In situmonitoring and control of moisture content in pharmaceutical powder processes using an open-ended coaxial probe

Abstract

An analysis of microwave measurements of the complex dielectric constant of different mixtures of pharmaceutical materials using an open-ended coaxial probe is presented. Using the probe in combination with a network analyser, measurements in the frequency range of 1–19 GHz were conducted. Calibration measurements on conditioned samples were first acquired in a controlled laboratory environment, and then in situ measurements, taken in a small-scale high-shear mixer, were also obtained. The dominating material in the investigated mixtures was microcrystalline cellulose. By using the suggested microwave method, a novel possibility for in situ measurements of the initial moisture content of the powder mixture before and at the beginning of the water addition stage is demonstrated. In situ density-independent estimation of the moisture content having a relative error of below 10% for the moisture interval of 2–14% is demonstrated. The possibility of performing an adaptive control of the evolution of the mixing process by utilizing the microwave sensor information is also presented.

Dielectric properties of pharmaceutical materials relevant to microwave processing: Effects of field frequency, material density, and moisture content

“…The ability to control and monitor pharmaceutical processes online has turned the emerging concept of “quality by design” into a reality. Recent additions to the list of techniques for the control and monitoring of granulation and drying processes involve the application of microwaves for in situ moisture determination of wetted powders and granules during high shear granulation26 and fluidized bed drying,25 respectively. In the former, changes to the impeller speed generated varying material density patterns in the mixer.…”

“…With the development of single pot processors and novel hybrid dryers, the use of microwaves has largely been confined to drying pharmaceutical powders and granules. Interest in microwave and related techniques for nondestructive, real time moisture determination of wet powders and granules in high shear and fluidized‐bed processes has caught on only in recent years 24–26. On a smaller scale, microwaves have been employed for modulating drug and excipient properties via specific material–microwave interactions which are nonthermal in nature 27–32.…”

Relevance of Dielectric Properties in Microwave Assisted Processes

“…In particular, microwaves have been applied in modulating drug and excipient properties via specific material microwave interactions (Wong et al, 2002;Nurjaya & Wong, 2005;Auriemma et al, 2011); tested in drying operations of powder and granules (Hegedus & Pintye-Hodi, 2007;Loh et al, 2008); used in single-pot devices to carry out mixing, granulation and drying of pharmaceuticals in one vessel (Kelen et al, 2005;McMinn et al, 2005;Hegedus & Pintye-Hodi, 2007). Moreover, dielectric properties measurements of pharmaceutical powders wet mixtures are used to control moisture / solvent residues (Gradinarsky et al, 2006).…”

Evaluation of the Physicochemical Properties and Compaction Behavior of Melt Granules Produced in Microwave-Induced and Conventional Melt Granulation in a Single Pot High Shear Processor

“…This stemmed from the paucity of information available on the dielectric properties of regular pharmaceutical materials in their dry states. Dielectric properties are fundamental electrical characteristics of materials which govern their behavior when subjected to microwaves for purposes of heating, drying, material processing as well as process monitoring (2,3). For microwaveinduced melt granulation (MMG) to be viable, knowledge of the dielectric properties of pharmaceutical materials is essential as material dielectric responses control the efficiency and extent to which microwave energy can be effectively coupled into the material for heat production and binder activation.…”