DRUG FORMULATION, SOLUBILITY & BIOAVAILABILITY

Transcription

1 EXECUTIVE SUMMARY EXECUTIVE SUMMARY 4th DRUG FORMULATION, SOLUBILITY & BIOAVAILABILITY SUMMIT The Modeling and Enabled Formulation Expertise You Need to Maximize Drug Developability, Avoid Particle Formation, and Maintain Stability and Bioavailability Join the Conversation Group: Enhancing Drug Bioavailability and Solubility

2 CONTENTS INTRODUCTION 3 PRESENTATIONS 4 RESOURCES FOR INFORMATION AND DISCUSSION 11 RECOMMENDED SERVICE PROVIDERS 12 2

3 INTRODUCTION: HERE S WHAT YOU MISSED AT EXL PHARMA S 4th DRUG FORMULATION & BIOAVAILABILITY CONFERENCE If you weren t able to join us earlier this year, here is what you missed at ExL Pharma s 4th Drug Formulation & Bioavailability Conference Dedicated to bringing together the industry s leading formulation experts to share and discuss emerging drug bioavailability and solubility enhancement strategies, the 4th annual summit was held January in Boston. The conferencefocused on breakthrough techniques in optimizing the screening, delivery, solubility and stability of drugs and biologics to enhance product life cycles. Built around specific industry feedback, 2015 s all-new program targeted the most immediate formulation, solubility, permeability and bioavailability challenges. With four unique program tracks, two in-depth interactive workshops, numerous networking opportunities and more than 100 of the industry s most distinguished drug formulation, preformulation and delivery experts, the conference helped attendees develop action plans for when real human data is lacking, explore the potential for solid-state chemistry as the next breakthrough in drug design, select the optimal technologies for advancing drug candidates and maintaining a robust pipeline and more. All-new case studies centered on agnostic modalities in future drug development, the latest challenges in simulating supersaturation, adjusting to shorter developmental timelines of fixed-dose combinations, optimal screening approaches for cocrystrals, risk protocols for photoreactivity and phototoxicity, and device-based oral biologic delivery, among others. Following are session summaries and highlights to give you an idea of what you may have missed at our 4th Drug Formulation & Bioavailability Conference. 3

4 SESSION SUMMARIES A keynote presentation on Future Trends in Drug Formulation: Agnostic Modality and Design for Delivery, presented by Rob Saklatvala of Merck & Co., discussed a broader focus beyond pill formulations, the design of delivery systems to support better patient adherence, minimally invasive delivery systems for poorly permeable drugs, and more. Pressures on the pharma industry include flat productivity, high development costs and pricing pressures. The future is fill of opportunity, with only 10 percent of the 3,000 genes believed to be linked to disease currently targeted with FDA-approved therapies; this will lead to a diverse portfolio to formulate. The industry is seeing a shift to more peptide drugs, because they are involved in various physiological/pathological processes and play important roles in regulating cell processes they may provide the best of small molecules and biologic approaches, not to mention a potential for fewer side effects, low tissue accumulation and high potency. Modality agnostic approaches will see greater Poor Adherence Leads to Poor Outcomes and Increased Healthcare Costs Figure 1: Adherence rates of select conditions in US Depression Pain Low back pain Chronic bronchitis GERD HIV/AIDS Incontinence Arthritis (Rheumatoid) 50% 52% 53% 54% 54% 54% 56% 57% In summary, drug discovery pipelines are becoming diverse in modality complexity will increase, but so will scientific opportunity. Formulation strategies and technologies will need to evolve to consider multiple modalities. Early consideration of drug delivery strategy is important it can identify gaps between potential delivery options and competitive product profiles. Understanding the needs and limitations of delivery systems across modalities can enable a design for delivery approach. John Comer of Sirius offered a session focused on Novel Automated Analysis Methods for Biorelevant Dissolution. He noted that in vitro methods show how APIs and formulations behave in the presence of simulated gastric and intestinal ph and biorelevant media and offered more details on in vivo predictive dissolution methodology and monitoring precipitation from supersaturated solutions. There are three ways to measure concentration: 1) ph metric, which is good for solutions whose ph is less than three units from pka; 2) in-situ UV, good for drugs that absorb UV; and 3) offline, the best method if samples are very turgid as well as different evaluation options. Sirius inform can set up a wide range of experimental conditions. Keys to success include designing experiments that discriminate well, deal with turgidity and use innovative tests for investigating IVIVC. Arthritis (Osteo) Parkinson's Cardiac problems Cancer Enlarged prostate 58% 60% 61% 62% 63% Inert gas 0% 20% 40% 60% 80% Source: Andree Bates, Ensuring Profitable Patient Adherence Programs, Eularis, March Overall cost of poor adherence is close to $310B annually Temperature probe ph electrode 7 interactions and synergy between small and large molecule delivery groups. Currently, the overall cost of poor adherence is about $310 billion annually, and Dip probe for lipid Lipid (25 ml) Reagent capillaries (6) Tablet holder Aqueous solution (30-70 ml) UV dip probe Stirrer (5-900 rpm) the success rates of various interventions further opportunities in drug delivery. The challenge is in 11/38 Cell and probes for biphasic dissolution Cell and probes for phmetric assays and biorelevant dissolution identifying drug delivery opportunities sufficiently 2015 early and compelling enough to warrant investments. 4

