Correlating mechanical and rheological filament properties to processability and quality of 3D printed tablets using multiple linear regression.

Filament formulation for FDM is a challenging and time-consuming process. Several pharmaceutical polymers are not feedable on their own. Due to inadequate filament formulation, 3D printed tablets can also exhibit poor uniformity of tablet attributes.

Development of Simvastatin-Loaded Particles Using Spray Drying Method for Ex Tempore Preparation of Cartridges for 2D Printing Technology.

In this work, a spray drying method was developed to produce drug/polymer (simvastatin/polycaprolactone) microparticles that have the potential to be used as a pre-formulation for ex tempore preparation of 2D printing cartridges. An experimental model was designed with the process parameters set to predict the smallest particle size required for successful 2D printing. Three different types of particles (lactose, nanocellulose/lactose, calcium silicate) were produced, and the average size of the dry particles varied depending on the sampling location (cyclone, collection vessel).

Influence of fused deposition modelling printing parameters on tablet disintegration times: a design of experiments study.

Despite the importance of process parameters in the printing of solid dosage forms using fused deposition modelling (FDM) technology, the field is still poorly explored. A design of experiment study was conducted to understand the complete set of process parameters of a custom developed FDM 3D printer and their influence on tablet disintegration time. Nine settings in the Simplify 3D printing process design software were evaluated with further experimental investigation conducted on the influence of infill percentage, infill pattern, nozzle diameter, and layer height.

The Effect of Design and Size of the Fluid-Bed Equipment on the Particle Size-Dependent Trend of Particle Coating Thickness and Drug Prolonged-Release Profile.

The focus of the current work is to study and demonstrate the impact of the design, the scale, and settings of fluid-bed coating equipment on the differences in pellet coating thickness, which in case of prolonged-release pellets dictates the drug release. In the first set of coating experiments, the pellet cores were coated with the Tartrazine dye with the aim of estimating the coating equipment performance in terms of coating thickness distribution, assessed through color hue. In the second set, drug-layered pellets were film-coated with prolonged-release coating and dissolution profile tests were performed to estimate the thickness and uniformity of the coating thickness among differently sized pellets.

Comparison of the Robustness of Pellet Film Coating with and without In-Process Coating Thickness Evaluation.

The robustness of the pellet coating process with and without the use of an in-process coating thickness analyzer (PATVIS APA) was investigated. Pellets containing model drug were coated with a prolonged release film coating, using different process conditions. In the first set of experiments film coating was performed as process repetitions with unintentional variation of process parameters, and in the second set, controlled changes (inlet air humidity, gap between distribution plate and Wurster partition, starting pellet load) were made.

Influence of the Binder Jetting Process Parameters and Binder Liquid Composition on the Relevant Attributes of 3D-Printed Tablets.

Binder jetting has the potential to revolutionize the way we produce medicine. However, tablets produced by binder jetting technology can be quite fragile and hard to handle. In this study, the printing process and ink composition were examined to optimize the mechanical properties of tablets.

Relative bioavailability enhancement of simvastatin via dry emulsion systems: Comparison of spray drying and fluid bed layering technology.

Comprehensive comparisons of similar lipid based drug delivery systems produced by different technologies are scarce. Spray drying and fluid bed layering technologies were compared with respect to the process and product characteristics of otherwise similar simvastatin loaded dry emulsion systems. Fluid bed layering provided higher process yield (83.

The Potential of Macroporous Silica-Nanocrystalline Cellulose Combination for Formulating Dry Emulsion Systems with Improved Flow Properties: A DoE Study.

The objective of this study was to explore the possible use of a new combination of two excipients, i.e., nanocrystalline cellulose (NCC) and macroporous silica (MS), as matrix materials for the compounding of dry emulsion systems and the effects these two excipients have on the characteristics of dry emulsion powders produced by the spray drying process.

Assessment of Mini-Tablets Coating Uniformity as a Function of Fluid Bed Coater Inlet Conditions.

This study concerned the quality of mini-tablets' coating uniformity obtained by either the bottom spray chamber with a classical Wurster distributor (CW) or a swirl distributor (SW). Mini-tablets with a diameter of 2.0, 2.

Particle properties and drug metastable solubility of simvastatin containing PVP matrix particles prepared by electrospraying technique.

In this work the preparation of drug loaded polymeric nanoparticles using electrospraying method and their subsequent characterization is presented. Our purpose was to incorporate the drug with extremely low solubility and low oxidative stability into polyvinylpyrolidone nanoparticles in order to improve its solubility and preserve its chemical stability and hence evaluate the ability of the technology to stabilize such systems in nanoparticulate form. Through the initial screening and optimization of process parameters and polymer solution properties, we detected different morphologies of electrosprayed product particles, where the use of lower molecular weight polymer resulted in a higher process instability as well as in a broader particle size distribution.

Preparation, Physicochemical Characterisation and DoE Optimisation of a Spray-Dried Dry Emulsion Platform for Delivery of a Poorly Soluble Drug, Simvastatin.

In the presented study, insight into the development and optimisation of the dry emulsion formulation and spray drying process is provided. The aim was to facilitate the dissolution of the poorly soluble, highly lipophilic drug, simvastatin, by forming spray-dried dry emulsion particles having adequate powder flow properties, while assuring sufficient drug content. Simvastatin and a mixture of caprylic, capric triglyceride and 1-oleoyl-rac-glycerol were employed as a model drug and solubilising oils, respectively.

Analytical Challenges of Spray Pattern Method Development for Purposes of Bioequivalence Testing in the Case of a Nasal Spray Product.

A spray pattern (SP) test is one of the most challenging tests for nasal spray products (NSPs) associated with a high degree of variation. The total results variation observed in such studies should be in major part representative of product performance to assure high confidence when making conclusions based on obtained results. Analytical methods should be developed in a way to minimize variation contribution of random factors.

