Friday, September 17, 2021

Problems Encountered During Trituration and Possible Solutions

by | November 13, 2020 0

As discussed in our article “Mixing of Pharmaceutical Powders in Small-Scale Operations”, trituration process involves direct rubbing or grinding of hard powder in a mortar and pestle. The trituration method is used for both pulverization and mixing.

Crystalline salts are mixed well by trituration in a mortar. The inner surface of Wedgewood mortars rows smooth with long-term use. When this happens, powders do not mix well. In such instances, the surface of a mortar can be made rough by triturating with a little powdered pumice or pharmaceutical sand.

This article will focus on identifying the most common problems encountered during trituration and possible solutions.

Problems encountered during trituration and possible solutions

1. Electrification

Electrification is a phenomenon in which some substances repel each other during mixing. This might be due to simple resistance to admixture, or it may be due to electrical charges.

This problem can be eliminated by moistening the powders very slightly with a few drops of alcohol or mineral oil.

Read Also: Mechanisms Involved in the Mixing of Pharmaceutical Powders

2. Packing

A packing problem is encountered when powders are pressed heavily during trituration. This problem can be avoided by triturating lightly and scraping the sides of the mortar frequently with a spatula.

3. Physical immiscibility

The phenomenon of physical immiscibility may occasionally present minor problems. Mixing resinous materials with granular salts and mixing heavy powder (starch) with a light one (zinc stearate) may lead to this incompatibility issue.

This problem can be minimized by triturating each substance separately to a fine state and then mixing by sifting or tumbling.

4. Dampening or Liquefaction

Dampening, or liquefaction, is the most troublesome problem in powder mixing and can happen for three different reasons:

a. Absorption of moisture from the air (deliquescent/ hygroscopic)

A substance that absorbs moisture from the air is termed hygroscopic (e.g., ephedrine sulfate, lithium bromide, ammonium chloride). A hygroscopic material that absorbs the moisture from the air to such an extent that it liquefies partially or fully is termed deliquescent.

Hygroscopic materials should not be ground finer than is necessary and should be wrapped in closed containers.

b. Giving up moisture to the air and liquefying during the process (efflorescent)

Some examples include atropine sulfate, quinine HCl, and scopolamine hydrobromide.

c. Lowering the melting point of the mixture (eutectic mixture)

Eutectic mixtures result when certain organic compounds (phenol, aldehydes, and ketones) are mixed in varying proportions. The melting point of a fixed composition of a mixture is considerably below that of any of the individual ingredients, and forms a damp mass or even liquefies when mixed together. When mixed in a definite composition from the following ingredients, some drug substances may form a eutectic mixture and liquefy:

  1. Acetylsalicylic acid
  2. Aminopyrine
  3. Camphor
  4. Menthol
  5. Phenol
  6. Salol
  7. Thymol
  8. Acetanilide
  9. Acetophenetidin
  10. Aminopyrine
  11. Antipyrine
  12. Aspirin
  13. Benzocaine
  14. Beta-naphthol
  15. Camphor
  16. Chloral hydrate
  17. Lidocaine
  18. Menthol
  19. Phenacetin
  20. Phenol
  21. Phenyl salicylate
  22. Prilocaine
  23. Resorcinol
  24. Salicylic acid
  25. Thymol

There are three ways to handle this problem:

  1. Separately dispense the individual components.
  2. Mix each compound with an equal amount of inert diluents (lactose, starch, talc) and finally combine the diluted powders with light trituration.
  3. Mix the materials together and allow them to liquefy, and then add sufficient amounts of adsorbents to adsorb the eutectic liquid mixture and remain as a free-flowing powder.

References

  • Allen, L and Ansel, H (2014). Ansel’s Pharmaceutical Dosage Forms and Drug Delivery Systems. Philadephia: Lippincott Williams and Wlkins.
  • Dash, A., Singh, S. and Tolman, J. (2014). Pharmaceutics – Basic Principles and Application to Pharmacy Practice. USA: Academic Press.



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