5 Nanoformulations to Enhance Bioavailability of APIs from Suresh Bandari of St. Peter s Institute of Pharmaceutical Sciences highlighted the increased need to identify potential lead molecules which had resulted in the discovery and development of many drug candidates. About 95 percent of all new potential therapeutics have poor pharmacokinetic and biopharmaceutical properties. Drug delivery has been an extremely demanding science because of the emergence of the more challenging molecules, increased use of biological materials and drug targeting. Barriers in absorption of oral delivery are solubility and permeability. Continued improvement and accelerating research and development in polymeric materials has played a vital role in the progress of drug delivery technologies. After sharing several case studies, he added that a host of current industry issues include scalability, stability, regulatory requirements for approval, cost of product, stability, safety issues, efficacy and market potential. Why worry about API solid form? Phase purity Excipient compatibility Hygroscopicity Stability Bioavailability API Solid Form Solubility Dissolution rate Precipitation Particle morphology Sticking tendency Compressibility Manufacturabilty Pfizer Confidential 3 be optimized as data from large-scale manufacturing becomes available to guide late-state development decisions. Overall, API solid form and the associated physical attributes play a key role in drug design from discovery to commercialization. Identification and selection of the appropriate API solid form at the earliest stage possible could be advantageous. Organizations should leverage computational tools and small-scale experiments with clinical and largescale manufacturing experience. 3 Solid State Chemistry: The Next Focal Point for Drug Design and Development was covered by Weili Yu of Pfizer, who discussed optimizing solid form selection strategies to improve bioavailability and stability. Conversion to a more stable form will generally occur more rapidly as the energy difference between the two forms increases; therefore, the common practice of selecting a more soluble form may not provide the highest level of the drug in solution in the GI track. Small-scale experiments can be performed to evaluate the potential for form conversion on the time scale of absorption. Accurate prediction of dosage form content uniformity allows the creation of meaningful particle size acceptance criteria at early stages of development. Prediction of the model can Stephen Tindal of Catalent focused on Lipid-based Systems for Oral Peptides. Lipid-based delivery in liquid-filled capsules involves the following: dissolve required dose of API in maximum tolerated volume of liquid; confirm stability/in vitro release/ in vivo performance; and develop as a capsule dosage form. Peptide therapy has challenges and several factors can influence oral absorption. Improved permeability of more lipophilic peptides is potentially related to the displacement of the paracellular to transcelluar route. In presenting a case study on the oral delivery of macromolecules, physiochemical and biochemical properties were examined and the formulating screening noted that lipid digestion products provide enhancement. Capsule batches retained in the stomach showed limited oral exposure while those 5

