Submit to Pharmaceutics Review for Pharmaceutics Propose a Special Issue

Journal Menu

Journal Browser

Pharmaceutical Solids: Advanced Manufacturing and Characterization

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Pharmaceutical Technology, Manufacturing and Devices".

Deadline for manuscript submissions: closed (20 November 2024) | Viewed by 17317

Share This Special Issue

Special Issue Editor

Dr. Vivek Verma

E-Mail Website
Guest Editor

Department of Chemical Engineering, Imperial College London, London SW7 2AZ, UK
Interests: (bio)pharmaceutical crystallisation; pharmaceutical formulations; secondary processing of powders; process analytical techniques; spray drying

Special Issue Information

Dear Colleagues,

Pharmaceutical solids play a pivotal role in drug development and delivery. Advanced manufacturing and characterization techniques are indispensable for ensuring the quality, safety, effectiveness, and swift time-to-market of these products. In recent times, significant progress has been made in the realm of pharmaceutical solid manufacturing and characterization, resulting in enhanced drug formulations, delivery systems, and overall patient well-being. Novel manufacturing and characterization technologies hold the potential to optimize pharmaceutical production and offer advantages to patients. However, the widespread adoption of these innovative pharmaceutical manufacturing technologies has encountered obstacles, as stakeholders highlight potential barriers to their implementation. This Special Issue, titled "Pharmaceutical Solids: Advanced Manufacturing and Characterization", aims to showcase the cutting-edge advancements in all facets of pharmaceutical solids manufacturing and characterization. The goal is to introduce new tools that address drug shortages and other challenges, ultimately contributing to improved pharmaceutical quality.

Dr. Vivek Verma
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

hot melt extrusion (HME)
nanotechnology (nanoparticles and nanosuspensions, nanoprecipitation and nano emulsification)
three-dimensional printing
spray drying including supercritical CO₂-assisted spray drying
quality-by-design (QbD) approach
continuous manufacturing
artificial intelligence and machine learning
template/surface assisted crystallisation
microwave assisted manufacturing
sono precipitation
mechanochemistry
advanced characterizations such as X-Ray Diffraction (XRD), Differential Scanning Calorimetry (DSC), Scanning Electron Microscopy (SEM), Raman Spectroscopy, Dynamic Vapor Sorption (DVS), Inverse Gas Chromatography (IGC), Quartz Crystal Microbalance (QCM), scanning white light interferometry, TOF-SIMS, XPS, Solid State Nuclear Magnetic Resonance, in situ PXRD, TEM, and SEM, SEM-Raman, and other solid state characterizations
hyperspectral imaging, MRI characterization of solid pharmaceutical dosage forms, X-ray tomography and terahertz pulsed spectroscopy and imaging, NIR spectroscopy
Process Analytical Technology (PAT)

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
e-Book format: Special Issues with more than 10 articles can be published as dedicated e-books, ensuring wide and rapid dissemination.

Further information on MDPI's Special Issue polices can be found here.

Published Papers (9 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Review

21 pages, 3774 KiB

Open AccessArticle

NIR-Guided Coating Optimization of Omega-3 Fatty Acid Mini Soft Capsules with Pitavastatin and Ezetimibe

by Hye-Ri Han, Ji Hoon Choi, Je Hwa Yoo, Jin-Hyuk Jeong, Sang-Beom Na, Ji-Hyun Kang, Dong-Wook Kim and Chun-Woong Park

Pharmaceutics 2024, 16(11), 1374; https://doi.org/10.3390/pharmaceutics16111374 - 26 Oct 2024

