Journal of Drug Nanopartcles for Improved Delivery of Poorly Soluble Drugs Vijaykumar Nekkant * and Javier Rueda Department of Pharmacy, Western University of Health Sciences, Pomona, CA, USA www.verizonaonlinepublishing.com J. Drug 1(1). Page | 18 *Corresponding author: Vijaykumar Nekkant, Ph.D. College of Pharmacy, Western University of Health Sciences, 309 E. Second Street, Pomona, CA 91766, USA; Tel: (909) 469-6476; Fax: (909) 469-5600; Email: vnekkant@westernu.edu Artcle Type: Review, Submission Date: 05 February 2016, Accepted Date: 07 March 2016, Published Date: 20 April 2016. Citaton: Vijaykumar Nekkant and Javier Rueda (2016) Nanopartcles for Improved Delivery of Poorly Soluble Drugs. J. Drug 1(1): 18-27. Copyright: © 2016 Vijaykumar Nekkant and Javier Rueda. This is an open-access artcle distributed under the terms of the Creatve Commons Atributon License, which permits unrestricted use, distributon, and reproducton in any medium, provided the original author and source are credited. Vol: 1, Issue: 1 Abstract Nanoparticle based drug products are of growing interest in the feld of pharmaceutics. Enhancing saturation solubility and dissolution velocity by preparing drug nanoparticles correlates with faster absorption rates. Te faster absorption rates can correlate into better bioavailability, reduction in fed and fast efects and inter-subject variability with improved therapeutic response. Drug nanoparticles have shown potential applications in developing several oral and parenteral dosage forms with improved therapeutics. Suitable formulations for the commonly used routes of administration can be identifed employing nanoparticle technology. Drug nanoparticles provide the discovery scientist an alternate avenue for screening and identifying a superior drug delivery system. For toxicologist, the approach provides a means for dose escalation with minimum amount of drug substance. In the recent years, formulating poorly water-soluble compounds using a nanoparticulate approach has evolved from a conception to a realization whose versatility and applicability are being vastly recognized. In the present review, industrially relevant production technologies are critically reviewed. Te nanoparticle characterization techniques and potential challenges involved in the development of drug nanoparticles were discussed in detail. Introducton With the advent of new technologies in drug discovery, combinatorial chemistry, and computer aided drug design, there was an exponential increase in the development of new chemical entities with good therapeutic potential. However because of the complex chemistry, nearly 40% of the drug candidates in the development pipeline and about 60% of new drugs produced by chemical synthesis are associated with poor aqueous solubility resulting in low and variable bioavailability [1,2]. Te poor solubility of drug may result in sub-optimal dosing and concomitantly poor therapeutic response. Parenteral administration of poorly soluble drugs as microsuspensions (e.g. i.m. or i.p.) ofen fails to achieve required drug concentration levels due to limited volume of solute at the site of injection. Tey are instances wherein the solubilizing agents used to improve the solubility of drug have resulted in allergic and toxic reactions. For example, Cremphor EL used as solubilizing agent in Taxol ® formulation have shown some adverse efects such as allergic shock [3]. Te commonly used approach to overcome poor aqueous solubility is by preparation of salts that had limited success. From a formulation stand point, a crystalline salt is preferred foreseeing the potential physical and chemical stability issues associated with an amorphous form of drug substance. Identifcation of a crystalline salt with adequate aqueous solubility requires screening of various counter-ions and crystallization conditions and at times isolation of a crystalline material itself is a tough task. In some instances the salt formed may be highly hygroscopic posing formulation challenges during drug product development [1]. An alternate approach is to identify analogs or prodrugs with enhanced solubility. Tis approach was not successful since the chemically modifed drug molecule is ofen abandoned in its early phase of development or the drug product is launched with suboptimal properties including poor bioavailability, fed and fast variability, lack of optimal dosing, presence of excipients at high concentrations that pose limitations with respect to dose escalation, and ultimately, poor therapeutic outcome. Generally, chemical modifcation methods are expensive compared to manipulation of drug with formulation strategies because once the chemical structure is modifed, the associated pharmacological activity may not be same and it is expensive to re-demonstrate the efcacy and safety of the chemically altered drug. Terefore, screening of suitable formulation technology for improving the therapeutic performance of drug is a preferred approach to develop a viable product for poorly soluble drug [4]. At present, they are limited formulation approaches available to address the problems associated with drug’s poor aqueous solubility and bioavailability. Te most commonly used approaches are incorporation of drug into complexing agents (cyclodextrins), using lipid carriers (liposomes, self-emulsifying systems), micronization, and solid dispersions of the drug in water-soluble carriers, etc. However the success of these techniques is mostly dependent on specifc properties of drug molecule therefore, have limited scope for general application. For example, ability to ionization, solubility in oils, lipids, molecular size, structure and shape to ft into the hydrophobic cavities, etc. Liposomes have demonstrated reasonable success in formulating poorly soluble drugs however because of the poor stability issues and expensive product costs, these approaches are not suitable for all the drugs, particularly of those which are not