Issue link: https://www.e-digitaleditions.com/i/1233462
Tablets & Capsules April 2020 39 The capsule-filling temperature should be high enough to maintain the formulation's free-flowing liquid state but low enough to minimize any potential harmful effects of ele- vated temperature on the formulation or capsules. An evaluation of the for- mulation's viscosity at various tem- peratures can be useful for finding the optimal filling temperature, as shown in the example thermo-rheo- gram chart in Figure 2. DO add antioxidant(s)! As previously stated, lipids should be stored under nitrogen. How- ever, it may also be necessary to add antioxidant(s) to prevent oxidation during processing and improve the formulations' shelf life. T&C Inayet Ellis, PhD, is scientific affairs manager at Gattefossé USA (201 265 4800, www.gattefosse.com), a global supplier of specialty excipients and for- mulation solutions for the healthcare industry. For additional information, please contact the author (iellis@gatte fossecorp.com). for large-scale or commercial manufacturing. During initial early stage screen- ing and small-scale manufacturing, two-piece capsules might be more viable for both liquid and solid for- mulations. However, softgels are more suitable for liquid formulations during large-scale manufacturing to avoid the extra band-sealing step that's required to prevent leakage with two-piece capsules. D O f o l l ow t h e h a n d l i n g instructions of each lipid excip- ient. DON'T use water baths to heat lipid-based systems, and DON'T scoop semi-solid excipi- ents from top. Lipid vehicles should be stored under nitrogen. Self-emulsifying excipients can absorb moisture, so you should avoid high humidity and water baths. Semi-solid or block excipients (such as Gelucire 44/14) need to be melted and homogenized before sampling rather than scooped from the top. DO evaluate the temperature and viscosity profiles of semi- solid formulations to find the optimal filling temperature. Figure 2 Example thermo-rheogram showing the optimal filling temperature for a solid excipient (Gelucire 48/16) Inflection point Viscosity (Cp) 600 500 400 300 200 100 0 Temperature (°C) 30 35 40 45 50 55 60 65 70 Filling temperature = inflection point + 5°C (37°C + 5°C = 42°C) FOLLOW US FOLLOW US