Eco-Friendly Selective Laser Sintered (SLS) 3D Printing of Tablets Using Starch 1500® as a Standalone Green Excipient

Abstract

Carbohydrate-based polymers are increasingly recognized as sustainable materials for additive manufacturing. For the first time, Starch 1500®, a partially pregelatinized maize starch, was used as the sole excipient in selective laser sintering (SLS) 3D printing of tablets. While previous studies relied on solubilizers or complex excipient blends, our approach shows that robust indomethacin (IND) tablets can be fabricated using only Starch 1500® or in combination with Kollidon® VA64, without the addition of surfactants or plasticizers. Optimized laser scanning (200-300 mm/s) created tablets that were mechanically strong and free of defects. The IND was completely amorphized, except for a minimal trace of crystallinity in one formulation. Dissolution studies conducted under a pH-shift protocol exhibited significantly improved release; starch-only tablets attained over 80% release within 45 minutes at pH 6.8, in contrast to approximately 23% for crystalline drug, whereas VA64 maintained supersaturation. Powder reusability exhibited no degradation, hence promoting sustainability. For quality control, an HPLC method that indicates stability was developed and validated (ICH Q2(R2)). This starch-enabled SLS platform highlights an excipient-minimum additive manufacturing approach and a sustainable, patient-tailored dose form. Thus, our research opens new possibilities for advancing eco-conscious pharmaceutical manufacturing through SLS 3D printing, especially in developing formulations that align with sustainability goals in the industry.

Introduction

Additive manufacturing is gaining traction in pharmaceutical development as a flexible, solvent-free route to produce patient-centric oral dosage forms with tunable geometry, porosity, and release behavior (Gueche et al., 2021; Zhang et al., 2023). The first attempt at using 3D printing (3DP) technology in pharmaceuticals dates back to 1996 (Wu et al., 1996), and the first selective laser sintering (SLS) printed pharmaceutical dosages were applied in 2017 (Fina et al., 2017a). SLS processes a bed of pharmaceutical powders using a laser to sinter particles with special patterns layer by layer. The technique allows quick on-demand production, minimal tooling, and efficient use of material (Kruth et al., 2003, 2005). While SLS has been applied to several active pharmaceutical ingredients, its broader adoption has been limited by two practical constraints in pharmaceutics. First, there is a small set of excipients that both print reliably under SLS thermal conditions and support immediate or modified release without the need for additional formulation aids such as plasticizers or surfactants (Kumar, 2003; Murkute et al., 2022; Trenfield et al., 2018). Second, there is a need for release assays that are demonstrably stability-indicating and validated to current regulatory expectations, since laser exposure, elevated build temperatures, and sintering agents can introduce matrix effects and unique degradant profiles that differ from conventionally manufactured tablets (Fina et al., 2018; A. G. Tabriz et al., 2023).

Carbohydrate-based polymers offer a sustainable pathway to address the excipient gap. Starch 1500®, a partially pregelatinized maize starch, is a multifunctional excipient with binding, disintegrant, and flow-enhancing properties (Di et al., 2022; Su et al., 2021). Its dual nature, with amorphous regions that soften near processing temperatures and residual crystallinity that preserves particle integrity during spreading, suggests it may enable direct SLS printing without additional binders. In parallel, hydrophilic vinylpyrrolidone-vinyl acetate copolymers such as Kollidon® VA64 are known to stabilize amorphous solid dispersions and maintain supersaturation during dissolution. A rational combination of Starch 1500® with Kollidon® VA64, therefore, has the potential to pair diffusion-controlled hydration and erosion of the starch matrix with polymer-enabled supersaturation control, yielding robust printability and enhanced release from simple, surfactant-free formulations (Barakh Ali et al., 2019).

Indomethacin (IND) is a poorly water-soluble, weakly acidic model drug that has been widely used to probe amorphization and dissolution enhancement in thermally driven processes. For SLS, the key scientific questions are whether a starch-based powder bed can be sintered at process temperatures that preserve drug integrity, whether the rapid localized heating can induce in situ amorphization without recrystallization during cooling and storage, and how formulation composition and laser parameters govern mechanical properties and in vitro performance (Thakkar, Jara, et al., 2021; Thakkar, Zhang, et al., 2021; Yang et al., 2021). These questions are coupled to an analytical need. Quality control for SLS printlets requires a release method that is specific for IND in the presence of excipients and laser absorbers, that resolves likely degradants generated under acidic or basic stress, oxidation, heat, and light, and that is validated per ICH Q2(R2) for specificity, linearity, accuracy, precision, range, sensitivity, robustness, and solution stability (Nováková et al., 2005).

