Friability Testing of Granules and Spheroids

In continuation to our previous article entitled “Friability testing of tablets“, we are hereby providing you the guidelines on Friability testing of granules and spheroids. British Pharmacopoeia and European Pharmacopoeia provides the method in detail. There are basically two methods for determination of the friability of granules and spheroids, which may be used during development studies. These tests are conducted to determine the friability of granules and spheroids.

Friability is defined as a reduction in the mass of the granules or spheroids or in the formation of fragments of granules or spheroids, occurring when the granules or spheroids are subjected to mechanical strain during handling (tumbling, vibration, fluidization, etc.). Examples of changes are abrasion, breakage or deformation of granules or spheroids.

The two methods for testing friability of granules and spheroids are as follows:

METHOD A

The apparatus used is fluidized bed apparatus. It consists of a glass cylinder (A) with a conical lower part. The cylinder is provided with a sieve lid (B) having an aperture size of 500 µm or any other suitable sieve. The conical end is connected to a U-shaped glass tube (C) that can be disconnected from the cylinder for removal of the granules or spheroids. The U-tube is attached to a T-coupling (D). One inlet of the T-coupling is joined by a silicone tube to a manometer for regulating the compressed-air flow, the other one is connected via a silicone tube to a by-pass flowmeter (E) (0.10-1.00 m³⋅h^-1). The compressed air being used shall comply with the test for water in the monograph Medicinal air.

Fig. Fluidized Bed Apparatus

Procedure:

Remove the fine particles by sieving (sieve having an aperture size of 710 µm or any other suitable sieve). Introduce about 8.0 g (m₁) of granules or spheroids into the cylinder (A). Close the apparatus with the sieve lid (B). Adjust the flow rate of the compressed air to 0.45 m³⋅h^-1. After 15 min, remove the granules or spheroids from the apparatus by disconnecting the U-tube and weigh again (m₂). Test 3 samples and calculate the mean value. It is recommended to spray the inside of the apparatus with an antistatic agent every 3 determinations in order to prevent electrostatic charging.

Loss on drying: Dry in an oven at 105 °C, unless otherwise prescribed. Alternatively, other drying conditions as described in pharmacopoeia may be used.

Calculation:

METHOD B:

The apparatus used is oscillating apparatus. It consists of a glass container, containing the granules or spheroids to be examined, which is subjected to horizontal oscillations. The frequency and duration of the oscillations can be varied continuously. The frequency can be adjusted, using a scale, to a value in the range 0-400 oscillations/min. The duration can be set to a value in the range 0-9999 s.

Fig.: Oscillating Apparatus

Procedure:

Remove the fine particles by sieving (sieve having an aperture size of 355 µm or any other suitable sieve). In the glass container, weigh about 10.00 g (m₁) of the granules or spheroids. Install the container in the apparatus. Shake for 240 s at the highest frequency for hard granules or spheroids, or for 120 s at a lower frequency (e.g. 140 oscillations/min) for soft granules or spheroids. Sieve (355 µm, or the same sieve as used previously) and weigh the granules or spheroids again (m₂). Test 3 samples and calculate the mean value.

Loss on drying:  Dry in an oven at 105 °C, unless otherwise prescribed. Alternatively, other drying conditions as described in Pharmacopoeia may be used.

Calculation:

References:

1. The British Pharmacopoeia