6 reaching the duodenum delivered proper absorption. In summary, LBS are a commercially viable but underutilized technology; LBS can incorporate excipients that are not feasible in powder-based solid dosage forms. Incorporating water-soluble molecules into LBS for peptide delivery requires advanced expertise and advanced screening techniques. Targeting the release of a permeation enhancer upon digestion as part of the formulation requires a reduced amount of PE and allows a healthy body to recover quickly with less impact to other drugs. Understanding the target product profile involves determining what you want from your clinical study, what dose range you need to cover, the route of administration and the most appropriate dosage form this entails some forward planning to ensure that the formulation choice meets your clinical need. Planning ahead will save time later and can help avoid costly mistakes and delays to the study he suggested keeping it simple when possible. The importance of physio-chemical properties includes preclinical challenges. In Vitro Experiments and Simulation Approaches to Identify and Address ph-dependent Absorption from Michael Perlman of Takeda Pharmaceuticals discussed the use of in vitro dissolution and simulation to design acidified formulations of weak bases that minimize the impact of variable gastric ph. About 50 to 70 percent of recently approved targeted oral cancer therapies display ph-dependent solubility. The therapeutic index for anticancer drugs is often very narrow, and altered gastric ph is known to impair absorption of many weakly basic drugs. Dissolution assays of weak acids are highly dependent on SIF buffer ph and capacity absorption is very dependent upon intestinal ph. He noted that acid-reducing agents (such as proton pump inhibitors) can impact absorption of weak bases, and that acidifying agents can reduce the impact of elevated gastric ph on absorption. Supersaturation can play an important role in weak base absorption, and non-sink in vitro dissolution methods create predictive models for ph-dependent absorption. Further, PBPK models can predict the risk of ph-elevation and guide formulation development. Paul Sabo of Patheon delivered a presentation with details on Stepwise Preformulation and Formulation Development to Maximize Clinical Success. Formulation approaches for Phase I studies should include a simple risk assessment bringing together target product profile and prior knowledge/api characterization. The main objective at this point is to keep it simple; there is no need to waste time and money on complex dosage forms unless you have a specific need. The Quick to Clinic program delivered by Patheon delivers in as little as 12 weeks from receiving your API you can have bulk clinical trial materials for First in Human trials. Quick to Clinic dosage forms include blend in capsule, API in capsule, blend in bottle, API in bottle, oral liquid and soft gel capsules. Bioavailability enhancement involves multi-factorial challenges no one solution works for all molecules so there is a need to consider integrated solutions. This is both time- and costsensitive. Overall, defining your target product profile, understanding the physical and chemical properties of your molecule, keeping the formulation development program simple and using good planning are keys to success. Mengwei Hu of Merck & Co. shared information on Early Investment in Controlled Release: Discovery Controlled Release Formulation Assessment and Case Studies. The why of early investment is to enable discovery to perform pharmacodynamics studies with CR in preclinical species and to reduce CR development risk by selecting candidates with 6

7 ideal properties. The how is early CrR investment by multiple functional areas to leverage technology/ expertise from development combined with the knowledge of discovery to achieve goals such as evaluating CR feasibility and establishing PK/PD relationship. And the what is API characterization, modeling and simulation, and CR formulation for in vivo evaluation to support PD studies. Challenges include the physiology of preclinical species. How: Cross-functional Collaboration Pharmacokinetics Perform CR PK studies Provide PK parameters Pharmacology Perform CR PD studies Safety Provide safety margin information for C max and AUC Saxena V, et al. J Pharm Sci. 2009;98: Discovery Chemistry Synthesize and identify lead candidates Discovery Formulation Physicochemical characterization, CR risk assessment, and formulation development Process Chemistry Scale up to grams of AP Development Formulation Provide specific technical expertise Biopharmaceutics Bioperformance assessment Simulation and modeling Material Characterization Phase selection Three different case studies showed different levels of CR assessment/support for discovery programs: Case 1: enable PD study in rate to address short half-life issue in a rat model using a chow formulation strategy; Case 2: moderate level of CR assessment with an extended PK profile to derisk AE and maintain efficacy for 24 hours with a strategy of CR formulation development to meet PK criteria; and Case 3: high level of CR assessment to provide CR formulation for PD study in dog with a focus on overcoming PK variation in dogs and achieving minimal peak/trough ration and smooth PD. Conclusions were that early investment in CR in discovery provides resolution for short half-life issues in preclinical disease models; further, early investment CR assessment in discovery can effectively reduce development risk. Finally, flexible assessment can be achieved in a fast-paced discovery space based on the specific PK/PD requirements and resources. Preclinical Utilization of IntelliCap Capsule in Combination with Absorption Modeling to Determine Key Oral Absorption Parameters from Manuel Sanchez-Felix of Novartis noted that assumptions are made in GastroPlus while the company wanted to determine if incorporating stomach ph and GI transit times would improve GastroPlus modeling for a compound. With poor understanding of patients, dogs in a fasting state were used to evaluated formulations. The study showed that stomach ph of fasted dogs is highly variable, and that pentagastrin and famotidine do not always control stomach ph. There is a correlation between stomach ph and gastric transit time of the IntelliCap capsule. The compound is not retained in the stomach for the same period as IntelliCap. Finally, G+ simulations using IntelliCap ph and optimized stomach transit time provided the best fits. Larry Rosen of Merck provided insight on Overcoming Fixed Dose Combination Development Challenges. Fixed dose combination products are two or more actives intended to be prescribed concurrently to treat one or more conditions; patient benefits include efficacy, safety, tolerability, reduced bill burden, adherence and cost. Fixed dose combinations are being developed earlier in the product lifecycle and those containing three-plus drugs are becoming more common. Next generation challenges include beginning development with less information and API supply, which may be a constraint. A case study revealed that increasing the concentration of the dispersion in the tablet from 60 to 75 percent looks promising, and increasing the NCE concentration in the amorphous solid dispersion significantly decreases AUC. NCE tablets all have disintegration times greater than one hour. Efforts to reduce tablet size must focus on increasing approved drug concentration in the tablet. Recommendations, then, included proactive 7

