The world does not have too much time to ensure that the fast-growing population has enough land, food, water and energy. The rising food demand has brought a positive surge in fertilizers' demand and agriculture-based economy. The world is using 170 million tons of fertilizer every year for food, fuel, fiber, and feed. The nitrogenous fertilizers are being used to meet 48% of the total food demand of the world. High fertilizer inputs augment the reactive nitrogen levels in soil, air, and water. The unassimilated reactive nitrogen changes into a pollutant and harms the natural resources. The use of controlled-release fertilizers for slowing down the nutrients' leaching has recently been practiced by farmers. However, to date, monitoring of the complete discharge time and discharge rate of controlled released fertilizers is not completely understood by the researchers. In this work, corn starch was thermally processed into a week gel-like coating material by reacting with urea and borate. The granular urea was coated with native and processed starch in a fluidized bed reactor having bottom-up fluid delivery system. The processed starch exhibited better thermal and mechanical stability as compared to the native starch. Unlike the pure starch, the storage modulus of the processed starch dominated the loss modulus. The release time of urea, coated with processed starch, remained remarkably larger than the uncoated urea.
Artemether (ARTM) is a very effective antimalarial drug with poor solubility and consequently low bioavailability. Smart nanocrystals of ARTM with particle size of 161±1.5 nm and polydispersity index of 0.172±0.01 were produced in <1 hour using a wet milling technology, Dena(®) DM-100. The crystallinity of the processed ARTM was confirmed using differential scanning calorimetry and powder X-ray diffraction. The saturation solubility of the ARTM nanocrystals was substantially increased to 900 µg/mL compared to the raw ARTM in water (145.0±2.3 µg/mL) and stabilizer solution (300.0±2.0 µg/mL). The physical stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C-8°C and 25°C were very stable compared to the samples stored at 40°C. The nanocrystals were also shown to be stable when processed at acidic pH (2.0). The solubility and dissolution rate of ARTM nanocrystals were significantly increased (P<0.05) compared to those of its bulk powder form. The results of in vitro studies showed significant antimalarial effect (P<0.05) against Plasmodium falciparum and Plasmodium vivax. The IC50 (median lethal oral dose) value of ARTM nanocrystals was 28- and 54-fold lower than the IC50 value of unprocessed drug and 13- and 21-fold lower than the IC50 value of the marketed tablets, respectively. In addition, ARTM nanocrystals at the same dose (2 mg/kg) showed significantly (P<0.05) higher reduction in percent parasitemia (89%) against P. vivax compared to the unprocessed (27%), marketed tablets (45%), and microsuspension (60%). The acute toxicity study demonstrated that the LD50 value of ARTM nanocrystals is between 1,500 mg/kg and 2,000 mg/kg when given orally. This study demonstrated that the wet milling technology (Dena(®) DM-100) can produce smart nanocrystals of ARTM with enhanced antimalarial activities.