Abstract:
Due to the application of combinatorial chemistry and high-throughput screening in drug discovery, the majority of new drug candidates have become extremely insoluble in water making the development of bioavailable clinical dosage forms very challenging. Two-thirds of compounds emerging from the drug discovery pipeline have an aqueous solubility of less than 100 µg/mL (0.1 mg/mL).

This would classify them as insoluble or practically insoluble according to the definitions of the United States Pharmacopeia. Although many drug candidates are categorized as poorly water-soluble, there is no limit as to how low aqueous solubility could be, since approximately one-third of newly discovered compounds have an aqueous solubility of less than 10 µg/mL. Aqueous solubilities of less than 1 µg/mL are increasingly more common. Lipid-based drug delivery systems in which the drug is solubilized by lipids or lipid-like excipients, have been recognized as an attractive approach for increasing the bioavailability of these compounds. Lipids have been employed to improve the dissolution rate, increase the solubility of API in the intestinal fluid and influence permeability. Additional benefits of lipids include protection of API from chemical and enzymatic degradation, elimination of the fast/fed effect and influencing the deposition of specific APIs within various tissues. New delivery vehicles and novel approaches utilizing lipids for ophthalmic, parenteral, nasal and transdermal delivery will be discussed.

Abstract:
Asahi Kasei Chemicals has developed high flowable and compactible Microcrystalline Cellulose, Ceolus UF-711 and UF-702, using own MCC particle processing technology. Our technology maximizes particle flowability while maintaining high compactibility. UF-711 shows the same flowability as PH-102 which is the standard grade in direct compression while having 1.5 times compactibility of PH-102. UF-702 shows the best flowability among all MCCs while having the same compacitibility as PH-101. High compactibility of UF-711 can reduce tableting troubles such as capping in case of high dose formulation with poor compactibility APIs and good flowability of UF-702 can reduce tablet weight variance in case of high dose formulation with poorly flowable APIs.

Therefore, Ceolus UF grades enable direct compression for high dose formulations which were only possible by wet granulation to contribute to cost saving. Also, Ceolus UF can maximize API content; in other words, Ceolus UF can minimize tablet size without reducing API content. Such tablet size reduction contributes to the improvement of compliance (easy administration) and the distinction of the product. Plus, decreasing excipients addition rate also contributes to cost saving. This presentation will show the examples of direct compression of high dose formulation using UF-711 and UF-702, and illustrate their cost saving effect.

Mr. Masayuki Kakizawa - Assistant Manager, Functional Additives Division, Ceolus R&D Department, Asahi Kasei Chemicals Corporation.
Mr. Kakizawa completed a master degree at Faculty of Engineering, The University of Tokyo, Japan in 2000. Immediately afterwards he began working in Functional Additives Division with Asahi Chemical Industry Co., which is now Asahi Kasei Chemicals Corporation. Mr. Kakizawa has been researching and developing new pharmaceutical additives for the past 11 years.

He has been responsible for several posters presented at the American Association of Pharmaceutical Society. He gave some presentations in The Symposium on Particulate Preparations and Designs and Association for Innovative Formulation Technology in Japan. This is the second time speaking at ExcipientFest.

Speaker:

Abstract:
Amongst modified release (MR)-formulations HPMC is the most important hydrophilic carrier material used for preparation of orally controlled drug delivery systems. However, in development of MR-formulations polymer properties as rate-controlling matrix formation and flowability, the diverse behaviour of various soluble API(s), or the design (composition and geometry) of a pharmaceutical device can be challenging and time consuming.

In order to increase robustness of new pharmaceutical products and minimize the number of necessary experiments in formulation strategy two possible tools for significant simplifying will be presented: The use of (i) co-processed excipients and a subsequent application of (ii) mathematical modelling. Combining two or more established excipients in an appropriate way may result in superior functional properties as e.g. more satisfying results in content uniformity or a reduced sensitivity against humidity. Elucidation of mass transport mechanism and a quantitative prediction of release kinetics will be shown, using a recently introduced material, RetaLac©, as an example. The presentation will provide a brief overview on the spectrum of mathematical models and its areas of application.