8 alignment with regulatory agencies on fixed dose combinations doses required for registration as well as selecting external API suppliers as early as possible, conducting a comprehensive preformulation program, and exploring multiple formulation approaches and initiating probe stability studies as early as possible. Aligning Multiple Prediction and Evaluation Methods for Preclinical Formulations from John Morrison of Bristol-Myers Squibb explained that a developable drug candidate is designed to balance physiochemistry, pharmacokinetics, pharmacodynamic activity and safety characteristics. Formulation performance criteria includes discovery and development (effectiveness, capacity and tolerability) and unique to discovery (throughput and universality). Poor solubility limits oral absorption, and solubilization can overcome slow dissolution, but not low inherent solubility. Supersaturation drives drug flux across the intestinal membrane and overcomes both dissolution rate and solubility limitations. In characterizing supersaturation, the goal is to distinguish solution from solid. When it comes to formula options in discovery, the key criteria are effectiveness, capacity, tolerability, throughput and universality. Furthermore, solubilization and supersaturation are complimentary enabling formulation strategies. Drug Discovery, Optimization and Selection PD Drug Candidate ADME clinical ADME preclinical Delivery Design Toxicology Adapted from: Morrison AAPS webinar, Oct 2014 (ref 1) JS Morrison, Drug Formulation & Bioavailability (Boston, January 2015) A developable drug candidate is designed to balance: 1) physicochemistry (Delivery) 2) pharmacokinetics (ADME) 3) pharmacodynamic activity (PD) 4) safety characteristics (Toxicology) 3 Konstantin Tsinman of Pion, Inc. presented In Situ Concentration Monitoring as a Measurement Tool within in vivo Predictive Dissolution Systems, which recognized the greater need for analyzing real-time free drug concentration. The low solubility of novel drug candidates poses challenges not only to formulators (how to make the drug more soluble while keeping the formulation stable and scalable), but also to analytic methods and techniques. There are limitations to the in situ UV technique real complex dissolution media can obscure or totally absorb the UV signal. Offline analytical methods like HPLC or LCMS are labor-consuming, low-throughput and lack real-time concentration monitoring benefits. In terms of uflux add on to in situ concentration monitoring platform, permeability measurements are allowed with real-time appearance/ disappearance monitoring, permeability assays allow for investigation of complex formulations and building realistic PK predictions, and complex formulations can be studied by the flux response in the receiver compartment. The permeability step can be combined with dynamic media change and other advanced dissolution studies. Finally, the potentiometric technique can be time- and laborsaving in comparison with HPLC when dealing with UV-obstructive media. A Strategic Approach to the Regulatory Challenges of Phototoxicity Assessment from Evan Thackaberry of Genentech examined phototoxicity, including regulatory guidance, testing, models and case studies. Phototoxicity is an acute light-induced tissue response to a photoreactive chemical. It can lead to cutaneous lesions or rashes in sun-exposed areas. Many commonly used drugs and drug classes have phototoxic liabilities, and therapeutic indication drives risk/benefits assessment for example, phototoxicity may be tolerated in antibiotic/ oncology drugs, but it s less desirable for chronically 8

