1. Properties:

Granule drugs must be dry, uniform in granule size, without moisture absorption, without softening and discoloration.

2. Moisture Content:

Requirement: <= 5% (except for other instructions)

Determination method: Determination of loss on drying (Appendix 9.6 DĐVN IV). For granule drugs containing essential oils, use the solvent distillation method (Appendix 12.13).

3. Weight Uniformity:

• Non-single-dose granules (Method 2):

  • < 300 mg ±10 %
  • ≥ 300 mg ±7.5%

  Testing method: Weigh the mass of one package (P1). Take out all the drugs, use a cotton swab to clean up the powder on the inside, weigh the mass of the package (P2). Proceed similarly with 19 other units taken at random.

  Drug mass = P1 – P2

  Evaluating the results: No more than 02 units may have a mass outside the specified limit and no unit may have a mass exceeding twice that limit.

• Multi-dose granules (Method 4):

  • All types ± 5%

  Testing method: Weigh the mass of one package (P1). Take out all the drugs, use a cotton swab to clean up the powder on the inside, weigh the mass of the package (P2). Proceed similarly with 04 other units taken at random.

  Drug mass = P1 – P2

  Evaluating the results:

  • All must have a mass within the limits specified compared to the label mass.
  • If one unit has a mass outside this limit, repeat the test with five other units taken at random. No more than one unit/10 units tested may have a mass outside the specified limit.

* The weight uniformity of granule drugs is an important parameter for assessing drug quality. It ensures that each dose contains the required amount of active ingredient.

* The methods for testing weight uniformity are prescribed in the Vietnamese Pharmacopoeia.

4. Dissolution (effervescent granules):

Put a quantity of granules packaged in a single dose unit into a beaker containing 200 ml of water at 15 – 25 oC, there must be many gas bubbles coming out. Granules are considered to have dissolved completely if they dissolve or disperse completely in water.

Test with 6 doses, the preparation meets the test requirements if each dose dissolves within 5 minutes, unless otherwise specified in the individual monograph.

5. Qualitative Identification (according to the individual monograph):

• Basis for choosing a qualitative identification method:
• Physicochemical properties of the active ingredient.
• Solubility of the active ingredient and excipients in the preparation.
• Techniques used in qualitative identification of powders – granules:
• Characteristic color reaction.
• Melting point determination*
• IR spectrum measurement: characteristic peaks.*
• UV spectrum measurement: max.*
• Thin layer chromatography Rf*
• Gas chromatography (GC) tR.*
• High performance liquid chromatography (HPLC) tR.*
• *Compare with standard*

6. Quantitative Determination (according to the individual monograph):

• Basis for choosing a quantitative determination method:
• Physicochemical properties of the active ingredient.
• Solubility of the active ingredient and excipients in the preparation.
• Techniques applied:
• Volumetric titration: Iodine, nitrite, acid-base…
• UV absorbance measurement, Colorimetry,*
• Fluorescence measurement:*
• Gas chromatography (GC).*
• High performance liquid chromatography (HPLC).*
• Bioassay*
• Comparative measurement of test sample and standard under the same conditions.

7. Unit Dosage Uniformity (PL 11.9):

Unless otherwise specified, this test applies to:

• Single-dose packaged granules containing one active ingredient with a content >= 25 mg and a proportion of active ingredient >=25 % (MV method).
• Single-dose packaged granules containing one active ingredient with a content >= 25 mg and a proportion of active ingredient <= 25 % (CU method).

8. Content Uniformity (PL 11.2):

Application: Unless otherwise specified, this test applies to granules presented in single-dose packaging, which contain active ingredients with a content below 2 mg or below 2% (w/w) relative to the mass of the drug.

Content uniformity test is performed after the quantitative determination test and the active ingredient content has reached the specified limit.

Principle: The content uniformity test of single-dose preparations is based on quantifying the content of the active ingredient in each unit (on 10 separate units taken at random after the quantitative determination test and the active ingredient content has reached the specified limit), to determine whether each individual content is within the permissible limit compared to the average content.

Assessing Content Uniformity (PL 11.2):

• Powder not for injection, granules (Method 1):
• First time: 10 units, Not satisfactory: if more than three units have a content outside the limits of 85 – 115%, or if one or more units have a content outside the limits of 75-125% of the MLC. If 2 -3 units have content values outside the range of ± 15%, retest on 20 other units taken at random.
• Second time: 20 units, Satisfactory: if no more than 3/30 units tested have a content outside the limits of 85 – 115% and no unit has a content outside the limits of 75-125% of the MLC.

* The technical specifications of granule drugs are prescribed in the Vietnamese Pharmacopoeia.

* Granule drug testing must be performed by authorized agencies to ensure drug quality and safety.