| 1. |
- Katsiotis, Christos S., et al.
(författare)
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Development of a simple paste for 3D printing of drug formulations containing a mesoporous material loaded with a poorly water-soluble drug
- 2024
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 198
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Tidskriftsartikel (refereegranskat)abstract
- Poorly soluble drugs represent a substantial portion of emerging drug candidates, posing significant challenges for pharmaceutical formulators. One promising method to enhance the drug’s dissolution rate and, consequently, bioavailability involves transforming them into an amorphous state within mesoporous materials. These materials can then be seamlessly integrated into personalized drug formulations using Additive Manufacturing (AM) techniques, most commonly via Fused Deposition Modeling. Another innovative approach within the realm of AM for mesoporous material-based formulations is semi-solid extrusion (SSE). This study showcases the feasibility of a straightforward yet groundbreaking hybrid 3D printing system employing SSE to incorporate drug-loaded mesoporous magnesium carbonate (MMC) into two different drug formulations, each designed for distinct administration routes. MMC was loaded with the poorly water-soluble drug ibuprofen via a solvent evaporation method and mixed with PEG 400 as a binder and lubricant, facilitating subsequent SSE. The formulation is non-aqueous, unlike most pastes which are used for SSE, and thus is beneficial for the incorporation of poorly water-soluble drugs. The 3D printing process yielded tablets for oral administration and suppositories for rectal administration, which were then analyzed for their dissolution behavior in biorelevant media. These investigations revealed enhancements in the dissolution kinetics of the amorphous drug-loaded MMC formulations. Furthermore, an impressive drug loading of 15.3 % w/w of the total formulation was achieved, marking the highest reported loading for SSE formulations incorporating mesoporous materials to stabilize drugs in their amorphous state by a wide margin. This simple formulation containing PEG 400 also showed advantages over other aqueous formulations for SSE in that the formulations did not exhibit weight loss or changes in size or form during the curing process post-printing. These results underscore the substantial potential of this innovative hybrid 3D printing system for the development of drug dosage forms, particularly for improving the release profile of poorly water-soluble drugs.
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| 2. |
- Katsiotis, Christos S.
(författare)
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Additive Manufacturing and Mesoporous Materials for Pharmaceutical Applications
- 2024
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Additive Manufacturing (AM), over the past decade, has evolved into a versatile technology with significant applications in pharmaceutical research. This technology enables the production of drug formulations tailored to individual patients, offering customization in both dosage and dissolution profiles. While challenges in mass production persist, 3D printing, particularly through techniques like Fused Deposition Modeling (FDM) and Semi Solid Extrusion (SSE), proves ideal for crafting smaller batches of personalized dosage forms.A prevalent issue in drug development revolves around poor water solubility, impacting bioavailability upon oral administration. To combat this, the integration of mesoporous materials emerges as a promising strategy to enhance the dissolution of poorly water-soluble drugs. Here, the applicability of mesoporous materials is explored, as well as their incorporation with various AM techniques. Overall, the thesis dives into the investigation of combinatorial formulations, incorporating at least one 3D printed component to address specific requirements in drug delivery. By combining FDM with Selective Laser Sintering (SLS), a hybrid two-compartmental formulation is developed. The durable FDM-printed shell regulates buffer medium access to the contained SLS-produced inserts loaded with the drug. Varying printing parameters and insert combinations within the shell showcase the adjustability and flexibility of this hybrid approach.Tablets with different infill percentages, containing drug-loaded mesoporous materials, are developed. Poorly water-soluble drugs are successfully amorphized within mesoporous material pores, formulated into filaments through Hot Melt Extrusion (HME), and printed via FDM. These tablets exhibit improved dissolution compared to the crystalline drug, with the dissolution behavior regulated also by the infill percentage.The study explores the impact of drug-loaded mesoporous materials on HME-produced filament properties, studying their effect on maximum tensile strength and Young’s modulus. The relationship between these properties and filament printability is investigated. Additionally, a protective effect of mesoporous materials on drugs from thermal degradation is revealed.For Semi Solid Extrusion (SSE) manufactured formulations, a paste is developed, comprising mesoporous material loaded with a poorly water-soluble drug and an excipient. This paste demonstrates favorable rheological properties and easy extrudability via a syringe. The formulation proves versatile for printing dosage forms for both oral and rectal administration, with the printed tablet and suppository exhibiting effective drug release.In conclusion, this work presents valuable strategies for developing patient-tailored dosage forms, addressing specific pharmaceutical challenges like poor solubility. The integration of mesoporous materials and various 3D printing techniques showcases a promising direction for personalized medicine in the pharmaceutical field.
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| 3. |
- Levine, Valerie, 1996-, et al.
(författare)
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Geometry impact on fundamental properties of theophylline-containing SLS printed pharmaceutical tablets
- 2024
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Ingår i: Frontiers in Drug Delivery. - 2674-0850. ; 4
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Tidskriftsartikel (refereegranskat)abstract
- Selective Laser Sintering (SLS) has the potential to offer a more accurate alternative to current-practice manipulation of oral dosage forms for pediatric, geriatric, and dysphagia-suffering patient groups. In order to create the best possible dosage forms for these patient groups, an in-depth look into how a dosage forms geometry impacts the overall properties is essential. In this study, the impact of geometry on SLS manufactured oral dosage forms on the tablet’s microstructure, actual-to-theoretical volume, mass deviation, disintegration, and dissolution was investigated. Three different shapes; cylinder, hollow cylinder, and conical frustum with similar surface area (SA), as well as three cylinders with different diameters, were investigated. The results indicate that the geometry has an impact on the mass uniformity, resultant volume, disintegration, and dissolution properties of the tablets. The mass uniformity analysis of the tablets provided the most variation between tablets of different sizes, with more uniformity for tablets with similar SA-to-volume ratio (SA/V). When examining the actual-to-theoretical volume of the tablets, a greater variance between the actual and theoretical volumes for shapes with higher overall SA was observed. The values found are approximately 1.05 for the three differently sized cylinders, 1.23 for the conical frustum, and 1.44 for the hollow cylinder, following this trend. Disintegration data supported a link between SA/V and average disintegration time, observed with the tablet of the highest SA/V disintegrating in 12 s and the tablet with the lowest SA/V disintegrating in 58 s. Dissolution results also indicated a strong dependence on SA/V. Hence, when novel ways to produce oral dosage form tablets become available by additive manufacturing, such as SLS, both geometry and SA/V must be taken into consideration in the tablet design process to ensure appropriate release kinetics and dosing standards.
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