Nanoparticle technologies have revolutionized the drug development process and change the landscape of the drug industry. Nanoparticles (NP) could improve the aqueous solubility, dissolution rate, and absorption of poorly water-soluble substances.

Addressing Pharmaceutical Unmet Need : Major issues associated with poorly water-soluble compounds are poor bioavailability, fed/fasted variation in bioavailability, lack of dose-response proportionality and that leads to suboptimal dosing, need a pharmacokinetic (PK) booster to enhance bioavailability, and noncompliance by the patient, i.e., inconvenience dosing schedules.

Characteristics: NP can be defined as solid particles with a size in the range of 10-1000nm. The increased surface area of NP will enhance the dissolution of poorly water soluble drug substances. The chance gravitational settling is less for NP  because of their small size and can be suspended easily in liquid formulation. The NP approach is suitable for highly potent compounds (low dose) but it is not practical when the dose requirement may be big. In recent years nanotechnology is gaining popularity by formulators for reformulating the old formulation of poorly soluble compounds. For marketed products requiring lifecycle extension opportunities, NP formulation strategies provide a means to develop a new drug-delivery platform with improved therapeutic outcome incorporating the existing drug, thus creating new avenues for addressing unmet medical needs.

Pharmaceutical Application : An increasing number of the drug candidates synthesized each year by pharmaceutical companies which may have poor water solubility and many of these promising compounds are rejected from development because traditional formulation approaches will not be able to improve bioavailability. Nanotechnology could rescue these compounds. For new chemical entities development, the nanotechnology can be of great value in preclinical pharmacokinetics and efficacy/ safety assessment studies in the early development phase. Drug formulation with NP could reduce or eliminate food-effect related variability resulting in no dosing restriction since NP improve the solubility of drug substances. There are several techniques to make drug NP out in the literature, e.g bottom-up (Precipitation methods), top-down etc.

Disposition : Enhancing solubility and dissolution rate of poorly soluble compounds correlates with improved PK profile since dissolution kinetics is the primary driving force behind the improved PK/ bioavailability of NP formulations of poorly water soluble compounds. The enhanced bioavailability should be translated to faster onset of action that may translate into improved therapeutic outcome.

Marketed products: Oral products developed using nanoparticle technology are in the market and listed below: Rapamune (Sirolimus); Emend (Aprepitant), TriCor (Fenofibrate), MegaceES (Megestrol). Avinaza (Morphine sulphate),  Focalin (Dexmethyl-phenidate HCl),  and Zanaflex (Trizanidine HCl) and the intravenous products: intravenous nutritional fat emulsion (Intralipid) and liposomal products (Doxil, AmBisome).


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