April 2009 Colorcon® News In This Issue: Shape Matters! Conversation with Dr. Tom Farrell  We Don't Miss a Beat with our BCP  Lower Solids Lead to Higher Gloss Mini-tablets - Mighty Advantages  Did You Miss the CRS Satellite Meeting?      Shape Matters!   Author: Sandip Tiwari                                                 Senior Manager - Product Development Hypromellose (hydroxypropyl methylcellulose [HPMC]) has been widely used in the formulation of hydrophilic matrices for oral extended release (ER) drug delivery. In addition to formulation and manufacturing variables, drug release from HPMC matrix tablets may be affected by characteristics of the dosage form such as tablet shape, size and surface area.  Colorcon® investigated the effect of various tablet shapes on drug release from HPMC matrices, using two model drugs; metformin HCl, as a freely soluble drug - used at a high dose (50% w/w), and indapamide as a practically insoluble drug - used at a low dose (0.75% w/w). The mechanism of release is expected to be primarily diffusion-controlled for metformin HCl and erosion-controlled for indapamide. In addition to round and caplet shapes, tablets with dumbbell and pentagon geometries were also evaluated. Results indicated that drug release from HPMC matrix tablets with similar values of surface area to volume ratio (SA/V ratio) was comparable among different tablet shapes. Tablets of same shape, but different SA/V ratio, did not result in similar drug release; tablets with larger SA/V ratio had faster release profiles. This was true regardless of the drug solubility, dose, and mechanism of drug release. Based on the findings, it was concluded that for HPMC matrices, SA/V ratio is an important parameter in controlling drug release. This finding is of paramount importance to pharmaceutical formulators, because by designing a particular size and shape of matrices, optimal drug release profiles can be achieved without modifications of formulation. In conclusion, Colorcon's ability to facilitate the design of unique tablet shapes, coupled with expertise in hydrophilic matrix design and release modulation capability, can assist in your formulation development and speed to market.       We Don’t Miss a Beat with Our BCP…     Author: Craig Palumbo                                                                              Vice President - Global Operations Colorcon® has developed a comprehensive Global Business Continuity Plan (BCP) to address the risk of a disruption to the supply of products or services to customers.  The BCP identifies potential risks, including: loss of a facility due to a natural or other disaster, loss of critical equipment, loss of key personnel due to a pandemic illness or catastrophic event, unavailability of key starting materials or loss of computer-based enterprise systems. The plan puts into place a series of policies and procedures, which tackle these risks in order that operations can continue normally or recover quickly after an unplanned event. Our dispersion products can be manufactured at multiple sites around the world with harmonized manufacturing and test methods that are equivalent in terms of quality and performance. Some products can only be manufactured at a single location and inventory of these products is maintained at multiple distribution centers around the globe. These single location facilities all have specific recovery plans, including detailed equipment information allowing a swift recovery from a disaster. Key starting materials are sourced from fully assessed suppliers. Preferably with multiple lines or facilities that are capable of producing material that can be qualified as equivalent. In circumstances where this is not possible, alternate suppliers are identified and qualified as being equivalent to the Colorcon application. As a distributor of key excipients, Colorcon also works with its principals to ensure BCP is in place and maintained. For example, Dow-Wolff Cellulosics, our Controlled Release Alliance partner, has a formal BCP program in place. Our extensive global distribution center network, as described above, complements Dow’s BCP in ensuring supply reliability. Both partners routinely review our collective BCP on an ongoing basis. Colorcon’s BCP is considered a key component of our business model, and as such, is constantly being reviewed, tested in simulation exercises and updated.           