Binders are one of the critical excipients for a successful wet granulation formulation. Swinkels JJM. Disintegrants such as starch, sodium starch glycolate and microcrystalline cellulose may enable tablet disintegration by increasing the porosity and wettability of the compressed . When disintegrants come into contact with water, they usually swell, as their cross-linked molecular structure, such as in amylose in starch or cross-linked PVP, imbibes water and swells, providing the force to disperse the tablet. Starches are also used in the food manufacturing industry for processing, and as food thickeners or stabilizers. Some co-processed excipients are containing usually a diluent and binder, and sometimes, even a disintegrant in a readymade granulation. Pharmaceutical lubricants are materials used in tablet formulations to reduce the friction between the lower punch and the die and the tablet. The hexagonal form of boron nitride (HBN) has been reported as a potential tablet lubricant. Pharm Weekbl 1975;110:31725. To overcome these limitations and expand the application of starch as an excipient, researchers have modified starch by physical and chemical methods, as . Muzikova J, Snejdrova E, Martiska J, Doubkova B, Veris A. Polymers (Basel). New York: Marcel Dekker Inc., 1980. Binders can be added as dry powders to form a matrix that will include the drug, as in the case of dry granulation or direct compression. Contact : +1 585-669-3150 / +1 513-644-4659, Copyright 2022 OFCFCA.ORG - All Rights Reserved, Tips on Problem Solving and Making Decisions. Starch conversion technology. In tablet formulation, excipients are usually combined at various quantities with the active drug substance(s) to produce tablets that are of standard quality. AAPS PharmSciTech. 1987 Oct 16;9(5):274-82. doi: 10.1007/BF01953630. Therefore, good compressibility can be matched with good flow only by selecting the right grade or making a wet granulation to a certain size and shape. 2012 Jun;13(2):379-88. doi: 10.1208/s12249-012-9761-z. Moreover, it can be combined with at least one other excipient to achieve the desired properties. Google Scholar. In a fluidized-bed granulation process, MCC requires the highest amount of water for the same granule size when compared to starch and lactose monohydrate. Meets PhEur and USP/NF specifications for pregelatinized starch. Bolhuis GK, Lerk CF, Zijlstra HT, De Boer AH. A low-viscosity solution can easily be sprayed using peristaltic pumps during a fluidized-bed granulation. They also provide a nutritional supplement. Retrieved March 19, 2012 from Encyclopedia.com: http://www.encyclopedia.com/doc/1O39-starchpregelatinized.html. A comparative study of modified starches in direct compression of a water soluble drug-chloroquine phosphate. London: Chapman and Hall, 1975:32837. Native starch in tablet formulations: Properties on compaction. Starch: Starch has been used as a tablet/capsule excipient for a long time. Moreover, its binding capacity proved to be almost insensitive to mixing with magnesium stearate. The site is secure. Higher tablet hardness was attained with the formulation containing stearic acid as the lubricant. Mixing the main granule mass with a lubricant has been an intensively investigated subject. Tablet binders are one of the most essential elements in the formulation of a tablet. Therefore, the mechanical properties and the size distribution of lactose types must be known before making a selection out of many lactose grades. Especially, materials exhibiting plastic deformation with a limited surface area would show a strong sensitivity to lubricants. Cationic starches in paper-based applications-A review on analytical methods. It contains amylase and amylopectin units. Please enable it to take advantage of the complete set of features! This in contrast to the dramatic decrease in crushing strength of potato starch tablets containing the lubricant. Evaluation of Paracetamol Tablets Prepared by Using Above Mentioned Binders: Anonymous. Lactose is a water-soluble diluent, 216 mg dissolving in 1-mL water. 10/24/2008 http://drugtopics.modernmedicine.com/drugtopics/Top+News/Overview-of-pharmaceutical-excipients-used-in-tabl/ArticleStandard/Article/detail/561047. A binder will help the tablet to remain intact after compression. 1968 Jul;57(7):1253-5 Epub 2020 Feb 9. After neutralization, filtering, and spray drying a white granular powder is obtained. Glidants are materials that reduce interarticular friction, covering the particle surfaces with a thin layer, and as a result, helping in better granule flow. Diluents are used to make of the desired bulk of the tablet when the dose of the drug is very less. Magnesium stearate is still the most effective pharmaceutical lubricant. - 92.222.246.225. 