Advantia™ Performance Coating Systems - Anshul Life Sciences

Product GuidePharmaceuticalsPerformanceEnhancingTechnologyAdvantia PerformanceCoating Systemsfor Delayed (Enteric) Drug ReleaseAdvancing the Science of Coatings

Table of ContentsIntroduction................................................................................................. 3ISP: A Partner for Film Coating.........................................................................................3Development of Advantia Performance Coating Systems .by Statistical Design of Experiments............................................................. 4Advantia Performance 190024HA49..............................................................................5Color Coating Systems.....................................................................................................5Application of Advantia Performance Coating Systems................................. 6Aspirin Tablets with Advantia Performance Coating System...........................................6Details of Coating Process Used......................................................................................7Overview of Results Obtained...........................................................................................9General Coating Guidelines for .Advantia Performance Coating Systems..................................................... 12Suspension Preparation Guidelines................................................................................12General Coating Condition Guidelines............................................................................12Sub-Coating Guidelines..................................................................................................13Technical Service and Support.................................................................... 14Technical Capabilities..................................................................................................14Regulatory and Safety................................................................................. 14Storage and Handling................................................................................. 15Getting Started.......................................................................................... 152 • Advantia Performance Coating Systems

IntroductionAdvantia Performance Coating Systems are pre-blended, ready-to-usepowders based on methacrylic acid ethyl acrylate copolymer for film coatingof pharmaceutical oral solid dosage forms (tablets, multiparticulates, two-piecegelatin capsules, and softgels) to produce a delayed-release (or enteric-release)effect. Available pigmented or unpigmented, Advantia Performance CoatingSystems are easy-to-use powders that can be readily dispersed in water and applied.With an Advantia Performance Coating Systems, suspension preparation issimple. The more traditional procedure for preparing enteric-coating suspensionsoften requires three steps. In the traditional process, the first step is to homogenizethe plasticizer, detackifier and, optionally, an antifoam agent in water to forma suspension. After a suitable mixing time, this suspension is then added, withmixing, to an acrylic polymer dispersion. This combined suspension is passedthrough a sieve. For colored enteric-coating formulation, a colorant must beadded using an additional processing step.With an Advantia Performance Coating Systems, powder is added to water(stirred in a suitable mixing tank to create a vortex) and mixed. With this process,there are fewer processing steps involved, and fewer ingredients to inventory andsubmit to quality control testing compared with a traditional system, thus savingtime and money.ISP: A Partner for Film CoatingExperience. As a supplier of high-quality excipients for solid dosage forms,including Plasdone® binders and Polyplasdone® super disintegrants, to thepharmaceutical, vitamin and nutritional industries for over 50 years, ISP hasdeveloped sound expertise in formulation of oral solid dosage forms. Thisexpertise complements our capabilities with respect to designing film-coatingsystems. ISP has over 50 sales specialists and 40 scientists dedicated to itspharmaceutical business, working in local offices and laboratories around theworld to respond to customer needs and ensure consistent product fromlaboratory to commercial production.Innovative. In addition to offering film coating systems based on conventionaltechnology, ISP is developing innovative coating systems based on its experienceas a leading polymer research company. The ISP technical team has core strengthsin design and development of novel functional systems based on molecularstructure-property relationships, to provide rapid solutions to customer needs.At ISP, our scientists are working to develop an enhanced range of film coatingsdesigned to meet the evolving needs of the pharmaceutical industry. We arecommitted to advancing the science of tablet film coatings.Worldwide. With over 70 locations worldwide, serving customers in more than90 countries, ISP can provide the global sales and service support our customersrequire from a film coating supplier. Our eight pharmaceutical laboratories arestaffed with scientists that have experience in the formulation of oral solid dosageforms, design of coating formulations, color matching, and coating applications.ISP Pharmaceuticals ISP Technologies Product Guide • 3