In this research, we addressed the formulation gap and developed and validated a simple, robust analytical method. We investigate Starch 1500® as a primary excipient for SLS of IND tablets, either as the sole matrix former or in binary blends with Kollidon® VA64, using a pharmaceutical pearlescent pigment as the laser energy absorber (the sintering agent). The powder flow and bed-forming behavior were evaluated. Also, we define a practical SLS process window by systematically varying laser scan speed while maintaining build and surface temperatures appropriate for excipient softening without API degradation. Solid-state and structural characterization by differential scanning calorimetry, Fourier transform infrared spectroscopy, powder X-ray diffraction, and proton nuclear magnetic resonance are used to confirm amorphization and probe drug–excipient interactions. Tablet geometry, mass uniformity, and mechanical integrity are quantified to link process conditions to print quality. In vitro dissolution is measured under a physiologically relevant pH-shift protocol to capture gastric exposure followed by intestinal conditions, allowing us to assess whether amorphization, matrix hydration, and polymer-mediated supersaturation translate to meaningful release gains relative to crystalline IND.

Because powder reuse and thermal exposure are intrinsic to powder-bed processes, we further examine chemical stability across repeated printing cycles using mass spectrometry to monitor assay and potential degradants. To enable reliable quality control, we develop a rapid reverse-phase HPLC method for IND quantitation in SLS printlets and validate it as stability-indicating to ICH Q2(R2). The method’s specificity is demonstrated by baseline resolution of IND from representative degradants under forced degradation, and its performance is established across linearity, accuracy, precision, limit of detection and quantitation, robustness to small method changes, and solution-state stability over relevant storage conditions.

While several carbohydrate excipients, such as pectin, alginate, and dextran, are useful for drug delivery, they usually work well as hydrogels for extrusion/inkjet routes and frequently require blending or modification to provide the powder flow and thermal softening needed for powder-bed laser sintering methods (Aghajani et al., 2025; Chang et al., 2023; Sabbatini et al., 2021; A. Tabriz et al., 2025; A. G. Tabriz et al., 2023; Wei et al., 2023; Zarandona et al., 2021). Only a small subset of polymers consistently sinters, and blue-diode systems often need absorbers to couple energy into the bed, as highlighted by recent SLS-focused reviews and polymer-suitability studies (Balasankar et al., 2023; A. Tabriz et al., 2025). These findings highlight the processing limitations for polysaccharides that lack intrinsic softenability. Starch 1500®, on the other hand, is a pharmaceutical/food-grade, partially pregelatinized maize starch that is compendial and has binder–disintegrant duality, improved flow/compatibility compared to native starch, and moisture-scavenging (low water activity) that can stabilize sensitive APIs (Aghajani et al., 2025; Wei et al., 2023; Zarandona et al., 2021). These characteristics are directly related to SLS powder spreading, interparticle fusion, and downstream performance (PA Cuthbert & Co, 2023). Its proven regulatory acceptance and scalability give it an advantage over niche biopolymers that require modification or blending for printability.

Based on the excipient gap in SLS 3DP, we propose that the partially pregelatinized structure of Starch 1500® supports direct powder fusion and promotes in situ amorphization of indomethacin without plasticizers or surfactants (Colorcon, 2019). This study further hypothesized that binary blends with Kollidon® VA64 would combine rapid hydration/disintegration from starch with polymer-mediated supersaturation control to improve release across gastrointestinal pH conditions, enabling simplified, sustainable, patient-specific manufacturing supported by a validated stability-indicating analytical workflow. The goal is to make SLS formulation design easier, reduce the number of excipients needed, and create a viable path to sustainable, patient-specific production by combining this formulation technique with a validated, stability-indicating analytical technology.

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Materials

Indomethacin was purchased from Tokyo Chemical Industries (Tokyo, Japan) and was used as a model drug. Starch 1500® (Partially Pregelatinized Maize Starch) was gifted by Colorcon (Indianapolis, USA). Kollidon® VA64 is a vinylpyrrolidone-vinyl acetate copolymer with an average molecular weight of 65,000 g/mol, donated by BASF Corporation (Tarrytown, NY, USA). Candurin® Gold Sheen was gifted to the Lab from EMD Performance Materials Corp. (Philadelphia, PA, USA). Monohydrate and dihydrate sodium phosphate salts were purchased from Fisher Scientific™ (Pittsburgh, PA, USA). HPLC-grade acetonitrile and methanol were purchased from Fisher Scientific™ (Pittsburgh, PA, USA).

Sujith Raj Bashetty, Yu Zhang, Navya Nalajala, Thirupathi Reddy Anekalla, Lakshmi Priyanka Gudipati, Nagarjuna Narala, Rohith Alluri, Mohammed Maniruzzaman, Eco-Friendly Selective Laser Sintered (SLS) 3D Printing of Tablets Using Starch 1500® as a Standalone Green Excipient, Carbohydrate Polymer Technologies and Applications, 2026, 101153, ISSN 2666-8939, https://doi.org/10.1016/j.carpta.2026.101153.