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Clinical studies involving the administration of 14C radio labelled drug substances provide critical information during development.The main application is the regulatory ADME study to assess the mass balance, routes and rates of elimination, and to provide plasma, urine and faecal samples for metabolite profiling and structural identification.

Presented at AAPS 2019: Phase I drug development for oncology compounds is traditionally conducted directly in patient populations. Oncology molecules have historically been cytotoxic, meaning their safety and risk:benefit profile makes them unviable for dosing in healthy subjects. While this ensures reduced nonclinical requirements, rapid access to patient data and an earlier assessment of efficacious potential, it can also present challenges. For example, patients recruited in Phase I trials typically are at end of life care and will be taking multiple co-medications and have multiple co-morbidities (e.g. liver and kidney function may vary greatly among the recruited subjects). Practically, recruiting patients into Phase I studies can also be problematic, requiring multiple clinical sites and protracted recruitment times for what would traditionally be single site, quickly recruited healthy volunteer studies.

Presented at AAPS 2019: Aqueous solubility is a prerequisite for oral absorption of a drug and the pH-dependence of aqueous solubility is critical information to guide formulation development strategies. The purpose of this study was to evaluate the physical property modules in two commercially available in-silico modelling programs in predicting the pH solubility profiles as described by the ionization constant (pKa) and the intrinsic solubility of the unionized form.

Presented at AAPS 2019: Translational Pharmaceutics was used to evaluate three BOS172767 formulations in on a integrated clinical study, and successfully identified the micronized capsule as the new lead formulation. This formulation had superior exposure compared to the IR reference capsules, and approximate proportional increase in exposure up to 800 mg. The food effect observed at 100 mg was reduced compared to that previously seen at 200 mg (FIH capsule) and elevated gastric pH (subjects taking PPIs) had minimal effect on exposure. A Level C IVIVC was achieved with a biorelevant dissolution test, which provides valuable information for future formulation development and setting of product specifications.

Presented at AAPS 2019: Both micronisation and co-micronisation can improve the rate and extent of drug dissolution. However, co-micronisation of Drug A with a precipitation inhibitor HPC and further blending with a wetting agent SLS could significantly increase the drug dissolution to achieve a supersaturated state for Drug A. In the presence of a precipitation inhibitor, the solubilized drug was maintained in the metastable over a period of time with a slow precipitation rate. The addition of precipitation inhibitor has successfully maintained Drug A in the solubilized form for an extended period allowing greater potential for drug absorption. In vivo studies will be conducted to evaluate the bioavailability of the final formulation. The final results demonstrate the co-micronisation process manage to improve the bioavailability of the poorly soluble drug investigated.

The aim of this development programme was to develop anaqueous,multi-dose oral suspension formulation of a novel drug candidate at a concentration of 20mg/ml that would be appropriate for the treatment of kidney disease in paediatric patients aged 2 years and older. A liquid formulation was favoured over a coated granule formulation.

The objective of the development programme was to design an age - appropriate multi-dose liquid product suitable for the neonate population (up to 28 days old).

Choosing the appropriate dosage form for first-in-human/Phase I trials Pharmacy preparation or GMP manufacturing? Bridging to robust and scalable Phase II drug products Flexible and adaptive clinical manufacturing strategies for patient trials Integrating pharmaceutical sciences and clinical testing

PUR1900 is an iSPERSE™ formulation incorporating a large, complex anti-fungal compound that can be administered at high therapeutic dose to the lung while minimizing systemic side effects.

The results of this study demonstrate that CMS delivered as ColistAir has a comparable safety profile to the comparator products and is well tolerated in healthy volunteers.

TOP1288 is a non-systemic kinase inhibitor (NSKI) being developed as a treatment for patients with ulcerative colitis. As a novel, locally-acting candidate, TOP1288 has low systemic bioavailability and therefore a dual-pronged formulation strategy was adopted with rectal and oral formulations being developed.

The main objective of the study is to apply the principles of QbD (Quality by Design) utilizing a predetermined risk-based approach to identify and optimize the Critical Process Parameters (CPPs) of roller compacted capsule product ensuring minimum impact on the Critical Quality Attributes (CQAs) to provide a product with desired quality.