Generic placeholder image

Current Pharmaceutical Analysis


ISSN (Print): 1573-4129
ISSN (Online): 1875-676X

Review Article

An Overview of Excipients Classification and Their Use in Pharmaceuticals

Author(s): Cansel Kose Ozkan*, Ozgur Esim, Ayhan Savaser* and Yalcin Ozkan

Volume 17, Issue 3, 2021

Published on: 05 June, 2020

Page: [360 - 374] Pages: 15

DOI: 10.2174/1573412916999200605163125

Price: $65


The content and the application of pharmaceutical dosage forms must meet several basic requirements to ensure and maintain efficiency, safety and quality. A large number of active substances have a limited ability to direct administration. Excipients are generally used to overcome the limitation of direct administration of these active substances. However, the function, behavior and composition of the excipients need to be well known in the design, development and production of pharmaceutical dosage forms. In this review, excipients used to assist in any pharmaceutical dosage form production processes of drugs, to preserve, promote or increase stability, bioavailability and patient compliance, to assist in product identification/separation, or to enhance overall safety and effectiveness of the drug delivery system during storage or use are explained. Moreover, the use of these excipients in drug delivery systems is identified. Excipient toxicity, which is an issue discussed in the light of current studies, also discussed in this review.

Keywords: Excipients, fillers, surfactants, active pharmaceutical ingredient, incompatibility, excipient toxicity.

