Residual Solvents|Classification of residual solvents

Residual solvents, as the name indicates, are the solvents that are left behind in any product after the completion of its manufacturing. According to ICH Q3 guidelines, residual solvents are defined as “Residual solvents are volatile organic chemicals which are used for manufacturing of excipients, active pharmaceutical ingredients or a drug product and are not completely removed from that product after its manufacturing”

Explanation

  • To explain the residual solvents, take the example of the tablet manufacturing process by wet granulation.
  • Suppose we manufacture a tablet by wet granulation method using an organic solvent like IPA( Isopropyl Alcohol).
  • After the wetting or kneading process we remove the IPA from granules by drying the granules using FBD or tray dryers but the used IPA is not completely removed from the granules and remains inside granules;this IPA is known as Residual solvent.
  • As we  know, IPA is volatile and may be harmful to the environment or human health.
  • If we compress these tablets the residual solvent will remain inside the tablet so we should test and calculate the amount of residual solvent.
  • Regulatory bodies define the limit of each solvent so if we use any organic solvent its value should be within range.

Also Read:

Basics of Pharmaceutics.

Analytical Procedures

Amount of residual solvents is determined by using chromatographic techniques like gas chromatography.

Classification

Residual solvents are classified into following three classes

  • Class 1 Solvent (To be avoided)
  • Class 2 Solvent (To be limited)
  • Class 3 Solvent (Low toxic potential)

Class 1 Solvent (To be avoided)

  • Class 1 solvents are the solvents which should always be tried to avoid the use in manufacturing of pharmaceuticals.
  • Class 1 solvents are human carcinogenic.
  • Environmental hazardous.

Examples

Following are some main examples of class 1 solvents,

  • Benzene
  • Carbon tetrachloride
  • 1,2 dichloroethane
  • 1,1 dichloroethene

Class 2 Solvent (To be limited)

  • Class 2 solvents are those which should always be used in limited amounts in manufacturing of pharmaceuticals.
  • Class 2 solvents are animal carcinogens.
  • May Cause neurotoxicity.
  • May cause teratogenicity.
  • Permitted daily exposure (PDE) is 0.1 mg per day.

Examples

Following are some main examples of class 2 solvents.

  • Acetonitrile
  • Chlorobenzene
  • Chloroform
  • Formamide
  • Hexane
  • Methanol
  • Nitromethane
  • Pyridine
  • Toluene
  • Sulfolane
  • Xylene

Also Read:

Biopharmaceutics FAQ

Class 3 Solvent (Low toxic potential)

  • Class 3 solvents are low toxic.
  • Health based limit of exposure is not required.
  • Permitted daily exposure (PDE) is 50 mg or more per day.

Examples

Following are some main examples of class 3 solvents.

  • Acetone
  • Acetic Acid
  • Anisol
  • Ethanol
  • 1 propanol
  • 2 propanol
  • Formic acid
  • Cumene

Reference: 

  • The theory and practice of Industrial Pharmacy (Lachman)
  • Practical Observations

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