Development of Advantia Performance .Coating Systems by Statistical Design .of ExperimentsIn the development of Advantia Performance Coating Systems, ISP used astatistical design of experiments (D.o.E.) approach to understand the impactof component levels on the performance of an enteric coating system to provideconsistent, reproducible enteric release profiles. Using the data generated andthe predictive capabilities of the D.o.E. software, ISP can identify the optimumformulation, and its performance attributes, best suited for each customer’sapplication. For example, the data facilitate the selection of enteric film coatingformulations with a broad range of potential attributes, such as:• Fastest drug release in buffer, pH 6.8• Most effective gastric resistance at lowest weight gain• Most suitable for enteric coating of intagliated tabletsThe last of these points often presents a challenge for enteric film coating since thecoating deposited within the intagliation is likely to be much thinner, and possessa less suitable coating structure, so that maintaining effective gastric resistance iscompromised. ISP scientists have studied enteric-coated intagliated tablets, usingTerahertz analysis technology. In Figure 1, Terahertz analysis of two intagliatedtablets is shown, indicating that the enteric film is significantly thinner within theintagliation and at the edges.Figure 1. Coating thickness assessed using Terahertz technology indicates potential forcompromising integrity of enteric film coating on an intagliated tablet.5Peak Intensity-5 500-50-2-4-5Peak Intensity30252015005105-54 • Advantia Performance Coating Systems

Advantia Performance 190024HA49Advantia Performance 190024HA49, a white coating formulation, has beenselected as our standard concept sample and is intended to be a startingpoint formulation. In cases where additional performance attributes arerequired, ISP scientists utilize the D.o.E. software in combination withresponses generated from the design of experiment, to produce a coatingformulation more suitable for a given application.Color Coating SystemsWhen a colored tablet is required, a colored Advantia Performance coatingcan be formulated to meet your individual color needs, limited only by specificcolor regulations. ISP maintains strict color control to ensure lot-to-lotconsistency. Typical colored examples are shown in Figure 2.Alternatively, tablets can be enteric-coated with a white AdvantiaPerformance Coating System and subsequently overcoated with acolored Advantia Prime Coating System (cellulosic film-coating system).For a colored product, please contact your local ISP sales office or accountrepresentative.Figure 2. Advantia Performance Coating Systems can be pigmented to reduce thenumber of processing steps.ISP Pharmaceuticals Product Guide • 5

Application of Advantia .Performance Coating SystemsAdvantia Performance Coating Systems have been used for a broad range ofapplications requiring a delayed-release coating, including the coating of tablets,capsules (softgels) and multiparticulates. Examples of active pharmaceuticalingredients (APIs) that ISP scientists have worked on with Advantia PerformanceCoating Systems are shown in Table 1.Table 1. APIs that have been the subject of coating projects with Advantia PerformanceClassNSAIDS/AnalgesicsProton Pump InhibitorsLaxativesAnti-epilepticsEnzymesProduct Examples• Diclofenac sodium• Ketoprofen• Indomethacin• Para-amino-salicylic acid• Aspirin• Omeprazole• Pantoprazole• Lansoprazole• Rabeprazole• Bisacodyl• Bisacodyl + docusate sodium• Sodium valproate• PancreatinWhile each coating application may have specific requirements (in terms of typeof process and specific process conditions used), a project involving the entericcoating of 325-mg aspirin tablets serves as an example of the applicationof Advantia Performance Coating Systems.Aspirin Tablets with Advantia Performance Coating SystemThe primary objective was to produce enteric-coated aspirin (325-mg) tablets thatmet all of the requirements of the U.S. Pharmacopeia (USP) in terms of entericperformance, while meeting the critical objectives imposed by accelerated stabilitytesting, especially with respect to levels of free salicylic acid formed after suchtesting for three months at 40°C, 75% RH.6 • Advantia Performance Coating Systems

