In-line indirect concentration measurement of ultralow dose API during twin-screw wet granulation based on NIR and Raman spectroscopy.

Twin-screw wet granulation (TWSG) is a promising continuous alternative of pharmaceutical wet granulation. One of its benefits is that the components dissolved in the granulation liquid are distributed homogeneously in the granules. This provides an elegant way to manufacture products with ultralow drug doses.

Impact of COVID-19 and Vaccination During Pregnancy on Placenta-Mediated Complications (COVIGRO Study).

Objectives: COVID-19 has been associated with preterm birth (PTB) and placental-mediated complications, including fetal growth restriction and preeclampsia (PE). This study aimed to estimate the impact of COVID-19 and vaccination on adverse pregnancy outcomes and markers of placental function.

Methods: We performed a study on a prospective cohort of women recruited in the first trimester of pregnancy during the early COVID-19 pandemic period (December 2020 to December 2021).

Integrated twin-screw wet granulation, continuous vibrational fluid drying and milling: A fully continuous powder to granule line.

Highly homogeneous low-dose (50 μg) tablets were produced incorporating perfectly free-flowing granules prepared by a fully integrated Continuous Manufacturing (CM) line. The adopted CM equipment consisted of a Twin-Screw Wet Granulator (TSWG), a Continuous Fluid Bed Dryer (CFBD) and a Continuous Sieving (CS) unit. Throughout the experiments a pre-blend of lactose-monohydrate and corn starch was gravimetrically dosed with 1 kg/h into the TSWG, where they were successfully granulated with the drug containing water-based PVPK30 solution.

Influence of Aqueous Solubility-Enhancing Excipients on the Microstructural Characteristics of Furosemide-Loaded Electrospun Nanofibers.

Electrospun nanofibers were prepared from furosemide-containing hydroxypropyl cellulose and poly(vinylpyrrolidone) aqueous solutions using different solubility enhancers. In one case, a solubilizer, triethanolamine, was applied, while in the other case a pH-modifier, sodium hydroxide, was applied. Scanning electron microscopy (SEM) was carried out for morphological characterization of the fibers.

Scale-up of electrospinning technology: Applications in the pharmaceutical industry.

Recently, electrospinning (ES) of fibers has been shown to be an attractive strategy for drug delivery. One of the main features of ES is that a wide variety of drugs can be loaded into the fibers to improve their bioavailability, to enhance dissolution, or to achieve controlled release. Besides, ES is a continuous technology with low energy consumption, which can make it a very economic production alternative to the widely used freeze drying and spray drying.

Continuous Formulation Approaches of Amorphous Solid Dispersions: Significance of Powder Flow Properties and Feeding Performance.

Preparation and formulation of amorphous solid dispersions (ASDs) are becoming more and more popular in the pharmaceutical field because the dissolution of poorly water-soluble drugs can be effectively improved this way, which can lead to increased bioavailability in many cases. During downstream processing of ASDs, technologists need to keep in mind both traditional challenges and the newest trends. In the last decade, the pharmaceutical industry began to display considerable interest in continuous processing, which can be explained with their potential advantages such as smaller footprint, easier scale-up, and more consistent product, better quality and quality assurance.

Continuous drying of a protein-type drug using scaled-up fiber formation with HP-β-CD matrix resulting in a directly compressible powder for tableting.

The goals of this work were to evaluate if high-speed electrospinning can be used as a gentle and continuous drying technology to produce protein-containing cyclodextrin-based fibers from an aqueous solution and to convert the produced protein-cyclodextrin fibers into a directly compressible powder. A 400 mL/h feeding rate was used during the electrospinning experiments, corresponding to a ~270 g/h production rate of the dried material. The produced fibers were collected in a cyclone.

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.

Scaled-Up Production and Tableting of Grindable Electrospun Fibers Containing a Protein-Type Drug.

The aims of this work were to develop a processable, electrospun formulation of a model biopharmaceutical drug, β-galactosidase, and to demonstrate that higher production rates of biopharmaceutical-containing fibers can be achieved by using high-speed electrospinning compared to traditional electrospinning techniques. An aqueous solution of 7.6 /% polyvinyl alcohol, 0.

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.

Application of artificial neural networks for Process Analytical Technology-based dissolution testing.

This work proposes the application of artificial neural networks (ANN) to non-destructively predict the in vitro dissolution of pharmaceutical tablets from Process Analytical Technology (PAT) data. An extended release tablet formulation was studied, where the dissolution was influenced by the composition of the tablets and the tableting compression force. NIR and Raman spectra of the intact tablets were measured, and the dissolution of the tablets was modeled directly from the spectral data.

Continuous alternative to freeze drying: Manufacturing of cyclodextrin-based reconstitution powder from aqueous solution using scaled-up electrospinning.

