We are pleased to present this special Controlled Release Edition of our newsletter.  In this issue you will find a summary of our multiparticulate formulation offerings and services, which underline our commitment to this challenging area of formulation. Multiparticulates Market - Pediatrics Update  Do You Know Your CPPs? ONE VISIT! (with Organic Solvent Processing) Surelease® Industry Demand = Supply Expansion Colorcon Launches Surespheres™, Drug Layering Substrate! Optimal ETHOCEL™, Premium Ethylcellulose Polymers Particular about Multiparticulate School?     Multiparticulates Market - Pediatrics Update   Author: David Bain, PhD Multiparticulate (MP) formulation remains a challenging area, with many potential customers being discouraged by development and manufacturing complexity. Costs of establishing infrastructure and internal expertise reinforce customer concerns. Despite these challenges, formulators increasingly are reaching for MP formats to deliver complex profiles often required to provide effective disease management. In 2007, based on 627 applications, Colorcon® estimated globally that 30% of all extended release and 40% of enteric new product applications (NDA/ANDA) were for MP forms. The need to deliver drugs with greater precision, increasing use of product combinations, and recent pediatric regulation changes, will drive broader use of this group of technologies. The latter is a current hot topic in the industry, due to pediatric regulation changes in the European Union (EC No 1901/2006). From July 2008, this obligates applicants to perform studies according to a Pediatric Investigation Plan; successful applications provide an additional six months marketing exclusivity. In addition, successful pediatric-use marketing authorizations (PUMA) for off-patent medicines benefit from 10 year data protection. These new regulations will favor formulations that can be co-administered to a range of patient populations with different dose requirements; formulations such as those based on MPs. Combinations of MP formulations provide formulation scientists with considerable flexibility to deliver a myriad of release profiles for different patient groups. Recognizing the challenges associated with MP development and growing market need for these forms, Colorcon has created fully-formulated aqueous rate-controlling systems, and technical experts are available to help our customers address these challenges. Colorcon has applications knowledge in mini-tabs and mini-matrices using conventional tableting and coating equipment. Our work in this area is enabling access to the benefits of MPs to a wider audience faced with such development challenges. For more information on multiparticulates, click here.     ONE VISIT! (with Organic Solvent Processing)     Author: Kurt Fegely, MS Colorcon has recently added and/or upgraded state-of-the-art processing laboratories around the world to provide assistance to customers during formulation development of granulations, multiparticulates, and tablets. Further non-GMP laboratory space has been dedicated to safely conduct pharmaceutical unit operations that employ the use of organic solvents in the preparation of a finished dosage form. Equipment additions include fluid bed units capable of drying, top spray, bottom spray and rotor processes (USA only) and side-vented pan coating.   Utilizing these new assets allows the pharmaceutical formulator to evaluate the influence of aqueous or organic processing options on the performance of a drug product during one visit to Colorcon. Customers are invited to work with Colorcon technical experts, and our portfolio of products, in developing a dosage form that meets the demands of your formulation project. Of our 18 technical service laboratories around the globe, the following centers have advanced formulation resources and capability including organic solvent processing: North America (Pennsylvania, USA) Latin America (Cotia, Brazil) Europe (Dartford, UK) Asia Pacific (Goa, India; Shanghai, China; and Gyeonggi-do, Korea) These recent additions complement the vast array of aqueous laboratory processing capabilities that Colorcon has offered to our customers for many years, and further support ETHOCEL™, premium ethylcellulose polymers, barrier membrane coating as well as organic enteric options for delayed release applications.           Surelease® Industry Demand = Supply Expansion     As part of our commitment to business continuity planning and expanding ahead of demand, Colorcon has announced new Surelease®, aqueous ethylcellulose dispersion, capacity.  Surelease is a platform of fully formulated, extended release, aqueous coating systems utilizing ethylcellulose as the rate-controlling polymer for drug release. The dispersions are a unique combination of film-forming polymer, plasticizer and stabilizers, predominantly used for controlled release and taste-masking applications. This advanced technology provides reliable and reproducible release profiles that are consistent from the laboratory to pilot and production scale processes. Demand for Surelease has accelerated due to the increasing preference for multiparticulate dosage forms as well as its use in nutritional enteric applications. Nutrateric®, nutritional enteric coating system (Colorcon patented), based on Surelease and an alginate pore former, has become the product-of-choice for fish oil, garlic and other dietary supplement products. Surelease is manufactured at our Indianapolis, IN production site. Colorcon’s expansion from two to three equivalent production lines assists in assuring supply availability and security to our customer base. The expansion also signifies our continued commitment to our modified release technologies and multiparticulate portfolios.           Colorcon Launches SureSpheres™, Drug Layering Substrate!     Author: Mike McDougal Colorcon has introduced its own line of sugar spheres… SureSpheres. These small, free flowing pellets are more spherical and less friable than other non-pareils, and ideal for use in the production of sustained or timed release formulations.  