Production of NSAID pharmaceutical molecular liquids via RESS processing

S. Kumar Sharma, A.D. Woldetsadik, M. Magzouband, R. Jagannathan
New York University Abu Dhabi,
United Arab Emirates

Keywords: drug nanoparticles, supercritical fluids, pharmacutical molecular liquids, hydrophobicity, ibuprofen, RESS, micronization


Abstract One of the prominent challenges in pharmaceutical drug development is the poor aqueous solubility of many pharmaceutical drugs and subsequently, their reduced bioavailability. Traditional drug delivery strategies are not target specific in the body and cause several adverse side effects. Such constraints were addressed by the use of formulations of nanoparticle carrier particles, functionalized with the drug molecules, in targeted drug delivery systems. This practice, however, introduced supposedly benign, nanoparticle foreign bodies into biological systems as drug carriers, and could potentially cause adverse effects in the biological systems, over a period of time. A unique solution would be to eliminate the use of such nanoparticle carriers and reduce the drugs to the size of molecular clusters which would readily result in the dissolution of the clusters in water, due to the dissociation of the weakly held cluster molecules. This would remove the problem of “poor” aqueous solubility of the drug molecules and they could further be functionalized to target specific biological sites, thereby serving as their own carrier. In this research, we investigated the production of pharmaceutical molecular clusters of most commonly implemented and prominent drug molecules such as ibuprofen and naproxen, via Rapid Expansion of Supercritical Solution (RESS) processing. The experimental process parameters used were, 325 bar and 40 0C. We have included the detailed description of experimental process, in our earlier publications[1–4]. These drug molecular clusters were first trapped in “dry ice” and subsequently solubilized in DI water under ambient conditions. These solutions are found to be stable over a period of several weeks. LC-MS and NMR of water solutions of the water solutions confirmed the presence of truly solubilized ibuprofen and naproxen, respectively. Drop casting and ambient drying of these solutions on a silicon substrate resulted in stable, viscous liquid films. Optical and electron microscopy showed typical liquid like behavior of these drop casted films, consistent with earlier observations with other compounds [3–5]. High quality, uniform films were observed under SEM (shown typically for ibuprofen in Fig. 1). It is interesting to note that, normally, ibuprofen and naproxen are found to be in solid powder form at room temperature and pressure, with melting points of 76o C and 1540 C, respectively. In-vitro cell viability studies, clearly demonstrated that the water-solubilized ibuprofen and naproxen exhibit similar cytotoxicity to the as received, raw drug powders (shown in Fig. 2), thus retaining their original potency. This platform would be expected to bring unique advantages to the field of drug delivery. References 1] S. Khapli, R. Jagannathan, J. Supercrit. Fluids 2014, 85, 49. [2] S. K. Sharma, R. Jagannathan, J. Supercrit. Fluids 2016, 109, 74. [3] R. Jagannathan, G. Irvin, T. Blanton, S. Jagannathan, Adv. Funct. Mater. 2006, 16, 747. [4] R. Jagannathan, G. C. Irvin, Adv. Funct. Mater. 2005, 15, 1501. [5] R. Jagannathan, R. V. Mehta, Adv. Funct. Mater. 2006, 16, 633.