3D Printing of Triamcinolone Acetonide in Triblock Copolymers of Styrene–Isobutylene–Styrene as a Slow-Release System

The 3D printing of pharmaceuticals has become an attractive alternative to conventional formulation technologies in the past decade [1,2,3,4]. The use of various printing technologies such as fused deposition modeling (FDM), stereo lithography (SLS), or binder jet printing and laser sintering has revolutionized formulation strategies by implementing solutions for personalized medicines [5,6] or complex dosage regimes, such as polypills or dosage of medicines with a low therapeutic index [1]. A variety of different drugs have been 3D-printed using various polymers, such as poly-ethylene glycol (PEG), poly-lactic acid (PLA), poly-vinyl alcohol (PVA), poly-caprolactone (PCL), poly-isobutylene (PIB), hydroxypropylmethylcellulose (HMPC), and poly-vinylpyrrolidon (PVP)-type polymers [5,7,8,9,10,11,12,13,14,15,16,17,18,19,20,21], always considering key parameters such as thermal stability of the drug, melt flow of the polymers, as well as their final shape persistence and (bio)-degradation, as desired.

Apart from the use of biodegradable polymers (such as PLA, PCL), 3D printing of non-degradable polymers for implantation and slow release over many years has gained notable importance in this context [8,11,19,20,21,22,23]. In particular, the use of poly-isobutylene (IB)-based polymers has become important as a 3D-printable medium [24,25,26], able to embed a variety of drugs (with a focus on paclitaxel^®), especially for long-term release [27,28,29,30,31,32,33,34,35,36,37,38]. To effect sufficient processability, and, most of all, 3D-printability, copolymers of IB with styrene (S) have been designed.

The triblock copolymer SIBS is known for its medical use, in e.g., the TAXUS^® coronary stent as a drug carrier for paclitaxel, which is a known antitumor drug/cell growth inhibitor [39,40,41]. For this application, a stent is spray-coated with a solution of drug and polymer, followed by solvent evaporation to generate a thin film containing the embedded drug. After implantation, the drug will be released over a long time period. It is reported that SIBS as a drug carrier forms a very slow-release system, releasing drugs over years [42,43]. Advantages of SIBS when compared to PLA or other biodegradable polymers include its excellent stability in the human body, where the structure can be kept over a long period of time, which leads to long-term drug exposure. Thus, synthetic heart valves have been designed using SIBS with low styrene content, a polyester fabric, and a second SIBS with higher styrene content for structural stability [36,44]. The mechanical properties, in particular, are important in such SIBS polymers, as they can be engineered relatively easily, by adjusting the ratios of hard and soft segments. For medical applications, these polymers are usually designed with a molecular weight in the range of 75–150 kDa [45]. To increase the mechanical properties, it is common to blend SIBS with thermoplastic polymers such as PS or PPO, which, due to their improved thermoplastic properties, can be used for additive manufacturing using FFF 3D printing [46].

Triamcinolone acetonide (TA) is known for its excellent thermal stability at up to 290 °C [47] and is commonly used to treat skin and joint conditions as well as ocular diseases [48]. The drug is conventionally applied as a topical medication or as an injection, and for a less troublesome treatment, a long-term delivery system would be advantageous. Formulations of TA using a polymer matrix are usually fast-release systems using biodegradable polymers such as PEG [49,50], PLA [51], or PCl [52,53]. With a strong burst release in the first hour, the drug content of the subsequent release is significantly smaller. A release system of the penta-block copolymer PLA-PCl-PEG-PCl-PLA was reported, showing full release after 40 days, depending on the length of hydrophobic segments inside the polymer backbone [54].

The use of a 3D-printable hydrophobic polymer such as SIBS, known as a slow-release system with adjustable properties, could lead to a new area of application of triamcinolone acetonide. Using 3D printing, various shapes can be designed, which opens up further applications. Here, we report studies on the 3D printing of SIBS/triamcinolone acetonide (TA) blends, based on the rheological properties of synthesized low-molecular-weight SIBS triblock copolymers containing TA, with a particular focus on shear rate dependence and the effect of higher printing temperatures on the release system (see Figure 1).