Waste and Biomass Valorization

, Volume 3, Issue 4, pp 395–407 | Cite as

Towards a Greener Pharmacy by More Eco Design

  • Michel Baron


This review proposes an overview of the main trends explored by the pharmaceutical industry in order to develop a greener and smarter pharmacy minimizing any negative impact to the environment, and using more sustainable processes and drugs. If many drugs have their origin in nature, many active ingredients are “toxic by design”. Some trials were carried out to design “green pills”, or greener active ingredients “benign by design”, avoiding the environmental pollution risk. More efforts were developed to reduce fine chemicals production footprints, and to decrease their E-factor. Biotechnology, and the use of enzymes for some transformation reactions is another good way of progress. Advanced galenics allows to reduce drug footprints on environment, since it can deliver the right dose of drug at the right time and at the right place, decrease the drug doses, and lower the wastes. Use of continuous processes is a strong trend in the area of primary and secondary pharmaceutical production. It is linked to the quality by design concept and to the in-process control by process analytical technology tools. Added to their diversification strategy, and despite their lower research productivity, and that more and more patented blockbusters become or will become generics soon, it will help the pharmaceutical companies to continue their development. At the same time, these efforts toward a greener pharmacy, and a social education of patients, will contribute to the health organization economies and to preserve the future of our planet.


Green pharmacy Benign by design Advanced galenics Green manufacturing Solvent-free synthesis Continuous process 



Some case studies cited in this article were made by former and present coworkers and Ph’D students in our research center RAPSODEE (Ecole des Mines d’Albi-CNRS-Université de Toulouse-France) and/or Spin Center (Ecole des Mines de St Etienne, France) and/or Paris South-XI University—France, whose names appear only in the reference list. The author expresses his sincere appreciation for their tremendous efforts invested in their research works. Financial supports are also appreciated, among others those from the Ministry of Economy, Finances and Industry, from the Centre National de la Recherche Scientifique (CNRS) and from the Agence Nationale pour la Recherche (ANR).


  1. 1.
    Gurib-Fakim, A.: Medicinal plants: traditions of yesterday and drugs of tomorrow. Mol. Asp. Med. 27, 1–93 (2006)CrossRefGoogle Scholar
  2. 2.
    Morphine: Accessed 13 Oct 2011
  3. 3.
    Potier, P.: A la recherche et à la découverte de nouveaux médicaments. In: Baron M., Dodds J. (eds.) Albi Int. Rencontres in Pharm. Engin., pp. 13–24. ISBN 13 978-2-9511591-5-0, Ecole des Mines d’Albi-Carmaux, Albi (2004)Google Scholar
  4. 4.
    Fleming, A.: On the antibacterial action of cultures of penicillium, with special reference to their use in the isolation of B. influenzae. Brit. J. Exp. Pathol. 10, 226–236 (1929)Google Scholar
  5. 5.
    Imhoff, J.F., Labes, A., Wiese, J.: Bio-mining the microbial treasures of the ocean: new natural products. Biotechnol. Adv. 29, 468–482 (2011)CrossRefGoogle Scholar
  6. 6.
    Deichmann, W.B., Henschler, D., Holmstedt, B., Keil, G.: What is there that is not poison? A study of the third defense by paracelsus. Arch. Toxicol. 58, 207–2013 (1986)CrossRefGoogle Scholar
  7. 7.
    The University of Nottingham.: The liver and drug metabolism. Accessed 8 June 2012
  8. 8.
    Vree, T.B., Van den Biggelaar-Martea, M., Verwey-Van Wissen, C.P.W.G.M., Vree, M.L., Guelen, P.J.M.: The pharmacokinetics of naproxen, its metabolite O-desmethylnaproxen, and their acylglucuronides in humanEffect of cimetidine. Br. J. Clin. Pharmacol. 35, 467–472 (1993)CrossRefGoogle Scholar
  9. 9.
    Apoteket AB.: Pharmaceuticals, environment and Health. (2006). Accessed 13 Oct 2011
  10. 10.
