Page 50 - IJB-10-6

International Journal of Bioprinting Semi-solid extrusion for pediatric medicine

The processes can be divided into three major groups, process does not meet the aforementioned criteria.
depending on the characteristics of the raw material and the Firstly, it is not suitable for manufacturing multiple
manufacturing requirements : (i) powder agglomeration different products for various patients. The use of a large
60
processes with powder bed fusion and binder jetting; quantity of powder implies significant constraints for
(ii) liquid material solidification processes with material product changeovers, with extensive cleaning required
jetting and vat photopolymerization; and (iii) extrusion for the powder container. Therefore, the risk of cross-
processes from solid or semi-solid materials. contamination is high. This process is better suited for

To determine which of these processes would be large-scale industrial production of a single product. In
most suitable for hospital and community pharmacy addition, hospital premises would need to handle the use
use in the coming years, the process should meet the and storage of large quantities of powder in controlled
following criteria: atmosphere zones, requiring extensive personal protective
equipment, particularly for chemotherapy drugs, which
(i) The process must be perfectly suited for present a major risk to operators. The process also does
manufacturing a wide range of different products, not accommodate heat-sensitive materials. Furthermore,
with minimal cleaning constraints and a low risk only a small proportion (10–15%) of the powder is sintered
of cross-contamination between batches. This is during the process. 61,62 The rest is recovered, but not all
crucial for hospital confounding, where equipment of it can be recycled. Each pass through the 3D printer
is used to produce various medications tailored to deteriorates the quality of the powder, necessitating the
individual patient needs. If this criterion is not met, mixing of recycled powder with approximately 50% or
the process is excluded. more fresh powder, 61,62 resulting in significant material
(ii) The materials used in the process (i.e., equipment loss. For all these reasons, this process may not be suitable
and pharmaceutical raw materials) must be well- for manufacturing drug products in hospitals.
established for clinical use. The process should Binder jetting involves selectively depositing a liquid
utilize a variety of excipients that are biocompatible binding agent on a powder bed to agglomerate the powder
and readily available. The process should be capable particles. 52,55 This process is used to produce Spritam®, the
of handling and processing thermosensitive or first and only 3D-printed medicine commercially available
photosensitive APIs or excipients.
in the United States of America (USA). Spritam® is prepared
(iii) The process must enable the manufacture of dosage using the patented ZipDose® technology, which allows
63
forms suitable for specific populations. Considering the drug formulation to disintegrate extremely rapidly.
64
oral dosage forms particularly suited for children, Binder jetting is similar to the powder bed melting process,
mini-printlets (mini 3D-printed tablets), except that it uses a solvent to bind the powder instead
orodispersible, fast disintegrating printlets, and of thermal energy. The powder is also placed in excess
chewable printlets have to be printable. These shapes in a container. Unlike the powder bed melting process,
must be appropriately sized for children’s mouths thermosensitive or photosensitive materials can be used,
and esophagus to ensure ease of administration. as binder jetting does not require thermal energy or a light
Suppositories are another type of solid dosage form source for production. However, like powder-bed fusion,
suitable for children that are administered rectally. the substantial use of powder is not suitable for hospital
In addition, the selected process should ideally compounding, but rather for industrial manufacturing.
facilitate the production of drugs with different API Therefore, this process is excluded.
release kinetics (immediate and controlled release).
The process is excluded if this criterion is not met. 2.1.2. Liquid photoreactive material
solidification processes
In the following sections, we will discuss the different
criteria for each process. Processes that are unsuitable Vat photopolymerization is an AM process where a liquid
photopolymer is placed in a vat and selectively exposed to a
for manufacturing printed medicines in hospitals are light source to create an object via light-induced curing. 52,55
excluded from the evaluation, with justification for their
exclusion. Finally, we will identify and detail the most However, this process has two main issues. First, there
appropriate process. are limited biocompatible photopolymerizable materials
available for drug production, and there is insufficient
65
2.1.1. Powder agglomeration processes information on their safety for human consumption.
Powder bed fusion involves using thermal energy (e.g., There may also be a risk of undesirable chemical reactions
scanning laser) to selectively melt areas of powder between the API and photopolymers. 65,66 As a result, the
which is placed in excess within a container. 52,55 This process may not yet be for drug manufacturing. Second,

Volume 10 Issue 6 (2024) 42 doi: 10.36922/ijb.4063