Quantifying cross-linking strength in sodium starch glycolate and its impact on tablet disintegration and dissolution

Abstract

The development of a robust oral solid dosage form requires knowledge of all the sources of variation that could impact the dosage form's performance and stability, in line with Quality-by-Design (QbD). This requires a deep understanding of the relationships between raw material properties, the process parameters and the final product quality. This paper presents a method to quantify the strength of cross-links (SXL) in SSG grades by comparing the sediment volume of precipitation after gelling before and after exposure to alkaline conditions. It is demonstrated that SSG grades with phosphorous cross-links are more resistant to hydrolysis than ester cross-links. The developed method can help formulators to assess the SXL of SSG before use in a formulation. The SXL was quantified for seven marketed SSG grades, showing a clear difference between SSG grades with phosphorous cross-links (SXL ≈ 1) and ester cross-links (SXL 0.4 – 0.7). The tablet disintegration and API dissolution of these SSG grades were evaluated for a wet granulation formulation with atenolol. Results show that all SSG grades with phosphorous cross-links realized 80 % atenolol dissolution within 25 min, whereas all grades with ester cross-links reached this threshold only after 45 min or more. This shows that the type of cross-link is a critical attribute that can result in dissolution success or failure. An excellent correlation was observed between the SXL and the time at which 80 % of the atenolol was dissolved. The findings of this study show that understanding the type of cross-link and the SXL of SSG can support formulators with the development of good, robust formulations, in line with a quality-by-design approach. The provided case study shows that formulators can make their formulations more robust to stress exposure before, during or after tablet manufacturing by using an SSG grade with phosphorous cross-links, thereby limiting the risk of product failure.</p