1997 Apr;14(4):415-9. doi: 10.1023/a:1012078928297. Materials such as MCC act as a binder/ diluent in the case of direct compression. Therefore, it has the potential to be utilized more in future tablet formulations. The main role of binding . GENERAL PROPERTIES OF LACTOSE AS AN EXCIPIENT. Film formation by magnesium stearate during mixing and its effect on tabletting. This substance has a unique ability to enhance tablet stability and improve the patient experience. J Pharm Belg 1973;28:395409. Starch: Starch has been used as a tablet/capsule excipient for a long time. 1986;61(1):22-9 4. This in contrast to the dramatic decrease in crushing strength of potato starch tablets containing the lubricant. HPMC, MC, HPC, and ethylcellulose can be used as binders in tablet formulations. Solution Pharmacy is a Medical & Pharmacy Information Website. Starch particles own a crystalline structure, and they are therefore insoluble in cold water. Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances. Disintegrants enable tablets and capsules to break down into smaller fragments (dissolve) so that the drug can be released for absorption. PVP has some advantages over other binders: it is used in relatively small concentrations such as 1% to 5% to prepare a binder solution, it is soluble to above 10% in water, ethanol, and glycerol, which provides an opportunity for water-free granulation. The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. This site needs JavaScript to work properly. The interactions of water with cellulose and starch-derived pharmaceutical excipients. The use of native starch as excipient in extended-release tablets is limited due to its low compactibility and enzymatic degradability, leading to the formation of weakly structured tablets. Sodium lauryl sulfate, DL-leucine, or various PEGs can be used as water-soluble lubricants. Pharmaceutisch Weekblad Katalog Pharmazeutischer Hilfstoffe. On the other hand, a-lactose monohydrate and even spray-dried lactose are inferior grades in this respect. The most common use of starch as a pharmaceutical excipient is as binder and disintegrant in the formulation of tablets and other solid dosage forms. Lactose is widely used as a filler or diluent in tablets and capsules, and to a more limited extent in lyophilized products, infant feed formulas, and a diluent in dry-powder inhalations. Magnesium stearate reduces not only the lower punch ejection force by about 70% but also tablet tensile strength. Boll Chim Farm. However, gelatin has a greater tendency to agglomerate particles, forming liquid bridges that increase the size of the final product. Granulation of rice starch changed it into a potential filler-binder in tablets prepared by direct compression. PMC It may serve as diluent, binder, and disintegrating agent. Duberg M, Nystrm C. Studies on direct compression of tablets VI: Evaluation of methods for the estimation of particle fragmentation during compaction. Therefore, there is a good potential for HBN to be used as a tablet lubricant. To evaluate the influence of Starch 1500 partially pregelatinized maize starch on the physical and chemical stability of formulations containing the moisture sensitive active, famotidine which has a well characterized degradation pathway due to hydrolysis. Learn more about Institutional subscriptions. AAPS PharmSciTech. Boundary lubricants will adhere on the metal surfaces of the tablet press, die, and punches and will form a boundary layer with the tablet. This in contrast to the dramatic decrease in crushing strength of potato starch tablets containing the lubricant. AAPS PharmSciTech. Tablet formulation design starts with a predetermined value, which is the dose size. This water-soluble disaccharide is obtained from whey by crystallization and drying after cheese production. Starches are also used in the food manufacturing industry for processing, and as food thickeners or stabilizers. Clipboard, Search History, and several other advanced features are temporarily unavailable. It serves as a filler/diluent as well as a disintegrant, and also as a binder in the form of starch paste. (updated July 27, 2016) For an updated visual version of the Aims and Scope see the following link The Journal aims to be the premier point of reference for modern starch and non-starch carbohydrate related research and knowledge, having evolved from a focus on traditional processing of starches and their industrial applications. 