Quality risk management in the pharmaceutical development of dispersible tablets for pediatric treatment of tuberculosis

LUCIANI GIACOBBE LC; BOLATTI, FG; OLIVERA ME

Congreso; 7ma Reunión Internacional de Ciencias Farmacéuticas; 2023

Quality risk management is essential in the early stages of pharmaceutical development to mitigate and prioritize risks (ICH Q8R2 and Q9). In the case of dispersible tablets for pediatric tuberculosis treatment, containing a fixed-dose combination of three antibiotics (rifampicin, isoniazid, and pyrazinamide), rapid disintegration and acceptable taste are critical. The objective of this study is to analyze the risks in the development of these tablets and plan experimental assays that would allow the design of an optimized formulation, ensuring its quality and acceptability.The quality profile of the product was established based on patient needs, and critical quality attributes were identified. Influencing factors on dispersible tablets quality were identified through a fishbone diagram. Early risk mitigation was performed through compatibility studies (DSC and isothermal stress associated with TLC) of drugs with excipients that had no previous concomitant use, particularly sweeteners, bitter taste inhibitors, and flavorings, to select potential candidates for inclusion in the formula. Risk prioritization was accomplished using the Preliminary Hazardous Analysis (PHA) methodology. Furthermore, the design of experiments (DOE) was carried out using the Design Expert® software, based on critical parameters established by PHA.The target product quality profile was defined as orally dispersible tablets, each containing 75 mg of rifampicin, 50 mg of isoniazid, and 150 mg of pyrazinamide. Critical quality attributes included efficacy, ensured through complete and very rapid disintegration (