Graphical Abstract
Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. 2010.
Martini, L.G.; Crowley, P. Excipients: Pharmaceutical Dosage Forms In: Encyclopedia of Biomedical Polymers and Polymeric Biomaterials; , 2015; pp. 3337-3349
Pifferi, G.; Restani, P. The safety of pharmaceutical excipients. Farmaco, 2003, 58(8), 541-550.
[] [PMID: 12875883]
The International Pharmaceutical Excipients Council. The International Pharmaceutical Excipients Council The Pharmaceutical Quality Group: The Joint Good Manufacturing Practices Guide For Pharmaceutical Excipients 2017, 1-40.
Prasanna Raju, Y.; Jayasri, V.; Rubia Yasmeen, B.; Harini Chowdary, V.; Satyanandam, S. Significance of pharmaceutical excipients – A review. Jitps, 2011, 2, 191-201.
Pifferi, G.; Santoro, P.; Pedrani, M. Quality and functionality of excipients. Farmaco, 1999, 54(1-2), 1-14.
[] [PMID: 10321025]
Chan, H-K.; Chew, N.Y.K. Excipients: Powders and Solid Dosage Forms Production of Nano-Composite Particles for Inhalational Delivery of Combination Drugs View Project Pulmonary Drug Delivery View Project Excipients: Powders and Solid Dosage Forms, 2002.
Warren, F. Handbook of Pharmaceutical Excipients; , 1987, Vol. 44, .
Debnath, S.; Yadav, C.N.; Nowjiya, N.; Prabhavathi, M. SaiKumar, A.; Krishna, P.S.; Babu, M.N. A review on natural binders used in pharmacy. Asian J. Pharm. Res., 2019, 9, 55.
Abrantes, C.G.; Duarte, D.; Reis, C.P. An Overview of Pharmaceutical Excipients: Safe or Not Safe? J. Pharm. Sci., 2016, 105(7), 2019-2026
[] [PMID: 27262205]
Desai, P.M.; Liew, C.V.; Heng, P.W.S. Review of disintegrants and the disintegration phenomena. J. Pharm. Sci., 2016, 105(9), 2545-2555.
[ ] [PMID: 27506604]
Challenges and Opportunities in Developing Up-to-Date USP–NF Excipient Monographs | American Pharmaceutical Review - The Review of American Pharmaceutical Business Technology.
Sheehan, C.; Amidon, G.E. Compendial standards and excipient performance in the QbD era: USP excipient performance chapter (1059),.
Bolhuis, G.K.; Armstrong, N.A. Excipients for direct compaction--an update. Pharm. Dev. Technol., 2006, 11(1), 111-124.
[] [PMID: 16544915]
Goto, K.; Sunada, H.; Danjo, K.; Yonezawa, Y. Pharmaceutical evaluation of multipurpose excipients for direct compressed tablet manufacture: comparisons of the capabilities of multipurpose excipients with those in general use. Drug Dev. Ind. Pharm., 1999, 25(8), 869-878.
[] [PMID: 10434130]
De Villiers, M.; Oral Conventional Solid Dosage Forms, M. Theory and Practice of Contemporary Pharmaceutics; CRC Press, 2004, pp. 279-332.
Shanmugam, S. Granulation techniques and technologies: recent progresses. Bioimpacts, 2015, 5(1), 55-63.
[] [PMID: 25901297]
Liu, L.X.; Marziano, I.; Bentham, A.C.; Litster, J.D.; White, E.T.; Howes, T. Effect of particle properties on the flowability of ibuprofen powders. Int. J. Pharm., 2008, 362(1-2), 109-117.
[] [PMID: 18652883]
Šantl, M.; Ilić, I.; Vrečer, F.; Baumgartner, S. A compressibility and compactibility study of real tableting mixtures: the effect of granule particle size. Acta Pharm., 2012, 62(3), 325-340.
[] [PMID: 23470346]
Cantor, S.; Augsburger, L.; Gerhardt, A. Pharmaceutical granulation processes, mechanism and the use of binders. Pharmaceutical Dosage Forms - Tablets, 3rd ed; CRC Press, 2008, pp. 261-301.
Palzer, S. Agglomeration of pharmaceutical, detergent, chemical and food powders - similarities and differences of materials and processes. Powder Technol., 2011, 206, 2-17.
Koo, O.M.Y. Pharmaceutical Excipients: Properties; Functionality, and Applications in Research and Industry, 2016.
Şensoy, D.; Cevher, E.; Altinkurt, T. Characterization of Apricot Gum as a Binder in Tablet Formulations. Acta. Pharm. Sci., 2006, 48(1), 35-43.