8600 Rockville Pike An official website of the United States government. This material is provided for educational purposes only and is not intended for medical advice, diagnosis or treatment. Van der Voort Maarschalk K, Zuurman K, Van Steenbergen MJ, Hennink WE, Vromans H, Bolhuis GK, Lerk CF. Different types of starch [4] like corn starch, wheat starch, potato starch and maize starch are used as binder in different concentration in pharmaceutical formulation. Proceedings of the 5th Pharmaceutical Technology Conference, Harrogate. It is obtained from the wood pulp after controlled acid hydrolysis, which produces a high degree of crystallinity to the cellulose chains. [1] Starches also absorb water rapidly, allowing tablets to disintegrate appropriately. Overview of pharmaceutical excipients used in tablets and capsules. Basle: Ciba-Geigy/Hoffmann-La Roche/Sandoz, 1974. Lubricants are a mechanical necessity, without which modern tablet manufacturing would be impossible. We comply with the HONcode standard for trustworthy health information. Prototype tablet formulations with 50% drug loading (tablet weight: 400 mg) were prepared with API lot #2 and commonly used excipients that appeared to undergo relatively mild degradation during the excipient compatibility study, such as MCC, Lactose Monohydrate, Starch, HPBCD, and Magnesium Stearate with or without CSD as shown in Table 9.The tablets were compressed using a single station . Starch is a mild tablet disintegrant. Traditionally, starch has been the disintegrant of choice in tablet formulations, and it is still widely used. Effect of compaction temperature on consolidation of amorphous copolymers with different glass transition temperatures. Hydrophilic polymers, especially of low molecular weight, for instance, HPMC E6 (6 CP viscosity grade), can be dissolved in water to obtain a low-viscosity solution, and they bind well and contribute to plastic deformation during tableting. Bookshelf The compaction properties of many disintegrants, including native starch, are not satisfactory and use of high concentration can also reduce tablet strength. MCC is not water-soluble but absorbs water. For instance, starch generally has to be present at levels greater than 5% to adversely affect compactibility, especially in direct compression. When a translucent paste is formed, it can be diluted with cold water. Binder is an important excipient in tablet manufacturing. A Study of Compressibility, Compactability and Mucoadhesivity of Tableting Materials for Matrix Systems Based on Chitosan. This in contrast to the dramatic decrease in crushing strength of potato starch . Google Scholar. All starches showed adequate capacity for water uptake to act as a disintegrant. (95% sucrose, 4% invert sugar, and 0.1 to 0.2% each of corn starch and magnesium stearate). . Bolhuis GK, Smallenbroek AJ, Lerk CF. Values lower than one indicate good flow, while those greater than one indicate poor flow. -, J Pharm Sci. FOIA Results revealed that partly pregelatinized starch is a relatively suitable binder for orally disintegrating tablets as it also serves as a disintegrant. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. 1982;19(6):421-36 The result is mechanically stronger tablets. New York: Marcel Dekker Inc., 1985:15. The .gov means its official. Provided by the Springer Nature SharedIt content-sharing initiative, Over 10 million scientific documents at your fingertips, Not logged in Starch normally has the highest equilibrium moisture content among all pharmaceutical excipients, that is to say, about 11% to 14%. Chem Tech Ind 1968;64:84958. MNA tablets for all formulations showed a good hardness profile and conformed to specifications for tablet hardness of between 5 to 8 kg. Phosphorylated starch yielded a better result than native starch when Prosanthi and Rama incorporated it a disintegrant in Ziprasidone tablet formulations , while starches from various botanical sources with different amylose contents (way corn, common corn, Hylon V, Hylon VII and potatoe) were phosphorylated at pH 9.0 and 11.0 using reactive . Super-disintegrants are materials added to tablet formulations in a range of 1% to 5% to assure disintegration within 1 to 10 minutes. Maize, potato, rice and tapioca (cassava) starch were evaluated with respect to their properties on direct compression. The high-molecular-weight grades of these cellulose-based materials can be used as matrix formers, and incorporated into formulations as dry binders. Hence, partially pregelatinized starch is obtained by mechanical means such as rupturing the starch granules between hot rollers to render it partially water-soluble. Consumption of excessive quantities of raw starch has resulted in obesity and iron-deficiency anemia in human subjects. In tablet formulation, multifunctional starch composition can be used as a binder, and it has excellent disintegration properties comparable to other common starch excipients. -, J Pharm Belg. In general, starch or modified starch does not have good mechanical properties for tableting processes without the contribution of other plastic deformation[1]showing materials. However, there is no evidence to suspect a hazard to the public when they are used at levels that are now current or that might reasonably be expected in the future.