Antimicrobial Effectiveness of L. Leaf Extracts Prepared in Natural Deep Eutectic Solvents (NaDESs).

Background: Blackcurrant ( L.) leaves are valuable sources of bioactive compounds, including phenolic acids, flavonoids, and tannins, which contribute to their potent antioxidant, anti-inflammatory, and antimicrobial properties.

Objectives: The overall aim of this study was to investigate the antimicrobial potential of extracts rich in bioactive compounds from blackcurrant leaves prepared in natural deep eutectic solvents (NaDESs).

Exploring Vacuum Compression Molding as a Preparation Method for Flexible-Dose Pediatric Orodispersible Films.

In recent years, solid dosage forms have gained interest in pediatric therapy because they can provide valuable benefits in terms of dose accuracy and stability. Particularly for orodispersible films (ODFs), the literature evidences increased acceptability and dose flexibility. Among the various available technologies for obtaining ODFs, such as solvent casting, hot-melt extrusion, and ink printing technologies, the solvent-free preparation methods exhibit significant advantages.

Expanding the Manufacturing Approaches for Gastroretentive Drug Delivery Systems with 3D Printing Technology.

Gastroretentive drug delivery systems (GRDDSs) have gained substantial attention in the last 20 years due to their ability to retain the drug in the stomach for an extended time, thus promoting an extended release and high bioavailability for a broad range of active pharmaceutical ingredients (APIs) that are pH-sensitive and/or have a narrow absorption window. The currently existing GRDDSs include floating, expanding, mucoadhesive, magnetic, raft-forming, ion-exchanging, and high-density systems. Although there are seven types of systems, the main focus is on floating, expanding, and mucoadhesive systems produced by various techniques, 3D printing being one of the most revolutionary and currently studied ones.

Testing the disintegration and texture-related palatability predictions for orodispersible tablets using an instrumental tool coupled with multivariate analysis: Focus on process variables and analysis settings.

Orodispersible tablets (ODTs) represent a growing category of dosage forms intended to increase the treatment acceptability for special groups of patients. ODTs are designed to rapidly disintegrate in the oral cavity and to be administered without water. In addition, ODTs are easy to manufacture using standard excipients and pharmaceutical equipment.

The Effect of Formulation Variables on the Manufacturability of Clopidogrel Tablets via Fluidized Hot-Melt Granulation-From the Lab Scale to the Pilot Scale.

Solid pharmaceutical formulations with class II active pharmaceutical ingredients (APIs) face dissolution challenges due to limited solubility, affecting in vivo behavior. Robust computational tools, via data mining, offer valuable insights into product performance, complementing traditional methods and aiding in scale-up decisions. This study utilizes the design of experiments (DoE) to understand fluidized hot-melt granulation manufacturing technology.

Polyvinyl Alcohol, a Versatile Excipient for Pharmaceutical 3D Printing.

Three-dimensional (3D) printing in the pharmaceutical field allows rapid manufacturing of a diverse range of pharmaceutical dosage forms, including personalized items. The application of this technology in dosage form manufacturing requires the judicious selection of excipients because the selected materials must be appropriate to the working principle of each technique. Most techniques rely on the use of polymers as the main material.

Development of a PAT platform for the prediction of granule tableting properties.

In this work, the feasibility of implementing a process analytical technology (PAT) platform consisting of Near Infrared Spectroscopy (NIR) and particle size distribution (PSD) analysis was evaluated for the prediction of granule downstream processability. A Design of Experiments-based calibration set was prepared using a fluid bed melt granulation process by varying the binder content, granulation time, and granulation temperature. The granule samples were characterized using PAT tools and a compaction simulator in the 100-500 kg load range.

Texture analysis - A versatile tool for pharmaceutical evaluation of solid oral dosage forms.

In the past few decades, texture analysis (TA) has gained importance as a valuable method for the characterization of solid oral dosage forms. As a result, an increasing number of scientific publications describe the textural methods that evaluate the extremely diverse category of solid pharmaceutical products. Within the current work, the use of texture analysis in the characterization of solid oral dosage forms is summarised with a focus on the evaluation of intermediate and finished oral pharmaceutical products.

The Use of the QbD Approach to Optimize the Co-Loading of Simvastatin and Doxorubicin in Liposomes for a Synergistic Anticancer Effect.

The present study aimed to optimize a liposomal formulation co-encapsulating simvastatin (SIM) and doxorubicin (DOX) that has future perspectives in anticancer therapy. The optimization process was performed by implementing the Quality by Design concept and by considering the results of a previous screening study. Failure Mode and Effects Analysis was used for the identification of the potential critical factors, i.

Challenges and Opportunities of Implementing Data Fusion in Process Analytical Technology-A Review.

The release of the FDA's guidance on Process Analytical Technology has motivated and supported the pharmaceutical industry to deliver consistent quality medicine by acquiring a deeper understanding of the product performance and process interplay. The technical opportunities to reach this high-level control have considerably evolved since 2004 due to the development of advanced analytical sensors and chemometric tools. However, their transfer to the highly regulated pharmaceutical sector has been limited.

In-Depth Understanding of Granule Compression Behavior under Variable Raw Material and Processing Conditions.

Tablet manufacturing involves the processing of raw materials through several unit operations. Thus, the mitigation of input-induced variability should also consider the downstream processability of intermediary products. The objective of the present work was to study the effect of variable raw materials and processing conditions on the compression properties of granules containing two active pharmaceutical ingredients (APIs) and microcrystalline cellulose.

QbD guided development of immediate release FDM-3D printed tablets with customizable API doses.

