FMC_AcDiSol_brochure_print:Layout 1 - FMC BioPolymer

FMC is the world leader in quality excipients for pharmaceuticals and supplements.As the world’s foremost manufacturer of high-quality pharmaceutical and supplement excipients, FMC has vastexperience in the areas of formulation and processing. When customers use Ac-Di-Sol, ® they get the benefit of thisunparalleled experience, in the form of exceptional technical support.FMC’s technical service professionals perform a number of vital tasks for customers, including conducting functionality,stability, and other tests, helping customers find solutions to their processing problems, conducting training for customerpersonnel, and providing access to comprehensive reference libraries.For further information on FMC’s outstanding products and services, contact us at 1-800-526-3649 or go to ourwebsite at www.fmc.comSales OfficesUnited StatesPhiladelphia, PAEuropeBrussels, BelgiumAsia-PacificHong KongLatin AmericaMontevideo, UruguaySales/TechnicalAssistance:Tel: 1-215-299-6534Fax: 1-215-299-6669Customer Service:Tel: 1-800-526-3649Fax: 1-215-299-6475Sales/TechnicalAssistance:Tel: +32-2-775-8311Fax: +32-2-775-8300Customer Service:Tel: +353-21-4354-133Fax: +353-21-4353-057Tel: +852-2839-6600Fax: +852-2576-3770Tokyo, JapanTel: +81-3-3402-3739Fax: +81-3-3402-3700Tel/Fax: +5982-6043030Tel/Fax: +5882-6043104Middle EastAmman, JordanTel: +962-5-4618150Fax: +962-5-4618156Why settle for superwhen you can have superior?PatentsFMC Corporation is owner and/or licensee of several patents related to its products. The products, processes, and uses of such products referred to in this document may becovered by one or more patents or pending applications in the United States and/or other countries. FMC does not warrant against any infringement claim arising from thesales and/or use of any FMC product in combination with other materials; the use of any FMC product in the operation of any process; any FMC product manufactured to acustomer’s designs or specifications; or any FMC product manufactured by any process requested by a purchaser.Product SuitabilityThe information contained in this document (as well as any advice or assistance) is provided by FMC only as a courtesy and is intended to be general in nature. Any usessuggested by FMC are presented only to assist our customers in exploring possible applications. FMC makes no warranty, express or implied, as to its accuracy or completeness,or the results to be obtained from such information, advice, or assistance. Each customer is solely responsible for determining whether the FMC products are suitable for eachcustomer’s intended use, and for obtaining any necessary governmental registrations and approvals for such customer’s production, marketing, sale, use and/or transportationof finished goods using or incorporating the FMC products.www.fmcbiopolymer.com/pharmaceuticalpharm_info@fmc.comFMC logo and Ac-Di-Sol ® are trademarks of FMC.© 2009 FMC Corporation. All rights reserved. ADS(1109)

High-quality Ac-Di-Sol ® offers all theadvantages of a superior disintegrant.Ac-Di-Sol ® croscarmellose sodium is an internally cross-linkedsodium carboxymethyl cellulose (NaCMC) that aids in thedisintegration and dissolution of pharmaceutical and dietarysupplement tablets, capsules, and granules.Originally created to solve formulators’ problems and improvebioavailability of a drug via faster disintegration and dissolution,Ac-Di-Sol ® is now widely recognized as the standard by whichtoday’s superdisintegrants are judged.Ac-Di-Sol ® exhibits consistent disintegrative functionalitydue to its excellent water uptake and rapid swelling properties.The result is a high-quality superdisintegrant whose fasterdisintegration and dissolution at low use levels andunmatched stability and functionality make it today’ssuperior superdisintegrant.Unmatched PurityLower Use LevelsEnhanced Long-Term StabilityBroader FunctionalityFMC’s quality standards help ensure theproduct purity of Ac-Di-Sol. ®FMC’s benchmark quality initiatives comply with recognizedglobal quality standards, helping to ensure the