A Novel Simulation-Based Approach for Comparing the Population Against Average Bioequivalence Statistical Test for the Evaluation of Nasal Spray Products on Spray Pattern and Droplet Size Distribution Parameters.

The aim of this work is to evaluate average bioequivalence (ABE) and population bioequivalence (PBE) statistical approaches so as to identify which approach is most suitable for in vitro bioequivalence (IVBE) testing of nasal spray products. For droplet size distribution (DSD) and spray pattern (SP), in vitro data were collected using a well-established nasal spray on the market (Nasonex®, manufactured by Merck Sharp & Dohme Limited). Simulations were performed using in vitro data to comparatively investigate ABE and PBE tests.

In-Line Film Coating Thickness Estimation of Minitablets in a Fluid-Bed Coating Equipment.

Film coating thickness of minitablets was estimated in-line during coating in a fluid-bed equipment by means of visual imaging. An existing, commercially available image acquisition system was used for image acquisition, while dedicated image analysis and data analysis methods were developed for this purpose. The methods were first tested against simulated minitablet's images and after that examined on a laboratory-scale fluid-bed Wurster coating process.

A redispersible dry emulsion system with simvastatin prepared via fluid bed layering as a means of dissolution enhancement of a lipophilic drug.

The purpose of the study was to develop a redispersible dry emulsion, containing a lipophilic, poorly water soluble model drug simvastatin, by employing fluid bed coating technology. The presented dry emulsion manufacturing approach produces pellets in a way, where a layer of the dry emulsion is applied to a neutral core. In the preliminary formulation development phase 1-oleoyl-rac-glycerol was chosen as the oily lipid phase, based on the high drug solubility and potential bioavailability enhancement capability.

Mechanics of Pharmaceutical Pellets-Constitutive Properties, Deformation, and Breakage Behavior.

To ensure robust manufacturing of unit-based oral solid dosage forms with minimal structural imperfections and high mechanical reliability across subsequent processing unit operations (e.g., withstanding mechanical stresses during coating, optional axial compression, handling, packaging, storage, and transport conditions), process design should include consideration of precise limits of accurate micro, macro, and bulk properties of the constituent pellets.

Analysis of pellet coating uniformity using a computer scanner.

A fast method for pellet coating uniformity analysis, using a commercial computer scanner was developed. The analysis of the individual particle coating thicknesses was based on using a transparent orange colored coating layer deposited on white pellet cores. Besides the analysis of the coating thickness the information of pellet size and shape was obtained as well.

Comparison of video analysis and simulations of a drum coating process.

Tablet coating is a common unit operation in the pharmaceutical industry. To improve currently established processes, it is important to understand the influence of the process parameters on the coating quality. One of the critical parameters is the tablet velocity.

Elucidation of Formulation and Delivery Device-Related Effects on In Vitro Performance of Nasal Spray with Implication to Rational Product Specification Identification.

Background: The aim of this work is to use an experimental design approach to identify and study influential formulation and delivery device properties, which can be controlled by final product manufacturer, to establish design space, within which desired in vitro performance can be reached.

Methods: Combining three factors, viscosity of suspension, nozzle orifice diameter (OD), and shot weight (SW), at three levels resulted in D-optimal experimental design with 20 runs. Responses within this study were droplet size distribution (DSD) and spray pattern (SP) in vitro tests.

The effect of material attributes and process parameters on the powder bed uniformity during a low-dose dosator capsule filling process.

The objective of this work was to assess the effect of process parameters of a dosator nozzle machine on the powder bed uniformity of inhalation powders with various characteristics during a low-dose dosator capsule filling process. Three grades of lactose excipients were extensively characterized and filled into size 3 capsules using different dosing chamber lengths (2.5, 5mm), nozzle diameters (1.

Evaluation of the tablets' surface flow velocities in pan coaters.

The tablet pan coating process involves various types of transverse tablet bed motions, ranging from rolling to cascading. To preserve satisfactory results in terms of coating quality after scale-up, understanding the dynamics of pan coating process should be achieved. The aim of this study was to establish a methodology of estimating translational surface velocities of the tablets in a pan coater and to assess their dependence on the drum's filling degree, the pan speed, the presence of baffles and the selected tablet properties in a dry bed system and during coating while varying the drum's filling degree and the pan speed.

Comparison of metoprolol tartrate multiple-unit lipid matrix systems produced by different technologies.

The aim of this study was to develop, evaluate and compare extended release mini-matrices based on metoprolol tartrate (MPT) and either glyceryl behenate (GB) or glyceryl palmitostearate (GPS). Mini-matrices were produced by three different techniques: hot melt extrusion, compression of melt granulates and prilling. Hot-melt extrusion and compression of granules obtained from melted material proved to be reliable, robust and reproducible techniques with aim of obtaining extended release matrices.

Granular Matter Transport in Vertical Pipes: The Influence of Pipe Outlet Conditions on Gravity-driven Granular Flow.

Gravity transport of granular materials in vertical pipes is one of the most fundamental steps in bulk powder handling and processing. Presented study investigates powder flow characteristics in vertical pipes with open and closed outlets and condition of free powder fall. Powder flow of pharmaceutical grade powders was observed in transparent, vertical pipe model.

Influence of pH modifiers on the dissolution and stability of hydrochlorothiazide in the bi- and three-layer tablets.

During the past few years, the studies of bi- and multi-layered tablets increased due to the consumption of several different drugs per day by a patient and requests for appropriate patient compliance. The demographic shift toward older population increases the use of combination therapy as polypharmacy. Hydrochlorothiazide (HCTZ), as a model drug, is most commonly used in the treatment of hypertension, congestive heart failure and as a diuretic.