The objective of this work was to develop a fused deposition modeling (FDM) 3D printed immediate release (IR) tablet with flexibility in adjusting the dose of the active pharmaceutical ingredient (API) by scaling the size of the dosage form and appropriate drug release profile steadiness to the variation of dimensions or thickness of the deposited layers throughout the printing process. Polyvinyl alcohol-based filaments with elevated API content (50% w/w) were prepared by hot melt extrusion (HME), through systematic screening of polymeric formulations with different drug loadings, and their printability was evaluated by means of mechanical characterization. For the tablet fabrication step by 3D printing (3DP), the Quality by Design (QbD) approach was implemented by employing risk management strategies and Design of Experiments (DoE).

Testing the Limits of a Portable NIR Spectrometer: Content Uniformity of Complex Powder Mixtures Followed by Calibration Transfer for In-Line Blend Monitoring.

(1) Background: Portable NIR spectrometers gain more and more ground in the field of Process Analytical Technology due to the easy on-site flexibility and interfacing versatility. These advantages that originate from the instrument miniaturization, also come with a downside with respect to performance compared to benchtop devices. The objective of this work was to evaluate the performance of MicroNIR in a pharmaceutical powder blend application, having three active ingredients and 5 excipients.

Multivariate feed forward process control and optimization of an industrial, granulation based tablet manufacturing line using historical data.

The purpose of this work was to understand the variability in disintegration time and tableting yield of high drug load (>60%) tablets prepared by batch-wise high shear wet granulation. The novelty of the study is the use of multivariate methods (Batch Evolution Models - BEMs and Batch Level Models - BLMs) to enhance process control, with a feed forward component, using prediction models built from a historical dataset acquired for 95 industrial scale batches. Time dependent process variables and significant influences on investigated parameters were identified.

Fluidised bed granulation of two APIs: QbD approach and development of a NIR in-line monitoring method.

The study focused on the fluid-bed granulation process of a product with two active pharmaceutical ingredients, intended for coated tablets preparation and further transfer to industrial scale. The work aimed to prove that an accurate control of the critical granulation parameters can level the input material variability and offer a user-friendly process control strategy. Moreover, an in-line Near-Infrared monitoring method was developed, which offered a real time overview of the moisture level along the granulation process, thus a reliable supervision and control process analytical technology (PAT) tool.

Videometric mass flow control: A new method for real-time measurement and feedback control of powder micro-feeding based on image analysis.

The present paper reports the first monitoring and control of ultra-low dose powder feeding using a camera image-based mass flow measurement system. Caffeine was fed via a single-screw microfeeder as a model active pharmaceutical ingredient (API). The mass, mass flow and sizes of the particles were successfully monitored in real-time by the developed videometric system consisting of a high-speed process camera coupled with an image analysis software.

Liposomal simvastatin sensitizes C26 murine colon carcinoma to the antitumor effects of liposomal 5-fluorouracil in vivo.

5-Fluorouracil-based therapy remains the main approach in colorectal cancer, even though there are still some drawbacks, such as chemoresistance. In this study we combined 5-fluorouracil encapsulated in long-circulating liposomes with simvastatin, also encapsulated in long-circulating liposomes, that was previously proved to exert antitumor actions on the same tumor model. The production of angiogenic/inflammatory proteins was assessed by protein array and the production of markers for tumor aggressiveness (Bcl-2, Bax, and nuclear factor [NF]-κB) were determined by western blot analysis.

Electrospun amorphous solid dispersions of meloxicam: Influence of polymer type and downstream processing to orodispersible dosage forms.

The objectives of this work were to develop meloxicam based amorphous solid dispersion through electrospinning technique and evaluate the effect of the polymeric matrix on the physicochemical properties of the fibers and the downstream processing ability to orodispersible dosage forms. Drug - polymer interactions formed between Eudragit E and meloxicam, confirmed through Raman and 1HNMR spectra, enabled the development of fibers from ethanol, thus allowing an increased production rate compared to PVPk30 where a DMF:THF solvent system was suitable. Microflux dissolution-permeation studies showed a significantly higher diffusion from amorphous solid dispersions compared to crystalline meloxicam.

Data fusion strategies for performance improvement of a Process Analytical Technology platform consisting of four instruments: An electrospinning case study.

The aim of this work was to develop a PAT platform consisting of four complementary instruments for the characterization of electrospun amorphous solid dispersions with meloxicam. The investigated methods, namely NIR spectroscopy, Raman spectroscopy, Colorimetry and Image analysis were tested and compared considering the ability to quantify the active pharmaceutical ingredient and to detect production errors reflected in inhomogeneous deposition of fibers. Based on individual performance the calculated RMSEP values ranged between 0.

Biologically Active Species Extracts Modulate Supportive Processes for Cancer Cell Development.

species have been used in traditional medicine for their diuretic, anti-inflammatory, wound-healing, and hepatoprotective properties. The phytochemical profile and anticancer potential of three sp. (, and ) from Romania was investigated.

The applicability of pharmaceutical polymeric blends for the fused deposition modelling (FDM) 3D technique: Material considerations-printability-process modulation, with consecutive effects on in vitro release, stability and degradation.

The three dimensional printing (3DP) in the pharmaceutical domain constitutes an alternative, innovative approach compared to the conventional production methods. Fused deposition modelling (FDM), is a simple, cost-effective 3DP technique, however the range of pharmaceutical excipients that can be applied for this methodology is restricted. The study set to define the requirements of the FDM printability, using as technical support custom made, pharmaceutical polymer based filaments and to evaluate if these new dosage forms can live up to the current GMP/GCP quality standards.