Design and development of Lornoxicam self-nanoemulsifying drug delivery system (SNEDDS) loaded 3D-printed tablet shells with tunable drug release profile

Abstract

This study explores the development of a self-nanoemulsifying drug delivery system (SNEDDS) to enhance the biopharmaceutical profile of lornoxicam, a poorly soluble BCS class II drug. Later, with the application of the 3D printing technique, a tablet shell was fabricated that delivers this nano formulation in a customized dose with tuned drug release profiles. The tablet shell was printed by using polylactic acid (PLA) and polyvinyl alcohol (PVA) in different geometries as a one-side-open shell and a closed shell with a varied number of drug-releasing windows, that has successfully altered the drug release characteristics of the encapsulated lornoxicam SNEDDS. The developed lornoxicam SNEDDS exhibited a nano droplet size of around 100 nm with a polydispersibility index value of <0.2, indicating narrow size distribution and uniformity in droplet size.

The lornoxicam SNEDDS were characterized by ATR-FTIR, DSC, and XRD, which confirms good compatibility between the drug and SNEDDS components and the existence of lornoxicam as molecularly dispersed in the solid matrix and in a dissolved state in the SNEDDS components. Based on the geometry of the 3D-printed tablet shell, one side open shell fabricated by using PLA and PVA exhibited an immediate drug release profile (>80% in 45 min) irrespective of the tablet shell material. Whereas the closed shell fabricated by using PLA with a varying number of drug-releasing windows showed varied drug release profiles based on the number of drug-releasing windows in the tablet shell. The tablet shell with a single drug-releasing window exhibited a sustained drug release of the SNEDDS formulation, achieving only around 46% of drug release in 3 h, whereas the tablet shells with two and four drug-releasing windows exhibited around 66% and 82% of drug release, respectively, in the same time period.

Thus, by altering the geometry of the tablet shell, the drug release profile of the encapsulated lornoxicam SNEDDS was tuned successfully. The drug release kinetics best fit the Korsmeyer-Peppas model, which showed the highest correlation coefficients (r²) and indicated that the drug release followed an anomalous (non-Fickian) transport mechanism. This approach not only improves the therapeutic performance of the drug but also aims to provide proof of concept for improving patient compliance through dose and drug release profile customization.

Introduction

The progress in the field of 3D printing technology in pharmaceutical product development achieved significant acknowledgement with the FDA approval of 3D-printed patient-specific devices, implants, and drug products [1,2]. Spritam® (Levetiracetam) is the first 3D-printed prescription medicine available in the market that disintegrates rapidly in the mouth with a sip of liquid and provides a new solution to epilepsy patients who struggle to take their medication [3,4]. With rapid advancement, four more 3D-printed drug products from Triastek received IND clearance from the FDA. Triastek, a leading global company in 3D printing pharmaceuticals, developed T19, T20, T21, and T22 micro structured 3D-printed drug products for chronotherapy, solubility enhancement, colon targeting, and gastric retention, respectively, by using the melt extrusion deposition (MED®) 3D printing process [1].

This progress will unlock the next generation of drug products and will lead to the transformation of the drug development process, drug delivery approaches, and drug production via digital technology and continuous manufacturing, benefiting the patients worldwide. 3D printing uses digitally designed prototypes that are sliced into many layers to be fabricated as 3D geometries by using 3D printers. These 3D printers, based on feed materials and printing techniques, are explored in different types such as inkjet printing, binder jet printing, fused deposition modeling (FDM) printing, semisolid extrusion (SSE) printing, stereolithographic printing (SLA), and selective laser sintering (SLS) [[3], [4], [5], [6], [7]]. These methods have been extensively explored to design 3D-printed drug products in the form of tablets, caplets, films, patches, microneedles, implants, and suppositories [[8], [9], [10], [11], [12], [13], [14], [15]]. The 3D-printed drug products were fabricated in the form of simple to complex geometries with tunable drug release characteristics such as bilayer tablets [16], polypills [17], capsular devices [18], intragastric floating tablets [19], chewable tablets [20], and complex-shaped products [21]. These 3D-printed drug products were tuned to exhibit different drug release profiles, such as immediate release, sustained release, delayed release, extended release, and/or pulsatile release [[22], [23], [24], [25]].

Moreover, the integration of these 3D printing methods with other drug delivery approaches would provide opportunities for the development and formulation of dosage forms in a myriad of ways. One such approach is coupling 3D printing with nanomedicine, and that has led to the design of 3D-printed solid lipid tablets from emulsion gel, 3D-printed SNEDDS tablets, and nanostructured lipid carrier-based 3D-printed buccal films [[26], [27], [28]].

