**3. Application of additive manufacturing in personalized orodispersible dosage forms**

The concept of personalized therapy is gaining attention in recent years with the aim of providing appropriate drug(s), dosage regiments, and/or medical care based on the individual patient's peculiarities such as age, medical history, diagnostic results, or genetic information aiming to minimize medication errors such as drug interactions, side effects, and adverse drug reactions and to obtain maximum therapeutic benefits [37, 38]. Technologically speaking, personalized therapy is centered towards personalized dosing, or dose precision and providing age-appropriate dosage forms capable of addressing patients' specific requirements. As an example, in the case of children, it has been estimated that the availability of authorized and commercially available medicine for children varies between 48% and 54% of all approved medicines and that up to 50% of pediatric patients receive an unlicensed or off-label prescription [39]. Indeed, it has been recognized that children are unable to or have difficulties with swallowing tablets or capsules. Moreover, crushing tablets, opening capsules, or mixing powders to extemporaneously prepare the required dose with liquids may lead to dose variability, contamination, drug instability, taste and solubility problems, and other consequences for safety of the patient and the efficacy of the treatment. It is therefore of paramount importance to develop age-appropriate dosage forms, as pointed out by the World Health Organization's (WHO) initiative 'better medicines for children'. Therefore, personalized orodispersible dosage forms such as ODF or ODT prepared on-demand by additive printing technologies can potentially legitimized personalized and precise dosing in patients with special needs.

Additive printing presents a promising future for the point-of-care manufacturing of medicines. Technologies such as two-dimensional (2D) and three-dimensional (3D) printing appeared capable of producing individualized oral drug delivery systems, such as ODF with customizable drug dose strengths, and in some cases with pre-defined drug release patterns [40, 41]. The use of computer-aided design (CAD) software to design different dimensions of a 3D objects prior to printing displays the potential of 3D printing for the concept of precision dosing of active pharmaceutical ingredients (APIs) [41]. Despite the significant technological advancements made so far during the 21st century on conventional pharmaceutical manufacturing processes, especially being cost-effective for large-scale industrial production, they can be inherently labour intensive, time-consuming, and dose inflexible. This poses significant challenges for certain groups of patients that require tailored dosing (particularly among pediatrics and geriatrics) or for certain medicines that require frequent dose adjustments (e.g., drugs

*Applications of Alginates in the Design and Preparation of Orodispersible Dosage Forms DOI: http://dx.doi.org/10.5772/intechopen.98610*

#### **Figure 2.**

*Schematic flow chart of additive printing process from design and material selection to the finished product characterization.*

with narrow therapeutic index). Therefore, to achieve pharmacotherapeutic goals with greater efficacy, quality and safety in patients with special needs, the use of innovative approach such as additive printing technologies are required within pharmaceutical field to facilitate the preparation of small-scale, on-demand and dose-flexible formulations such as ODF. Additive printing process which enables the design of a customized oral dosage forms is triggering a paradigm shift in the way medicines are manufactured and administered [42]. Furthermore, this process could make possible the printing of medicines in pandemic outbreak areas to mitigate drug shortages and supply chain disruptions, and potential for making available printing of medicines in war zones, in clinical trials in hospital settings [43, 44] and preparation of individualized fixed-dose combination products [44–46]. Perhaps, the current regulatory landscape on additive printing is flexible enough to accommodate this technology for mass production in addition to its benefits in extemporaneous compounding of medicines. Thus, according to United States Food and Drug Administration's (FDA) guidelines for additive printing, once the printing device/equipment is optimized, the first step is the design process, which can include a standard design with distinct pre-specified dimensions, in the case of ODF for instance; the design of an ODF area and desired thickness which ultimately defined the dose of loaded API according to individual patient needs. Once the device design is converted to a digital file, the software workflow phase begins, and that file is further processed to prepare it for printing (**Figure 2**), at this stage, the printing parameters are optimized. Concurrently with this step, material controls are established for materials used in the printing of the dosage form (i.e., rheological evaluation, and printability). After printing is complete, post-processing of the built dosage form (e.g., packing and labelling) takes place. After post-processing, the final finished dosage form is ready for characterization [47].