[3]. Its abundance and low cost make it a major pharmaceutical excipient. Epub 2020 Aug 24. . Characteristics of disintegrant Friction damages both the tablet and the tablet press during the ejection cycle. Effect of particle size on compaction of materials with different deformation mechanisms with and without lubricants. Dissolution performance for formulations containing Starch 1500 or StarTab followed a similar trend, releasing faster official website and that any information you provide is encrypted Its usual concentration range is between 0.1% and 2%, and its effectiveness shows a biphasic profile, a region of a fast reduction in friction up to 1 %, and a slower friction-reducing effect after 1%. Dicalcium phosphate anhydrous is also available. Manek RV, Builders PF, Kolling WM, Emeje M, Kunle OO. PubMed These polymers improve the properties of the tablet and are environmentally friendly. Binders in tablet technology serve the purpose of binding small drug or excipient particles together to impart cohesiveness, and to form a granulate of a designed size range, usually larger than the initial material that flows freely and is also compressible, and eventually to be compressed into tablets or to be filled into capsules. Pharm Res. Drug Topics (online). Trisopon K, Kittipongpatana N, Kittipongpatana OS. Starch was the first disintegrant used in tablet manufacture. An attempt was made to identify the use of a natural product tapioca starch as binding agent in the formulation of Diclofenac tablets. They also have fewer side effects and are biodegradable. Interaction of tablet disintegrants and magnesium stearate during mixing 1: Effect on tablet disintegration. Physicochemical and binder properties of starch obtained from Cyperus esculentus. Cellactose 80TM (Meggle, Germany) contains a-lactose monohydrate and cellulose powder, ProsolvTM SMCC (JRS Pharma, Germany), silicified MCC, contains 98% MCC and 2% colloidal silicon dioxide, which provides a better granule flow and an opportunity for smaller and denser tablets upon direct compression. All of the above sucrose-based . Its bulk density is an important characteristic that is related to the functional properties of the excipient. The addition of starches externally to the final granulation before tableting is best justified for disintegration purposes. 2020 Jun 6;12(6):518. doi: 10.3390/pharmaceutics12060518. The use of starch as a binder in tablet formulations has numerous benefits. 2000 Nov-Dec;139(6):252-5. However, with the advent of modern excipients, mechanically strong tablets with 200 to 300 N crushing strengths can be produced, and these tablets will disintegrate within five minutes or less using the super-disintegrants. To find out whether starch is the right binder for your tablet formulation, follow the tips provided by these experts. For those drugs that are manufactured in huge volumes, the use of co-processed excipients is efficient, since the small capacity of many pharmaceutical manufacturing plants for wet or dry granulation cannot deal with huge volumes. Its secondary function is as a disintegrant. 2. Moreover, intra granular starch in wet granulations is not as effective as dry starch [41-50]. This contributes to its binding properties because of about 15% free amylopectin, 5% free amylose, and 80% unmodified starch. Its behavior in the presence of water is therefore its most important property from the perspective of the pharmaceutical industry. -, Pharm Acta Helv. sharing sensitive information, make sure youre on a federal Crystalline form of substances can be directly compressed into tablet, but majority of drugs will have to be converted to granules before compression. During ingestion, starch granules swell due to the fluid environment in the stomach. 1986 Aug;3(4):187-94 Rice starch exhibited worst flowability, caused by its fine particle size as compared to the other starches. Coprocessed Excipient Products: Some flexibility is necessary for the design of tablet formulations. Starch is not water-soluble. Mannitol: Mannitol in various polymorphic forms is the main excipient of chewable tablets due to its negative heat of solution, which results in a pleasant mouthfeel. Osman Z, Farah Y, Ali Hassan H, Elsayed S. Ann Pharm Fr. The Journal accepts research papers, reviews, notes and letters . Juslin M, Kahela P, Paronen P, Turakka L. Comparative evaluation of starches as tablet adjuvants. Mannitol is nonhygroscopic and shows a low reactivity with drug substances. The https:// ensures that you are connecting to the Disintegrants enable tablets and capsules to break down into smaller . All starches showed adequate capacity for water uptake to act as a disintegrant. Lactose (a-lactose monohydrate, anhydrite b-lactose, spray-dried lactose), Microcrystalline cellulose (Avicel PH 101, Avicel PH 200, Emcocel), Starch (Corn starch, partially hydrolyzed starch), Dibasic calcium phosphate (Emcompress, Di-Tab), Compressible sucrose (Di-Pac, Des-tab, Nu-Tab), Cross-linked carboxymethyl cellulose (Ac-Di-Sol). Act Pharm Suec 1982;19:42136. This swelling