A novel evaporation assisted solvent antisolvent interaction method for the nanocrystalization of organic compounds

Abstract

The dramatic change in properties of materials with particle size reduction into nanometer length scales led to the advancement of nanoscience and development of nanotechnology. A plethora of methods were developed to prepare nanoparticles of inorganic materials such as metals, metal oxides and semiconductors with efficient control of their size and shape. However, there are only a few methods available for the preparation of nanoparticles of simple organic compounds. Nanosizing of simple organic compounds such as lipids, dyes, high energetic compounds and pharmaceutical drugs leads to enhancement in some of their desirable properties. Hence, there is a need to develop novel methods for the preparation of simple organic compounds. Development of a novel evaporation assisted solvent antisolvent interaction (EASAI) method is detailed in the present thesis. A number of experimental parameters that affects the particle size such as nature of solvent, solvent to antisolvent ratio, concentration, temperature of antisolvent and presence of stabilizers have been optimized during this study. The applicability of this method has been established by successfully preparing nanoparticles of some high energetic compounds and a number of pharmaceutical drugs with average particle size well below 100 nm. The objective of nanosizing is to enhance the energetic performance while reducing the sensitivity of high energetic compounds. Whereas, particle size reduction leads to substantial increase in solubility and bioavailability of poorly water soluble pharmaceutical drugs. Infact, poor water solubility of pharmaceutical drugs is a major challenge for pharmaceutical companies as nearly 40 % potential drug targets suffers from poor water solubility.Nanoparticles of military explosives such as RDX and HMX were prepared with the desired crystal morphology. Interestingly, it was found that both the particle size as well as the shape of these high energetic compounds can be controlled by using the EASAI method by choosing an appropriate solvent. Similarly, nanoparticles of Carbamazepine which is an antiepileptic drug were prepared and this has resulted in enhanced solubility and rate of dissolution. It was also found that we can control the particle size of drug nanoparticles by using water soluble and biocompatible polymers as stabilizers, even with high concentration of the drug. Food and drug administration (FDA) approved polymers such as polyvinyl pyrrolidone (PVP), polyvinyl alcohol (PVA) and hydroxyl propyl methyl cellulose (HPMC) can be used to control the particle size of drugs effectively using EASAI method. Thus, polymer stabilized nanoparticles of Griseofulvin, a potential drug for anticancer therapy and fenofibrate, a widely used hypolipidemic drug having average particle size below 30 nm could be prepared. Interestingly, anti-leukemia activity of the non-steroidal anticancer drugs such as ibuprofen, ketoprofen and naproxen were found to be enhanced by the nanosizing. Naproxen nanoparticles that are stabilized using PVP showed two times higher anti-leukemia activity compared to Doxorubicin. Thus, a novel EASAI method has been developed for the preparation of nanoparticles of simple organic compounds during the present study and a patent has been filed on this invention. The method can be used to lower the sensitivity of energetic compounds and thus alleviate consequences that are associated with accidental explosions during transportation and storage. At the same time solubility, rate of dissolution and bioavailability of poorly water soluble drugs can be enhanced by nanoformulation using EASAI method. While this can result in more effective therapy of approved drugs it can also lead to the repositioning of them for novel applications and thus save a lot of time and cost associated with drug development.