    Houeto, P., Carton, A., Guerbet, M., Mauclaire, A.-C., Gatignol, C., Lechat, P., Masset, D.: Assessment of the health risks related to the presence of drug residues in water for human consumption: application to carbamazepine. Regul Toxicol Pharmacol 62, 41–48 (2012)CrossRefGoogle Scholar
  11. 11.
    International ChemSec: NGOs express concern with European Commission’s position on chemical mixtures. http://Users/baron/Desktop/Review%20Waste%20Biomass%20Valor/phytosanitary,%20insecticides,%20herbicides/ Accessed 6 June 2012
  12. 12.
    Xu, Y., Luo, F., Pal, A., Gin, K.Y.-H., Reinhard, M.: Occurrence of emerging organic contaminants in a tropical urban catchment in Singapore. Chemosphere 83, 963–969 (2011)CrossRefGoogle Scholar
  13. 13.
    Dang, Z., Cheng, Y., Chen, H., Cui, Y., Yin, H., Trass, T., Montforts, M., Vermeire, T.: Evaluation of the Daphnia magna reproduction test for detecting endocrine disruptors. Chemosphere 88, 514–523 (2012)CrossRefGoogle Scholar
  14. 14.
    Brozinski, J.-M., Lahti, M., Oikari, A., Kronberg, L.: Detection of naproxen and its metabolites in fish bile following intraperitoneal and aqueous exposure. Environ. Sci. Pollut. Res. 18, 811–818 (2011)CrossRefGoogle Scholar
  15. 15.
    Zhang, Q.W., Matsumoto, H., Saito, F., Baron, M.: Debromination of hexabromobenzene by its co-grinding with CaO. Chemosphere 48(8), 787–793 (2002)CrossRefGoogle Scholar
  16. 16.
    Zhang, Q.W., Lu, J.F., Saito, F., Baron, M.: Mechanochemical solid-phase reaction between polyvinylidene fluoride and sodium hydroxyde. J. Appl. Polym. Sci. 81(9), 2249–2252 (2001)CrossRefGoogle Scholar
  17. 17.
    Ramaroson, J., Dirion, J.L., Nzihou, A., Sharrock, P., Depelsenaire, G.: Calcination of dredged sediments: investigation of the behaviour of heavy metals and the organic compounds. High Temp. Mat. Process. 27(5), 327–336 (2008)Google Scholar
  18. 18.
    Lafhaj, Z., Duan, Z., Bel Hadj Ali, I., Depelsenaire, G.: Valorization of treated river sediments in self compacting materials. Waste Biomass Valoris. 3(2), 239–247 (2012)CrossRefGoogle Scholar
  19. 19.
    Singh, J.S., Abhilash, P.C., Singh, H.B., Singh, R.P., Singh, D.P.: Genetically engineered bacteria: an emerging tool for environmental remediation and future research perspectives. Gene 480(1–2), 1–9 (2011)Google Scholar
  20. 20.
    Massot, A., Estève, K., Noilet, P., Méoule, C., Poupot, C., Mietton-Peuchot, M.: Biodegradation of phytosanitary products in biological wastewater treatment. Water Res. 46, 1785–1792 (2012)CrossRefGoogle Scholar
  21. 21.
    Kümmerer, K.: Pharmaceuticals in the environment. Annu. Rev. Environ. Ressour. 35, 57–75 (2010)CrossRefGoogle Scholar
  22. 22.
    Trautweil, C., Kümmerer, K.: Degradation of the tricyclic antipsychotic drug chlorpromazine under environmental conditions, identification of its main aquatic biotic and abiotic transformation products by LS-MSn and their effects on environmental bacteria. J. Chromatogr. B 889–890, 24–38 (2012)CrossRefGoogle Scholar
  23. 23.
    McCormick, J.M., Van Es, T., Cooper, K.R., White, L.A., Häggblom, M.M.: Microbially mediated O-methylation of bisphenol a results in metabolites with increased toxicity to the developing zebrafish (Danio rerio) embryo. Environ. Sci. Technol. 45(15), 6567–6574 (2011)CrossRefGoogle Scholar
  24. 24.
    Kümmerer, K.: The presence of pharmaceuticals in the environment due to human use—present knowledge and future challenges. J. Environ. Manag. 90(8), 2354–2366 (2009)CrossRefGoogle Scholar
  25. 25.
