Stable sugar and sugar-free suspensions of pretomanid

Abstract

BACKGROUND: Pretomanid (PMD) tablets are indicated as part of a combination regimen for the treatment of adults with pulmonary extensively drug-resistant, treatment-intolerant or non-responsive multidrug-resistant TB. No commercial liquid formulation is currently available for patients unable to swallow these tablets.OBJECTIVE: To develop stable extemporaneous liquid formulations of PMD that can be stored at room temperature or 30°C for at least 4 weeks.METHODS: Crushed PMD tablets were formulated into 20 mg/mL suspensions in a simple syrup and sugar-free formulation. The PMD formulations were stored at room temperature and at 30°C for 30 days in dispensing bottles. Appearance, pH, potency and microbial counts of the suspensions were determined on Days 0, 15 and 30.RESULTS: The potency of PMD remained at 99.7–103.4% of the theoretical concentration in each formulation. The appearance, pH and microbial count did not change during the 30-day storage period. Simple syrup formulations did not require preservatives for microbial stability.CONCLUSIONS: PMD oral suspension formulations in simple syrup or in sugar-free vehicle were easily prepared by utilising commonly available equipment and ingredients and were stable for 30 days. These formulations are appropriate alternatives for patients with swallowing difficulties.

A novel home-based method for preparing suspensions of anti-TB drugs

“…We recently described the methodology for the preparation of extemporaneous formulations of BDQ, CFZ, DLM, and Pa in a pharmacy/dispensary setting. 11 – 14 However, access to a pharmacy may be limited in many situations. We have therefore developed a device and methodology that permits extemporaneous formulation preparation at home by the caregiver or patient.…”

“…We follow previously described preparation procedures for compounded formulations of these drugs in simple syrup. 11 – 14 The concentrations selected for the four drugs were BDQ 20 mg/mL, CFZ 10 mg/mL, DLM 5 mg/mL, and Pa 20 mg/mL, based on discussions with clinicians and pharmacists in the field and the age-appropriate doses provided in the Field Guide by the Sentinel Project. 2 Within these concentrations, it is possible to accurately measure dosing volumes at home using oral syringes, spanning from half a teaspoon (2.5 mL) to 4 teaspoons (20 mL).…”

“…Stability-indicating high-performance liquid chromatographic (HPLC) methods were developed for each drug and verified using forced degradation studies, as previously described. 11 – 14 Details of the analytical methods are given in Table 1 ( Supplementary Data ).…”

“…In a series of recently published papers, we have described the process for preparing extemporaneous formulations of key second-line TB drugs – bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), and pretomanid (Pa) – in a pharmacy or a dispensary setting under the supervision of a pharmacist. 11 – 14 In this paper, we describe a novel simple device and the methodology of using this device to convert BDQ, CFZ, DLM, and Pa tablets into liquid suspensions at home. This is especially beneficial for patients who do not have access to child-friendly or dysphagia-friendly formulations, or easy access to compounding pharmacies.…”