Telmisartan Tablets Repackaged into Dose Administration Aids: Physicochemical Stability under Tropical Conditions.

Dose administration aids (DAAs) are commonly used to assist patients with chronic disease to manage multiple medications and thus improve adherence. Several brands of telmisartan, commonly prescribed for hypertension, are available in Australia. Manufacturer's storage advice is to leave tablets in the blister strip until administered to patients. This study aimed to investigate the stability of telmisartan tablets when repackaged and stored in DAAs, to identify a brand, which is sufficiently stable to be repackaged. All available brands of telmisartan tablets in Australia, which contain different excipients, were repackaged into DAAs and stored at 30 °C, 75% RH for 28 days before screening, using visual inspection and physical testing. A candidate brand was then selected for physicochemical and photostability testing using pharmacopoeial methods. Repackaged Mizart® tablets were shown to be sufficiently stable, when repackaged and stored under tropical conditions (30 °C, 75% RH) for 28 days. Several of the other brands were deemed inappropriate for repackaging, due to physical instability, highlighting the importance of considering not only the drug, but also excipients to ensure the stability of repackaged medicines. Although the repackaging of telmisartan tablets is not advised, this study provides evidence to support the Mizart® brand as an option for pharmacists to recommend for repackaging.

Prevalence of Substandard Amoxicillin Oral Dosage Forms in the National Capital District of Papua New Guinea.

Antibiotics are commonly reported as being substandard or falsified in low- to middle-income countries, having potential to contribute to the development of antimicrobial resistance and drug-resistant infections. Amoxicillin, used to treat a number of infections and listed by the WHO as an essential medicine, presented as a good drug candidate for this study. We aimed to measure the prevalence of substandard and falsified amoxicillin oral products (tablets, capsules, and suspensions) in the National Capital District of Papua New Guinea (PNG). These oral products were surveyed in 2018 and 2019 from retail pharmacies, private and public health facilities, and the Area Medical Store, representing more than 90% of licensed medicine outlets. The product packaging was visually inspected, and the samples were analyzed for amoxicillin content using a validated high-performance liquid chromatography method. Although no falsified products were identified, 15% of the 190 products analyzed contained substandard amounts of amoxicillin. Quality varied with the dosage form (P = 0.002), with capsules exhibiting the lowest incidence of substandard content (4% in 2019) and tablets collected in 2018 experiencing the highest failure rate (50%). Suspension (40%) quality was compromised by failure to achieve homogeneity on reconstitution. A higher incidence of substandard content (P = 0.002) was associated with one major retail group. Routine testing of medicines by resource-poor countries is often unachievable, leading to the circulation of poor quality drugs, which is a global public health concern. Our study highlighted that substandard amoxicillin oral products are indeed prevalent in the NCD of PNG.

The efficacy and pharmacokinetics of terbinafine against the frog-killing fungus (Batrachochytrium dendrobatidis).

Captive and wild amphibians are under threat of extinction from the deadly fungal pathogen Batrachochytrium dendrobatidis (Bd). The antifungal drug terbinafine (TBF) is used by pet owners to treat Bd-infected frogs; however, it is not widely used in academic or zoological institutions due to limited veterinary clinical trials. To assess TBF's efficacy, we undertook treatment trials and pharmacokinetic studies to investigate drug absorption and persistence in frog skin; and then we correlated these data to the minimal lethal concentrations (MLC) against Bd. Despite an initial reduction in zoospore load, the recommended treatment (five daily 5 min 0.01% TBF baths) was unable to cure experimentally infected alpine tree frogs and naturally infected common eastern froglets. In vitro and in vivo pharmacokinetics showed that absorbed TBF accumulates in frog skin with increased exposure, indicating its suitability for treating cutaneous pathogens via direct application. The MLC of TBF for zoosporangia was 100 µg/ml for 2 h, while the minimal inhibitory concentration was 2 µg/ml, suggesting that the drug concentration absorbed during 5 min treatments is not sufficient to cure high Bd burdens. With longer treatments of five daily 30 min baths, Bd clearance improved from 12.5% to 50%. A higher dose of 0.02% TBF resulted in 78% of animals cured; however, clearance was not achieved in all individuals due to low TBF skin persistence, as the half-life was less than 2 h. Therefore, the current TBF regime is not recommended as a universal treatment against Bd until protocols are optimized, such as with increased exposure frequency.

Stability of repackaged dabigatran etexilate capsules in dose administration aids.

OBJECTIVE: This study is aimed at assessing the stability of dabigatran etexilate (Pradaxa) capsules repackaged into a dose administration aid (DAA), in order to inform appropriate storage conditions that ensure quality. Although Pradaxa is used chronically by patients, and DAAs are known to improve adherence, removal of the capsules from their original packaging is not recommended by the manufacturer due to sensitivity to moisture. METHODS: Pradaxa capsules containing dabigatran etexilate 110 mg were repackaged into a commercially available DAA and stored under ambient conditions (30°C±2°C and 75%±5% relative humidity) for periods of 14 and 28 days and in a domestic refrigerator for 28 days. The capsules were evaluated for changes in their physical appearance and weight. Content uniformity and the drug concentration during dissolution were determined using a validated high-performance liquid chromatography method. RESULTS: Storage at ambient conditions for 14 and 28 days resulted in a percentage drug remaining of 92.5% and 71.6%, respectively, indicating a lack of compendial compliance (88.4%-111.8%) for the 28-day ambient sample. There was a statistically significant difference (p=0.015) in the dissolution behaviour of the 14-day samples, when compared with control capsules. In contrast, repackaged capsules stored in the refrigerator for 28 days had a drug content of 98.2% and dissolution was not significantly affected (p=0.132). CONCLUSION: This study has clearly demonstrated that if repackaging of Pradaxa capsules is required, storage under refrigerated conditions ensures quality for 28 days.

Addressing varenicline adherence through repackaging in a dose administration aid.

BACKGROUND: Ensuring adherence to prescribed smoking cessation medications, such as Champix® (varenicline), is essential during a quit attempt as non-adherence can significantly reduce the likelihood of achieving prolonged smoking abstinence. The use of dose administration aids may improve adherence, though medication stability on repackaging is not guaranteed, due to a lack of available data from manufacturers supporting this practice. OBJECTIVE: To determine the suitability for repackaging varenicline tartrate tablets into a dose administration aid, by assessing its physical and chemical stability after being repackaged and stored at ambient conditions for 6 weeks. METHODS: Varenicline tartrate (1.0 mg) tablets were repackaged into commercially available Webster-pak® blister compartments and stored for 42 days at ambient conditions characteristic of a Zone IVB climate (30 ± 2°C and 75 ± 5% relative humidity) according to the World Health Organization (WHO) guidelines on pharmaceutical stability testing. Physical and chemical tests were performed on the repackaged and control tablets, including an assessment of: tablet thickness, hardness, weight uniformity, friability, dissolution, disintegration, and content uniformity after exposure to ambient conditions and light according to International Council on Harmonisation of Technical Requirements of Pharmaceuticals for Human Use guideline Q1B. RESULTS: Weight, friability, and thickness of the tablets complied with compendial standards. A validated high performance liquid chromatography method was used to confirm that after exposure to light, and repackaging at 30°C/75% relative humidity, the tablets remained within the required 95%-105% of the stated drug content. However, tablet hardness and disintegration decreased over time, with tablets becoming softer and undergoing more rapid disintegration in water. CONCLUSION: Repackaging 1.0 mg varenicline tartrate tablets into a dose administration aid can be undertaken to improve adherence rates and therefore smoking abstinence rates. This can be performed without compromising either the physical or chemical stability of the tablets.