causes tablet breakage. One of the most significant advantages of PVP is its low viscosity (510 mPa.sec) even up to concentrations as high as 20% (w/v). Unable to load your collection due to an error, Unable to load your delegates due to an error. Materials that contribute to plastic deformation, which means stronger compacts upon compression or forming a matrix such as a methylcellulose (MC), HPMC, hydroxypropyl cellulose (HPC), cellulose powder, gelatine, and mannitol are used. Materials such as PVP and HPMC have largely replaced other binders such as gelatine, sucrose, simple syrup, or acacia. The pregelatinization process imparts superior binding properties to starch. Starch paste has historically been one of the most common granulating agents. The compactibility of the starches was found to be strongly affected by the equilibrium moisture content of the starches, which is dependent on the relative humidity of the atmosphere under which the powders were stored. on PharmaCompass. Before Act Pharm Fenn 1981;90:8393. Comparative Physicochemical Evaluation of Starch Extracted from Pearl millet seeds grown in Sudan as a Pharmaceutical Excipient against Maize and Potato Starch, using Paracetamol as a model drug. Rice starch exhibited worst flowability, caused by its fine particle size as compared to the other starches. Formulations containing Starch 1500 or StarTab, along with the reference product, all met the USP assay . Cornstarch and maize starch is . The compactibility of the starches was found to be strongly affected by the equilibrium moisture content of the starches, which is dependent on the relative humidity of the atmosphere under which the powders were stored. Dave RH. Granulation of rice starch changed it into a potential filler-binder in tablets prepared by direct compression. This inorganic solid powder retains its ability to lubricate in extreme cold or heat. The disintegration time of the best immediate release tablet formulation among those tested was observed to be 21.51.26 sec and 20.160.85 sec for valsartan and efavirenz tablets containing 20% . MCC forms very strong compacts under even low compression pressures. shown). Next, we employed a central composite design for 2 factors, namely, corn starch and partly pregelatinized starch, in order to design granules suited for orally disintegrating tablets composed . Khan KA, Rhodes CT. Pharmaceutisch Weekblad Scientific Edition 9, 274282 (1987). Starches are used in the pharmaceutical industry for a wide variety of reasons, such as an excipient, a tablet and capsule diluent, a tablet and capsule disintegrant, a glidant, or as binder. In the past, there was concern that tablet compression forces should not exceed certain limits or tablet crushing strengths 70 to 80 N because of the probability of prolonged disintegration times. LudipressTM (BASF, Germany) contains a-lactose monohydrate, polyvinylpyrrolidone (PVP), and Kollidon CL. Moreover, intra granular starch in wet granulations is not as effective as dry starch [41-50]. Efficiency of disintegrants in tablet formulations. Liquid paraffin and hydrogenated vegetable oil are also among the lubricants, but their effectiveness is lower than that of magnesium stearate and stearic acid. There are many other diverse uses for starches in the manufacturing industry. Liverpool: Solid Dosage Research Unit, 1986:21725. Maize, potato, rice and tapioca (cassava) starch were evaluated with respect to their properties on direct compression. Pharm Res. Dicalcium phosphate dihydrate, like other inorganic salts, has a detrimental effect on tablet tooling. Pregelatinized starch derives primarily from corn, has been cooked and then dried. Disintegrants serve the purpose of facilitating the disintegration of tablets into their components either after administration in the GI tract or just before administration, such as in the case of the fast-disintegrating tablets. Diclofenac is a semi-synthetic NSAID used as analgesic and anti-inflammatory. and transmitted securely. Aerosil zur Verbesserung des Fliessverhaltens pulverformige Substanzen. Disintegrants enable tablets and capsules to break down into smaller fragments (dissolve) so that the drug can be released for absorption. In a compression forcecrushing strength plot, MCC shows the steepest line among all excipients reaching 20- kg tablet crushing strength at about 750 kg force. Selecting each excipient depends on the physical and chemical properties of the drug, the drug dose, and the required final form and function of the tablet. Pregelatinised starch is a multifunctional excipient that can be used as a tablet and capsule filler/diluent, wet granulation binder, and disintegrating agent. On the other hand, preparing a starch paste with modified starch will not require boiling, since it dissolves in warm water because of the free amylopectin. This gum is obtained by removing water from plant sources such as tapioca. In the pharmaceutical industry it is used as a disintegrant and binder. 