Viewed by 659

Abstract

Background: This study aimed to optimize the coating process of Omega-3 fatty acid (OM3-FA) mini soft capsules containing the active pharmaceutical ingredients (APIs) pitavastatin and ezetimibe using near-infrared (NIR) spectroscopy for in-process monitoring. Cardiovascular disease treatments benefit from combining OM3-FA with lipid-lowering agents, but formulating such combinations in mini soft capsules presents challenges in maintaining stability and mechanical integrity. Methods: The coating process was developed using a pan coater and real-time NIR monitoring to ensure uniformity and quality. NIR spectroscopy enabled precise control of coating thickness, ensuring consistent drug distribution across the capsule surface. Results: The optimized process minimized OM3-FA oxidation and preserved the mechanical integrity of the capsules, as confirmed by texture analysis and in-vitro dissolution testing. This integration of NIR spectroscopy as a process analytical technology (PAT) significantly improved coating quality control, resulting in a stable and effective combination therapy for pitavastatin and ezetimibe in a mini soft capsule form. Conclusion: This approach offers an efficient solution for enhancing patient adherence in cardiovascular disease management. The application of NIR spectroscopy for real-time monitoring highlights its broader significance in pharmaceutical manufacturing, where it can serve as a versatile tool for ensuring product quality and optimizing production efficiency in diverse formulation processes. By incorporating NIR-based PAT, manufacturers can not only achieve product-specific improvements but also establish a foundation for continuous manufacturing and automated quality assurance systems, ultimately contributing to a more streamlined and robust production environment. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Figure 1

17 pages, 5453 KiB

Open AccessArticle

Process-Induced Crystal Surface Anisotropy and the Impact on the Powder Properties of Odanacatib

by Isha Bade, Vikram Karde, Luke Schenck, Marina Solomos, Margaret Figus, Chienhung Chen, Stephanus Axnanda and Jerry Y. Y. Heng

Pharmaceutics 2024, 16(7), 883; https://doi.org/10.3390/pharmaceutics16070883 - 30 Jun 2024

Cited by 1 | Viewed by 1325

Abstract

Crystalline active pharmaceutical ingredients with comparable size and surface area can demonstrate surface anisotropy induced during crystallization or downstream unit operations such as milling. To the extent that varying surface properties impacts bulk powder properties, the final drug product performance such as stability, dissolution rates, flowability, and dispersibility can be predicted by understanding surface properties such as surface chemistry, energetics, and wettability. Here, we investigate the surface properties of different batches of Odanacatib prepared through either jet milling or fast precipitation from various solvent systems, all of which meet the particle size specification established to ensure equivalent biopharmaceutical performance. This work highlights the use of orthogonal surface techniques such as Inverse Gas Chromatography (IGC), Brunauer–Emmett–Teller (BET) surface area, contact angle, and X-ray Photoelectron Spectroscopy (XPS) to demonstrate the effect of processing history on particle surface properties to explain differences in bulk powder properties. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Figure 1

21 pages, 23871 KiB

Open AccessArticle

Transformation of ABT-199 Nanocrystal Suspensions into a Redispersible Drug Product—Impact of Vacuum Drum Drying, Spray Drying and Tableting on Re-Nanodispersibility

by Barbara Schönfeld, Julius Sundermann, Benjamin-Luca Keller, Ulrich Westedt and Oliver Heinzerling

Pharmaceutics 2024, 16(6), 782; https://doi.org/10.3390/pharmaceutics16060782 - 8 Jun 2024

Viewed by 1206

Abstract

The present study compared vacuum drum drying (VDD) and conventional spray drying (SD) for solidifying crystalline ABT-199 nanosuspensions into redispersible oral drug products. The aim was to optimize formulation compositions and process conditions to maintain nanoparticle size after tablet redispersion. The impact of drug load (22%, 33%, 44%) and type of drying protectant (mannitol, mannitol/trehalose mix (1:1), trehalose) on redispersibility and material powder properties were investigated. Moreover, compression analysis was performed assessing the influence of compaction pressure on primary nanocrystal redispersibility and tablet disintegration. Higher drug loads and lower drying protectant levels resulted in particle growth, confirming a drug load dependence on redispersibility behavior. Notably, all drying protectants showed similar protection properties at properly chosen drying process parameters (T_g-dependent), except when VDD was used for mannitol formulations. Differences between the applied drying processes were observed in terms of downstream processing and tabletability: mannitol-containing formulations solidified via VDD showed an improved processability compared to formulations with trehalose. In conclusion, VDD is a promising drying technique that offers advantageous downstream processability compared to SD and represents an attractive novel processing technology for the pharmaceutical industry. As demonstrated in the present study, VDD combines higher yields with a leaner manufacturing process flow. The improved bulk properties provide enhanced tabletability and enable direct compression. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Graphical abstract

