A Time-Domain NMR Study of the State of Water in Wet Granules with Different Fillers and Its Contribution to the Wet Granulation Process and to the Characteristics of Granules

Abstract

The different states of water incorporated in wet granules were studied by a low-field benchtop 1 H-NMR time-domain NMR (TD-NMR) instrument. Wet granules consisting different fillers [cornstarch (CS), microcrystalline cellulose (MCC), and D-mannitol (MAN)] with different water contents were prepared using a high-speed granulator, and then their spin-spin relaxation time (T 2 ) was measured using the NMR relaxation technique. The experimental T 2 relaxation curves were analyzed by the two-component curve fitting, and then the individual T 2 relaxation behaviors of solid and water in wet granules were identified. According to the observed T 2 values, it was confirmed that the molecular mobility of water in CS and MCC granules was more restricted than that in the MAN granule. The state of water appeared to be associated with the drying efficiency and moisture absorption capacity of wet granules. Thus, it was confirmed that the state of water significantly affected the wet granulation process and the characteristics of the resultant granules. In the final phase of this study, the effects of binders on the molecular mobility of water in granulation fluids and wet granules were examined. The state of water in granulation fluids was substantially changed by changing the binders. The difference was still detected in wet granules prepared by addition of these fluids to the fillers. In conclusion, TD-NMR can offer valuable knowledge on wet granulation from the viewpoint of molecular mobility of water.

Fabrication of Agglomerated Lactose Using Fluidized Bed for Good Compressibility

“…These values have great influence on the physical and chemical properties of pharmaceutical preparations, such as disintegration and dissolution and bioequivalence in vivo and in vitro. In practice, solid dosage forms require different types of excipients to be added to the API in order to obtain the desired physicochemical properties, such as flowability, compressibility, disintegration, solubility, and stability [4][5][6][7][8], for the medication. The excipients are mixed and granulated with the APIs using different equipment to ensure their mixing uniformity.…”

“…Agglomeration is the technique that binds small particles to create large aggregates. It is also presented as granulation in a macro sense, where pharmaceutical ingredients are frequently granulated with some excipients to create visible round particles for production of tablets and capsules [5,6]. Through agglomeration/granulation technology, the APIs and excipients can be evenly mixed with a suitable particle size distribution and provide good material uniformity, fluidity, and compressibility for the subsequent preparation process, such as the tableting process [7].…”

Quantitation of Commercially Available API Solid Forms by Application of the NMR-qSRC Approach: An Optimization Strategy Based on In Silico Simulations

“…Time domain-NMR (TD-NMR) over the years has been proven to be a valuable tool to carry out experiments upon relaxation analysis of heterogeneous solid samples. − Recently, a method has been proposed to use TD-NMR to reveal the amorphous content in mixed drug samples. According to this approach, quantitation of different solid forms in binary mixtures could be achieved by exploiting the different species’ longitudinal relaxation times ( T 1 ) registered in a saturation recovery curve (SRC), hence the name quantitative saturation recovery curve (qSRC). − …”