Parenteral

This chapter gives an overview of parenteral dosage forms and the rationale for their use. Parenterals are sterile preparations that are injected intravascularly, administered into body tissues or into visceral cavities. The parenteral route of administration is often chosen for active substances that are poorly absorbed via the oral route or when rapid systemic availability and effects are required, or both. An introduction to the formulation and preparation of parenteral dosage forms is provided. Parenteral medicines can be formulated as solutions, colloidal dispersions, emulsions or suspensions. Products, such as implants and microspheres are only briefly discussed.

Knowledge about the specialties of parenteral products is a prerogative for the safe use of parenterals in- and outside the hospital. Therefore, strategies for the reconstitution and preparation of ready to administer medicines are described in detail. Special attention is paid to formulation, preparation, and quality control of parenteral nutrition admixtures. Finally, the administration methods of the parenteral dosage forms are described.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Subscribe and save

Springer+ Basic €32.70 /Month

Buy Now

Price includes VAT (France)

eBook EUR 160.49 Price includes VAT (France)

Softcover Book EUR 52.74 Price includes VAT (France)

Hardcover Book EUR 210.99 Price includes VAT (France)

Tax calculation will be finalised at checkout

Purchases are for personal use only

Similar content being viewed by others

Parenteral

Chapter © 2015

Commercial Parenteral Formulas and Nutrition Support Team

Chapter © 2014

Commercial Parenteral Formulas and Nutrition Support Team

Chapter © 2015

References

  1. Koch A, Henke S (2021) Mikronadelsysteme und microarray patches. Pharm Ind 83(6):844–850 CASGoogle Scholar
  2. Resolution CM/Res (2016) 1 on quality and safety assurance requirements for medicinal products prepared in pharmacies for the special needs of patients. https://www.edqm.eu/sites/default/files/medias/fichiers/About_us/About_EDQM/History/resolution_cm_res_2016_1_quality_and_safety_assurance_requirements_for_medicinal_products_prepared_in_pharmacies.pdf. (edCounciqm.eu)
  3. Council of Europe (2021) European pharmacopeia, 10th edn. Council of Europe, Strasbourg Cedex Google Scholar
  4. Resolution CM/Res (2016) 2 on good reconstitution practices in health care establishments for medicinal products parenteral use. https://www.edqm.eu/sites/default/files/resolution_cm_res_2016_2_good_reconstitution_practices_in_health_care_establishments_for_medicinal_products_for_parenteral_use_.pdf. (edqm.eu)
  5. EMA/CHMP development/QWP/799402/2011 (2012) Reflection paper on the pharmaceutical of intravenous medicinal products containing active substances solubilised in micellar systems Google Scholar
  6. Broadhurst D, Cooke M, Sriram D, Gray B (2020) Subcutaneous hydration and medications infusions (effectiveness, safety, acceptability): a systematic review of systematic reviews. PLoSOne 15(8):e023757 ArticleGoogle Scholar
  7. DIN EN ISO 80369-6:2018-10 Verbindungsstücke mit kleinem Durchmesser für Flüssigkeiten und Gase in medizinischen Anwendungen - Teil 6: Verbindungsstücke für neuroaxiale Anwendungen (ISO 80369-6:2016, korrigierte Fassung 2016-11-15) Google Scholar
  8. Imbelloni LE, Beato L, Gouveia MA, Cordeiro JA (2007) Low dose isobaric, hyperbaric, or hypobaric bupivacaine for unilateral spinal anesthesia. Rev Bras Anestesiol 57(3):261–270 CASPubMedGoogle Scholar
  9. Sheth RA, Murthy R, Hong DS et al (2020) Assessment of image-guided intratumoral delivery of immunotherapeutics in patients with cancer. JAMA Netw Open 3(7):e207911–e207911 ArticlePubMedGoogle Scholar