9 administered therapies. The most widely accepted regulatory guidance on photosafety testing recommends a stepwise approach therapeutic and route of exposure are critical. Predictivity of current Practical Approach to Photosafety Testing Page 8 Photochemical Assessment Preclinical Assessment Clinical Assessment Does the drug absorb within nm? In vivo Rodent Assay Positive Positive Clinical Phototoxicity Evaluation PK studies. Based on three different case studies, it was determined that an in vitro dissolution method assessing the extent of supersaturation in SIF may be a viable tool to predict in vivo performance for a basic drug. The viability of in vitro tools and animal models to predict human bioavailability is compoundand formulation-dependent. And early availability of human pharmacokinetic data provides a more confident basis for dosage form development. Yes In vitro 3T3 Assay Positive Is the MEC >1000 L/mol/cm? Yes Yes Does the drug distribute to the eyes/skin? Recommend light protective measures in the clinic preclinical phototoxicity assays is poor (there is a high false positive for in vitro 3T3 and predictivity of in vivo rat assay is unknown). Further, understanding the pharmacokinetics and distribution of drug in preclinical species is critical; there are no known models of ocular phototoxicity for ITV drugs. Dongmei Qiang of Boehringer Ingelheim Pharmaceuticals shared case studies on An Action Plan for the Lack of Real Human Data. Following are notable issues related to PK and PD data from human clinical trials: bioavailability and exposure (API solid form and formulation approach), dose proportionality (impact of dose change on in vivo exposure), food effect (API solid form and formulation approach), half-life and clearance (dose regime), absorption window in GI tract (feasibility of extended release formulations), and pharmacodynamics response and efficacy data (clinical proof of concept, dose and exposure requirement). Physiological, physiochemical, and formulation and process aspects all impact bioavailability. Human PK studies may not be feasible at early development stages, and predictive in vitro tools are needed to select formulations for human David Sperry of Eli Lilly and Co. delved into Formula Bridging and Bioavailability Risk Assessment through Development, sharing the drug development and formulation path. Any time a drug product changes, it is important to consider chemical and physical stability, manufacturing capability, product design attributes, analytical methods, packaging and in vivo performance. The goal is to achieve the desired therapeutic outcome for the changed drug product. Pharmacokinetic studies (RBA and BE) can be used to determine if formulations are equivalent. In vivo studies are the gold standard for product performance assessment, but that doesn t mean the result is always right. New standard methodology has been introduced to determine if an RBA study is necessary. Risk-based methods utilize well-established scientific principles, and risk is quantified for CMC and PK considerations. Output is then used to determine if an RBA study is Drug Development and Bioavailability Development path Pre- clinical Phase I Phase II Phase III Commercial FormulaIon First human dose formulaion Clinical formulaion has the potenial to change many Imes before the product is launched Commercial formulaion 26 Jan Eli Lilly and Company 3 9

10 necessary. The impact is a consistent method that diverse disciplines can all agree on, making the RBA decision process much more efficient. The Latest Challenges in Simulating Supersaturation, presented by Stephanie Dodd of Novartis, discussed in vivo solubility and examples of GastroPlus predictions with in vivo solubility. While formulators generate a tremendous amount of solubility data, rarely is this data useful in explaining the in vivo profiles observed for BCS Class II/IV molecules. In terms of magnitude and duration of supersaturation, behavior is key to predicting what dose of a drug will fully absorb. For most species, 1,000 seconds is a good approximation encompassing the main site of absorption for most molecules, the duodenum. However, all poorly soluble molecules are not created equal, and there is no correlation between equilibrium solubility and supersaturation solubility (in vivo solubility). She shared an experiment that determined the in vitro method for determining in vivo solubility values can provide an accurate solubility value for understanding drug absorption and solubility limitations, when used in conjunction with GastroPlus simulation software in both fasted and fed states. The in vivo solubility can be utilized across species and may potentially give an accurate forecast of dose plateau in a species from an enabled formulation. In vivo solubility can forecast how an enabled formulation will perform in vivo. development and commercialization of new drugs. Likewise, most new chemical entities (NCE) are not progressed to pre-clinical evaluation because of the formulation challenges presently by poorly watersoluble drugs. An opportunity lies in the fact that more than 90 percent of drugs approved since 1995 have poor solubility, poor permeability or both. Nanoparticles can be produced by spray freezing into liquid, emulsification, rapid expansion from a liquefied gas solution, high pressure homogenization and bead milling, among others. When insoluble APIs are reduced to the nanoscale, it leads to increased bioavailability, reduced fed/fast variability in bioavailability, better performance of the API and lower dosages. Further, benefits of nanoparticles for oral absorption include increased bioavailability, increased rate of absorption, improved dose proportionality and avoidance of uncontrolled precipitation after dosing. A host of commercialized products take advantage of the numerous benefits of nanotechnology and nanosuspension. Benefits of Nanoparticles (Oral Delivery) Window of Absorption Large API Particles dissolution time >> GI transit time API Nanoparticles dissolution time < GI transit time ExL s 4th Drug Formulation & Bioavailability Conference, Nanonization of API to Enhance Solubility, delivered by David Watkins of Netzsch, explored opportunities, challenges and applications of poorly soluble drugs to new chemical entities and provided an overview of the clinical benefits and commercialized drugs utilizing nanotechnology. Challenges for pharma are that 40 percent of newly discovered drugs have little or no water solubility, which presents a serious challenge to the successful 10