Abstract:
The current microcrystalline cellulose (MCC) monograph degree of polymerization (DP) specification states that in order for cellulose to be classified as MCC, it must possess a DP no greater than 350. However, the industry has been taught, and in many cases, continues to believe that MCC should possess a DP in a range of 215 to 240 in order to be most effective in tableting. Evidence suggests optimal DP is reliant on the raw material used in MCC manufacture, and that the 215 to 240 DP range has no impact material performance. Other physical characteristics, such as loss on drying (LOD), particle size, and bulk density, have greater influence on material performance. It is the speaker’s intent to demonstrate this through several examples during the presentation.

Abstract:
Economic adulteration is a realized threat to patient safety. It is critical that materials acquired through an extended supply channel have the same rigor of pre-selection supplier evaluation and risk mitigation practices in place as local source suppliers. There is a need to assure quality risk factors and potential mitigation costs are built into the sourcing process to understand the total cost for quality products and prevention of economic adulteration. This presentation will focus on consideration of the quality risk and total cost of the extended supply channel for materials. Predictive factors can be utilized at the point of supplier selection to understand the true cost of Supplier Management prior to selection of the Suppliers. This session focuses on understanding a supplier’s quality risk profile as pre-selection criteria, in order to understand the cost of maintaining each supplier within the acceptable risk threshold.

Speaker:

Speaker:

Mr. Alex Peña – Warner Chilcott (IPEC)

Julio Alexander Peña is a certified Six Sigma Black Belt with over 10 years of experience in various fields, most prominently in the procurement and planning arena. He currently works for Warner Chilcott as Global Procurement Manager for Direct Materials. Previously, Alex held Procurement management roles at Merck’s Commercial Operations for the Caribbean and Central America and at Schering Plough Manufacturing Division in Las Piedras, Puerto Rico for 7 years where he led and participated in important initiatives, such as, MRP Class A, Reduced Testing, Kanban systems and Supplier Performance Management. Previously, Julio Alexander worked in various engineering roles in General Electric, mainly in the area of quality and process improvement.

Alex has a Bachelor Degree in Electrical Engineering from the University of Puerto Rico in Mayagüez,  a Master Degree in Electric Power Engineering from Rensselaer Polytechnic Institute in Troy, NY and an MBA from the University of Turabo in Gurabo, PR.

Abstract:
This presentation introduces a novel binder for dry granulation technologies, such as roller compaction. This process consists of two consecutive compaction steps; the first to obtain a compact, which is then milled down to granules; the second to obtain tablets. Both compactability and recompactability are therefore crucial to the success of this granulation process. Current excipients might struggle to produce the desired compacts or tablets. Indeed most materials are sensitive to reworking and will become less recompactable or tablet-able after the initial compaction step.

The use of blends of multiple excipients is therefore common to obtain the most suitable balance between different excipients properties. Avicel® DG, a novel dry granulation binder, is the result of a synergistic combination of microcrystalline cellulose and anhydrous dibasic calcium phosphate. The wet dispersion and spray-drying of these two excipients results in an intimate physical combination, which cannot be achieved by traditional dry blending. The use of Avicel DG improves yields as a result of dramatically enhanced recompactability and reduces costs by minimizing steps in the production process.

Mr. Gregory Thoorens – Senior Scientist – FMC BioPolymer, European Technical Center:
Gregory Thoorens graduated as Industrial Engineer with a specialization in biochemistry. He also obtained a Master Degree in Pharmaceutical Engineering from UCL, Brussels. Gregory joined the European Technical Center of FMC BioPolymer in 2002. Since then he has been involved in characterizing Avicel PH and evaluating their use in solid dosage form applications.

Gregory has more recently been involved in the development of a novel binder for dry granulation roller compaction, Avicel® DG. Avicel DG was optimized to meet formulators’ needs for a recompactible excipient, which enables the production of strong tablets without using extragranular binders. Gregory has spoken numerous times at ExcipientFest.

