Starch-based controlled release matrix tablets: Impact of the type of starch

• Published in: Journal of drug delivery science and technology Vol. 61; p. 102152
• Main Authors: Elgaied-Lamouchi, D., Descamps, N., Lefevre, P., Rambur, I., Pierquin, J.-Y., Siepmann, F., Siepmann, J., Muschert, S.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.02.2021; Elsevier
• Series: Journal of Drug Delivery Science and Technology
• Subjects: Controlled release; Diprophylline; Life Sciences; Pre-gelatinization; Starch; Tablet; Tablet; Diprophylline; Starch; Pre-gelatinization; Controlled release
• ISSN: 1773-2247
• DOI: 10.1016/j.jddst.2020.102152

Different types of starches were used to prepare controlled release tablets loaded with diprophylline by direct compression. The impact of the natural origin of the starch, potential chemical modifications (e.g., cross-linking with phosphate or adipate, hydroxypropylation, acetylation to different degrees, partial hydrolysis) and type of pre-gelatinization process (laboratory scale with ethanol and oven drying versus industrial scale drum drying) on the resulting drug release kinetics were studied. Texture analysis of the hydrogels created upon exposure to the release medium, optical and scanning electron microscopy as well as X-ray powder diffraction measurements were used to better understand the observations. Also, a “quick test” using a texture analyzer to rapidly estimate the capacity of a specific starch type to control the resulting drug release rate was proposed. Two types of hydroxypropyl methylcellulose (HPMC K100 M and K100 LV) were studied for reasons of comparison. Interestingly, the “quick test” allowed to detect differences in the mechanical strength of the hydrogels formed upon contact with aqueous fluids, which correlated well with the observed drug release patterns from tablets when measured using a USP III (“Bio’-Dis”) apparatus at 30 rpm. However, diprophylline release was not very much affected by the investigated starch types when using a USP basket apparatus at 75 rpm. This can be attributed to the much lower mechanical stress experienced by the hydrogels under these conditions. Furthermore, caution must be paid when studying starch types, which are pre-gelatinized at the laboratory scale using ethanol precipitation and oven drying. The obtained starch granules can have significantly different key properties compared to granules obtained by industrial scale drum drying, resulting in substantially different drug release patterns. [Display omitted]