Fundamental study of interactions between water and modified starch products for inclusion in moisture management of solid oral dosage forms

Starch I 500® (ST 1500) is the product of the physical modification of native corn starch (NCS). It is one of the widely used excipients in pharmaceutical formulations, particularly oral dosage forms. As ST 1500 is mainly used as a diluent in oral solid dosage forms, it makes up the bulk of the formulations (probably the highest concentration compared to other excipients such as binder disintegrants and lubricants). Therefore, understanding the water inclusion effect with ST 1500 to scavenge the moisture (water)-sensitive drugs is essential. The states of water associated with ST1500 and the water inclusion effect were investigated extensively. Comprehension of the interaction between moisture and ST 1500 or starched-based excipients allows formulation scientists to design better formulations. The data obtained from DYS suggest that water interacts with ST1500 either by the formation of a monolayer, multilayer coverage, or bulk absorption. DYS analysis revealed that type II (sigmoidal (S) shape isotherm) is the characteristic feature of starch­-based products, showing hysteresis. The appearance of hysteresis reveals that desorption is irreversible, indicating that some water molecules are entrapped within the physical structure. Bulk diffusion was found to be the predominant mechanism of water sorption in starch-based excipients, irrespective of the degree of pregelatinization. The kinetics of the water sorption-desorption is governed by the particle size and the pregelatinization degree. By increasing the particle size, the rate of sorption-desorption decreases. According to DSC and TO analysis, it was confinned that water exists either as free or bound water. Non-freezable water (hydration water) only gets removed at high temperatures before the physical structure of the starch molecules collapse (310-314 °C). The BET model data fit represents no significant change in the concentration of monolayer formation after aw of ~0.34. Multilayer coverage exponentially increases over the range of aw, and the gap indicating hysteresis is seen for the internally absorbed water. All starch-based excipients follow a similar trend, irrespective of the degree of pregelatinization. The specific surface area (SSA) was reduced by increasing the particle size (237.17 m2/g, 233.89 m2/g, and 228.14 m2/g for ST1500 <45 µm, STl00 45-125 µm, and Sl500 >125 µm respectively). Similarly, as the particle size of ST1500 increases, the amount of monolayer formation increases. Unlike NCS, the SSA of ST1500 and LPGS increase by elevating the temperature from 25°C to 50°C. In addition, increasing the temperature from 50°C to 70°C reduces the surface area of ST 1500 and LPGS. There was a significant difference in preserving ASA when 11 %RH compared with 44%RH and 86%RH. However, the difference was not significant for 44%RH and 86%RH moisture-scavenging power due to chemical hydrolysis. NCS was physically modified to investigate the effect of drug release with and without the addition of PYPK30 (as a binder), moisture scavenging power, and lubricant sensitivity of the formulations to magnesium stearate (as a lubricant). The principal mechanism of disintegrating the Mod. NCS was found to be via the volcanic effect that releases the drug in the dissolution media. It was shown that understanding the interaction of moisture with starch-based excipients makes it possible to design multi-functional starch-based excipients with better performance than the original excipient NCS.