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It is key to understand powder blend characteristics in relation to tablet characteristics when using pharmaceutical 3D printing, in order to obtain 3D powder bed printed tablets that comply with the pharmaceutical specifications. There is limited literature available on excipient selection for 3D printing, even though the only marketed 3D printed drug is prepared with powder bed printing. In this study, the impact of different particle size distributions of lactose-starch base formulations on key critical material attributes such as wettability, consolidation and flowability was studied. It was found that fewer fines in the particle size of the blend is beneficial for a fast penetration time of the ink (liquid) into the powder bed. The impact of varying the print settings or binder type on primary tablet properties such as hardness and dissolution was studied using formulations with Acetaminophen or Diclofenac Sodium. It was found that optimizing the base formulation and print settings have to be in conjunction as they are closely related. This study shows in detail how hydrophilic/hydrophobic API's can be successfully formulated into 3D printed tablets taking into account the formulation considerations as described.

Stimulated by Pharma 4.0, the pharmaceutical industry is changing from batch-wise to continuous manufacturing. Therefore, individual processing steps such as blending of the active pharmaceutical ingredient (API) with excipients have to be re-designed to continuous operations. In this study, batch and continuous powder blending are directly compared for API with three different excipients with varying material properties. Content uniformity analysis of the blends shows that the continuous process results in more homogeneous blends for all excipients, independent of API dosage. The type of excipient used, however does impact the consistency of the continuous blending process over time. The results presented here reveal the impact of the physical material properties of excipients on blending with API in batch and continuous processes.

The current paper shows how excipient properties impact the process parameters and the final tablet properties in a fully integrated continuous direct compression line. Blend properties of low-dose (1% w/w) and high-dose (40% w/w) paracetamol formulations were evaluated and linked to the blending and tableting performance via multivariate models (Partial Least Squares analysis, PLS). Feeding behavior was analyzed separately, as the amount of active pharmaceutical ingredient (API) that ended into tablets was driven by random fluctuations in the API feeding behavior. The developed PLS models elucidated that formulation behavior was mainly driven by the concentration of the active pharmaceutical ingredient (API), explained by the distinct API properties. Excipient properties also had a substantial impact on formulation behavior. Generally, formulations with microcrystalline cellulose as a filler showed better compactability, lower hold-up mass, lower flowability and higher cohesion than formulations with different lactose grades. The relative performance of a formulation with different fillers differed for 1% w/w and 40% w/w drug loading. Granular and spray dried lactose grades increased in compactability ranking compared to anhydrous lactose when evaluating higher drug loading, due to the difference in morphology. It was shown that besides understanding the impact of excipients on the formulation performance, processability of ingredients is crucial for formulation design.

With the emergence of quality by design in the pharmaceutical industry, it becomes imperative to gain a deeper mechanistic understanding of factors impacting the flow of a formulation into tableting dies. Many flow characterization techniques are present, but so far only a few have shown to mimic the die filling process successfully. One of the challenges in mimicking the die filling process is the impact of rheological powder behavior as a result of differences in flow field in the feeding frame. In the current study, the rheological behavior was investigated for a wide range of excipients with a wide range of material properties. A new parameter for rheological behavior was introduced, which is a measure for the change in dynamic cohesive index upon changes in flow field. Particle size distribution was identified as a main contributing factor to the rheological behavior of powders. The presence of fines between larger particles turned out to reduce the rheological index, which the authors explain by improved particle separation at more dynamic flow fields. This study also revealed that obtained insights on rheological behavior can be used to optimize agitator settings in a tableting machine.

Lactose is the most commonly used excipient in carrier-based dry powder inhalation (DPI) formulations. Numerous inhalation therapies have been developed using lactose as a carrier material. Several theories have described the role of carriers in DPI formulations. Although these theories are valuable, each DPI formulation is unique and are not described by any single theory. For each new formulation, a specific development trajectory is required, and the versatility of lactose can be exploited to optimize each formulation. In this review, recent developments in lactose-based DPI formulations are discussed. The effects of varying the material properties of lactose carrier particles, such as particle size, shape, and morphology are reviewed. Owing to the complex interactions between the particles in a formulation, processing adhesive mixtures of lactose with the active ingredient is crucial. Therefore, blending and filling processes for DPI formulations are also reviewed. While the role of ternary agents, such as magnesium stearate, has increased, lactose remains the excipient of choice in carrier-based DPI formulations. Therefore, new developments in lactose-based DPI formulations are crucial in the optimization of inhalable medicine performance.

This chapter describes the application of lactose as excipient in the pharmaceutical industry. About 60%–70% of pharmaceutical dosage forms contain lactose, and in volume it is one of the biggest pharmaceutical excipients. Lactose can have several functions in a dosage form: as a filler to provide bulk to for instance tablets, as a binder to provide the strength to a dosage form to keep it together, and to provide the flow to a formulation to be capable of producing it. Next to that, the excipient can assist in delivering the drug to the place of action. A wide range of commercial pharmaceutical grades of lactose is available with specific properties for each specific formulation challenge. There are many different production processes in the pharmaceutical industry that all require specific grades of lactose. Lactose is a versatile excipient that is safe to use, relatively cheap, and widely available in many forms.