SureSpheres are manufactured in Colorcon’s pharmaceutically dedicated Stoughton, WI facility. They provide formulation flexibility by allowing precise control of drug application and subsequent release, due to narrow particle size distribution and overall batch-to-batch consistency. SureSpheres also exhibit high mechanical strength and low friability to withstand the rigors of drug layering. Colorcon’s global research and development team has characterized the physical and mechanical properties of nine (9) batches of SureSpheres (20/25 US Standard Mesh, NF26). The team has evaluated a two-year manufacturing period to demonstrate batch-to-batch consistency. Properties such as friability, hardness, surface roughness, roundness, particle size distribution, bulk density and loss on drying were examined. These properties are known to affect process efficiency and robustness in drug layering operations. Results show that SureSpheres are high quality, consistent substrates for pharmaceutical drug layering and coating applications. Surespheres complement our ethylcellulose barrier membrane options, ETHOCEL™ and Surelease. Study Link (PDF 92.61 KB) >>           Optimal ETHOCEL™     Author: Rita Steffenino, MS In the development of multiparticulate products, one must consider multiple process and formulation variables. To assist customers in developing these challenging products, Colorcon is currently undertaking a systematic examination of critical formulation and process parameters for the application of ETHOCEL™ from organic solvents.   In applications intended for extending release, it is important to understand how the choice of solvent type can affect the drug release profile of ethylcellulose-coated (EC) multiparticulates. In our Asia Pacific organic facility, four pharmaceutically acceptable solvent combinations (Table 1) were investigated for their influence on EC solution viscosity and subsequent drug release from chlorpheniramine maleate coated beads. Results showed that solvent composition had an influence on the viscosity of EC dispersions, thereby effecting coating process efficiency. However, drug release profiles were relatively unaffected among the solvent combinations evaluated.   Study Link (PDF 404.07 KB) >> Colorcon is committed to meeting our customers’ needs and providing the best possible advice for use of our products. To this end, further studies focused on EC polymer molecular weight, and plasticizer type and concentration, are in progress. These studies will be presented at the 2009 Controlled Release Symposium in Copenhagen, as well as summarized in subsequent market communications.

Download PDF Version  Do You Know Your CPPs?   Author: Charles Vesey, RPh, MS Cellulosic polymers have been extensively used in the film coating of solid dosage forms to prepare oral sustained release formulations. Knowledge and understanding of the process parameters used in the manufacture of the latter is critical to successful product development, scale-up and launch.  While coating organically is still common, aqueous polymer dispersions eliminate the potential hazards and costs associated with organic solvents. However, when compared to organic polymer solutions, film formation from aqueous dispersions is a complex process. During the coating process, water evaporates and colloidal polymer particles are drawn together, deform, and coalesce into a continuous film, or barrier membrane. Drug release from these dosage forms can be strongly affected by coating process variables, which influence the coalescence of the polymer particles and subsequent film formation. Each process parameter contributes to the final film coat quality and other important response variables, such as coating process efficiency and product agglomeration. When determining critical process parameters (CPP’s) for any coating process, one must first determine the critical quality attributes (CQA’s) for the final marketed product. For coated multiparticulates, control of CPP should result in a stable drug release pattern over the shelf life of the product. Use of design of experiments (DOE) can assist identification of CPP and help define scale-up protocols to eliminate potential for unwanted surprises. The necessity of a post-coating thermal treatment should also be evaluated on an individual basis and continually evaluated through the scale-up process. Post-coating thermal treatment (commonly defined as a ‘curing’ step) helps complete the film formation process and eliminate any changes that may occur in film structure during shelf life. Surelease®, aqueous ethylcellulose dispersion, has been successfully applied on a myriad of manufacturers’ equipment from laboratory scale through production. Colorcon also continues to develop applications data to assist customers in process optimization and minimize any real or perceived need for curing. Study Link (PDF 176.97 KB) >>    Conversation with the Author...   Charles Vesey (pronounced “v-z”), RPh, MS, is a Product Development Manager at Colorcon. Even though his responsibilities include formulation and development of solid oral dosage forms, with particular emphasis on controlled release products, it’s his personal research interest that inspires him to research and write about CPPs. “My experience has proven quite valuable to be in the position to write about our processes to effectively use our products. The experience has enabled me to talk about a topic like this with customers and colleagues, and I find it very interesting,” says Vesey.  With 12 years of product development experience, covering both immediate release and modified release areas, including product scale-up from laboratory to production of various pharmaceutical unit operations, Vesey is a seasoned researcher. He has contributed to numerous research publications and conference presentations in the area of film coating technologies. Vesey also holds several patents related to immediate and modified release film coating. Vesey likes to use his expertise to lead his research team and most of all to help customers in their formulations. Here’s what he had to say when asked why it was important to write this newsletter article. “The value is to help our customers better understand how process parameters can affect final product quality of what they want to bring to market. A better understanding can shorten their time-to-market, avoid unforeseen problems during development and scale-up of the process (coating).”        Particular about Multiparticulate  School?   If you're looking for a multiparticulate (MP) course that offers instruction on the features and benefits of the different types of MPs, drug loading best practices, principles of extrusion spheronization, mini-tablet formulation guidelines, equipment review and more. The Formulation School® for Multiparticulates brings together leading experts from industry, academia and Colorcon to provide valuable information on the theory and practical approach to core formulation. In most cases, the format is a two-day venue; one day of theory and practical presentations followed by a day of hands-on work in a Colorcon technical center. Click here for more information. _______________________ Need Samples or Trial Support?  Colorcon product samples, resources, expertise and global network of technical labs are always available for supporting your development efforts – at no cost to you. Please contact us or your regional business development / technical manager to request samples, consultation and/or schedule your trial!