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. 2021 Mar 13;13(3):387. doi: 10.3390/pharmaceutics13030387

Table A1.

Most important characteristics of the excipients discussed in this paper (in alphabetical order).

Excipient Functions DAI * Recommendations Adverse Effects References
Aspartame Artificial Sweetener 40 mg/kg
  • -

    Contraindicated in patients with phenylketonuria
  • -

    Neurological involvement: neurotoxicity, epilepsy, headache, panic attack, hallucinations

  • -

    Hypersensitivity reactions: vascular, granulomatous panniculitis

  • -

    Cross reaction with sulfamides

 [29,35]
Benzalkonium chloride Preservative NA
  • -

    Caution in asthmatic patients
  • -

    Bronchoconstriction

  • -

    Ototoxicity

  • -

    Hypersensitivity

 [29]
Benzyl alcohol Preservative 5 mg/kg
  • -

    Contraindicated in children under 3 years of age by immature their metabolism

 In new-borns and children under 3 years of age cause:
  • -

    Metabolic acidosis and respiratory depression

  • -

    Intraventricular haemorrhage

  • -

    Cerebral palsy and developmental delay

  • -

    Hypersensitivity reactions

 [29,35,36,39,40,41,42,43,44]
Ethyl alcohol Solvent and preservative 6 mg/kg/dose (<6 years) Paediatric formulations should not exceed the following limits of ethanol:
  • -

    In children over 12 years of age: less than 10% (v/v)

  • -

    In children 6–12 years old: less than 5% (v/v)

  • -

    In children under 6 years of age: less than 0.5 (v/v)
  • -

    Hypoglycaemia, acidosis and hydroelectrolytic alterations

  • -

    Stupor, coma respiratory and CNS depression, cardiovascular toxicity

 [17,26,27,29,31,32]
Glycerol Solvent, sweetener, viscosizer and preservative 10 g/dose
  • -

    Caution in paediatric population

  • -

    Do not exceed the safe daily dose (1.0–1.5 g/kg body weight)
  • -

    Mucositis in the stomach

  • -

    Diarrhoea and electrolyte disturbances

 [1,29]
Lactose Diluent NA
  • -

    Caution in patients with lactose intolerance

  • -

    Contraindicated in galactosemia

 Symptoms of lactose intolerance: severe abdominal pain, flatulence, bloating or swelling and diarrhoea.
  • -

    Systemic symptoms such as muscle and joint pain and eczema

  • -

    In children it can cause dehydration, bacterial proliferation and metabolic acidosis

 [1,28]
Parabens Preservative 10 mg/kg
  • -

    It is recommended to avoid its use in neonates
  • -

    Cross hypersensitivity reactions in patients allergic to acetylsalicylic acid

  • -

    Hyperbilirubinemia in new-borns

 [29,35,36]
Phthalates Coating agents (plasticizers) NA
  • -

    Not recommended for use in pregnant women or children under 3 years of age
  • -

    Anomalies in the development of the foetus: cleft palate and skeletal malformations. May lead to stillbirth

 [28]
Polyethylene glycol Solvent, suspensor and viscosity agent 10 mg/kg
  • -

    Caution in new-borns and infants
  • -

    Nephrotoxicity

  • -

    Gastrointestinal disorders

  • -

    Laxative effect

 [1,28]
Polysorbates Dispersing, emulgent, surfactants, solubilizing and moisturizing agents NA
  • -

    Caution in new-borns
  • -

    Serious adverse effects: deaths in low-weight neonates who received vitamin E preparations with polysorbates.

  • -

    Polysorbate 80: increased mortality in new-borns

 [25,42]
Propyl gallate Antioxidant NA
  • -

    Caution in new-borns
  • -

    In neonates it can cause dermatitis, skin allergy and methemoglobinemia

 [29]
Propylene glycol Solvent, moisturizing and preservative
  • -

    Neonates: 1 mg/kg

  • -

    Under 5 years: 50 mg/kg

  • -

    Adults: 500 mg/kg
  • -

    It is recommended to avoid in children under 4 years of age because of lack of metabolic maturation
  • -

    CNS depression

  • -

    Laxative effect from high osmolality after oral administration

 [29,33,34]
Saccharine Sweetener 2.5 mg/kg
  • -

    It is recommended to limit the daily dose in pregnant women and children
  • -

    Urticaria, itching and eczema

  • -

    Photosensitization

  • -

    GI disturbances: Nausea and diarrhoea

 [29,48]
Sorbitol Sweetener and diluent
  • -

    Children 0–2 years 5 mg/kg

  • -

    Over 2 years: 140 mg/kg
  • -

    Contraindicated in patients with fructose intolerance

  • -

    Not recommended for use in patients with hypoglycaemia
  • -

    Gastrointestinal disorders

  • -

    It can cause hepatic damage with comma and even death

 [28,29,30]
Starch Diluent and added NA
  • -

    Conservation in dry environment

  • -

    Well tolerated by children
  • -

    In case of moisture, carcinogenic aflatoxins may occur

 [29]
Sucralose Sweetener 15 mg/kg
  • -

    Caution in patients with metabolic disorders

 Alters the composition of the digestive tract microbiome
  • -

    At high temperatures chloropropanol may form

  • -

    May alter glucose, insulin and GLP-1 *2 levels

 [29]
Sucrose Sweetener NA
  • -

    Not recommended for use in children with type I diabetes
  • -

    Dental damage

  • -

    At very high doses on a daily basis I could be carcinogenic

 [29]
Sulphites Antioxidant NA
  • -

    Avoid in asthmatic patients
  • -

    Hypersensitivity and bronchospasm reactions

 [29]
Tartrazine, quinolines, triphenylmethane, xanthines Colorants NA
  • -

    It is recommended not to use them in paediatric formulations
  • -

    Hypersensitivity reactions in patients’ sensitive to tartrazine

  • -

    Azo colorants: cross-sensitivity reactions with acetylsalicylic acid

Erythromycin: photosensitization reactions 		[28,29]
Thiomersal Preservative NA
  • -

    Avoid use in vaccines as a preservative due to its side effects
  • -

    Hypersensitivity reactions

  • -

    Autism spectrum disorders

 [28,29]

* ADI: Admissible Daily Intake; *2 GLP-1: Glucagon Like Peptide; NA: Not Available.