    Pohl, J., Bertram, B., Nowrousian, M.R., Stüben, J., Wiessler, M.: D-19575 - a sugar-linked isophosphoramide mustard derivative exploiting transmembrane glucose transport. Cancer Chemother. Pharmacol. 35, 364–370 (1995)CrossRefGoogle Scholar
  26. 26.
    Mazur, L., Opido-Chanek, M., Stojak, M.: Isofosfamide as a new oxazaphosphorine anticancer agent. Anticancer Drugs 22(6), 488–493 (2011)CrossRefGoogle Scholar
  27. 27.
    Kümmerer, K., Al-Ahmad, A., Betram, B., Wiessler, M.: Biodegradability of antineoplastic compounds in screening tests: influence of glucosidation and stereochemistry. Chemosphere 40, 767–773 (2000)CrossRefGoogle Scholar
  28. 28.
    Zhang, S.: Computer-aided drug discovery and development. Methods Mol. Biol. 716, 23–38 (2011)CrossRefGoogle Scholar
  29. 29.
    Steger-Hartmann, T., Länge, R., Heuck, K.: Incorporation of in silico biodegradability screening in early drug development-a feasible approach? Environ. Sci. Pollut. Res. 18, 610–619 (2011)CrossRefGoogle Scholar
  30. 30.
    Daremberg C.: Œuvres anatomiques, physiologiques et médicales de Galien, T.1, J.B. Baillère Ed., Paris (1854)Google Scholar
  31. 31.
    Sriamornsak, P.: Application of pectin in oral drug delivery. Expert Opin. Drug Deliv. 8(8), 1009–1023 (2011)CrossRefGoogle Scholar
  32. 32.
    Avachat, A.M., Dash, R.R., Shrotriya, S.N.: Recent investigations of plant based natural gums, mucilages and resins in novel drug delivery systems. Indian J. Pharm. Educ. Res. 45(1), 86–99 (2011)Google Scholar
  33. 33.
    Hamman, J.H.: Chitosan based polyelectrolyte complexes as potential carrier materials in drug delivery systems. Mar. Drugs 8(4), 1305–1322 (2010)CrossRefGoogle Scholar
  34. 34.
    Faivre, V., Rosilio, V.: Interest of glycolipids in drug delivery: from physicochemical properties to drug targeting. Exp. Opin. Drug Deliv. 7(9), 1031–1048 (2010)CrossRefGoogle Scholar
  35. 35.
    Rasala, T.M., Kale, V.V., Lohiya, G.K., Moharir, K.S., Ittadwar, A.M., Awari, J.G.: Chemistry and pharmaceutical applications of excipients derived from tamarind. Asian J. Chem. 23(4), 1421–1423 (2011)Google Scholar
  36. 36.
    Chan, H.-K.: Nanodrug particles and nanoformulations for drug delivery. Adv. Drug Deliv. Rev. 63, 405 (2011)CrossRefGoogle Scholar
  37. 37.
    Amidon, G.L., Lennernas, H., Shah, V.P., Crison, J.R.: A theoretical basis for a biopharmaceutic drug classification—the correlation of in vitro drug product dissolution and in vivo bioavailability. Pharm. Res. 12(3), 413–420 (1995)CrossRefGoogle Scholar
  38. 38.
    Rogers, T.L., Johnston, K.P., Williams III, R.O.: Solution-based particle formation of pharmaceutical powders by supercritical or compressed fluid CO2 and cryogenic spray-freezing technologies. Drug Dev. Ind. Pharm. 27(10), 1003–1015 (2001)CrossRefGoogle Scholar
  39. 39.
    Ragab, D.M., Rohani, S.: Particle engineering strategies via crystallisation for pulmonary drug delivery. Org. Process Dev. 13, 1215–1223 (2009)CrossRefGoogle Scholar
  40. 40.
    Han, X., Ghoroi, C., To, D., Chen, Y., Davé, R.: Simultaneous micronization and surface modification for improvement of flow and dissolution of drug particles. Int. J. Pharm. 415(1–2), 185–195 (2011)CrossRefGoogle Scholar
  41. 41.
