(111a) The Effects of Mixing Processes on Critical Quality Attributes of Strip Films

This work is part of an overall objective of being able to create patient compliant drug loaded thin polymeric films that are uniform in drug content or where the amount of drug varies by a minuscule amount and has negligible effects to the drug dosage. Three mixing processes, impeller, planetary, and high-intensity vibratory mixer (HIVM), are investigated for preparation of polymer-drug slurry based film precursors. The study examines key process parameters and key formulation parameters and their effect on critical quality attributes of strip film. Since each mixing process has different mixing efficiencies, a proper design of experiment (DOE) study is conducted to better understand the processes. Key DOE variables were process intensity, process time, and the mixing device. The drug used was fenofibrate (FNB) and the drug loading used to determine these three parameters was 20% in the end product. It was found that of the three mixing processes, HIVM may be the poorest choice because it tends to give sporadic results with different parameters for the uniformness of the precursor, which leads to uneven drug distribution in the dried films. The film product drug content uniformity, measured using relative standard deviation (RSD) for intermediate and end-product, was better correlated for the planetary mixer, and somewhat correlated for the impeller mixer. Based on the DOE outcomes, the mixing parameter with the lowest RSD for each mixer type was selected to be used in creating homogeneous precursors with low drug loadings; ranging from 6% to 0.6% FNB in the dried film. The outcomes indicate that the planetary mixer with its higher-intensity mixing capability allows for a more uniform product and in a shorter processing time. It is worth noting that the RSD of films is based on 1/10th the dose in this study. Thus, the overall results suggest that both the impeller and planetary mixers are successful in preparing film precursors for product with acceptable CQAs even at 0.6 % drug loading.