unsurpassedproduct purity of Ac-Di-Sol ® and its uniform, batch-to-batchconsistency.Ac-Di-Sol ® croscarmellose sodium meets NF standards aspublished by the USP, and the standards of the EuropeanPharmacopoeia (Ph. Eur) and the Japanese Pharmacopeia(JP).Ac-Di-Sol ® is manufactured under cGMP conditions at twoISO registered manufacturing sites in the United States andIreland. These plants produce consistent Ac-Di-Sol ® that meetsgiven physical and chemical specifications.Functional properties are systematically evaluated to assurethat the product from each manufacturing site is equivalentchemically, physically, and functionally.Higher quality and unmatched purity make Ac-Di-Sol ® superior.Ac-Di-Sol ® has a dual mechanism for rapiddisintegration and dissolution.Ac-Di-Sol ® Chemical StructureCH2OCH 2COONa CHThe product purity of Ac-Di-Sol ® assuresoptimal performance.Water wicking and swelling are the two most importantmechanisms of disintegrant action for Ac-Di-Sol. ®Water wicking is the ability to draw water into the tablet matrix.Both the extent of water uptake and the rate of water uptakeare critically important. Exposure to water can cause ingredientsto swell and exert pressure against surrounding tablet orcapsule ingredients, causing existing bonds between particlesto break.The fibrous nature of Ac-Di-Sol ® provides many sites for fluiduptake and gives it excellent water wicking capabilities. Thecross-linked chemical structure of Ac-Di-Sol ® creates aninsoluble, hydrophilic, and highly absorbent excipient thatresults in exceptional swelling properties.OCHOOHOCHAc-Di-Sol ® MorphologyOCH2OCH 2COONaThere is growing concern about impurities in excipients, suchas ethanol, methanol, and phosphorus, because they cancause an interaction with the active pharmaceutical ingredient(API) of a drug and compromise its efficacy and safety.To prevent such an interaction, FMC adheres to the highestAc-Di-Sol ® 0XL-CMC A 0 ~ 0.01Ethanol%global quality benchmarks to produce Ac-Di-Sol, ® a superdisintegrantwhose unmatched purity enables it to deliveroptimal performance.A recent study compared Ac-Di-Sol ® with four other brandsof commercial superdisintegrants and clearly revealed theXL-CMC BXL-CMC CXL-CMC D2.5 ~ 3.20.12 ~ 1.30 ~ 0.01Purity:Ac-Di-Sol ® vs. Other SuperdisintegrantsMethanolmg/kg0 ~ 14 ~ 1020 ~ 1339 ~ 791Phosphorousmg/kg

Ac-Di-Sol ® shows faster disintegration atlower use levels.Various studies have shown that Ac-Di-Sol ® can be used atvery low levels to achieve desired disintegration results.Sakr, et al* studied the effectiveness of Ac-Di-Sol ® in a directcompression hydrochlorothiazide (HCT) tablet.Ac-Di-Sol ® was evaluated at concentrations of 1 to 5%. At anoptimum concentration of 2%, Ac-Di-Sol ® was found to exhibitappreciably low disintegration time with the percent releaseof HCT in compliance with USP requirements. The hardnessand friability of the tablet was not adversely affected by theincreased concentration of the disintegrant.Percent Release10080604020Effect of Ac-Di-Sol ®on the Dissolution of HCT00 15 30 45 60Time (minutes)Ac-Di-Sol ®Concentrations*Sakr, et al, Comparative Effectiveness of SuperDisintegrants on the Characteristics of DirectlyCompressed Triamterene HydrochlorothiazideTablets. Pharm, Ind. 1993, 55 (nr.10) p. 953-957.= 0%= 1%= 2%= 3%= 4%= 5%Ac-Di-Sol ® assures long-term stabilityin disintegration.Ac-Di-Sol ® does more than show superior performance ininitial disintegration and dissolution. Ac-Di-Sol ® also impartsexceptional long-term dissolution stability in comparison toother superdisintegrants.A comprehensive study by Dr. Yeli Zhang of FMC testedthe long-term stability of Ac-Di-Sol, ® SSG (Sodium StarchGlycolate) and PVP-XL (Crospovidone).Results reveal that Ac-Di-Sol ® provides much faster initial andover-storage tablet disintegration in comparison to the othercommercial superdisintegrants, in all ranges of studied tabletcompaction forces.CompactionForce(kN)Stability of Commercial Superdisintegrants(DCP model & at 0.5% disintegrant level)2015105PVP-XL *SSGAc-Di-Sol ®150 1501 50 150 1 50 150Time (day)181614121086420500 mg