The aims of this study were to evaluate electrospinning as a continuous alternative to freeze drying in the production of a reconstitution injection dosage form, and to prove that aqueous electrospinning can be realized with a high production rate at room temperature. High-speed electrospinning with a novel continuous cyclone collection was used to manufacture a formulation of the poorly water-soluble antifungal voriconazole (VOR) with sulfobutylether-β-cyclodextrin (SBE-β-CD). The freeze-dried, marketed product of this drug substance, Vfend® also contains SBE-β-CD as excipient.

Drying technology strategies for colon-targeted oral delivery of biopharmaceuticals.

In chronic intestinal diseases like inflammatory bowel disease, parenteral administration of biopharmaceuticals is associated with numerous disadvantages including immune reactions, infections, low patient compliance, and toxicity caused by high systemic bioavailability. One alternative that can potentially overcome these limitations is oral administration of biopharmaceuticals, where the local delivery will reduce the systemic exposure and furthermore the manufacturing costs will be lower. However, the development of oral dosage forms that deliver the biologically active form to the intestines is one of the greatest challenges for pharmaceutical technologists due to the sensitive nature of biopharmaceuticals.

Homogenization of Amorphous Solid Dispersions Prepared by Electrospinning in Low-Dose Tablet Formulation.

Low-dose tablet formulations were produced with excellent homogeneity based on drug-loaded electrospun fibers prepared by single-needle as well as scaled-up electrospinning (SNES and HSES). Carvedilol (CAR), a BCS II class compound, served as the model drug while poly (vinylpyrrolidone--vinyl acetate) (PVPVA64) was adopted as the fiber-forming polymer. Scanning electron microscopy (SEM) imaging was used to study the morphology of HSES and SNES samples.

Spectroscopic characterization of tablet properties in a continuous powder blending and tableting process.

By the advent of continuous pharmaceutical manufacturing, fast and accurate characterization of product quality has become of a major interest. Although it also promotes the real-time release testing approach, so far mainly content uniformity studies were performed by near-infrared (NIR) spectroscopy. This paper proposes the simultaneous application of NIR and Raman spectroscopy to nondestructively analyze the critical quality attributes of continuously produced tablets in a real-time release testing procedure.

Application of hydroxypropyl methylcellulose as a protective agent against magnesium stearate induced crystallization of amorphous itraconazole.

Itraconazole is a fungicide drug which has low bioavailability due to its poor water solubility. Amorphous solid dispersion (ASD) is a tool that has the potential to greatly increase the dissolution rate and extent of compounds. In this work, the dissolution of tablets containing the ASD of itraconazole with either hydroxypropyl methylcellulose (HPMC) or vinylpyrrolidone-vinyl acetate copolymer (PVPVA) was compared in order to find a formulation which can prevent the drug from the precipitation caused by magnesium stearate.

Real-time feedback control of twin-screw wet granulation based on image analysis.

The present paper reports the first dynamic image analysis-based feedback control of continuous twin-screw wet granulation process. Granulation of the blend of lactose and starch was selected as a model process. The size and size distribution of the obtained particles were successfully monitored by a process camera coupled with an image analysis software developed by the authors.

Preformulation Studies of Furosemide-Loaded Electrospun Nanofibrous Systems for Buccal Administration.

Furosemide loaded electrospun fibers were prepared for buccal administration, with the aim of improving the oral bioavailability of the poorly soluble and permeable crystalline drug, which can be achieved by the increased solubility and by the circumvention of the intensive first pass metabolism. The water soluble hydroxypropyl cellulose (HPC) was chosen as a mucoadhesive polymer. In order to improve the electrospinnability of HPC, poly (vinylpyrrolidone) (PVP) was used.

Investigation of Deteriorated Dissolution of Amorphous Itraconazole: Description of Incompatibility with Magnesium Stearate and Possible Solutions.

Disadvantageous crystallization phenomenon of amorphous itraconazole (ITR) occurring in the course of dissolution process was investigated in this work. A perfectly amorphous form (solid dispersion) of the drug was generated by the electroblowing method (with vinylpyrrolidone-vinyl acetate copolymer), and the obtained fibers were formulated into tablets. Incomplete dissolution of the tablets was noticed under the circumstances of the standard dissolution test, after which a precipitated material could be filtered.

In-line Raman spectroscopic monitoring and feedback control of a continuous twin-screw pharmaceutical powder blending and tableting process.

The integration of Process Analytical Technology (PAT) initiative into the continuous production of pharmaceuticals is indispensable for reliable production. The present paper reports the implementation of in-line Raman spectroscopy in a continuous blending and tableting process of a three-component model pharmaceutical system, containing caffeine as model active pharmaceutical ingredient (API), glucose as model excipient and magnesium stearate as lubricant. The real-time analysis of API content, blend homogeneity, and tablet content uniformity was performed using a Partial Least Squares (PLS) quantitative method.