Pharmaceutical Technology Europe - October 2012 - (Page 12)

Producing Cocrystals The Executive Editor of Pharmaceutical Technology Europe, Patricia Van Arnum, discusses the issue of cocrystals with Colin Minchom, vice president, Particle Design Business Unit, at Hovione. PTE: Under what type of situations would cocrystallisation be used? How does it facilitate the delivery of poorly soluble drugs? Minchom: Interest in cocrystals has increased in recent years, and the recent FDA guidance on a proposed classification of cocrystals has prompted further discussion and counter proposals from the industry. The proposed US FDA classification of cocrystals as crystalline materials containing two or more molecules in the same crystal lattice is limited but can serve as a starting point for discussion. The addition of a cocrystal former into the crystalline structure of the API changes its physical and chemical properties. It is possible, in some cases, to improve bioavailability to adequate levels while preserving the stability of a crystalline form. For APIs with low glass-transition temperatures, a cocrystal may be favoured over the amorphous form. As such, the use of a cocrystal may be an attractive platform to overcome the solubility limitations of Biopharmaceutics Classification System Class II and Class IV drugs. Cocrystal formation is a favoured approach for increasing apparent aqueous solubility for poorly watersoluble molecules that have no ionisable groups, and for which salt formation is not possible, or for where the physical properties of the salts formed are not desirable. Solvates and hydrates are wellaccepted crystal forms. In many ways, a cocrystal can be thought of as a solvate, but one whose components are solid at room temperature. The cocrystal will form if the resulting crystal is thermodynamically more stable than the components. Resulting cocrystal properties are dependent upon many factors, including the starting properties of the API, the physical properties of the co-former and the mechanism by which the cocrystal is formed. PTE: Controlling nucleation during crystallisation is an important task. What are the mechanisms for controlling crystallisation? Minchom: Controlled crystallisation is where the desired particle-size distribution is achieved from the bottom up. The objectives of a crystallisation process are twofold. On the one hand, the aim is to isolate the API in the right crystal form, typically a polymorph that provides the required level of exposure and stability. On the other G Gl Glow Images/Gett y Images Im ges/Gett Images I G hand, crystallisation may also be a purification stage, whereby the impurities remain mostly dissolved in the mother liquors. The kinetics of crystallisation are driven by the imposed supersaturation levels. The degree of supersaturation, temperature ramp, mixing, filtration and final drying process all contribute to the final particle-size distribution. An extended version of this article is available at: PharmTech.com/Ingredients10 2 OUTSOURCING 11 REGULATORY COOPERATION 7 QUALITY BY DESIGN 12 COCRYSTALS 8 NEWS 13 BLOGS 10 ENERGY EFFICIENCY 15 STAFF http://www.PharmTech.com/Ingredients10

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

Pharmaceutical Technology Europe - October 2012
Contents
Cover Story: CROs and CMOs Have Cause to celebrate Annual survey shows growth for outsourcing providers
Quality by Design: A Contract Organisation’s Perspective on Overcoming Obstacles to Implementing QbD
News Bites and Trends on Twitter
Outsourcing Pharmaceutical Infrastructure Operations
EMA Focuses on Greater International Collaboration
Producing Cocrystals
Blogs: Sanofi job cuts; confidential data risk; Alzheimer’s research; and patent cliff.

Pharmaceutical Technology Europe - October 2012