Lower Solids Lead to Higher Gloss     Author: Adam Kevra                                                                           Manager - Product Development When a pharmaceutical manufacturer turned to Colorcon® for help in order to increase their process efficiency for a marketed sugar-coated product, we immediately set out to offer a formulation solution. Initial studies identified that Opadry® II, complete film coating system, could produce gloss levels approaching sugar coated tablets. These results prompted further studies on how to maximize gloss with Opadry II 85 Series, PVA-based film coatings, through application studies. Gloss levels of coated tablets increase as coating suspension solids decrease. Both gloss and productivity can be maximized by applying a clear coating at low solids over a pigmented sub-coat. Gloss of a tablet coated with an 85 Series yellow, applied at 20% solids, increased from 79 GU (gloss units) to 156 GU after the application of only a 0.5% weight gain of 85 Series clear sprayed at 5% solids. This series of coatings are low viscosity, high productivity. The products' low permeability protects the tablet core from atmospheric oxygen and water vapor. Additionally, high adhesion to tablet surfaces helps produce crisp clear logo definition, even on waxy cores. Opadry II 85 Series film coatings produce a smooth, elegant, low-friction tablet finish, which is visually appealing and aids in tablet packaging. Study Link (PDF 516.59) >>            Mini-tablets – Mighty Advantages…     Author: Kurt Fegely, MS                                                                           Market Development Manager - Excipients It is well known that solid oral dosage forms, particularly tablets, are the most acceptable form of delivering medication. However, some new variations are beginning to emerge such as mini-tabs, which offer formulation flexibility.  Mini-tabs are small tablets with a diameter typically equal to or less than 3 mm that are typically filled into a capsule, or occasionally, further compressed into larger tablets. It is possible to incorporate many different mini-tablets, each one formulated individually and programmed to release drug at different sites within the gastrointestinal track, into one capsule. These combinations may include immediate release, delayed release, and/or controlled release mini-tabs. It is also possible to incorporate mini-tabs of different drugs to treat concurrent diseases or combinations of drugs to improve overall therapeutic outcome, while delivering distinct release rates of each according to disease requirements. Mini-tabs could also offer a solution to the current issue in the pharmaceutical industry representing a lack of dosage forms which are suitable for pediatrics. Mini-tabs combine the advantages of multiparticulate dosage forms with the established manufacturing techniques of tableting. They can be produced via direct compression and can be manufactured using conventional tableting machines with only minor equipment modifications. For example, in order to increase production speeds, multiple-tip tooling has been employed routinely. Furthermore, mini-tabs can be coated using either a perforated coating pan or a fluid bed apparatus. Colorcon® provides several functional polymers and coatings for mini-tab formulations and has developed application knowledge in mini-tabs and mini-matrices using conventional tableting and coating equipment. As your formulation partner, we would like to share this information with you. The study below investigates enteric coating of lansoprazole mini-tabs, and is just one example of our formulation expertise. Study Link (PDF 453.69) >>            Did You Miss the CRS Satellite Meeting in Vienna - March 2009?     A two-day CRS satellite meeting titled, “Oral Multiparticulate Drug Delivery Systems: “Challenges and Opportunties” was co-chaired by Ali Rajabi-Siahboomi, Colorcon’s Director of Scientific Affairs, to hear from experts and discuss the challenges and opportunities that MP systems may create. The meeting started with an overview of market trends in oral drug delivery systems and recent product approvals that favor MPs. Then a presentation on the suitability of the gastrointestinal tract (GIT) for MP systems showed that oral multi-unit platforms offer statistical advantage for drug delivery to the heterogeneous environment of the GIT. Even though the formulation and processing of MP systems can be complex, it was shown that major advances in formulation of polymers and application technologies have been made. These advances have facilitated the acceptance of MP systems as platforms for achieving a range of drug release profiles, combination drug delivery, and effective pediatric/geriatric dosing. Other key topics covered were: The challenges of compressing multiparticulates into tablets Scale-up, PAT, QbD, IVIVC and regulatory aspects of MPs Drug delivery to pediatrics using MP systems in relation to EU Pediatric Regulation (No. 1901/20060) In addition to the excellent scientific content, we managed good interactions and exchanges of ideas during and after each presentation. Everyone walked away with a greater appreciation for the opportunities and an awareness of the challenges of developing, scaling up and introducing MP products in the market place. The next CRS Satellite meeting will be held June 17-18, 2009 in Shanghai, China: “Oral Controlled Drug Delivery Using Tablets; From Laboratory to Production.”

