Evidence of Reliable Gastro-Resistance of Novel Enteric Ready-to-Fill Capsules Simplifying Pharmaceutical Manufacturing.

Developing delayed-release formulations for acid-sensitive actives can be a costly and time-consuming process. However, ready-to-fill functional capsules, such as EUDRACAP® can significantly mitigate these challenges. The in vitro performance of EUDRACAP® enteric was evaluated in two typical delayed-release scenarios: for diclofenac (a drug that can cause irritation to gastric mucosa), and for omeprazole (a drug susceptible to degradation due to the acidity of gastric fluid). The prototypes were tested in HCl 0.1N according to the USP <711> for at least 2 h and compared to commercial products. The results showed that the performance of EUDRACAP® was below LOD and in compliance with the requirements for drug release in acidic media (NMT 10%). Additionally, the impurities were evaluated after the acidic stress. The low total percentage of impurities of 0.44% for diclofenac (NMT 1.50%) and 0.22% for omeprazole (NMT 2.00%) indicates a very good protection by EUDRACAP®. A comprehensive comparative analysis of the in vitro performance clearly showed the acid protection capability of EUDRACAP® enteric capsules making them a serious alternative to existing enteric dosage forms alternatives. EUDRACAP® is an accessible solution both in large-scale industrial and smaller pharmacy settings. Offering increased accessibility, affordability, and convenience to manufacturers and consumers alike and leading to improved healthcare outcomes.

Prediction of dissolution performance of uncoated solid oral dosage forms via optical coherence tomography.

Real-time prediction of the dissolution behavior of solid oral dosage forms is an important research topic. Although methods such as Terahertz and Raman can provide measurements that can be linked to the dissolution performance, they typically require a longer time off-line for analysis. In this paper, we present a novel strategy for analyzing uncoated compressed tablets by means of optical coherence tomography (OCT). Using OCT, which is fast and in-line capable, makes it possible to predict the dissolution behavior of tablets based on images. In our study, OCT images were obtained of individual tablets from differently produced batches. Differences between tablets or batches in these images were hardly visible to the human eye. Advanced image analysis metrics were developed to quantify the light scattering behavior captured by the OCT probe and depicted in the OCT images. Detailed investigations assured the repeatability and robustness of the measurements. A correlation between these measurements and the dissolution behavior was established. A tree-based machine learning model was used to predict the amount of dissolved active pharmaceutical ingredient (API) at certain time points for each immediate-release tablet. Our results indicate that OCT, which is a non-destructive and real-time technology, can be used for in-line monitoring of tableting processes.

Toward a new generation of vaginal pessaries via 3D-printing: Concomitant mechanical support and drug delivery.

To improve patient adherence, vaginal pessaries - polymeric structures providing mechanical support to treat stress urinary incontinence (SUI) - greatly benefit from 3D-printing through customization of their mechanics, e.g. infill modifications. However, currently only limited polymers provide both flawless printability and controlled drug release. The current study closes this gap by exploring 3D-printing, more specifically fused filament fabrication, of pharmaceutical grade thermoplastic polyurethanes (TPU) of different hardness and hydrophilicity into complex pessary structures. Next to the pessary mechanics, drug incorporation into such a device was addressed for the first time. Mechanically, the soft hydrophobic TPU was the most promising candidate for pessary customization, as pessaries made thereof covered a broad range of the key mechanical parameter, while allowing self-insertion. From the drug release point of view, the hydrophobic TPUs were superior over the hydrophilic one, as the release levels of the model drug acyclovir were closer to the target value. Summarizing, the fabrication of TPU-based pessaries via 3D-printing is an innovative strategy to create a customized pessary combination product that simultaneously provides mechanical support and pharmacological therapy.

Development and Validation of a Stability-Indicating UPLC Method for the Determination of Hexoprenaline in Injectable Dosage Form Using AQbD Principles.

A novel and efficient stability-indicating, reverse phase ultra-performance liquid chromatographic (UPLC®) analytical method was developed and validated for the determination of hexoprenaline in an injectable dosage form. The development of the method was performed using analytical quality by design (AQbD) principles, which are aligned with the future requirements from the regulatory agencies using AQbD principles. The method was developed by assessing the impact of ion pairing, the chromatographic column, pH and gradient elution. The development was achieved with a Waters Acquity HSS T3 (50 × 2.1 mm i.d., 1.8 µm) column at ambient temperature, using sodium dihydrogen phosphate 5 mM + octane-1-sulphonic acid sodium salt 10 mM buffer pH 3.0 (Solution A) and acetonitrile (Solution B) as mobile phases in gradient elution (t = 0 min, 5% B; t = 1 min, 5% B; t = 5 min, 50% B; t = 7 min, 5% B; t = 10 min, 5% B) at a flow rate of 0.5 mL/min and UV detection of 280 nm. The linearity was proven for hexoprenaline over a concentration range of 3.50-6.50 µg/mL (R2 = 0.9998). Forced degradation studies were performed by subjecting the samples to hydrolytic (acid and base), oxidative, and thermal stress conditions. Standard solution stability was also performed. The proposed validated method was successfully used for the quantitative analysis of bulk, stability and injectable dosage form samples of the desired drug product. Using the AQbD principles, it is possible to generate methodologies with enhanced knowledge, which can eventually lead to a reduced regulatory risk, high quality data and lower operational costs.

A solution for low-dose feeding in continuous pharmaceutical processes.

Continuous feeding of small quantities of powder is increasingly applied in pharmaceutical manufacturing. With that regard, what is crucial is not only the feasibility, but also the accuracy and stability. To enable stable processing, low amounts of various agents, e.g., lubricants, can be used. Even more important is the exact dosage of highly potent active pharmaceutical ingredients (APIs), which require feed rates within the range of grams per hour. Conventional feeders cannot supply powder at such rates, especially when the material properties are challenging. In this work, a novel micro-feeder was integrated into a continuous manufacturing line and its capability to supply API at feed rates down to one gram per hour was tested. The micro-feeder system is based on the principle of active volumetric displacement: a piston pushes the powder out of the cartridge upwards to the end of a plate, where a scraper places it into the process inlet. In this study, a hot melt extrusion process was used, during which the API was dissolved in a polymer matrix. Samples of the strand were analysed with regard to their content by means of HPLC. The results showed that the novel micro-feeder system can feed powder with good accuracy and reproducibility, indicating its high potential for continuous process implementation.