Details of Coating Process UsedAll coating trials were performed in an O’Hara LabCoat IIX fitted with a19” coating pan using a Schlick ABC spray gun. Initially, 325-mg aspirin tabletswere sub-coated with an Advantia Prime 199989HA09 clear coat to a 2% w/wtarget weight gain, then enteric-coated using Advantia Performance (9% w/wtarget weight gain). Process details for the application of the sub-coat and theenteric coat are shown in Table 2 and Table 3. In the case of application of theenteric coat, details are provided for two sets of process conditions (one at alower spray rate and inlet temperature, the other at a higher spray rate andinlet temperature).Table 2. Process conditions used for application of Advantia Prime sub-coating to325-mg aspirin tabletsProcess ParameterProcess SettingQuantity of tablets used (kg) 7.5Sub-coating solutionAdvantia Prime 199989HA09(sprayed at 10% w/w solids)Process air flow 200 cfm/340 m 3 h -1Atomizing air pressure (bar) 1.7Pattern air pressure (bar) 2.4Pan speed (rpm) 14.5Spray rate (g min -1 ) 30Inlet temperature (°C) 70*Exhaust temperature (°C) 51*Tablet bed temperature (°C) 50** These temperature conditions are higher than typically recommended forapplication of Advantia Prime coatings, but ISP’s experience has been that thestability of enteric-coated aspirin tablets can be improved when drier processconditions are used during the early phases of the coating process.ISP Pharmaceuticals Product Guide • 7

Table 3. Process conditions used for application of Advantia Performance enteric coating to325-mg aspirin tabletsProcess ParameterQuantity of tablets used (kg)Enteric-coating suspensionProcess Setting7.5 (previously sub-coated)Advantia Performance (sprayed at 20% w/w solids)Process air flow 200 cfm/340 m 3 h -1Atomizing air pressure (bar) 1.7Pattern air pressure (bar) 2.8Pan speed (rpm) 15.0Trial ATrial BSpray rate (g min -1 ) 25 30Inlet temperature ( ° C) 50 60Exhaust temperature ( ° C) 40 45Tablet bed temperature ( ° C) 41 45At the conclusion of the coating trials, enteric-coated aspirin tablets wereevaluated for:• Gastric resistance, where 100 tablets were exposed for two hours in 0.1NHCl solution, after which the number of failures was determined (failuresin this case consisted of tablets that either disintegrated or had softenedand become swollen).• Gastric juice uptake, where, again using 100 tablets exposed to 0.1N HClsolution for two hours, the weight of tablets was determined (after carefullydrying the surface of each tablet before weighing).• Drug release in gastric juice, after two hours, using the USP apparatus 2and 0.1N HCl solution as the dissolution medium.• Dissolution in phosphate buffer, pH 6.8, again using USP apparatus 2.In addition, samples of enteric-coated tablets were packaged into HDPE bottles,with desiccant packs and subsequently foil sealed, and then set up for stabilitytesting under accelerated conditions for three months at 40°C and 75 %RH. At theconclusion of the testing period, tablet samples were subjected to analysis for:• Drug release in gastric juice, after two hours, using the USP apparatus 2and 0.1N HCl solution as the dissolution medium.• Dissolution in phosphate buffer, pH 6.8, again using USP apparatus 2.• Free salicylic acid content.8 • Advantia Performance Coating Systems

Overview of Results ObtainedThe results obtained for 325-mg aspirin tablets, enteric-coated as described earlier,are shown in Table 4.Table 4. Enteric test and stability results obtained for 325-mg aspirin tablets coated withAdvantia Performance Coating SystemTest ConditionResults ObtainedInitialTrial ATrial BAcid uptake (%, mean for 100 tabletsafter 2 hours exposure)Gastric failures (% for 100 tablets after2 hours exposure at 100 rpm)Dissolution in 0.1N HCl solution (% after2 hours exposure)Dissolution in phosphate buffer, pH=6,8(% after 90 minutes at 100 rpm)5.5 3.85.0* 3.0*0.61** 1.86**100*** 100***After 3 Months at 40 ° C, 75 %RHDissolution in 0.1N HCl solution (% after2 hours exposure at 100 rpm)Dissolution in phosphate buffer, pH=6,8(% after 90 minutes at 100 rpm)1.43** 2.64**100*** 100***Free salicylic acid (%) 0.09**** 0.06***** No tablets disintegrated, and the only failures observed were tablets with a slightsoftening of the coating** USP limit – nmt 10%*** USP Q value > 80%**** USP limit – nmt 3.0%ISP Pharmaceuticals Product Guide • 9