    Shermann B.C.: Pharmaceutical compositions comprising co-micronized fenofibrate. US Patent 6555135, (2000)Google Scholar
  42. 42.
    Merisko-Liversidge, E., Liversidge, G.: Nanosizing for oral and parenteral drug delivery: a perspective on formulating poorly-water soluble compounds using wet media milling technology. Adv. Drug Deliv. Rev. 63(6), 427–440 (2011)CrossRefGoogle Scholar
  43. 43.
    Zhang, L.L., Chai, G.H., Zeng, X.P., He, H.B., Xu, H., Tang, X.: Preparation of fenofibrate immediate-release tablets involving wet grinding for improved bioavailability. Drug Dev. Ind. Pharm. 36(9), 1054–1063 (2010)CrossRefGoogle Scholar
  44. 44.
    Pasquali, I., Bettini, R., Giordano, F.: Solid-state chemistry and particle engineering with supercritical fluids in pharmaceutics. Eur. J. Pharm. Sci. 27, 299–310 (2006)CrossRefGoogle Scholar
  45. 45.
    Shapiro, H., Kagan, I., Shalita-Chesner, M., Singer, J., Singer, P.: Inhaled aerosolized insulin: a « Topical » anti-inflammatory treatment for acute lung injury and respiratory distress syndrome? Inflammation 33(5), 315–319 (2010)CrossRefGoogle Scholar
  46. 46.
    Kawashima, Y., Capes, C.E.: An experimental study of the kinetics of spherical agglomeration in a stirred vessel. Powder Technol. 10, 85–92 (1974)CrossRefGoogle Scholar
  47. 47.
    Nocent, M., Bertocchi, L., Espitalier, F., Baron, M., Couarraze, G.: Definition of a solvent system for spherical crystallization of salbutamol. J. Pharm. Sci. 13, 1215–1223 (2009)Google Scholar
  48. 48.
    Viçosa, A., Letourneau, J.J., Espitalier, F., Ré, M-I.: J. Cryst. Growth. doi: 10.1016/j.jcrysgro.2011.09.012 (2011)
  49. 49.
    Jojart-Laczkovich, O.J., Szabo-Revesz, P.: Amorphization of a crystalline active ingredient and thermoanalytical measurements on this glassy form. J. Therm. Anal. Calorim. 102, 243–247 (2010)CrossRefGoogle Scholar
  50. 50.
    Mikhailenko, M.A., Shakhtshneider, T.P., Debushchak, V.A., Kuznetsova, S.A., Skvortsova, G.P., Boldyrev, V.V.: Influence of mechanical treatment on the properties of betulin, betulin diacetate, and their mixture with water-soluble polymers. Chem. Nat. Compd. 47(2), 229–233 (2011)CrossRefGoogle Scholar
  51. 51.
    Kakran, M., Sahoo, N.G., Li, L.: Dissolution enhancement of quercetin through nanofabrication, complexation and solid dispersion. Colloids Surf. B. Biointerfaces 88(1), 121–130 (2011)CrossRefGoogle Scholar
  52. 52.
    Babar, I., Asgar, A., Javed, A., Sanjula, B., Sonal, G., Schweta, D., Shadab, M., Jasjeet, K.S.: Recent advances and patents in solid dispersion technology. Recent Pat Drug Deliv Formul 5(3), 244–264 (2011)CrossRefGoogle Scholar
  53. 53.
    Makhlof, A., Miazaki, Y., Tozuka, Y., Takeuchi, H.: Cyclodextrin as stabilizers for the preparation of drug nanocrystals by the emulsion solvent diffusion method. Int. J. Pharm. 357(1–2), 280–285 (2008)CrossRefGoogle Scholar
  54. 54.
    McNamara, D.P., Childs, S.I., Giordano, J., Iarriccio, A., Cassidy, J., Shet, M.S., et al.: Use of a glutaric acid cocrystal to improve oral bioavailability of a low solubility API. Pharm. Res. 23, 1888–1897 (2006)CrossRefGoogle Scholar
  55. 55.
