The Andrographis herba extract (AHE), a traditional Chinese medicine (TCM), was developed to directly compactible powders by fluid bed coating with 6% to 12% hydroxypropyl methylcellulose (HPMC). The process-, instrument-, and formulation-related variables of the coating process were simultaneously optimized with the Hunter L18 screening design. Yield (Y1), compactibility (Y2), and angle of repose (Y3) were measured as the responses. The optimized variables were 50 °C for inlet air temperature, 150 m3/h for inlet airflow, 6.5 rpm for binder feed rate, 1.2 bar for spray atomisation pressure, L3 for air distributor plate, 1.5 cm for the distance between the air distributor plate and the bottom of guide cylinder, 6% for the ratio of HPMC to AHE, and 16% for the concentration of coating solution. The small errors (0.51% for Y1, 3.17% for Y2, and 4.78% for Y3) between the experimental and predicted values indicated the high degrees of prediction. All above results, together with the application data of the novel direct compaction-grade TCM extract powders, confirm that the design of experiment is effective to optimize the composition and the preparation process of composite materials mainly composed of TCM extracts. It is promising to produce high TCM-loading tablets with such composite materials by direct compaction.