Abstract:
Taste masking is one of the most important targets for the coating of solid dosage forms containing unpleasant taste. The common used polymers for fast release coatings like HPMC or PVA have the disadvantage of being soluble in the mouth. Taste masking is just achieved for a very short time even after coating of high amounts of film which accompanies long coating time as well. Taste masking optimized polymers like the methacrylic based polymer Eudragit EPO are very efficient in taste masking at low amounts of coating but the preparation of suspension is very complex.

BioGrund has formulated in cooperation with Evonik and Abbott a ‘one step ready to use’ coating system for taste masking purposes based on the Eudragit EPO polymer. Simple and short time preparation of the high solid content suspensions leads to short preparation and coating time for coating of tablets, granules or pellets. There are two other new coating products developed which are optimized for taste masking in combination with short process times: One based on shellac for coating of tablets and capsules and a second one based on Isomalt for sugar free dragification. All new developed products do not modify the release of APIs and are to be understood as fast release coating systems.

Legislative Update on Food Safety

Congressional Staffer – Pending.

Continuous Manufacturing; Challenges of Going Back to the Future
Moderated by Pharmaceutical Technology

Sponsored by ISP Corporation

Abstract:
Continuous manufacturing has been widely used in multiple industries for a number of years to both reduce costs and improve quality.  However, the pharmaceutical industry has predominately remained focused on batch operations for a variety of reasons.  Recently, continuous manufacturing has become an area of increasing discussion and focus for pharmaceutical manufacturers as well as well as suppliers as they look to obtain some of the operational benefits that other industries have realized for years.  Today, there are increasing pressures to increase manufacturing efficiencies to reduce costs and achieve operational excellence with lean manufacturing while maintaining high quality standards and product performance.  Development efforts to transition from batch operations to continuous operations are ongoing with varied levels of success.  In order to make the transition from batch to continuous production more successful, new developments are needed in equipment, excipients and regulatory/quality practices.
For this roundtable, we will look to bring to together representatives from excipient suppliers equipment manufacturers, a regulatory representative and a pharmaceutical manufacturer to share knowledge and address the benefits and challenge of continuous operations.

1. Dr. Stu Porter, Senior Director, Global Pharmaceutical Applications R&D - ISP
2. Ms. Steven Wolfgang, FDA CDER
3. Mark Neidlinger, GEA Process Engineering Inc., Columbia, MD
4. Dr. Brett Alexander, Senior Scientist, AstraZeneca, Charnwood, UK
5. Chris Moreton, FinnBrit Consulting, IPEC Member

Moderated by Angie Drakulich – Editor of Phamaceutical Technology:
Angie joined Pharmaceutical Technology in 2007. She previously served as editor and assistant communications director at the United Nations Association of the USA where she directed a quarterly magazine, among other publications, on US-UN relations. Angie has worked an editor, writer, and researcher for Grunar & Jahr USA, Time Inc., and Rodale publishing. She holds a Master of Arts from Seton Hall University’s John C. Whitehead School of Diplomacy and International Relations and a bachelor’s degree from James Madison University. Her articles have appeared in The InterDependent, UN Chronicle, Rosie, McCall's, Parenting, Travel Holiday, Bridal Guide, The Washington Times, and U.S. News & World Report.

Effective Cleaning of Time Release & Color Coatings

USP Excipient Performance Chapter <1059>: Excipient QbD as it relates to performance and functionality

Abstract:

Excipient function or functionality is a general qualitative and descriptive term used to describe the purpose or role of an excipient used in a drug formulation. More importantly, are the quantitative performance requirements (e.g., critical material attributes in FDA’s Q8 Pharmaceutical Development) of excipients that must be evaluated and controlled to ensure consistent performance throughout the product life-cycle. An excipient may have different functional purposes and may possess certain necessary characteristics (e.g., particle size), depending on its use in a formulation or manufacturing process.

The excipients chosen, their concentration and characteristics can influence drug product performance (e.g., stability) or manufacturability. Performance related tests help formulators identify and ‘monitor’ properties that they determine are important to excipient function and performance for a particular application. Not all critical material attributes of an excipient may be identified or evaluated by specific tests and specifications in excipient monographs. <1059> provides an overview of the key functional categories of excipients in USP–NF, along with tests that may relate to excipient performance not typically included in compendial monographs.