  10. Nisbet AC (2006) Intramuscular gluteal injections in the increasingly obese population: retrospective study. BMJ 332(7542):637–638 ArticlePubMedPubMed CentralGoogle Scholar
  11. Maggio ET (2008) Novel excipients prevent aggregation in manufacturing and formulation of protein and peptide therapeutics. Bioprocess Int 6(10):58–65 CASGoogle Scholar
  12. Salgueiro-Oliveira A, Parreira P, Veiga P (2012) Incidence of phlebitis in patients with peripheral intravenous catheters: the influence of some risk factors. Aust J Adv Nurs 30(2):32–39 Google Scholar
  13. Szmuk P, Szmuk E, Ezri T (2005) Use of needle-free injection systems to alleviate needle phobia and pain at injection. Expert Rev Pharmacoecon Outcomes Res 5(4):467–477 ArticlePubMedGoogle Scholar
  14. Pérez Fidalgo JA, García Fabregat L, Cervantes A, Margulies A, Vidall C et al (2012) Management of chemotherapy& extravasation: ESMO- EONS clinical practice guidelines. Ann Oncol 23(Suppl 7):169–173 Google Scholar
  15. Steffens KJ (1989) Parenterale Therapie und Fremdpartikeln 1. Mitt: Die Bedeutung partikulärer Verunreinigung bei der parenteralen Therapie. Pharm Ind 51:799–806 Google Scholar
  16. Anderson JM, McNally AK (2011) Biocompatibility of implants: lymphocyte/macrophage interactions. Semin Immunopathol 33:221–233 ArticleCASPubMedGoogle Scholar
  17. Van Hoogewst P, Höllig P (2021) Synthetische Phospholipide als Hilfsstoffe zur parenteralen und pulmonalen Verabreichung. Pharm Ind 83(6):830–843 Google Scholar
  18. Kinine-injectie 600 mg = 5 ml (120 mg/ml) FNA. Jaar 2009. Formularium der Nederlandse Apothekers. Den Haag: Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie (KNMP) Google Scholar
  19. Feng A, Kaye A, Kaye R, Belanie K, Urman R (2017) Novel propofol derivatives and implications for anesthesia practice. J Anaesthesiol Clin Pharmacol 33(9):9–15 CASPubMedPubMed CentralGoogle Scholar
  20. Wu HH, Garidel P, Michaela B (2021) HP-β-CD for the formulation of IgG and Ig-based biotherapeutics. Int J Pharm 601:120531 ArticleCASPubMedGoogle Scholar
  21. Strickley RG (2004) Solubilizing excipients in oral and injectable formulations. Pharm Res 21(2):201–230 ArticleCASPubMedGoogle Scholar
  22. Zheng L et al (2019) Efficacy of management for obstruction caused by precipitated medication or lipids in central venous access devices: a systematic review and meta-analysis. J Vascular Access 20(6):583–591 ArticleGoogle Scholar
  23. Mottu F, Laurent A, Rüfenacht DA et al (2000) Organic solvents for pharmaceutical parenterals and embolic liquids: a review of toxicity data. PDA J Pharm Sci Techn 54(6):456–469 CASGoogle Scholar
  24. Yingchoncharoen P, Kalinowski D, Richardson D (2016) Lipid-based drug delivery systems in cancer therapy: what is available and what is yet to come. Pharm Rev 68(3):701–787 ArticleCASPubMedPubMed CentralGoogle Scholar
  25. Rahnfeld L, Luciani P (2020) Injectable lipid-based depot formulations: where do we stand? Pharmaceuticals 12(6):567 ArticleCASGoogle Scholar
  26. Technov R, Bird R, Curtze AE, Zhou Q (2021) Lipid nanoparticles – from liposomes to mRNA vaccine delivery, a landscape of research diversity and advancement. ASC Nano 15:16982–17015 ArticleGoogle Scholar
  27. Lengyel M et al (2019) Microparticles, microspheres, and microcapsules for advanced drug delivery. Sci Pharm 87(3):20. https://doi.org/10.3390/scipharm87030020ArticleCASGoogle Scholar
  28. Stranz M, Kastango ES (2002) A review of pH and osmolarity. Int J Pharm Comp 6(3):216–220 Google Scholar
  29. Heeb RM et al (2017) Stability of ready-to-administer and ready-to-use epinephrine and norepinephrine injection solutions. Pharm Technol Hosp Pharm 2(4):159–171 Google Scholar