tablet, 7/16” standard concave tooling*Small particle sizeDisintegration Time (minutes)Lower use levels and greater long-term stability make Ac-Di-Sol ® superior.Ac-Di-Sol ® offers greater dissolution atlower use levels.Tablet disintegration is essential for the fast release of activeingredients, but dissolution is the most important criterion.The dissolution efficacy of Ac-Di-Sol ® compared to othersuperdisintegrants was tested in the study by Augsbergeret al*, “A Contribution to Understanding DissolutionFunctionality Based on a Comparison of Disintegrationand Dissolution of Model Aspirin Tablets.”The results show that Ac-Di-Sol ® allows a greater level ofdissolution of tablets prepared by direct compression thanother superdisintegrants evaluated at a 2% use level.Aspirin% Dissolved12010080604020Dissolution in Aspirin Tablet Model(2% Superdisintegrants)Ac-Di-Sol ®Sodium Starch GlycolateCrospovidone XL-10Control00 10 20 30 40 50Mean +_ SD; n=6Time, min*L. Augsberger et al, 2004 AAPS Meeting,Baltimore MDAc-Di-Sol ® assures long-term stabilityin dissolution.In one key study, a hydrochlorothiazide (HCT) model drugsystem was evaluated in order to assess how the superdisintegrantsAc-Di-Sol, ® SSG (Sodium Starch Glycolate), andPVP-XL (Crospovidone) perform over time.HCT was selected since it is relatively water insoluble. HCT’sinsolubility in water creates interference effects relative tofluid uptake and penetration, resulting in slower tabletdisintegration and dissolution.The results indicate that wet granulated HCT tablets withAc-Di-Sol ® exhibit virtually no change in drug availability afterbeing stored for 28 months at a controlled room temperature.Both SSG and PVP-XL showed significant drops in both initialdissolution rates and in HCT dissolution after storage.Percent Dissolved100908070605040302010Long-Term Stability ofCommercial Superdisintegrants2% Ac-Di-Sol ® 28 mo2% Ac-Di-Sol ® Initial2% Sodium Starch Glycolate 28 mo2% Sodium Starch Glycolate Initial2% PVP-XL 28 mo2% PVP-XL Initial00 10 20 30 40 50 60 70Time (minutes)3 4

Ac-Di-Sol ® works effectively in directcompression formulations.Ac-Di-Sol ® can be used at very low levels to achieve desireddisintegration results in tablets made by direct compression,which are a blend of active ingredients and excipientscompressed without any granulation step.The amount of Ac-Di-Sol ® used depends on the tabletformulation. Solubility of the major tablet component, eitherthe drug or filler, significantly affects the rate and mechanismof tablet disintegration. Tablets composed primarily ofwater-soluble ingredients tend to dissolve rather thandisintegrate, resulting in much longer disintegration times.As the active ingredient or filler dissolves on the outer layerof the tablet matrix, the rate of fluid diffusion into successivelayers is retarded, particularly if highly concentrated or viscoussolutions are formed. Tablets containing insoluble drugs andfiller often disintegrate rapidly if sufficient disintegrant is present.Ac-Di-Sol ® delivers excellent performancein roller compaction tablet formulations.Used for many years by the pharmaceutical industry, rollercompaction, or granulation by compression, is a processemployed when the active ingredients in drugs are sensitiveto moisture or heat or both. It is also used when formulationsare found to resist compression when prepared by wetgranulation methods.Studies at Purdue University have shown that Ac-Di-Sol ®functions effectively as a disintegrant for tablets fromgranulations prepared by roller compaction. Avicel ® PH-101microcrystalline cellulose was roller compacted with 3%Ac-Di-Sol ® added extragranularly, intragranularly, or distributedequally (50/50) and compressed into tablets.The results show that for these study conditions, Ac-Di-Sol ®is most effective when added intragranularly, or whendistributed equally between the two phases.Roller Compaction Studies:Ac-Di-Sol ® /Avicel ® PH-101 Mixturesin Tablet Form0% Ac-Di-Sol ®3.0% Ac-Di-Sol ®(outside)1.5% Ac-Di-Sol ®(inside and outside)3.0% Ac-Di-Sol ®(inside)Hardness12.8 kp11.7 kp11.6 kp10.6 kpFriability