A representative sample of the enteric-coated aspirin tablets is shown in Figure 3.Figure 3. Enteric-coated aspirin tablets (325-mg) with Advantia Performance Coating SystemAs can be seen, all samples of aspirin tablets that had been enteric-coated withan Advantia Performance Coating System easily met the pre-requisites of the USPmonograph for delayed-release aspirin tablets.10 • Advantia Performance Coating Systems

In terms of gastric resistance, further improvements could be obtained, if required,by adjusting the levels of enteric coating applied. Typical enteric dissolution resultsto be obtained by doing so are shown in Figure 4.Figure 4 . Influence of amount of Advantia Performance Coating System applied on drug releasefrom enteric-coated tablets120100% Drug Released8060402000 30 60 90 120 125 130 135 140 145 150Time (min)6% Weight Gain12% Weight Gain8% Weight Gain14% Weight Gain10% Weight Gain16% Weight GainNote: First two hours of test were conducted in 0.1N HCl, after which the medium was changedto buffer, pH=6.8.ISP Pharmaceuticals Product Guide • 11

General Coating Guidelines for .Advantia Performance Coating SystemsSuspension Preparation GuidelinesIt is recommended to use Advantia Performance Coating Systems at 20% solidsin water. The maximum solids level will depend on the particular spray gun, pumpand coating equipment used.The suspension is prepared in a one-step process that involves:• Adding the required quantity of water into a suitable mixing vessel andcentering the propeller stirrer in the mixing vessel as close to the bottomas possible.• Setting the mixer to the fastest possible speed that maintains a vortex withoutdrawing air into the water.• Adding the Advantia Performance powder to the vortex as quickly as possible,avoiding flotation of the powder and increasing the mixer speed as necessaryto maintain the vortex.• Maintaining mixer speed to ensure a reasonably vigorous mixing of thesuspension throughout the 60-minute reconstitution period.• At the end of the reconstitution period, the suspension should ideally be passedthrough a 60-mesh screen to remove any undispersed material.Advantia Performance Coating System suspensions should be gently mixed duringthe coating process in order to prevent sedimentation of suspended ingredientsand thus a change in the respective ratios of critical ingredients in the coatingformulation.General Coating Condition GuidelinesThe suggested coating conditions for application of Advantia Performance CoatingSystem from an aqueous coating suspension with solids content of ~20% on tabletsare provided in Table 5. As the methacrylic polymers have a lower glass transitiontemperature (Tg) than hydroxypropylmethyl cellulose (HPMC), lower inlet, exhaustand bed temperatures are recommended compared with those conditions used fora typical cellulosic film-coating process.12 • Advantia Performance Coating Systems

Table 5. General coating conditions for application of aqueous coating suspension of Advantia Performance Coating System using a 19” fully perforated pan fitted with a Schlick ABC spraygun and loaded with 7-8kg of tablets.ParameterSettingsInlet temperature ( o C) 50-60Tablet bed temperature ( o C) 36-42Exhaust temperature ( o C) 38-44Spray rate (g min -1 ) 22-32Air Flow 175-225 cfm/297-382 m 3 h –1Atomizing air pressure (bar) 2.2-2.5Pattern air pressure (bar) 2.4-2.8Pan speed (rpm) 12-18Sub-Coating GuidelinesWhile application of a sub-coat to the surface of the dosage form being coated isnot a pre-requisite for using Advantia Performance coatings, this practice is oftenbeneficial since it:• Minimizes surface abrasion of the core prior to application of the entericcoating, thus ensuring a more reproducible result in terms of drug release.• Minimizes the potential for interaction between the core and the entericcoating, especially when such interaction may compromise the functionalityof the enteric coating (as is potentially the case when the core contains alkalinematerials) or may affect the stability of the API should it be sensitive to theinherent acidity of the enteric-coating polymer.ISP typically recommends Advantia Prime 199989HA09 (Table 6). However, a widerange of cellulosic-based film-coating formulations can be used as a sub-coating,depending on the tablet core and local regulations. Please consult your local ISPsales office or account representative.Table 6. Prior to application of an Advantia Performance enteric-release coating,Advantia Prime 199989HA09 should be applied as a sub-coating.Product NameColorSuggestedSuspensionSolids (%)SuggestedWeight Gain(%)*Advantia Prime 199989HA09 Clear 10-12 1.5-3.0* Depending on the size, shape and surface characteristics of the core (tablets, capsulesor multiparticulates).ISP Pharmaceuticals Product Guide • 13