Yüksel, N.; Karataş, A.; Baykara, T. Comparative evaluation of granules made with different binders by a fluidized bed method. Drug Dev. Ind. Pharm., 2003, 29(4), 387-395.
[] [PMID: 12737532]
Kaigai Boeki Kaihatsu Kyokai. Natural Polymers - A Comprehensive Review 1989, 3, 1597-1613..
Simionescu, B.C.; Ivanov, D. Natural and Synthetic Polymers for Designing Composite Materials. Handbook of Bioceramics and Biocomposites.Springer International Publishing; , 2016, pp. 233-286.
Nakamura, S.; Ishii, N.; Nakashima, N.; Sakamoto, T.; Yuasa, H. Evaluation of sucrose fatty acid esters as lubricants in tablet manufacturing. Chem. Pharm. Bull. (Tokyo), 2017, 65(5), 432-441.
[] [PMID: 28458365]
Li, J.; Wu, Y. Lubricants in pharmaceutical solid dosage forms. Lubricants, 2014, 2, 21-43.
Morin, G.; Lauren Briens, S. The Effects of Lubrication on Pharmaceutical Granules, 2012.
Bandelin, F.J. Compressed tablets by wet granulation; Pharmaceutical Dosage Forms, 1989, pp. 131-193.
Three, I.; Volillvle, V.; Lieberman, H.A.; Lachman, L.; Schwartz, J.B.; Dekker, M.N. Pharmaceutical dosage forms tablets second edition; revised and expanded,; , 1989.
Derry, M.J.; Smith, T.; O’Hora, P.S.; Armes, S.P. Block copolymer nanoparticles prepared via polymerization-induced self-assembly provide excellent boundary lubrication performance for next-generation ultralow-viscosity automotive engine oils. ACS Appl. Mater. Interfaces, 2019, 11(36), 33364-33369.
[] [PMID: 31430432]
Allam, K.V.I.; Kumar, G.P. Colorants - the Cosmetics for the Pharmaceutical Dosage Forms, 2011, 3.
Janiszewska-Turak, E.; Pisarska, A.; Królczyk, J.B. Natural food pigments application in food products nauk.Przyr. Technol., 2017, 10.
Peck, G.E.; Baley, G.J.; McCurdy, V.E.; Banker, G.S. Tablet formulation and design. Pharmaceutical Dosage Forms; Marcel Dekker, 1989, pp. 75-130.
Marmion, D. Updated by Staff.Colorants for Foods. Kirk-Othmer Encyclopedia of Chemical Technology; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2007;
[ 2]
Ham, A.S.; Buckheit, R.W. Jr Designing and developing suppository formulations for anti-HIV drug delivery. Ther. Deliv., 2017, 8(9), 805-817.
[] [PMID: 28825395]
Akhtar, M.I.I.; Akhtarz, N.; Ahmad, M.; Ardf, A. Sh; P.A. Drug release from peg suppository bases and from their combination with polymers. 2000, Vol. 33.
Jones, D. FASTtrack pharmaceutics - dosage form and design. 2013, 53.
De Muynck, C.; Cuvelier, C.; Van Steenkiste, D.; Bonnarens, L.; Remon, J.P. Rectal mucosa damage in rabbits after subchronical application of suppository bases. Pharm. Res., 1991, 8(7), 945-950.
[] [PMID: 1924149]
Hermann, T.W. Recent research on bioavailability of drugs from suppositories. Int. J. Pharm., 1995, 123, 1-11.
Kalász, H.; Antal, I. Drug excipients. Curr. Med. Chem., 2006, 13(21), 2535-2563.
[] [PMID: 17017910]
Mastropietro, J; Rheology, D Rheology in pharmaceutical formulations- a perspective. J. Dev. Drugs, 2013, 02.
Doye, P.; Mena, T.; Das, N. Formulation and bio-availability parameters of pharmaceutical suspension. Int. J. Curr. Pharm. Res., 2017, 9, 8.
Manoharan, C.; Basarkar, A.; Singh, J. Various Pharmaceutical Disperse Systems. Pharmaceutical Suspensions: From Formulation Development to Manufacturing; Springer: New York, 2010, pp. 1-37.
Gedar, S.; Kataria, M.K.; Bilandi, A.; Taneja, R. Advancements and patents in pharmaceutical suspension technologies. J. Biol. Sci. Opin., 2013, 1, 372-380.
Chapter 10, Dispersion of Particles in Liquids. Stud. Interface Sci., 2005, 20, 517-558.
Steinberg, M.; Borzelleca, J.F.; Enters, E.K.; Kinoshita, F.K.; Loper, A.; Mitchell, D.B.; Tamulinas, C.B.; Weiner, M.L. The safety committee of the international pharmaceutical excipients council. a new approach to the safety assessment of pharmaceutical excipients. Regul. Toxicol. Pharmacol., 1996, 24(2 Pt 1), 149-154.
