Physicochemical stability of DELSTRIGO®: A combination of three active substances (tenofovir disoproxi fumarate [TDF], lamivudine [3TC] doravirine [DOR]) in the management of occupational in the management of HIV post‐exposure prophylaxis (PEP)

31 Introduction: The first-line PEP recommended by the French National Authority for Health is the combination of TDF, 3TC or emtricitabine and DOR. DELSTRIGO® combines the advantages of a single tablet, simplifying daily administration and reduced cost. However, DELSTRIGO® is only available in bottles of 30 tablets (cp) which is not sized for the appropriate management of PEP. In addition, once opened, the stability of the tablets in the bottle remains unknown. This study aimed to assess the physicochemical stability of DELSTRIGO® film-coated tablets under various storage conditions to support their repackaging for emergency kit use in hospital-based PEP management. Materials and methods: DELSTRIGO® tablets marketed by MSD Laboratory containing the three active ingredients (TDF/3TC/DOR) were used. European Pharmacopoeia-quality reference substances for TDF, 3TC and DOR and liquid chromatography (LC) solvents were used. Tablets were repackaged in individual PVC blisters. Film-coated tablets were stored under different storage conditions for 6 months: closed bottle 20°C–25°C (control), repackaged in blisters stored at 25°C with 60% residual humidity (RH) and under intentionally unfavourable stress conditions (40°C and 75% RH, H₂O₂, HCl and NaOH). An LC method was developed to track variations in TDF, 3TC and DOR content in tablets. The appearance of compounds resulting from the degradation of these three compounds was also monitored by comparing chromatographic profiles. Results: The analytical conditions for monitoring the quantities of DOR, TDF and 3TC have been developed and validated in line with current recommendations. When the tablets were stored at 25°C and 60% RH, the levels of each active substance remained between 95.0% and 105.0% of the expected values, and the chromatographic profiles showed no appearance of additional products compared with the control. On the other hand, under certain stress conditions, significant degradation (>0.15%) of TDF and DOR was observed, leading to changes in chromatographic profiles compared with the control. Conclusion: This study demonstrates that if DELSTRIGO® tablets are stored for 90 days under controlled, degradation-limiting conditions (tinted blister pack, 25°C/60% RH), they present an acceptable content and no substantial degradation appears to occur. These results pave the way for unitary repackaging of DELSTRIGO®, thus improving PEP management. Further analysis is underway to extend these conclusions to a 6-month period. Reference 1. Houssen, M et al, Pharmaceutics vol. 16,8 977. 24 Jul. 2024.