Technical Service and SupportISP is committed to providing service and support to customers globally duringthe development process through full-scale commercial production. At ISP, wehave eight technical centers dedicated to supporting our customers and theirefforts with respect to pharmaceutical oral solid dosage forms with our excipientsand film coating systems. Each laboratory is fully equipped and staffed withpharmaceutical scientists who have experience in pharmaceutical formulationand film-coating technology.Technical CapabilitiesAs a supplier of high-performance Plasdone® binders and Polyplasdone® superdisintegrants, ISP has core capabilities in tablet formulation, including orallydisintegrating tablets, and tablet process technology, involving wet granulation,direct compression and roller compaction. We routinely evaluate tabletperformance, including tablet strength, friability, compaction profiles, anddissolution characteristics. We employ a compaction simulator in our Wayne, NJR&D laboratory to study the fundamentals of compaction and assist customers informulation development, excipient selection and scale-up.To support our Advantia Coating Systems, ISP has a broad range of tools availablefor characterizing and assessing the properties of film coatings and film-coatedproducts, including those suitable for determining:• Film mechanical properties• Film adhesion• Opacity of applied coatings• Film surface qualities, including gloss and coating roughness• Coating uniformity, structure and density• Coating permeability• Rheological characteristics of coating liquids• Coated product stability• Color matching• Dissolution characteristicsRegulatory and SafetyAdvantia Performance 190024HA49 contains ingredients acceptable for use onpharmaceutical products sold in North America, the European Union and Japan.The polymer in Advantia Performance 190024HA49 is produced from dispersionsthat comply with the United States Pharmacopeia/National Formulary (USP/NF)designation for Methacrylic Acid Copolymer Dispersion and JPE monograph forMethacrylic Acid Copolymer LD. The polymer conforms to Ph.Eur 5.7 MethacrylicAcid – Ethyl Acrylate Copolymer 1:1 (Type B)14 • Advantia Performance Coating Systems

Advantia Prime 199989HA09 contains ingredients acceptable for use onpharmaceutical products sold in North America, the European Union and Japan.ISP maintains Type IV Drug Master Files (DMFs) with the United States Foodand Drug Administration (FDA) for Advantia Prime and Advantia Performanceproducts (Table 8).Table 8. To support regulatory filings of drug products with U.S. FDA, ISP supports DMFs forAdvantia Coating SystemsProduct FamilyType IV DMF NumberAdvantia Prime 20851Advantia Performance 21613Please consult your local ISP sales office for information concerning the suitabilityfor use on pharmaceutical products to be sold in other regions. ISP recognizesthe importance of providing leadership in health, safety and regulatory productoversight as a fundamental part of our business. As a leading global specialtychemical company operating in over 90 countries, ISP has experience in addressinglocal and global regulatory concerns.Storage and HandlingAll Advantia Coating Systems should be stored in a cool, dry place out of directsunlight. The containers should be tightly closed when not in use.The retest intervals for Advantia Performance Coating Systems are shown inTable 9.Table 9. Retest intervals for Advantia Performance Coating SystemsProduct Family Color Retest IntervalAdvantia Performance Clear and White 24 monthsAdvantia Performance Color 12 monthsThe retest interval for Advantia Prime 199989HA09 is 24 months.Getting StartedTo get started, contact your local ISP sales office to discuss your requirementsfor film coatings or visit us at www.ispcorp.com.ISP Pharmaceuticals Product Guide • 15