[] [PMID: 8933628]
Šantl, M.; Ilić, I.; Vrečer, F.; Baumgartner, S. A compressibility and compactibility study of real tableting mixtures: the impact of wet and dry granulation versus a direct tableting mixture. Int. J. Pharm., 2011, 414(1-2), 131-139.
[] [PMID: 21605646]
Zhang, T.; Marchant, R.E. Novel polysaccharide surfactants: the effect of hydrophobic and hydrophilic chain length on surface active properties. J. Colloid Interface Sci., 1996, 177, 419-426.
Nielloud, F. Pharmaceutical Emulsions and Suspensions, Second Edition, Revised and Expanded; Marcel Dekker; , 2000.
Bouyer, E.; Mekhloufi, G.; Rosilio, V.; Grossiord, J.L.; Agnely, F. Proteins, polysaccharides, and their complexes used as stabilizers for emulsions: alternatives to synthetic surfactants in the pharmaceutical field? Int. J. Pharm., 2012, 436(1-2), 359-378.
[]] [PMID: 22759644]
Saengsorn, K.; Jimtaisong, A. Determination of hydrophilic–lipophilic balance value and emulsion properties of sacha inchi oil. Asian Pac. J. Trop. Biomed., 2017, 7, 1092-1096.
De Feijter, J.A.; Benjamins, J.; Tamboer, M. Adsorption displacement of proteins by surfactants in oil-in-water emulsions. Colloids Surf., 1987, 27, 243-266,
Sivaramakrishnan, C.N. Amphoteric surfactants. Colourage, 2018, 65.
Park, J.W.; Jaffé, P.R. Partitioning of three nonionic organic compounds between adsorbed surfactants, micelles, and water. Environ. Sci. Technol., 1993, 27, 2559-2565.
Perinelli, D.R.; Petrelli, D.; Vitali, L.A.; Bonacucina, G.; Cespi, M.; Vllasaliu, D.; Giorgioni, G.; Palmieri, G.F. Quaternary ammonium leucine-based surfactants: the effect of a benzyl group on physicochemical properties and antimicrobial activity. Pharmaceutics, 2019, 11(6), 11.
[] [PMID: 31248093]
Lémery, E.; Briançon, S.; Chevalier, Y.; Bordes, C.; Oddos, T.; Gohier, A.; Bolzinger, M.A. Skin toxicity of surfactants: structure/toxicity relationships. Colloids Surf. A Physicochem. Eng. Asp., 2015, 469, 166-179.
Snejdrova, E.; Dittrich, M. Pharmaceutical applications of plasticized polymers. Recent Advances in Plasticizers; InTech, 2012.
Snejdrova, E.; Dittrich, M. Pharmaceutically used plasticizers. Recent Advances in Plasticizers; InTech, 2012.
Petrak, K. Pharmaceutical applications of functionalized polymers. Reactive Polymers, 1989, 10, 231-237.
Vuddanda, P.R.; Montenegro-Nicolini, M.; Morales, J.O.; Velaga, S. Effect of plasticizers on the physico-mechanical properties of pullulan based pharmaceutical oral films. Eur. J. Pharm. Sci., 2017, 96, 290-298.
[] [PMID: 27629498]
Qiu, Y.; Chen, Y.; Zhang, G.G.Z.; Yu, L.; Mantri, R.V. Developing solid oral dosage forms: pharmaceutical theory and practice, 2016.
Reader, M.J. Influence of isotonic agents on the stability of thimerosal in ophthalmic formulations. J. Pharm. Sci., 1984, 73(6), 840- 841.,
[] [PMID: 6429316]
Almeida, H.; Amaral, M.H.; Lobão, P.Sousa; Lobo, S. J.M. Applications of poloxamers in ophthalmic pharmaceutical formulations: an overview. Expert Opin. Drug Deliv., 2013, 10(9), 1223-1237.
[] [PMID: 23688342]
Pramanick, S.; Singodia, D.; Chandel, V. Excipient selection in parenteral formulation development; , 2013, Vol. 45, .
Ayenew, Z.; Puri, V.; Kumar, L.; Bansal, A.K. Trends in pharmaceutical taste masking technologies: a patent review. Recent Pat. Drug Deliv. Formul., 2009, 3(1), 26-39.
[]] [PMID: 19149727]
Deepak, S.; Dinesh, K.; Mankaran, S.; Gurmeet, S.; Singh, R.M. Taste masking technologies: a novel approach for the improvement of organoleptic property of pharmaceutical active substance; , 2012, Vol. 3, .
Abraham, J.; Mathew, F. Taste masking of peadiatric formulation: a review on technologies, recent trends and regulatory aspects. Int. J. Pharm. Pharm. Sci., 2014, 6, 12-19.