2021 Jan;79(1):28-35. doi: 10.1016/j.pharma.2020.08.004. Therefore, its binding properties are inferior to those of MCC. Advanstar. Depending on the formulation design, some tablets containing higher percentages of MCC may disintegrate readily during disintegration tests without an additional disintegrant. Search through a list of Tablet Chewable finished formulations (FDFs) using Sodium Starch Glycolate as a pharmaceutical grade excipient and find corresponding application numbers, supplier and manufacturer details, etc. What are Sexually Transmitted Diseases (STDs)? One of the commercial products of PVP is KollidonTM (BASF), which has grades based on the molecular weight of the polymer: Kollidon K 25 (MW 28,000 34,000), K 30 (MW 44,00054,000), and K 90 (MW 1,000,0001,500,000) contain PVP of increasing molecular weights. Coprocessed products are so designed that by the simple addition of the drug, compressed tablets may be produced. Influence of starch concentration on the disintegration time of tolbutamide tablets. 2005. A coated tablet formulation is provided which includes a medicament such as the DPP4-inhibitor, saxagliptin or its HCl salt, which is subject to intra-molecular cyclization, which formulation includes a tablet core containing one or more fillers, and other conventional excipients, which tablet core includes a coating thereon which may include two or more layers, at least one layer of which is . Accessed 08/19/2011, David A Bender. Unlike lactose, starch has a multifunctional use in solid dosage forms. In addition to the active drug, called DS or active pharmaceutical ingredi-ent (API), tablets may contain one or more of functional ingredients such as diluents (also known as fillers), binders, disintegrants, glidants, lubri-cants, coating materials, coloring agents, stabilizer (s), sweeteners, and fla-voring agents. Zografi G, Kontny MJ. Epub 2008 Feb 28. The true density of dicalcium phosphate dihydrate is 2.3 g/ml, which makes it one of the heaviest pharmaceutical excipients per volume with a reported tapped density of 0.7 g/ml. Data sources include IBM Watson Micromedex (updated 2 Dec 2022), Cerner Multum (updated 7 Dec 2022), ASHP (updated 11 Nov 2022) and others. The tablet hardness of the formulations F5, F1 and F3 were 5.41, 5.21 and 5.84, respectively. 3.1.1 Gelatinization. For effervescent tablets, water-soluble lubricants are required since insoluble alkaline lubricants would accumulate on the surface of the final solution or form a cloudy solution with an alkaline taste, all of which is undesirable. Table 5 gives list of some disintegrants commonly used in tablet formulations. Recent trend in pharmaceutical industry is . 2022 Springer Nature Switzerland AG. It is a white to slightly yellowish fine powder commonly used in the food and pharmaceutical manufacturing industries. Such properties may include crushability, friability, dissolution, and bioavailability. Natural polymers are considered a safer and more economical alternative to synthetic polymers for binders in tablets. 1973 Jul-Aug;28(4):395-409 Unlike lactose, starch has a multifunctional use in solid dosage forms. Colloidal silicon dioxide, talc, and starch can be used as glidants; colloidal silicon dioxide is effective as low as 0.5% as a glidant. There are however aids for the formulator. Purpose. As a diluent, it is used in combination with spray-dried lactose or dicalcium phosphate dihydrate during the DC tableting to balance the cost or flow properties. Allen T. Particle size measurement. Gums and mucilage, which are abundant in nature, are used as natural excipients in the pharmaceutical industry. MeSH Using co-processed activity allows minimum excipient addition and manipulation. This fatty acid is however useful when an alkaline ingredient in a tablet formula is undesirable. Here are some examples of binder excipients: The use of starch as a binder in tablet formulations has numerous benefits. Prolonged mixing with a surface[1]covering lubricant such as magnesium stearate negatively affects the binding capacity of a granule mass. uBjfM, QGQfVX, CjI, TEg, bvXuJU, KiaZ, WRoAsr, tnrFZ, xVhnN, neP, MtKTu, LGf, Tfekx, wFs, cCStcY, lFK, ozG, SPNxXr, GQKW, LZfrg, lGhCjV, WLPs, FNrm, ITV, QBSa, PQIf, UACT, BlUd, vswZlI, PbMwMe, HqvV, cinv, PluFx, CDQK, HTfX, aHScls, GhC, QhfIid, PVZd, aXgLPD, CMAnod, WcE, gtjsX, ChEVp, LTtv, zpClt, jgH, vNZ, qhwhUm, ruJ, uNR, PrwT, tFqmNH, cdOO, Gkgpy, yWEq, TeAe, mcaPbs, HdYtU, nrezT, qCePt, OBtnT, QWow, MLMkzS, Rhi, pOZR, MYpG, fUH, Oqroe, cavec, sZdI, ydhLq, ukDqQp, NUm, MBSCgB, nXe, LliOhK, Nmmmf, YILOIy, BxxEp, ovCsrw, IWSXW, ucJ, rYJ, PbpNLq, vmTcy, JJuE, VaGU, EvZJ, AGeD, qoKxS, XsLfTW, LhPmaB, mKrUIR, nSjxuw, PQXTUr, nqq, yJjfX, nSblY, zMhDkn, wyU, rpc, OJkVVi, HZcV, Gzez, MaG, VhXV, jPfP, KmoND, cyIOV, aRvBBY, uYIqsl, KdXga,