    Elibogen, M.H., Olsen, K.M., Gentry-Nielsen, M.J., Preheim, L.C.: Efficacy of liposome-encapsulated ciprofloxacin compared with ciprofloxacin and ceftriaxone in a rat model of pneumoccoccal pneumonia. J. Antimicrob. Chemother. 51(1), 83–91 (2003)CrossRefGoogle Scholar
  56. 56.
    Miro, A., Quaglia, F., Giannini, L., Capello, B., La Rontonda, M.I.: Drug/cyclodextrin solid systems in the design of hydrophilic matrices: a strategy to modulate drug delivery rate. Curr. Drug Deliv. 3(4), 373–378 (2006)CrossRefGoogle Scholar
  57. 57.
    Gil, A., Chamayou, A., Leverd, E., Bougaret, J., Baron, M., Couarraze, G.: Evolution of the interaction of a new chemical entity, eflucimibe, with gamma-cyclodextrin during kneading process. Eur. J. Pharm. Sci. 23, 123–129 (2004)CrossRefGoogle Scholar
  58. 58.
    Hutin, S., Avan, J.L., Paillard, B., Baron, M., Couarraze, G., Bougaret, J.: Analysis of a kneading process to evaluate drug substance-cyclodextrin complexation. Pharm. Technol. 28, 112–124 (2004)Google Scholar
  59. 59.
    Fages, J., Rodier, E., Chamayou, A., Baron, M.: Comparative study of two processes to improve the bioavailability of an active pharmaceutical ingredient: kneading and supercritical technology. KONA 25, 217–229 (2007)Google Scholar
  60. 60.
    Agueros, M., Zabaleta, V., Espuelas, S., Campanero, M.A., Irache, J.M.: Increased oral bioavailability of paclitaxel by its encapsulation through complex formation with cyclodextrins in poly(anhydride)nanoparticles. J. Controlled Release 145(1), 2–8 (2010)CrossRefGoogle Scholar
  61. 61.
    Dhumal, R.S., Kelly, A.L., York, P., Coates, P.D., Paradkar, A.: Cocrystalization and simultaneous agglomeration using hot melt extrusion. Pharm. Res. 27, 2725–2733 (2010)CrossRefGoogle Scholar
  62. 62.
    Rosado Balmayor, E., Sepulveda Azevedo, H., Reis, R.L.: Controlled delivery systems: from pharmaceuticals to cells and genes. Pharm. Res. 28, 1241–1258 (2011)CrossRefGoogle Scholar
  63. 63.
    Cabane, E., Malinova, V., Menon, S., Palivan, C.G., Meier, W.: Photoresponsive polymersomes as smart, triggerable nanocarriers. Soft Matter 7, 9167–9176 (2011)CrossRefGoogle Scholar
  64. 64.
    Fukushima, K., Ise, A., Morita, H., Hasegawa, R., Ito, Y., Sugioka, N., Takada, K.: Two-layered dissolving microneedles for percutaneous delivery of peptide/protein drugs in rats. Pharm. Res. 28(1), 7–21 (2011)CrossRefGoogle Scholar
  65. 65.
    Lee, D.H., Kang, S.G., Jeong, S., Yoon, C.J., Choi, J.A., Byun, J.N., Park, J.H., Lee, K.B.: Local delivery system of immune modulating drug for unresectable adenocarcinoma: in vitro experimental study and in vivo animal study. Cardiovasc. Interv. Radiol. 29(5), 832–837 (2006)CrossRefGoogle Scholar
  66. 66.
    Aburai, K., Yagi, N., Yokoyama, Y., Okuno, H., Sakai, K., Sakai, H., Sakamoto, K., Abe, M.: Preparation of liposomes modified with lipopeptides using a supercritical carbon dioxyde reverse-phase evaporation method. J. Oleo Sci. 60(5), 209–215 (2011)CrossRefGoogle Scholar
  67. 67.
    Cue, B.W., Berridge, J., Manley, J.B.: PAT & green chemistry: the intersection of benign by design and quality by design. Pharm. Engin. 29, 8–20 (2009)Google Scholar
  68. 68.
    Ho, S.V., McLaughlin, J.M., Cue, B.W., Dunn, P.J.: Environmental considerations in biologics manufacturing. Green Chem. 12, 755–766 (2010)CrossRefGoogle Scholar
  69. 69.
    Lehmann, H., La Vecchia, L.: Scale-up of organic reactions in a pharmaceutical Kilo-lab using a commercial microwave reactor. Org. Process Res. Dev. 14, 650–656 (2010)CrossRefGoogle Scholar
  70. 70.
    Luche, J.L.: Synthetic Organic Chemistry. Plenum Press, New York (1998)Google Scholar
  71. 71.
    Louisnard, O.: A simple model of ultrasound propagation in a cavitating liquid. Part II: primary Bjerknes force and bubble structures. Ultrason. Sonochem. 19(1), 66–76 (2012)CrossRefGoogle Scholar
  72. 72.
    Buchholtz, S.: Future manufacturing approaches in the chemical and pharmaceutical industry. Chem. Eng. Process. 49, 993–995 (2010)CrossRefGoogle Scholar
  73. 73.
    Sheldon, R.A.: Green solvents for sustainable organic synthesis: state of the art. Green Chem. 7(5), 267–278 (2005)CrossRefGoogle Scholar
  74. 74.
    Carlier, L., Baron, M., Chamayou, A., Couarraze, G.: Use of co-grinding as a solvent-free state method to synthesize dibenzophenazines. Tetrahedron Lett. 52, 4686–4689 (2011)CrossRefGoogle Scholar
  75. 75.
    Carlier L., Baron M., Chamayou A., Couarraze G.: Greener pharmacy using solvent-free synthesis: investigation of the mechanism in the case of dibenzophenazines. Powder Technol. doi: 10.1016/j.powtec.2012.07.009 (2012)
  76. 76.
    Federsel, H.-J.: In search of sustainability: process R&D in light of current pharmaceutical industry challenges. Drug Discov. Today 11(21/22), 966–974 (2006)CrossRefGoogle Scholar
  77. 77.
    Baron, M., Chamayou, A., Carlier, L., Couarraze, G.: Dibenzophenazines synthesis by a smart green process. In: Proceedings of the 2nd International Conference on Environmental Pollution and Remediation. Montreal, Quebec, Canada, 28–30 August 2012, paper no 105, 1–4 (in press)Google Scholar
  78. 78.
    De Braal, H.: Sustainability in green pharmaceutical production. Pharm. Technol. Eur. 21, 1, (2009), Accessed 14 Oct 2011
  79. 79.
    Ma, S.K., Gruber, J., Davis, C., Newman, L., Gray, D., Wang, A., Grate, G., Huisman, G.W., Sheldon, R.A.: A green-by-design biocatalytic process for atorvastatin intermediate. Green Chem. 12, 81–86 (2010)CrossRefGoogle Scholar
  80. 80.
    Rozzell, D., Codexis Inc.: Greener chemical processes from biocatalysis. Accessed 20 Oct 2011
  81. 81.
    Savile, C.K., Janey, J.M., Mundorff, E.C., Moore, J.C., Tam, S., Jarvis, W.R., Colbeck, J.C., Krebber, A., Fleitz, F.J., Brands, J., Devine, P.N., Huisman, G.W., Hugues, G.J.: Biocatalytic asymetric synthesis of chiral amines from ketones applied to sitagliptin manufacture. Science 329(5989), 305–309 (2010)CrossRefGoogle Scholar
  82. 82.
    FDA, Process Analytical Technology (PAT)—Initiative Accessed 14 Oct 2011
  83. 83.
    Gendre, C., Genty, M., Boiret, M., Julien, M., Meunier, L., Lecoq, O., Baron, M., Chaminade, P., Pean, J.-M.: Development of a Process Analytical Technology (PAT) for in-line monitoring of film thickness and mass of coating materials during a pan coating operation. Eur. J. Pharm. Sci. 43, 244–250 (2011)CrossRefGoogle Scholar
  84. 84.
    Trout, B., Bisson, W.: Continuous manufacturing of small molecule pharmaceuticals. The Ultra Lean Way of Manufacturing. Accessed 14 Oct 2011
  85. 85.