Bagade, O.M.; Pujari, R.R.; Nemlekar, N.A.; Kharat, P.P.; Shete, A.M.; Vanave, M.D. Appraisal on: tablet coating and its outcome with complementary sprouting technology. Res. J. Pharm. Biol. Chem. Sci., 2014, 5, 298-315.
Joshi, S.; Petereit, H.U. Film coatings for taste masking and moisture protection. Int. J. Pharm., 2013, 457(2), 395-406.
[] [PMID: 24148666]
Cerea, M.; Zheng, W.; Young, C.R.; McGinity, J.W. A novel powder coating process for attaining taste masking and moisture protective films applied to tablets. Int. J. Pharm., 2004, 279(1-2), 127-139.
[] [PMID: 15234801]
Porter, S.C.; Felton, L.A. Techniques to assess film coatings and evaluate film-coated products. Drug Dev. Ind. Pharm., 2010, 36(2), 128-142.
[] [PMID: 20050727]
Balamurali, V.; Pramodkuma, T.M.; Srujana, N.; Venkatesh, M.P.; Gupta, N.V.; Krishna, K.L.; Gangadhara, H.V. PH sensitive drug delivery systems: a review. Am. J. Drug Discov. Dev., 2011, 1, 24-48.
Mudie, D.M.; Amidon, G.L.; Amidon, G.E. Physiological parameters for oral delivery and in vitro testing. Mol. Pharm., 2010, 7(5), 1388-1405.
[] [PMID: 20822152]
Jiménez-Castellanos, M.R.; Zia, H.; Rhodes, C.T. Design and testing in vitro of a bioadhesive and floating drug delivery system for oral application. Int. J. Pharm., 1994, 105, 65-70.
Obara, S.; Maruyama, N.; Nishiyama, Y.; Kokubo, H. Dry coating: an innovative enteric coating method using a cellulose derivative. Eur. J. Pharm. Biopharm., 1999, 47(1), 51-59.
[] [PMID: 10234527]
Missaghi, S.; Fassihi, R. A novel approach in the assessment of polymeric film formation and film adhesion on different pharmaceutical solid substrates. AAPS PharmSciTech, 2004, 5(2)e29
[] [PMID: 15760087]
Kaynak, M.S. Formulation of controlled release glipizide pellets using pan coating method; , 2007, Vol. 27, .
Akers, M.J. Sterile Drug Products; CRC Press, 2016.
Niazi, S. Sterile Products.Handbook of Pharmaceutical Manufacturing Formulations. 2009, pp. 172-426;
Cantrell, S.A. Improving the quality of compounded sterile drug products: a historical perspective. Ther. Innov. Regul. Sci., 2016, 50(3), 266-269.,
[] [PMID: 30227062]
Bisutti, I.; Hilke, I.; Raessler, M. Determination of total organic carbon - an overview of current methods. TrAC. Trends Analyt. Chem., 2004, 23, 716-726.,
Visco, G.; Campanella, L.; Nobili, V. Organic carbons and TOC in waters: an overview of the international norm for its measurements. Proceedings Microchem. J., 2005, 79, 185-191.
Adeyeye, M.C.; Brittain, H.G.; Brittain, H.G. Part 1: Introduction 2008, 19-34.
DiFeo, T.J. Drug product development: a technical review of chemistry, manufacturing, and controls information for the support of pharmaceutical compound licensing activities. Drug Dev. Ind. Pharm., 2003, 29(9), 939-958.
[] [PMID: 14606659]
Gibson, M.; Steele, G. Preformulation as an Aid to Product Design in Early Drug Development; Pharm. Preformulation Formula, 2001, pp. 175-237.
Bharate, S.S.; Bharate, S.B.; Bajaj, A.N. Interactions and incompatibilities of pharmaceutical excipients with active pharmaceutical ingredients: a comprehensive review. J. Excip. Food Chem., 2010, 1, 3-26.
Bharate, S.S.; Vishwakarma, R.A. Impact of preformulation on drug development. Expert Opin. Drug Deliv., 2013, 10(9), 1239-1257.
[] [PMID: 23534681]
Sezgin-Bayindir, Z.; Yuksel, N. Investigation of formulation variables and excipient interaction on the production of niosomes. AAPS PharmSciTech, 2012, 13(3), 826-835.
[]] [PMID: 22644706]
Patel, P.; Ahir, K.; Patel, V.; Manani, L.; Patel, C. Drug-excipient compatibility studies : first step for dosage form development.2015, 4.,