The development of lipid-based carrier systems has gained much attention for delivering poorly water-soluble drugs, with its improved solubility providing a faster drug release and better absorption profile. Among the various lipid-based carrier systems, self-nanoemulsifying drug delivery systems (SNEDDS) are the widely investigated lipid-based platform coupled with 3D printing techniques to develop personalized drug products with improved therapeutics. With this approach, a dapagliflozin propanediol monohydrate self-nanoemulsifying tablet was created via SSE-based 3D printing technique. The system comprised of liquid and solid phases that includes oil system (caproyl 90 and octanoic acid), a co-surfactant (PEG 400), and a solid matrix containing surfactant (PEG 6000 and poloxamer 188). 3D-printed SNEDDS tablets of different sizes (8, 10, and 12 mm) were printed. The drug release study demonstrated that the smaller tablets (8 mm) releases 95% of the drug, while larger ones (10 mm or more) releases 89% of the drug. The higher SA/V ratio of smaller tablets explains their faster release compared to bigger ones. The study found that poloxamer 188 and PEG 6000, as emulsifying and solidifying agents, did not hinder or delay the self-nanoemulsification of solid-SNEDDS, since the drug-lipid phase remained evenly distributed in the solidifying matrix microstructure [28].

Similarly, a capsular device was designed by using FDM 3D printing technique to encapsulate Cyclosporine loaded SNEDDS formulations. This study demonstrated design of nano lipid-based formulation of cyclosporine to enhance its solubility and bioavailability profile followed by its dose customization according to individual patients need to enhance the survival rate of organ transplant patients. The in-vitro drug release profiles exhibited complete cyclosporine release from the encapsulated SNEDDS formulation irrespective of capsular shell size and filled in volume. This innovative approach showed the potential to create customized doses of cyclosporine to align with the patient’s profile in a hospital pharmacy set up in the near future [18]. The development of SNEDDS results in molecular dispersion of poorly water-soluble drugs in an isotropic mixture of oil, surfactant, and co-surfactant, which upon contact with gastric fluid forms a nano-emulsion system. These nano-emulsified oil droplets encapsulating the poorly soluble drug molecules not only facilitate drug solubilization but also improve gastrointestinal absorption of drugs. Basically, SNEDDS exist in liquid form, and many commercially available SNEDDS products are liquid-based formulations designed as soft gelatin capsules, such as Accutane®, Neoral®, and Fortovase®.

The SNEDDS are evolving continuously, driven by many innovative approaches to overcome the limitations associated with liquid SNEDDS transformation into solid SNEDDS. The recently emerged revolutionary approach is the integration of 3D printing technology to design solid SNEDDS that enable solid-form fabrication of SNEDDS with precise dosing and improved biopharmaceutical performance. Extrusion-based 3D printing techniques such as pressure-assisted microsyringes (PAM) and fused deposition modelling (FDM) techniques have been explored to design 3D-printed SNEDDS. The SNEDDS formulations developed so far through 3D printing techniques include the fabrication of SNEDDS tablets [28,29], the design of SMEDDS in different geometries [30], multidrug-containing container tablets [31], multi-compartment tablets [32], capsule shells [18], and SNEDDS-based suppositories [33,34].

Lornoxicam, a non-steroidal anti-inflammatory drug (NSAID) that exhibits potent anti-inflammatory and analgesic action, is highly recommended for symptomatic treatment in rheumatoid arthritis, osteoarthritis, and for pre-operative and post-operative pain management [35,36]. Owing to its low aqueous solubility, short elimination half-life, and frequent dosing constraint [37], it is a suitable candidate to design SNEDDS-based 3D-printed pills with tuned geometries and drug release characteristics [38,39]. Although SNEDDS based formulation have been reported in the literature to enhance the solubility and dissolution profile of lornoxicam, there is no research on converting these systems into 3D printed oral dosage form that could achieves the need of personalized dosing and controlled release characteristics through tablet geometry. 3D-printed personalized dosage forms will not only deliver the drug in a better and more efficient therapeutic dose but also minimize adverse reactions and possible side effects [1,40]. This work aims to develop a 3D-printed tablet shell specifically designed to encase lornoxicam SNEDDS. The tablet shell is customized to achieve tuned drug release profiles, thereby enhancing the therapeutic efficacy of the drug.

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Materials

Lornoxicam was purchased from Sigma Aldrich (Gillingham, UK). Capmul MCM NF, Captex 355 EP/NF, Acconon MC8-2, Capmul PG12 EP/NF was purchased from Abitech Corporation (Janesville, WI, USA). Kolliphor® EL, Kolliphor® RH 40, Kolliphor® HS 15, Tween 80, Tween 20, Span 80, Octanoic acid, triacetin, Labrafac PG, Sefsol 218F was purchased from Sigma Aldrich (Gillingham, UK). Transcutol-P, Caproyl 90, oleic acid, Polyethylene glycol (PEG) 200, PEG 400, PEG 4000 was purchased from UFC Biotech (Amherst).

Abdul Aleem Mohammed, Prameela Rani Avula, Design and development of Lornoxicam self-nanoemulsifying drug delivery system (SNEDDS) loaded 3D-printed tablet shells with tunable drug release profile, Journal of Drug Delivery Science and Technology, Volume 124, 2026, 108623, ISSN 1773-2247, https://doi.org/10.1016/j.jddst.2026.108623.