  30. Fysostigminesalicylaatinjectie 2 mg = 2 ml (1 mg/ml) FNA. Jaar 2009. Formularium der Nederlandse Apothekers. Den Haag: Koninklijke Nederlandse Maatschappij ter bevordering der Pharmacie (KNMP) Google Scholar
  31. Belayneh A, Tadesev E, Molla F (2020) Safety and biopharmaceutical challenges of excipients in off-label pediatric formulations. Int J General Med 13:1051–1066 ArticleCASGoogle Scholar
  32. EMA/CPMP/463/00 (2003) Guideline Excipients in the label and package leaflet of medicinal products for human use Google Scholar
  33. EMA/CHMP/302620/2017 (2019, November 2) Rev. 1* Annex to the European Commission guideline on ‘Excipients in the labelling and package leaflet of medicinal products for human use’ (SANTE-2017-11668) Excipients and information for the package leaflet Google Scholar
  34. Gibaldi M, Desai A, Lee M (2007) Gibaldi’s drug delivery systems in pharmaceutical care. American Society of Health-System Pharmacists, Bethesda Google Scholar
  35. Baheti A, Kumar L, Bansal AK (2010) Excipients used in lyophilisation of small molecules. J Excip Food Chem 1(1):41–54 CASGoogle Scholar
  36. EMA/CPMP/QWP/159/96 (1998) Note for guidance on maximum shelf-life for sterile products for human use after first opening or following reconstitution Google Scholar
  37. Patel RM (2010) Parenteral suspension: an overview. Int J Curr Pharm Res 2(3):1–13 Google Scholar
  38. Karan M, Inderbir S, Manju N, Sandeep A (2010) Atrigel: a potential parenteral controlled drug delivery system. Pharmacia Sinica 1(1):74–81 Google Scholar
  39. Klemm K (2001) The use of antibiotic-containing bead chains in the treatment of chronic bone infections. Clin Microbiol Infect 7(1):28–31 ArticleCASPubMedGoogle Scholar
  40. Moncalvo F, Martinez Espinoza MI, Cellesi F (2020) Nanosized delivery systems for therapeutic proteins: clinically validated technologies and advanced development strategies. Front Bioeng Biotechnol 8:89 ArticlePubMedPubMed CentralGoogle Scholar
  41. Ciolli A, Leoni F, Bosi A (2006) The value of PegFilgastrim for the therapy of acute myeloid leukemia. Haematol Rep 2(7):96–98 Google Scholar
  42. Zander R (2006) Infusion fluids: why should they be balanced solutions. EJHP Pract 12:60–62 Google Scholar
  43. EMA/422341/2018 (2018, June 29) Hydroxyethyl starch solutions: CMDh introduces new measures to protect patients https://www.ema.europa.eu/en/documets/press-release/hydroxyethyl-starch-solutions-cmdh-introduces-new-measures-protect-patients_en.pdf
  44. Manrique-Rodriguez S et al (2021) Standardization and chemical characterization of intravenous therapy in adult patients: a step further in medication safety. Drugs R&D 21(1):39–64 ArticleCASGoogle Scholar
  45. Bryland A, Broman M, Erixon M, Klarin B, Lindén T, Friberg H et al (2010) Infusion fluids contain harmful glucose degradation products. Intensive Care Med 36(7):1213–1220 ArticleCASPubMedPubMed CentralGoogle Scholar
  46. Good preparation practices (PIC/S GPP): “Guide to good practices for the preparation of medicinal products in health care establishments”, in Pharmaceutical Inspection Convention and Pharmaceutical Inspection Co-operation Scheme (PIC/S) Guide PE 010 Google Scholar
  47. EU-GMP Guide, Annex 1 manufacture of sterile medicinal products Google Scholar
  48. Crauste-Manciet S et al (2020) GERPAC consensus conference–guidance on the assignment of microbiological shelf-life for hospital pharmacy aseptic preparations. Pharm Techn Hospital Pharm 5(1). https://doi.org/10.1515/pthp-2020-0001
  49. Shintani H (2013) Rapid assay of bioburden, endotoxin and other contamination. J Cromat Separat Techniq 4(8):2–7 Google Scholar
  50. Smeets OSNM, Le Brun PPH (2004) Zuurstof meten en verwijderen bij parenterale apotheekbereidingen. Meer stabiliteit door minder oxidatie. Pharm Weekbl 139(37):1207–1210 Google Scholar