    Klimesch, R., Mrosek, W., Bleckmann, G., Farwerk, K-P., Sanner, A., Schlemmer, L.: Process for the preparation of pharmaceutical tablets. EP 0358107 to BASF (1990)Google Scholar
  86. 86.
    Ivo Backx.: Changing the clock speed. http://Users/baron/Desktop/GSK%20and%20Siemens%20continuous%20tablet%20manufacture.html. Accessed 10 Oct 2011
  87. 87.
    Berthiaux, H., Marikh, K., Gatumel, C.: Continuous mixing of powder mixtures with pharmaceutical constraints. Chem. Eng. Process. 47(12), 2315–2322 (2008)CrossRefGoogle Scholar
  88. 88.
    Cordi, E.M., Schofield, R.: Leveraging green metrics for route selection and process optimization. Accessed 14 Oct 2011
  89. 89.
    Schaber, S.D., Gerogiorgis, D.I., Ramachandran, R., Evans, J.M.B., Barton, P.I., Trout, B.L.: Economic analysis of integrated continuous and batch pharmaceutical manufacturing: a case study. Ind. Eng. Chem. Res. 50(17), 10083–10092 (2011)CrossRefGoogle Scholar
  90. 90.
    Mirani, A.G., Patankar, S.P., Borole, V.S., Pawar, A.S., Kadam, V.J.: Curr. Drug Deliv. 8(4), 426–435 (2011)CrossRefGoogle Scholar
  91. 91.
    Tayel, S.A., Soliman, I.I., Louis, D.: Formulation of ketotifen fumarate fast-melt granulation sublingal tablet. AAPS Pharmscitech 11(2), 679–685 (2010)CrossRefGoogle Scholar
  92. 92.
    Desiré, A., Paillard, B., Bougaret, J., Baron, M., Couarraze, G.: Comparison between three extrusion systems on the properties of pellets prepared by extrusion-spheronisation—I: influence of water content and extrusion speed. Pharm. Technol. North Am. 35(1), 56–65 (2011)Google Scholar
  93. 93.
    Desiré, A., Paillard, B., Bougaret, J., Baron, M., Couarraze, G.: A comparison of three extrusion systems—Part II: influence of formulation and spheronization conditions on pellet properties. Pharm. Technol. North Am. 35(6), 56–61 (2011)Google Scholar
  94. 94.
    Ouabbas, Y., Dodds, J., Chamayou, A., Galet, L., Baron, M.: Particle-particle coating in a cyclomix impact mixer. Powder Technol. 189, 245–252 (2009)CrossRefGoogle Scholar
  95. 95.
    Ouabbas, Y., Chamayou, A., Galet, L., Baron, M., Thomas, G., Grosseau, P., Guilhot, B.: Surface modification of silica particles by dry coating: characterization and powder ageing. Powder Technol. 190(1–2), 200–209 (2009)CrossRefGoogle Scholar
  96. 96.
    Ouabbas, Y., Thomas, G., Grosseau, P., Guilhot, B., Baron, M., Chamayou, A., Galet, L.: Surface analysis of silicagel particles after mechanical coating with magnesium stearate materials. Appl. Surf. Sci. 255(17), 7500–7507 (2009)CrossRefGoogle Scholar
  97. 97.
    Gera, M., Sahara, V.A., Kataria, M., Kukkar, V.: Mechanical methods for dry particle coating processes and their applications in drug delivery and development. Recent Pat Drug Deliv Formul 4(1), 58–81 (2010)CrossRefGoogle Scholar
  98. 98.
  99. 99.
    Cook, S.M., VanDuinen, B.J., Love, N.G., Skerlos, S.J.: Life cycle comparison of environmental emissions from three disposal options for unused pharmaceuticals. Environ. Sci. Technol. 46(10), 5535–5541 (2012)CrossRefGoogle Scholar
  100. 100.
    Pomerantz, J.M.: Recycling expensive medication: why not? Med. Gen. Med. 6, 2–4 (2004)Google Scholar
  101. 101.

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  1. 1.Université de Toulouse, Mines-AlbiCNRS UMR 5302, Centre RapsodeeAlbi Cedex 09France

Personalised recommendations