18 pages, 2826 KiB

Open AccessArticle

Novel Dry Hyaluronic Acid–Vancomycin Complex Powder for Inhalation, Useful in Pulmonary Infections Associated with Cystic Fibrosis

by María S. Magi, Yanina de Lafuente, Eride Quarta, María C. Palena, Perla del R. Ardiles, Paulina L. Páez, Fabio Sonvico, Francesca Buttini and Alvaro F. Jimenez-Kairuz

Pharmaceutics 2024, 16(4), 436; https://doi.org/10.3390/pharmaceutics16040436 - 22 Mar 2024

Viewed by 1572

Abstract

Polyelectrolyte–drug complexes are interesting alternatives to improve unfavorable drug properties. Vancomycin (VAN) is an antimicrobial used in the treatment of methicillin-resistant Staphylococcus aureus pulmonary infections in patients with cystic fibrosis. It is generally administered intravenously with a high incidence of adverse side effects, which could be reduced by intrapulmonary administration. Currently, there are no commercially available inhalable formulations containing VAN. Thus, the present work focuses on the preparation and characterization of an ionic complex between hyaluronic acid (HA) and VAN with potential use in inhalable formulations. A particulate–solid HA-VAN₂₅ complex was obtained by spray drying from an aqueous dispersion. FTIR spectroscopy and thermal analysis confirmed the ionic interaction between HA and VAN, while an amorphous diffraction pattern was observed by X-ray. The powder density, geometric size and morphology showed the suitable aerosolization and aerodynamic performance of the powder, indicating its capability of reaching the deep lung. An in vitro extended-release profile of VAN from the complex was obtained, exceeding 24 h. Microbiological assays against methicillin-resistant and -sensitive reference strains of Staphylococcus aureus showed that VAN preserves its antibacterial efficacy. In conclusion, HA-VAN₂₅ exhibited interesting properties for the development of inhalable formulations with potential efficacy and safety advantages over conventional treatment. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Graphical abstract

20 pages, 3201 KiB

Open AccessArticle

Natural Stabilizers and Nanostructured Lipid Carrier Entrapment for Photosensitive Compounds, Curcumin and Capsaicin

by Wipanan Jandang, Chadarat Ampasavate and Kanokwan Kiattisin

Pharmaceutics 2024, 16(3), 412; https://doi.org/10.3390/pharmaceutics16030412 - 17 Mar 2024

Cited by 1 | Viewed by 1585

Abstract

Capsaicin and curcumin, the active components of chili and turmeric, are prone to instability when exposed to light. Therefore, this research aimed to enhance the photostability of both extracts via the use of antioxidants, natural sunscreen, and nanostructured lipid carriers (NLCs). NLCs were chosen for this this study due to their advantages in terms of stability, drug loading capacity, occlusive effect, skin penetration, and controlled release. The photostability of each extract and extracts mixed with antioxidants, including grape seed extract, tea extract, and chlorogenic acid, were determined. Chlorogenic acid can enhance the photostability of capsaicin from 6.79 h to 16.50 h, while the photostability of curcumin increased from 9.63 h to 19.25 h. In addition, the use of natural sunscreen (sunflower oil) also increased the photostability of capsaicin and curcumin. The mixed extracts were then loaded into NLCs. The particle size of the formulation was 153.73 nm with a PDI value of 0.25. It exhibited high entrapment efficiency (more than 95%). In addition, it effectively reduced the decomposition of capsaicin and curcumin. Importantly, the natural stabilizers chosen for NLC fabrication significantly improved the photostability of curcumin and capsaicin by 600% and 567% compared to the unstabilized counterparts. This improvement contributes to the sustainability and bioavailability of these compounds in both cosmeceutical and pharmaceutical products. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Figure 1

