Pharmacies are currently unable to stock proper oral dosage forms for pediatric populations. This leads to manipulation of medications or the need to compound specialized medications, which can be a time-consuming process. Using Semisolid Extrusion (SSE) additive manufacturing (AM), specialized medications can be produced in an expedited process from off-the shelf medication in a hospital or outpatient pharmacy setting. In this study, tablets with a desired dose of 5 mg of metoprolol tartrate derived from commercial Seloken™ 50 mg tablets were 3D printed in a hospital setting. Validation testing was done on five batches, highlighting tablets with a high uniformity in mass and dimension, drug content, acceptable microbial assays, and prolonged release during in-vitro analysis. The average drug content found for the tablets was within ±6% of 5 mg for all batches produced. Comparisons were done between the SSE tablets and capsules produced in an external compounding facility, highlighting several positive aspects of SSE-produced tablets beyond simply shortening the production timeline. The SSE tablets printed in this study are characterized by their smaller size, enhanced prolonged release properties, and more uniform drug content across the tested samples. Additionally, interviews with pharmaceutical professionals were conducted to determine the positive aspects of SSE and further improvements to bring this technique as seamlessly as possible into the pharmacy. This study underscores the feasibility of employing SSE in the production of specialized medications within a hospital environment. Furthermore, it highlights the methodological advantages SSE offers over existing production standards, demonstrating its potential to improve pharmaceutical manufacturing in healthcare settings.

Dose-adjustment is a very common practice in pharmacies, with accuracy particularly relevant for medications on a tapering schedule. Semisolid extrusion (SSE) has shown potential to provide a more accurate form of dose-adjustment than traditional methods (i.e. tablet splitting and liquid solutions). These methods, however, usually lack validation and quality assurance, as no validation is typically conducted post dose-adjustment. Machine learning (ML) based image analysis can provide this necessary validation. Fluoxetine-containing SSE tablets of three tapering steps were created to investigate with image analysis using a MLM. The tablets had a high degree of uniformity in mass and dimensional measurements. The average drug content of the SSE tablets was within ±3.5% of the desired dose for all tapering steps, showing higher accuracy than doses made via tablet splitting (±28.2% dose accuracy) and liquid solutions (±17.0% dose accuracy) produced by a licensed pharmacist. Utilizing a MLM for image analysis and images of tablets taken from the top and bottom of each tablet, the ability to categorize tablets based on the view of the tablet in the image (top or bottom of the tablet) and identification of the dose in the image showed over 99.87% confidence. The MLM also had the ability to identify mass outlier and non-outlier tablets well, with 90% correct identification of test images for tablets with a tablet height consistent with the average. Here, the need for more than one tablet viewpoint (i.e. greater variety of data), was more evident than for determining the drug dose, where the test tablets were all still identified correctly with over 99.65% confidence in all cases. This study identifies the feasibility of using a MLM to identify tablets as a means of validation based on images. 

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.

The aim of this study is to investigate the influence of polymer chemistry on the properties of oral dosage forms produced using selective laser sintering (SLS). The dosage forms were printed using different grades of polyvinyl alcohol or copovidone in combination with indomethacin as the active pharmaceutical ingredient. The properties of the printed structures were assessed according to European Pharmacopoeia guidelines at different printing temperatures and laser scanning speeds in order to determine the suitable printing parameters.

The results of the study indicate that the chemical properties of the polymers, such as dynamic viscosity, degree of hydrolyzation, and molecular weight, have significant impact on drug release and kinetics. Drug release rate and supersaturation can be modulated by selecting the appropriate polymer type. Furthermore, the physical properties of the dosage forms printed under the same settings are influenced by the selected polymer type, which determines the ideal manufacturing settings.

This study demonstrates how the chemical properties of the polymer can determine the appropriate choice of manufacturing settings and the final properties of oral dosage forms produced using SLS.