Nanoparticles in the Pharmaceutical Industry and the Use of Supercritical Fluid Technologies for Nanoparticle Production

Abstract

Poor aqueous solubility of drug candidates is a major challenge for the pharmaceutical scientists involved in drug development. Particle size reduction appears as an effective and versatile option for solubility improvement. Nanonization is an attractive solution to improve the bioavailability of the poorly soluble drugs, improved therapies, in vivo imaging, in vitro diagnostics and for the production of biomaterials and active implants. In drug delivery, application of nanotechnology is commonly referred to as Nano Drug Delivery Systems (NDDS). In this article, commercially available nanosized drugs, their dosage forms and proprietors, as well as the methods used for preparation like milling, high pressure homogenization, vacuum deposition, and high temperature evaporation were listed. Unlike the traditional methods used for the particle size reduction, supercritical fluid-processing techniques offer advantages ranging from superior particle size control to clean processing. The primary focus of this review article is the use of supercritical CO2 based technologies for small particle generation. Particles that have the smooth surfaces, small particle size and distribution and free flowing can be obtained with particular SCF techniques. In almost all techniques, the dominating process variables may be thermodynamic and aerodynamic in nature, and the design of the particle collection environment. Rapid Expansion of Supercritical Solutions (RESS), Supercritical Anti Solvent (SAS) and Particles from Gas Saturated Solutions (PGSS) are three groups of processes which lead to the production of fine and monodisperse powders. Few of them may also control crystal polymorphism. Among the aforementioned processes, RESS involves dissolving a drug in a supercritical fluid (SCF) and passing it through an appropriate nozzle. Rapid depressurization of this solution causes an extremely rapid nucleation of the product. This process has been known for a long time but its application is limited. Carbon dioxide, which is the only supercritical fluid that is preferentially used in pharmaceutical processes, is not a good solvent for many Active Pharmaceutical Ingredients (API). Various researchers have modified the RESS process to overcome its solubilizing limitations, by introducing RESOLV, RESAS, and RESS-SC. Overall, all RESS based processes are difficult to scale up. The SAS processes are based on decreasing the solvent power of a polar organic solvent in which the substrate (API & polymer of interest) is dissolved, by saturating it with carbon dioxide (CO2) at supercritical conditions. CO2 causes precipitation and recrystalization of the drug. SAS is scalable and can be applied to a wide variety of APIs and polymers. Minor modifications of basic SAS process include GAS, ASES, SAS-DEM and SAS-EM. Processes where SCF is used as an anti solvent and dispersing agent include SEDS, SAA, and A-SAIS. The mechanisms and applications of these processes were briefly discussed. In PGSS, CO2 is dissolved in organic solutions or melted compound...

Nanomedicine Scale-up Technologies: Feasibilities and Challenges

“…SCF can be used for various purposes in the nanoparticle production as follows: [A] solvent-rapid expansion from supercritical solutions process; [B] swelling and plasticizing agent-gas saturated solutions process; [C] an antisolvent-gas antisolvent or supercritical antisolvent process or aerosol solvent extraction system process and solution-enhanced dispersion by SCF process; [D] a solvent for polymerization in dispersed media. The formulation scientist gets advantages like particle de-aggregation, improved solubility and dissolution rate, controlled release, and drug absorption enhancement with this method (21)(22)(23). In order to get desired properties of nanoparticles such as size and size distribution, morphology, inner core structure, and minimal residual solvent concentration, this method is the most suitable.…”

“…The remarkable feature of SCF technique is that particles with smooth surfaces, small particle size and distribution, and free flowing can be obtained. However, the poor solvent power of CO 2 , the cost, and use of large amount of the CO 2 are few limitations as well (21).…”

Bioavailabilty Study of Nicardipine Liquisolid Compact Tablets in Rabbits After Oral Administration.

“…Nicardipine have low bio availability due to its low aqueous solubility. So many methods are present to increase solubility of the drug (David et., 2012;Yoshida et al, 2012;Zhang et al, 2012;Sheth et al, 2012). Solubility of nicardipine was increases 10 folds when nicardipine was complexation with carboxylic acid buffer system (Maurin et al, 1994).…”

Preparation of 10-hydroxycamptothecin-loaded glycyrrhizic acid-conjugated bovine serum albumin nanoparticles for hepatocellular carcinoma-targeted drug delivery

“…5,6 It is well known that the poor aqueous solubility of drug candidates is a major challenge for pharmaceutical scientists involved in drug development. 7 As HCPT has poor water solubility and there are other physiologically more acceptable solvents, as yet, there have been limited clinical applications of HCPT. The lactone ring of HCPT is open in an alkaline environment and the sodium salt of HCPT (ring-opened form) is very soluble in water.…”