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The purpose of this investigation was to address the content uniformity challenge faced during the scale up for a low dose tablet formulation of Drug X on an accelerated development program. Experiments were performed to demonstrate optimized processing prior to clinical trial manufacturing (CTM).

To improve the existing formulation composition and manufacturing process of compound X which was designed for early phase development Process optimization activities focused on improving the flow characteristics of the granules, minimizing or eliminating segregation and increasing the manufacturing yield with the aim of achieving a robust process prior to the product registration campaign.

Compound X (Cmp-X) belongs to the class of PDE-5 inhibitors and is a BCS Class II candidate with equilibrium solubility <3 μg/mL, thus exhibiting a dissolution rate limited bioavailability. The purpose of this work is to develop an amorphous solid dispersion (ASD) by spray drying and monitor and improve the physical and chemical stability upon storage for developing a successful solid dosage formulation.

Guidance issued by the European Medicines Agency (EMA) states that patient acceptability must be an integral part of paediatric formulation development and described in the paediatric investigation plan (PIP). However, the methodology used to assess acceptability and the timing of this assessment is unclear. Previous reviews have used literature sources to review methods to assess acceptability with diverse methods reported

Applied Molecular Transport Inc. are evaluating targeted drug delivery capsules for administration of locally acting drugs directly to the site of action in the gastrointestinal (GI) tract. This study used gamma scintigraphy to evaluate GI transit and release from 3 capsule prototypes with different coating systems (1). In addition, data on pH, temperature and pressure during GI transit was obtained using SmartPill® and correlated with scintigraphy data (2).

Typically, in the development of dry powder inhaler (DPI) formulations the use of a stable crystalline form of the active pharmaceutical ingredient (API) is desired. However, often in order to produce crystalline particles of suitable size for inhalation, micronization processes will be required, resulting in surface amorphous material which may affect the efficacy of the product. If required, additional conditioning/processing steps may then be applied to the API (or to ensure drug product stability under use) without requiring any additional solid state characterization of the API in the drug product.

Presented at AAPS 2019: An integrated CMC and clinical development program successfully identified a commercializable formulation of DRGT-46 meeting required taste and PK attributes as per the Target Product Profile. Real time, adaptive GMP ensured formulation development decisions were taken based on human clinical data.

HBI-3000 (sulcardine sulfate trihydrate; Bai, et al. 2012) is a multi-ion channel blocker with effects on INa-Peak, INa-Late, ICa,L, and IKr with similar in vitro potencies across these various ion channels in human atrial cardiomyocytes. It is being eveloped by HUYA Bioscience International® (HUYABIO™) for the conversion of recent onset atrial fibrillation (AF).

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.