 | NO3 | Monochloroacetate | Heavy metals | Trace metals | ||
| Microcrystalline cellulose, PH102 | FMC/1 | 79.6 | 4.8 | <2 | N/A | N/A | N/A | <10 | <5 Mg, Mn; <10 Al, Cr, Cu, Fe, Ni, Zn; 10 Ca |
| FMC/2 | 59.5 | 5.1 | <2 | 9.4 | 23.0 | 0.9 | N/A | N/A | |
| FMC/3 | 40.7 | 4.1 | ND | N/A | N/A | N/A | N/A | N/A | |
| Lactose Fast Flo | Foremost | ND | N/A | <2 | 10.4 | 12.4 | 12.0 | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al; 15 Ca |
| Lactose monohydrate | Foremost/1 | ND | 1.4 | <2 | 5.1 | 9.1 | 1.0 | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al, Ca |
| Foremost/2 | ND | ND | <2 | 5.5 | 8.0 | 0.9 | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al, Ca | |
| Lactose anhydrous | Quest/1 | ND | 7.4 | <2 | 5.4 | 4.3 | 0.6 | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al; 37 Ca |
| Quest/2 | ND | 3.6 | <2 | 3.7 | 6.0 | 0.6 | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al; 32 Ca | |
| Pre-gelatinized starch | Colorcon/1 | ND | 14.7 | <2 | 14.5 | 29.2 | 4.4 | <10 | <10 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <20 Al, Ca |
| Colorcon/2 | ND | 10.9 | <2 | 11.8 | 22.9 | 2.3 | <10 | <10 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <20 Al, 21 Ca | |
| Colorcon/3 | ND | 11.1 | N/A | N/A | N/A | N/A | N/A | N/A | |
| Povidone | ISP/1 | INC | INC | 37 | 2.2 | 13.6 | ND | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al, Ca |
| ISP/2 | INC | INC | 72 | 1.6 | 13.1 | ND | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al, Ca | |
| Crospovidone | ISP/1 | ND | 40.8 | 66 | 17.2 | 52.4 | ND | N/A | <5 Mn; <10 Al, Cr, Cu, Fe, Ni, Zn; 5 Mg; 10 Ca |
| ISP/2 | ND | 8.5 | 69 | 10.5 | 30.4 | ND | N/A | <5 Mg, Mn; <10 Al, Ca, Cr, Cu, Fe, Ni, Zn | |
| Sodium starch glycolate | Roquette/1 | – | 4.6 | <2 | 279.2 | 183.1 | ND | <10 | <5 Cr, Cu, Fe, Mn, Ni, Zn; <10 Al, 79 Ca; 9 Mg |
| Roquette/2 | – | 1.5 | <2 | 285.6 | 117.3 | 135.8 | <10 | <5 Cr, Cu, Fe, Mn, Ni, Zn; <10 Al, 75 Ca; 8 Mg | |
| Croscarmellose Na | FMC/1 | ND | 6.5 | <2 | 2.4 | 23.8 | 52.2 | N/A | N/A |
| FMC/2 | ND | 6.6 | <2 | 1.4 | 10.3 | 21.6 | <10 | <10 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <20 Al, 42 Ca | |
| Magnesium stearate | Mallincrodt/1 | ND | 3.8 | <2 | 2.1 | 6.0 | ND | <10 | <5 Mn; <10 Al, Ca, Cr, Cu, Fe, Ni, Zn; |
| Mallincrodt/2 | ND | 3.7 | <2 | 5.3 | 12.5 | 0.7 | N/A | N/A | |
| Stearic acid | Crompton | ND | 3.1 | <2 | 3.5 | 6.6 | ND | ND | <5 Mn; <10 Al, Ca, Cr, Cu, Fe, Ni, Zn; 30 Mg |
| Hydroxypropyl cellulose | Hercules/1 | ND | 11.4 | 13 | N/A | N/A | N/A | N/A | N/A |
| Hercules/2 | ND | 9.4 | 13 | 0.9 | 3.5 | ND | <10 | <5 Cr, Cu, Fe, Mg, Mn, Ni, Zn; <10 Al, 23 Ca | |
| Silicone dioxide | Degussa/1 | ND | 6.1 | <2 | 5.8 | 12.5 | ND | N/A | 7 Mg; <5 Mn; <10 Al, Ca, Cr, Cu, Fe, Ni, Zn |
| Degussa/2 | N/A | N/A | <2 | 1.5 | 8.7 | ND | N/A | 200 Al; 480 Ca; 30 Fe; 130 Mg; <5 Mn, <10 Cr, Cu, Ni, Zn | |
ND not detectable, N/A not available, INC incompatible
Heavy metals and trace metals analysis conducted using Inductively Coupled Plasma Atomic Emission Spectroscopy (ICP-AES) - Microwave digestion in acid was used for treatment of insoluble excipients