Microwave drying of naproxen sodium drug formulations
Creators: name: AL-ALI, Maha
Publisher: name: RMIT University
Year: 2024
Subjects: classificationCode: 400406
subject: Powder and particle technology
classificationCode: 400499
subject: Chemical engineering not elsewhere classified

description: The pharmaceutical powder is a dry form of a mixture of fine particles containing chemicals which can be used internally or externally for treating ailments. Pharmaceutical solids, particularly the hydrophilic solids such as naproxen sodium (NS), are usually moisturised during production steps such as wet granulation. The absorbed moisture can impact the textural characteristics, physical or chemical stability, and medicinal activity of the drug. Therefore, moisturised powders are often subjected to drying during pharmaceutical manufacturing. The energy consumption and costs involved in the drying operation are very significant, and therefore, the pharmaceutical industry always seeks to find and use energy-efficient and cost-effective drying processes. This work aims to investigate the influence of microwave drying (MWD) on drying energy consumption and characteristics of pharmaceutical powder and its tablet to determine whether MWD is a satisfactory drying operation. The pharmaceutical powder chosen for this study is a new formulation involving naproxen sodium (NS), which is a non-steroidal, anti-inflammatory drug used in the tablet dosage form in the treatment of many medical conditions as a painkiller. Wet granules of NS that were used in the study contained 10, 20, 30, 40 and 50 wt% water and they are designated as 10WG, 20WG, 30WG, 40WG, and 50WG, respectively.

In the first part of the study, 10WG, 20WG, and 30WG were dried using microwave drying and conventional drying (COVD) techniques including freeze-drying (FD), vacuum drying (VD) and convective drying (CD) to investigate their impacts on the textural properties of the pharmaceutical powder. MWD removed up to 91.6% of undesirable moisture rapidly with no significant changes to the chemical structures of the above formulations. However, FD removed the lowest amount of moisture (&lt; 90.7%) whereas the CD removed the highest amount (&lt; 93.6%). The morphology, size and surface area, and the crystallinity/amorphous contents of particles changed due to MWD and COVD. MWD produced particles with a smaller mean size (30.3 µm) and larger surface area (333.0 m2/kg) while VD yielded larger particles (59.2 µm) with smaller surface area (194.2 m2/kg). High crystallinity (52.4%) was found for particles from VD whereas highest amorphous (59.1%) content was obtained for particles from FD.

The impact of MWD heating rate at different temperatures (50, 70, 90 °C) on the textural characteristics of wet granules was studied using 40WG. The moisture removal efficiency increased with increasing heating rate and temperature to reach maximum efficiency of 97% at 9 °C/min. The particle size and morphology of dried particles changed at all drying rates. However, lower heating rates preserved the textural characteristics of the pharmaceutical powder better compared to higher heating rates.

The characterisation of oral tablets produced from dried pharmaceutical powder is essential to determine whether the drug can be released efficiently and safely after ingestion. Therefore, in the second part of this study, 20WG subjected to MWD, FD, VD, and CD were used to prepare tablets designated as MW-TAB, FD-TAB, VD-TAB, and CD-TAB, respectively, which were then subjected to investigations including textural characterisation, bioavailability and stability measurements. While the morphology of dried particles was irregular, those of all tablets were smooth and flat with some minor cracks. The amorphous content of all tablets except that of VD-TAB increased, which led to decreased crystallinity. These results confirmed that the tablets acquired their textural characteristics from respective dried particles.

The tablet drug release and solubility tests conducted using simulated gastric and intestinal fluids with pH of 1.3 and 6.8, respectively showed that the results for MW-TAB were close to those for the tablets prepared using dry reference powder (RF-TAB). The drug release and solubility can be ranked in the following decreasing order: FD-TAB &gt; RF-TAB &gt; MW-TAB &gt; CD-TAB &gt; VD-TAB. The drug release results showed that it was influenced mainly by the particle size and surface area, and the amorphous structure of tablets. Furthermore, the mechanical stability tests showed that MW-TAB and FD-TAB had adequate tensile strength and friability with high hardness while VD-TAB and CD-TAB produced friable tablets with lower hardness and reasonable tensile strength. Thus, MWD was found potentially to be an efficient and economical process that can ensure mechanically stable tablet with appropriate drug release rate for pharmaceutical granules containing a polar drug such as NS.

In the third part, the kinetics of drying was studied using MWD for 50WG. Ten semi-theoretical and empirical thin-layer models were tested for their suitability in predicting the drying kinetics at microwave powers of 30, 60 and 90W. Experimental results at all drying powers showed that the drying rate increased with increasing time, reached a maximum and then decreased to reach a steady-state value.  Among the ten semi-theoretical and empirical thin-layer models tested, the logarithmic model provided the best fit for the experimental results for all microwave powers. Also, two new empirical models were proposed to predict the moisture content and drying rate as a function of drying time and microwave power with higher accuracy.

Lastly, in the fourth part, the energy consumption and drying performance of MWD, FD, CD, and VD were compared for drying 10WG, 20WG, and 30WG. The energy and drying efficiency values calculated from experimental results indicated that MWD had the lowest energy consumption values but with the highest drying performance.
 
Thus, MWD was found to be an energy-efficient process for drying wet pharmaceutical granules containing a polar drug such as NS, while maintaining the drug textural characteristics, bioavailability and mechanical stability. The other physicochemical properties of MW-TAB such as drug release, solubility, hardness, friability, and tensile strength are also acceptable and comparable to those of tablets prepared using other COVD methods. Therefore, MWD is an economical process and has the potential to be used widely in the pharmaceutical industry.