GLOBAL LOCATIONS FOR SALES & CUSTOMER SERVICEWORLD HEADQUARTERSINTERNATIONAL SPECIALTY PRODUCTS1361 Alps Road, Wayne, New Jersey 07470, USATel: +1 973 628-4000 Fax: +1 973 628-3311www.ispcorp.com info@ispcorp.comCUSTOMER SERVICEToll Free: 1 (800) 622-4423Fax: +1 973 628-4001info@ispcorp.comSAMPLE CENTERToll Free: 1 (800) 243-6788isp@chemicalmarketing.comUSA & CANADA REGIONAL SALES OFFICESPERSONAL CARELOMBARD, ILLINOISToll Free: 1 (800) 323-2272Tel: +1 630 932-4022Fax: +1 630 495-0245personalcareinfo@ispcorp.comPHARMACEUTICALSWAYNE, NEW JERSEYToll Free: 1 (877) 389-3083Fax: +1 973 628-4117pharmaceuticalinfo@ispcorp.comPERFORMANCE CHEMICALSWAYNE, NEW JERSEYToll Free: 1 (877) 389-3083Fax: +1 973 628-4117perfcheminfo@ispcorp.comFOOD INGREDIENTS – USATech Service: 1 (888) 472-5446Cust Service: 1 (800) 622-4423Fax: +1 973 628-4001foodinfo@ispcorp.comFOOD INGREDIENTS – CANADATech Service: 1 (888) 472-5446Cust Service: 1 (800) 465-5094Fax: +1 905 607-9086ispcanada@ispcorp.comLATIN AMERICA CUSTOMER SERVICEARGENTINATel: +54 11 4314-8971+54 11 4314-0659+54 11 4314-3293Fax: +54 11 4314-8976ispargentina@ispcorp.comBRAZILLATIN AMERICAREGIONAL OFFICETel: +55 11 3649-0420+55 11 3649-0455+55 11 3649-0468ispbrasil@ispcorp.comCHILETel: +56 2 229-9601+56 2 229-9547+56 2 229-9483Fax: +56 2 229-1098ispchile@ispcorp.comCOLOMBIATel: +57 (1) 636-0618Fax: +57 (1) 691-8540ispcolombia@ispcorp.comMEXICOTel: +52 55 5276-6110Fax: +52 55 2614-2939isp_mexico@ispcorp.comVENEZUELATel: +58 212 325-5544+58 414 241-3551ispvenezuela@ispcorp.comEUROPE, MIDDLE EAST, & AFRICA CUSTOMER SERVICEAFRICATel: +49 (0) 2236 9649-237Fax: +49 (0) 2236 9649-212info.africa@ispcorp.comAUSTRIATel: +43 (0) 1 360 27-71220Fax: +43 (0) 1 360 27-71221info.austria@ispcorp.comBELGIUMTel: +32 (0) 2 626-49 30+32 (0) 2 626-49 34Fax: +32 (0) 2 626-49 32info.belgium@ispcorp.comBULGARIATel: +359 (0) 2 971-1135Fax: +359 (0) 2 971-2861info.bulgaria@ispcorp.comCZECH REPUBLICTel: +420 272 123 332Fax: +420 272 123 305info.czech@ispcorp.comFRANCETel: +33 (0) 1 49 93 21-58+33 (0) 1 49 93 21-59Fax: +33 (0) 1 49 93 21-62info.france@ispcorp.comGERMANYEUROPE REGIONAL OFFICETel: +49 (0) 2236 9649-260+49 (0) 2236 9649-264+49 (0) 2236 9649-266Fax: +49 (0) 2236 9649-295info.germany@ispcorp.comHUNGARYTel: +36 1 209 2629Fax: +36 1 466 2550info.hungary@ispcorp.comITALYTel: +39 0275 419 642Fax: +39 0275 419 644info.italy@ispcorp.comNETHERLANDSTel: +31 (0) 20 65 45-361Fax: +31 (0) 20 65 45-368info.netherlands@ispcorp.comNORDEN(Denmark, Estonia, Iceland,Finland, Norway, Sweden)Tel: +46 (0) 8 519 920-10Fax: +46 (0) 8 519 920-12info.norden@ispcorp.comPOLANDTel: +48 (0) 22 607 25 20Fax: +48 (0) 22 607 25 22info.poland@ispcorp.comRUSSIATel: +7 495 981 39 53Fax: +7 495 981 39 54info.russia@ispcorp.comSPAIN & PORTUGALTel: +34 93 298 07 00Fax: +34 93 298 07 05info.spain@ispcorp.cominfo.portugal@ispcorp.comSWITZERLANDTel: +41 (0) 1 439 53-66Fax: +41 (0) 1 439 53-68info.switzerland@ispcorp.comTURKEY & MIDDLE EASTTel: +90 216 538 0800Fax: +90 216 538 0880info.turkey@ispcorp.cominfo.middleeast@ispcorp.comUKTel: +44 (0) 207 519-5054+44 (0) 207 519-5055Fax: +44 (0) 207 519-5056info.uk@ispcorp.comASIA PACIFIC CUSTOMER SERVICEAUSTRALIATel: +612 9648-5177Fax: +612 9647-1608info.australia@ispcorp.comHONG KONGTel: +852 2881-6108Fax: +852 2895-1250info.china@ispcorp.comOSAKA, JAPANTel: +816 6838-5752Fax: +816 6838-5566info.japan@ispcorp.comPHILIPPINESTel: +632 848-7188Fax: +632 848-7191info.philippines@ispcorp.comTHAILANDTel: +662 267-8103Fax: +662 236-0041info.thailand@ispcorp.comBEIJING, CHINATel: +8610 6515-6265Fax: +8610 6515-6267info.china@ispcorp.comGUANGZHOU, CHINATel: +8620 3758-9970Fax: +8620 3758-9907info.china@ispcorp.comSHANGHAI, CHINATel: +8621 6249-3900Fax: +8621 6249-3908info.china@ispcorp.comHYDERABAD, INDIATel: +9140 5584-4000Fax: +9140 2331-1090info.india@ispcorp.comMUMBAI, INDIATel: +9122 2837-0472Fax: +9122 2837-0449info.india@ispcorp.comINDONESIATel: +6221 530-7181+6221 530-7182Fax: +6221 530-7183info.indonesia@ispcorp.comTOKYO, JAPANTel: +813 5566-8661Fax: +813 5566-8682info.japan@ispcorp.comKOREATel: +82 2 554-6622Fax: +82 2 554-6944info.korea@ispcorp.comMALAYSIATel: +60 5513-1498Fax: +60 5512-8311info.malaysia@ispcorp.comSINGAPOREASIA PACIFIC REGIONAL OFFICETel: +656 223-3778Fax: +656 226-0853info.singapore@ispcorp.comTAIWANTel: +886 2 2508-0212Fax: +886 2 2504-3543info.taiwan@ispcorp.comVIETNAMTel: +84 8 910-7620Fax: +84 8 910-7621info.vietnam@ispcorp.com Trademark registration applied for ® Registered trademark of the ISP group © International Specialty Products. 2008 Designed & Printed in USA.Product Code: PHAR_C1020 07/2008The information contained in this brochure and the various products described are intended for use only by persons having technical skill and at their own discretion and risk after they have performednecessary technical investigations, tests and evaluations of the products and their uses. While the information herein is believed to be reliable, we do not guarantee its accuracy and a purchaser must make its owndetermination of a product’s suitability for purchaser’s use, for the protection of the environment, and for the health and safety of its employees and the purchasers of its products. Neither ISP nor its affiliates shallbe responsible for the use of this information, or of any product, method, formulation, or apparatus described in this brochure. Nothing herein waives any of ISP’s or its affiliates’ conditions of sale, and WE MAKE NOWARRANTY, EXPRESS OR IMPLIED, OF MERCHANTABILITY OR FITNESS OF ANY PRODUCT FOR A PARTICULAR USE OR PURPOSE. We also make no warranty against infringement of any patents by reason of purchaser’suse of any information, product, method or apparatus described in this brochure.