11 RESOURCES FOR INFORMATION AND DISCUSSION 5th DRUG FORMULATION, SOLUBILITY & BIOAVAILABILITY SUMMIT The Modeling and Enabled Formulation Expertise You Need to Maximize Drug Developability, Avoid Particle Formation, and Maintain Stability and Bioavailability January 25-27, 2016 The Rittenhouse Hotel, Philadelphia, PA The 5th Drug Formulation, Solubility & Bioavailability Summit will take place January 25-27th, 2016 at The Rittenhouse Hotel in Philadelphia, PA. Our 2016 event features an entirely revamped program that focuses on strategies for the constant day-to-day solubility challenges faced by the industry. Special features include: n More than 30 speakers and 8 hours of networking in a 3-day program, featuring experts from Abbvie, Amgen, Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Ferring, Genentech, GlaxoSmithKline, Johnson & Johnson, Lundbeck, Merck, Novartis and many other organizations n By popular demand, a full-day Solubility Seminar intensively devoted to the challenges of working with amorphous solid dispersions n Optimal techniques for managing dose loading while avoiding particle formation n In-depth insights on the latest advances in subcutaneous, inhalation, oral and ocular delivery methods n A road map for improving drug characterization techniques without getting swamped by an overabundance of data and much more! For more information about our 2016 event and to register, please visit: Interested in sponsorship or exhibition opportunities? Please contact Dave Borrok at or dborrok@exlevents.com 11

12 RECOMMENDED SERVICE PROVIDERS Assembly Biosciences is an infectious disease-focused biopharmaceutical company developing novel treatments for hepatitis B virus (HBV) infection and C. difficile-associated diarrhea (CDAD). Both programs have breakthrough potential to provide better cure rates for these highly debilitating infectious diseases. Assembly and its employees are committed to advancing science and enhancing the health and well-being of patients. This commitment, along with a vibrant team culture, drives our efforts to develop and commercialize novel approaches to treating HBV and CDAD. Our Mission Discover, develop and commercialize drugs with the potential to treat and cure HBV and CDAD Our Strategy Assembly is building a fully integrated infectious-disease focused company around its two proprietary technology platforms The novel mechanism of core protein allosteric modulators targeting a key viral protein for the treatment of HBV and potentially other viral infections A delivery technology enabling oral administration of beneficial bacteria to treat diseases associated with pathologic intestinal microbes (such as C. difficile infections and potentially others) Assembly is headquartered in New York and operates research and development facilities in San Francisco and New York. Assembly s team consists of approximately 20 full-time management and technical employees with deep expertise in drug development and commercialization. This team is augmented by an accomplished Board of Directors and world-class scientific and clinical advisors. Website: From drug and biologic development services to delivery technologies to supply solutions, we are the catalyst for your success. With over 75 years of experience, we have the deepest expertise, the broadest offerings, and the most innovative technologies to help you get more molecules to market faster, enhance product performance and provide superior, reliable manufacturing and packaging results. Catalent. More products. Better treatments. Reliably supplied. Website: 12

13 RECOMMENDED SERVICE PROVIDERS Cytec Specialty Additives is a premier supplier of specialty surfactants used in a wide range of industries from emulsion polymerization to pharmaceuticals. Cytec s vision is to deliver specialty material and chemical technologies beyond our customers imagination. This focus enables us to make products that change the way our customers do business. Our products serve a diverse range of markets from aerospace and industrial materials to mining and plastics. Website: Sirius Analytical offers both instrumentation and CRO services for measurement of pka, logp/ logd, Solubility and Dissolution in aqueous, solvent, biorelevant media and in the presence of formulation additives. Our unique solutions for automated supersaturation measurement reveal new insights about the ph-dependent supersaturation a compound can exhibit and how supersaturation may be enhanced or suppressed via the use of formulation additives and excipients. Our real-time ph control expertise can be used to experiment with co-crystal formation and analysis. With facilities in the US and UK Sirius offers global coverage with detailed and reliable analysis, expert staff and rapid turnaround. Website: 13