Savaşer, A.; Taş, Ç.; Bayrak, Z.; Özkan, C.K.; Özkan, Y. Effect of different polymers and their combinations on the release of metoclopramide HCl from sustained-release hydrophilic matrix tablets. Pharm. Dev. Technol., 2013, 18(5), 1122-1130.
[] [PMID: 22881478]
Crowley, P.; Martini, L. Drug-excipient interactions.,
Van Dooren, A.A. Design for drug-excipient interaction studies. Drug Dev. Ind. Pharm., 1983, 9, 43-55.
Chadha, R.; Bhandari, S. Drug-excipient compatibility screening-- role of thermoanalytical and spectroscopic techniques. J. Pharm. Biomed. Anal. 2014, 87, 82-97
[] [PMID: 23845418]
Pastoriza, S. Maillard Reaction - an overview | ScienceDirect Topics,.
ASHOOR. S.H.; ZENT, J.B. Maillard browning of common Amino acids and sugars. J. Food Sci., 1984, 49, 1206-1207.
Ahlneck, C.; Zografi, G. The molecular basis of moisture effects on the physical and chemical stability of drugs in the solid state.Int. J. Pharm., 1990, 62, 87-95,
Mroso, P.V.; Li, Wan Po, A.; Irwin, W.J. Solid-state stability of aspirin in the presence of excipients: kinetic interpretation, modeling, and prediction. J. Pharm. Sci., 1982, 71(10), 1096-1101.
[] [PMID: 7143203]
Reepmeyer, J.C.; Kirchhoefer, R.D. Isolation of salicylsalicylic acid, acetylsalicylsalicylic acid, and acetylsalicylic anhydride from aspirin tablets by extraction and high-pressure liquid chromatography. J. Pharm. Sci., 1979, 68(9), 1167-1169.
[] [PMID: 501542]
Mitrevej, A.; Hollenbeck, R.G. Influence of hydrophilic excipients on the interaction of aspirin and water. Int. J. Pharm., 1983, 14, 243-250.
Botha, S.A.; Lötter, A.P. Compatiblity study between oxprenolol hydrochloride, temazepam and tablet excipients using differential scanning calorimetry. Drug Dev. Ind. Pharm., 1990, 16, 331-345.
Voigt, R.; Pergande, G.; Keipert, S. Comparative studies on the study of drug-excipient interactions with vapor pressure osmometry and equilibrium dialysis. Pharmazie, 1984, 39(11), 760-763.
[PMID: 6531380]
Fluoride stability in dicalcium phosphate dihydrate composition background of the invention. Patent number US5037636A.
Pignatello, R.; Spadaro, D.; Vandelli, M.A.; Forni, F.; Puglisi, G. Characterization of the mechanism of interaction in ibuprofen-Eudragit RL100 coevaporates. Drug Dev. Ind. Pharm., 2004, 30(3), 277-288.
[] [PMID: 15109027]
Yohana Chaerunisaa, A.; Sriwidodo, S.; Abdassah, M. Microcrystalline cellulose as pharmaceutical excipient. Pharmaceutical Formulation Design - Recent Practices; IntechOpen.2019. Working Title;
Cory, W.C.; Harris, C.; Martinez, S. Accelerated degradation of ibuprofen in tablets. Pharm. Dev. Technol., 2010, 15(6), 636-643.
[] [PMID: 19941407]
Hall, C.M.; Milligan, D.W.A.; Berrington, J. Probable adverse reaction to a pharmaceutical excipient.Arch. Dis. Child. Fetal Neonatal Ed., 2004, 89(2), F184.,
[] [PMID: 14977910]
Golightly, L.K.; Smolinske, S.S.; Bennett, M.L.; Sutherland, E.W.; Rumack, B.H. Pharmaceutical Excipients: Adverse Effects Associated with Inactive Ingredients in Drug Products (Part I), . Baldrick, P. Pharmaceutical excipient development: the need for preclinical guidance. Regul. Toxicol. Pharmacol., 2000, 32(2), 210- 218.
[] [PMID: 11067777]
Baldrick, P. Pharmaceutical excipient development: the need for preclinical guidance. Regul. Toxicol. Pharmacol., 2002, 32, 377-380.
Osterberg, R.E.; See, N.A. Toxicity of Excipients - A Food and Drug Administration Perspective. Proceedings Int. J. Toxicol., 2003, 22, 377-380.
Park, J.D.; Zheng, W. Human exposure and health effects of inorganic and elemental mercury. J. Prev. Med. Public Health, 2012, 45(6), 344-352.
[] [PMID: 23230464]
Yochana, S.; Yu, M.; Alvi, M.; Varenya, S.; Chatterjee, P. Pharmaceutical Excipients and Pediatric Formulations; , 2012, Vol. 30, .

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy