Applying terahertz technology for nondestructive detection of crack initiation in a film-coated layer on a swelling tablet

Abstract

Here, we describe a nondestructive approach using terahertz wave to detect crack initiation in a film-coated layer on a drug tablet. During scale-up and scale-down of the film coating process, differences in film density and gaps between the film-coated layer and the uncoated tablet were generated due to differences in film coating process parameters, such as the tablet-filling rate in the coating machine, spray pressure, and gas-liquid ratio etc. Tablets using the PEO/PEG formulation were employed as uncoated tablets. We found that heat and humidity caused tablets to swell, thereby breaking the film-coated layer. Using our novel approach with terahertz wave nondestructively detect film surface density (FSD) and interface density differences (IDDs) between the film-coated layer and an uncoated tablet. We also found that a reduced FSD and IDD between the film-coated layer and uncoated tablet increased the risk of crack initiation in the film-coated layer, thereby enabling us to nondestructively predict initiation of cracks in the film-coated layer. Using this method, crack initiation can be nondestructively assessed in swelling tablets after the film coating process without conducting accelerated stability tests, and film coating process parameters during scale-up and scale-down studies can be appropriately established.

Keywords: Coating; Process analytical technology; Quality by design; Spectroscopy; Swelling; Terahertz.

Graphical abstract

Fig. 1

Film-coated tablets stored in a high-temperature oven (60 min at 70 °C) (a) without a crack and (b) with a crack.

Fig. 2

Block diagram of the terahertz wave measurement system TAS7000 and schematic optical system for reflection measurement of film-coated tablets.

Fig. 3

Terahertz reference signal. e_ref(t) (green signal) and measurement signal e_sam(t) (blue signal). (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 4

(a) Scaled reference terahertz signal (green signal) and measured signal from the tablet (blue signal). (b) Difference between scaled reference and measured signals. (For interpretation of the references to color in this figure legend, the reader is referred to the web version of this article.)

Fig. 5

Histogram of FCSI for 11 film-coated tablets: (a) batch X6-1, (b) batch X6-2, (c) batch X6-3, (d) batch Z6-1, (e) batch Y9-1 and (f) batch W9-1.

Fig. 6

Appearance of film-coated tablets in batch W9-1 during and after degradation test (80 min at 70 °C).

Fig. 7

Relationship between FCSI values and crack initiation.

Fig. 8

Crack initiation results during degradation tests for film-coated tablets with different FCSI values (80 min at 60 °C).

Fig. 9

Crack initiation results after degradation tests for film-coated tablets with different FCSI values (80 min at 60 °C).