Selection of tests and appropriate specifications that are necessary to assure consistent and reliable excipient performance requires a thorough understanding of the formulation, the manufacturing processes, and the physical and chemical properties of each ingredient.

Ms. Catherine Sheehan  – Director of Excipients in the Documentary Standards Division - United States Pharmacopeia (USP):

Ms. Sheehan is Director of Excipients in the Documentary Standards Division, United States Pharmacopeia, Rockville, MD. In her current role, she is responsible for development and update of excipient monographs and related chapters, and participates in the Pharmacopeial Discussion Group’s compendial harmonization of excipient monographs and excipient chapters.

Ms. Sheehan is active in AAPS and RAPS. She was a member on the Product Quality Research Institute, Excipient Working Group from 2006-2007 and was co-author of the group’s two published articles that appeared in Pharmaceutical Technology , “PQRI survey of Pharmaceutical Excipient testing and Control strategies used by excipient manufacturers, excipient distributors and drug product manufacturers”, and “PQRI Joint Position Paper on Pharmaceutical Excipient testing and Control strategies”.

Ms. Sheehan is a graduate of University College Cork, Ireland. She holds a B.Sc. Degree from University College Cork, Ireland. She holds an M.S. Bioscience Regulatory Affairs from Johns Hopkins University, USA. This is her second time speaking at ExcipientFest.

Harmonization - PDG Progress

Mrs. Susan DeMars - Chief Documentary Standards Officer and General Counsel, USP:

Susan de Mars is Chief Documentary Standards Officer and General Counsel for the United States Pharmacopeia (USP). She also serves as secretary to the USP Board of Trustees and the USP Convention. She is responsible for all legal, regulatory, and governance issues affecting USP. As Chief Documentary Standards Officer, Ms. de Mars oversees development of the documentary standards that comprise USP's publications, including the United States Pharmacopeia – National Formulary (USP–NF), the Food Chemicals Codex (FCC), the Pharmacists Pharmacopeia, and the Dietary Supplements Compendium (DSC).

Atypical Actives

Janeen Skutnik was chair of IPEC Americas in 2009, she has been involved in IPEC as chair of the Compendial Review committee from 1998-2007, she has also been a member of the IPEC Board of Trustees since 2002, and a member of the Executive Committee since 1999. She has given many presentations on excipients in various countries over the past decade and a half. Ms. Skutnik has also been the chair of PhRMA’s Compendial Liaison Committee and the Technical Leadership Committee since 1998. She has been a member of PDA for many years and a speaker at several PDA meetings and conferences both in the USA and Europe. She has been a member of RAQC since 2007.

Handling the Overpressure Challenges of Taste-Masked APIs

Abstract:

Taste-masking of APIs is often essential for developing a successful formulation. The process of tableting is a taste-masking system rupture risk. To avoid the risk often plasticization of the coating is used reducing coating brittleness. This makes the coating sticky and product can lose dissolution rate with age. This presentation features experiences formulating with SPI Pharma’s Tasteshield™ technologies, using two Actimask™ core materials, acetaminophen and ibuprofen, one a hard crystalline and the other a soft core, and combining these core materials with a new highly ductile excipient, XP-600, which is designed for low pressure tableting.

Mr. John Tillotson – Senior Scientist - SPI Pharma

John Tillotson is a Senior Scientist and ARTS (Applications, Research and Technical Services) Department Lead at SPI Pharma, Inc. Dr. Tillotson received his B.S. in Pharmacy from Ferris State University, Big Rapids, MI and his PH.D. in Industrial Pharmacy from the University of Cincinnati, Cincinnati, OH. He has held Industrial positions in Guatemala and the United States. Dr. Tillotson’s primary areas of interest are quick dissolve tablet technologies, particularly directly compressible modalities. He is a member of the Rho Chi Pharmaceutical Honor Society and of the American Association of Pharmaceutical Scientists.