  51. Veale J (2009) New inspection developments. In: Lysfjord J (ed) Practical aseptic processing, fill and finish, 1st edn. Davis Healthcare International Publishing, River Grove Google Scholar
  52. Anonymous (2021) Pharmaceutical dosage forms. injections . In: The United States pharmacopeia 44 and the National formulary 39. United States Pharmacopeial Convention, Rockville, USA Google Scholar
  53. Morton Guazzo D (2010) Sterile product package integrity testing, current practice, common mistakes, new developments. Paper presented at PDA Metro Chapter Meeting, New Brunswick, 17 May 2010 Google Scholar
  54. Wolf H, Stauffer T, Chen S, Lee Y, Forster R, Ludzinski M et al (2009) Vacuum decay container/closure integrity testing technology. Part 2. Comparison to dye ingress tests. PDA J Pharm Sci Technol 63(5):489–498 PubMedGoogle Scholar
  55. Kennedy L, Vaughan LM, Steed LL, Sahn SA (1995) Sterilisation of talc pleurodesis. Available techniques, efficacy, and cost analysis. Chest 107(4):1032–1034 ArticleCASPubMedGoogle Scholar
  56. Melchore JA (2011) Sound practices for consistent human visual inspection. AAPS PharmSciTech 12(1):215–221 ArticlePubMedPubMed CentralGoogle Scholar
  57. Krämer I, Thiesen J, Astier A (2020) Formulation and Administration of Biological Medicinal Products. Pharm Res 37:159 ArticlePubMedGoogle Scholar
  58. Kenedy S (2011) Home infusion. Int J Pharm Comp 15(4):270–276 Google Scholar
  59. Gross I, Fischer A, Knoth H (2021) Medikationsmanagement im Krankenhaus. Deutscher Apotheker Verlag, Stuttgart Google Scholar
  60. Beaney AM (ed) (2016) Quality assurance of aseptic preparation services: standards handbook part A & B, 5th edn. Royal Pharmaceutical Press, London Google Scholar
  61. Riskin A, Picaud JC, Shamir R (2018) ESPGHAN/ESPEN/ESPR/CSPEN working group on pediatric parenteral nutrition. ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: standard versus individualized parenteral nutrition. Clin Nutr 37(6):2409–2417 ArticlePubMedGoogle Scholar
  62. Hartman C, Shamir R, Simchowitz V, Lohner S, Cai W, Desci T (2018) ESPGHAN/ESPEN/ESPR guideline on pediatric parenteral nutrition: Complications. Clin Nutr 38:2418–2429 ArticleGoogle Scholar
  63. FDA Safety Alert. Hazards of precipitation associated with parenteral nutrition18 Apr 1994. http://www.fda.gov
  64. Boullata JI, Mirtallo JM, Sacks GS et al (2022) Parenteral nutrition compatibility and stability: a comprehensive review. J Parenter Enter Nutr 46:273–299 ArticleGoogle Scholar
  65. Pluhator-Murton MM, Fedorak RN, Audette RJ, Marriage BJ, Yatscoff RW, Gramlich LM (1999) Trace element contamination of total parenteral nutrition, 2. Effect of storage duration and temperature. J Parenter Enteral Nutr 23:228–232 ArticleCASGoogle Scholar
  66. Steger P, Mühlebach S (2000) Lipid peroxidation of intravenous lipid emulsions and all-in-one admixtures in total parenteral nutrition bags: the influence of trace elements. J Parenter Enter Nutr 24:37–41 ArticleCASGoogle Scholar
  67. Schröder AM (2008) Total parenteral nutrition-problems in compatibility and stability. EJHP Pract 14(1):65–67 Google Scholar
  68. Anonymous (2021) Globule size distribution in lipid injectable emulsions. In: The United States Pharmacopeia 44 and National Formulary 39, United States Pharmacopeial Convention, Rockville Google Scholar
  69. Klang MG (2015) PFAT5 and the evolution of lipid admixture stability. J Parenter Enter Nutr 39(1 Suppl):67S–71S ArticleGoogle Scholar
  70. Allwood MC, Kearney MCJ (1998) Compatibility and stability of additives in parenteral nutrition admixtures. Nutrition 14(9):697–706 ArticleCASPubMedGoogle Scholar
  71. De Cloet J, van Biervliet S, van Winckel M (2018) Physicochemical stable standard all-in-one parenteral nutrition admixtures for infants and children in accordance with the ESPGHAN/ESPEN guidelines. Nutrition 49:41–47 ArticlePubMedGoogle Scholar
