Pharmaceutical Technology Europe - August 2012 - (Page 5)

Tackling Solubility Issues with Nanoparticle Engineering More and more potential drug candidates are emerging with poor stability. We speak with Dedong Wu, senior scientist at AstraZeneca, to find out how nanoparticle engineering and crystal engineering techniques are being used to solve solubility challenges. PTE: Why has nanoparticle engineering become an important strategy for tackling solubility, stability and other drug delivery challenges? Wu: For poorly soluble drug candidates, various enabling techniques have been used to enhance the apparent solubility and dissolution rate. Bioavailability can benefit from a higher API concentration achieved by the formation of a supersaturated solution. However, some compounds exhibit very fast crystallisation and it is extremely difficult to inhibit this property from a compound’s meta-stable solid-state form (e.g., amorphous or solid dispersions) during shelflife periods. Moreover, these compounds will quickly precipitate and/or crystallise in the body, which can significantly reduce the in vivo drug concentration leading to poor drug efficacy. Nanoparticle engineering is an alternative method for such compounds in a formulation that uses the special physical property of nanoparticles. The high-surface area to volume ratio of nanoparticles provides a tremendous driving force for diffusion so that nanoparticles of a poorly soluble compound can be distributed as nano-sized particles in the body, thereby avoiding crystallisation or precipitate issues. The smaller size helps to improve the surface–volume ratio of drug candidates, increasing the dissolution rate and improving API bioavailability. PTE: What advantages does nanoparticle engineering offer over other approaches being used to address solubility and drug delivery issues? Wu: Several commercialised nanoparticle drug products have successfully demonstrated that nanoparticle engineering can increase bioavailability and improve pharmacokinetic profile, reducing the frequency of dosing. Furthermore, food– drug interactions (the food effect) can be reduced because the pharmacokinetic profile of nanoparticle formulations are not affected by the Fed and Fasted state, as exampled by the cholesterol lowering drug, TriCor (Abbott Laboratories). By using nanoparticle technology, Janssen’s Invega Sustenna (Xeplion in Europe) became the first once-monthly atypical antipsychotic medicine approved for schizophrenia in the US. All of these advantages were achieved using nanocrystal technology. Various nanocarrier techniques have also been used to provide 2 Enhancing Bioavailability 10 German Pricing 5 Nanoparticle Engineering 11 Blogs 7 News and Twitter Trends 13 Top Technologies 9 Peer Reviewed Research 14 Staff

Table of Contents for the Digital Edition of Pharmaceutical Technology Europe - August 2012

Pharmaceutical Technology Europe - August 2012
Bioavailability Enhancement: When to use Hot-Melt Extrusion Versus Spray Drying
Tackling Solubility Issues with Nanoparticle Engineering
News Bites and Trends on Twitter
Peer-Reviewed Research: Carbon Measurement Methods for Cleaning Validation
Changing German Market Depresses the Pharma Industry
Blogs: Big data; the Olympics and GSK; FDA lawsuit; and unlicensed medicines
Top Technologies: Biopharmaceutical Equipment

Pharmaceutical Technology Europe - August 2012