Download PDF Version   Conversation with…   Dr. Tom Farrell Your Formulation Partner™ is not just a slogan; it is the essence of the people at Colorcon® – like Dr. Tom Farrell. As the Director of Product Development, Farrell leads his team by focusing on product innovation with customers’ needs at the forefront. Farrell says, “Colorcon understands, and solely focuses on, the pharmaceutical industry. Our field teams constantly evaluate market and performance gaps impeding our customers’ oral solid dose development programs. Our Product Development Group prides itself on the continued development of innovative products and tools to improve performance, boost productivity, and reduce costs.”  During this conversation with Dr. Tom Farrell, he explains how Colorcon has become a technology leader; more than “a coating company” and why they are becoming the industry’s “Formulation Partner.” Q: What sort of customer requests do you manage? A: Colorcon’s product development team fields a myriad of customer requests from around the world. Some customers ask for “starting” formulations based on our experience and applications data. Others seek advice on how to adjust dissolution release profiles and processing best practice guidelines. In many instances, customers are extremely pressed for time and are looking to leverage our broad expertise in formulation and coating for a product they have decided to market. We draw on the collective know-how of our scientists, many of whom have worked for pharmaceutical companies or contract research organizations (CROs) in the past. Since we have provided formulations for literally hundreds of different APIs, we can quickly consider our customers’ requests and provide recommended formulations. Our most satisfying moments are when we receive positive feedback that our formulation recommendations were adopted and resulted in a marketed product. Q: Can you give an example of a product that your group developed in answer to a specific industry or customer need? A: Colorcon introduced Opadry®, complete film coating system, to the pharmaceutical industry in the 1970’s. The Opadry concept offered many advantages versus the laborious and time-consuming in-house preparation of film coatings that was standard. The original Opadry products are still successfully used today; however, we have continuously developed the concept further in terms of increased productivity, enhanced product performance, and improved cost-in-use. Colorcon’s latest innovation – Opadry® II 85-series, based on polyvinyl alcohol – meets all of these challenges. The product offers enhanced functionality in terms of moisture and oxygen barrier protection. And, compared to the original Opadry products, Opadry II 85-series can be applied at much faster spray rates, increasing product throughput and overall production capacity. Switching from Opadry to Opadry II 85-series has resulted in some customers canceling plans to purchase additional coatings pans, significantly reducing capital expenditures. Q: In addition to developing new products, how else do you and your group provide value? A: Developing a wealth of applications data for a product is standard operating procedure at Colorcon. We ensure that we have developed processing parameters on all common film coatings sold globally, for both tablets and multiparticulates. We routinely develop best practice guidelines and decision trees to achieve maximium efficiency for specific parameters, such as moisture barrier or gloss, and how to apply coatings optimally for maximum tablet elegance. Optimizing dissolution release profiles and CR formulation modeling are other areas of investment for us. And, we always develop stability data with a range of APIs, showing good compatibility with our products. Q: From what other perspectives does Product Development work as a “partner?” A: While we believe our products and service model are best-in-class, we are not complacent. We continuously look for alternative polymers and additives that might allow us to develop immediate or modified release film coatings, which may fill some niches or potentially become the new first-line product. Additionally, we have excellent relationships with our polymer and additive suppliers globally and ensure that any raw material changes are managed as seamlessly as possible. Our scientists proactively monitor advances in processing and material technologies, so that we can anticipate future opportunities for our customers. As a conclusion to this conversation, it is clear that Farrell and his team contribute a great deal to the Colorcon organization. As a distinguished scientist, Farrell earned a PhD from Princeton University, and has a record of achievement with eight patents and 20 published articles. Most recently, he was elected to be the 2010 Chair of the Excipients Focus Group of AAPS. Dr. Tom Farrell truly has the credentials for a great formulation partner.      Dont Forget About...   Nutrateric®, nutritional enteric coating system Nutrateric® was uniquely designed by Colorcon® to provide a regulatory compliant enteric coating system, based on ethylcellulose, for the nutritional and dietary supplement markets in North America and Europe. The product is supported by applications data on garlic tablets and gelatin capsules, where outstanding performance is shown. Nutrateric is also pharmaceutically compliant and can be used in taste masking and enteric applications on tablets, multiparticulates and hard-shell capsules. Application guidelines are available and products can initially be tested at no risk or cost to the customer in one of 17 Colorcon global locations, where a variety of equipment configurations and scales are available.   _______________________________   For more information on any products or services mentioned in this newsletter, please Contact Us!