  72. Watrobska-Swietlikowska D, Macloughlin R (2019) The effect of UV-protected ethylene vinyl acetate (EVA) bags on the physicochemical stability of pediatric parenteral nutrition admixtures. DARU J Pharm Sci 27(1):255–264 ArticleCASGoogle Scholar
  73. Uccello-Barretta G, Balzano F, Aiello F, Falugiani N, Desideri I (2015) Stability of hydrophilic vitamins mixtures in the presence of electrolytes and trace elements for parenteral nutrition: a nuclear magnetic resonance spectroscopy investigation. J Pharm Biomed Anal 107:7–10 ArticleCASPubMedGoogle Scholar
  74. Hoff DS, Michaelson AS (2009) Effects of light exposure on total parenteral nutrition and its implications in the neonatal population. J Pediatr Pharmacol Ther 14(3):132–143 PubMedPubMed CentralGoogle Scholar
  75. Robinson DT et al (2021) Recommendations for photoprotection of parenteral nutrition for premature infants: an ASPEN position paper. Nutr Clin Pract 36(5):927–941 ArticleCASPubMedGoogle Scholar
  76. Puntis J et al (2018) ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: organisational aspects. Clin Nutr 37(6):2392–2400 ArticlePubMedGoogle Scholar
  77. Boullata JI et al (2014) ASPEN clinical guidelines: parenteral nutrition ordering, order review, compounding, labeling, and dispensing. J Parent Enteral Nutr 38(3):334–377 ArticleGoogle Scholar
  78. American Society of Health-System Pharmacists (2021) ASHP guidelines on the safe use of automated compounding devices for the preparation of parenteral nutrition admixture. Am J Health-Syst Pharm. ASHP Guidelines on the Safe Use of Automated Compounding Devices for the Preparation of Parenteral Nutrition Admixtures
  79. Timmer JG, Schipper HG (1991) Peripheral venous nutrition: the equal relevance of volume load and osmolarity in relation to phlebitis. Clin Nutr 10(2):71–75 ArticleCASPubMedGoogle Scholar
  80. Kesten JM, Ayres R, Neale J, Clark J, Vickerman P, Hickman M, Redwood S (2017) Acceptability of low dead space syringes and implications for their introduction: a qualitative study in the West of England. Int J Drug Policy 39:99–108 ArticlePubMedGoogle Scholar
  81. ISO 594/1-1986. Conical fittings with a 6% (Luer) taper for syringes, needles and certain other medical equipment Google Scholar
  82. DIN EN 1707–1997. Conical fittings with a 6% (Luer) taper for syringes, needles and certain other medical equipment-Lock fittings Google Scholar
  83. Council of the European Union, Directive implementing the Framework Agreement on prevention from sharp injuries in the hospital and healthcare sector concluded by HOSPEEM and EPSU (PDF) Google Scholar
  84. Kim SH, Stollhof B, Krämer I (2018) Auswahl und Umgang mit In-Line-Filtern zur parenteralen Applikation von Tumortherapeutika. Krankenhauspharmazie 39(11):11–18 Google Scholar
  85. Kommission für Krankenhaushygiene und Infektionsprävention beim Robert Koch-Institut (RKI) (2017) Prävention von Infektionen, die von Gefäßkathetern ausgehen Bundesgesundheitsblatt 02/2017 Google Scholar
  86. Pittiruti M, Hamilton H, Biffi R, MacFie J, Pertkiewicz M (2009) ESPEN guidelines on parenteral nutrition: central venous catheters (access, care, diagnosis and therapy of complications). Clin Nutr 28(4):365–377 ArticlePubMedGoogle Scholar
  87. Magallón-Pedrera I et al (2020) ECO-SEOM-SEEO safety recommendations guideline for cancer patients receiving intravenous therapy. Clin Transl Oncol 22(11):2049–2060 ArticlePubMedPubMed CentralGoogle Scholar

Author information

Authors and Affiliations

  1. Department of Pharmacy, University Medical Centre, Johannes Gutenberg University Mainz, Mainz, Germany Marija Tubic-Grozdanis & Irene Krämer
  1. Marija Tubic-Grozdanis