21 pages, 9487 KiB

Open AccessEditor’s ChoiceArticle

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

by Béla Kovács, Erzsébet-Orsolya Tőkés, Éva Katalin Kelemen, Katalin Zöldi, Francisc Boda, Edit Suba, Boglárka Kovács-Deák and Tibor Casian

Pharmaceutics 2024, 16(3), 391; https://doi.org/10.3390/pharmaceutics16030391 - 13 Mar 2024

Cited by 1 | Viewed by 1542

Abstract

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. Exploratory data analysis (MVDA) highlights similarities and differences in tablet manufacturability and dissolution profiles at both the lab and pilot scales. The study sought to gain insights into the application of multivariate data analysis by identifying variations among batches produced at different manufacturing scales for this technology. DoE and MVDA findings show that the granulation temperature, time, and Macrogol type significantly impact product performance. These factors, by influencing particle size distribution, become key predictors of product quality attributes such as resistance to crushing, disintegration time, and early-stage API dissolution in the profile. Software-aided data mining, with its multivariate and versatile nature, complements the empirical approach, which is reliant on trial and error during product scale-up. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Graphical abstract

15 pages, 7305 KiB

Open AccessArticle

Customizable Three-Dimensional Printed Earring Tap for Treating Affections Caused by Aesthetic Perforations

by Ludmila A. G. Pinho, Ana Luiza Lima, Yong Chen, Livia L. Sa-Barreto, Ricardo N. Marreto, Guilherme M. Gelfuso, Tais Gratieri and Marcilio Cunha-Filho

Pharmaceutics 2024, 16(1), 77; https://doi.org/10.3390/pharmaceutics16010077 - 5 Jan 2024

Cited by 1 | Viewed by 1572

Abstract

This work aimed to develop a three-dimensional (3D) wearable drug-loaded earring tap to treat affections caused by aesthetic perforations. The initial phase involved a combination of polymers to prepare filaments for fused deposition modeling (FDM) 3D printing using a centroid mixture design. Optimized filament compositions were used in the second phase to produce 3D printed earring taps containing the anti-inflammatory naringenin. Next, samples were assessed via physicochemical assays followed by in vitro skin permeation studies with porcine ear skin. Two filament compositions were selected for the study’s second phase: one to accelerate drug release and another with slow drug dissolution. Both filaments demonstrated chemical compatibility and amorphous behavior. The use of the polymer blend to enhance printability has been confirmed by rheological analysis. The 3D devices facilitated naringenin skin penetration, improving drug recovery from the skin’s most superficial layer (3D device A) or inner layers (3D device B). Furthermore, the devices significantly decreased transdermal drug delivery compared to the control containing the free drug. Thus, the resulting systems are promising for producing 3D printed earring taps with topical drug delivery and reinforcing the feasibility of patient-centered drug administration through wearable devices. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Graphical abstract

12 pages, 2724 KiB

Open AccessArticle

The Cocrystal of Ubiquinol: Improved Stability and Bioavailability

by Qi Zhang, Mengyuan Xia, Chenxuan Zheng, Yinghong Yang, Junjie Bao, Wenjuan Dai and Xuefeng Mei

Pharmaceutics 2023, 15(10), 2499; https://doi.org/10.3390/pharmaceutics15102499 - 20 Oct 2023

Cited by 3 | Viewed by 3000

Abstract

Coenzyme Q10 (CoQ10) exists in two forms, an oxidized form and a reduced form. Ubiquinol is the fully reduced form of CoQ10. Compared to the oxidized form, ubiquinol has a much higher biological absorption and better therapeutic effect. However, ubiquinol has an important stability problem which hampers its storage and formulation. It can be easily transformed into its oxidized form—ubiquinone—even at low temperature. In this work, we designed, synthesized, and characterized a new cocrystal of ubiquinol with vitamin B3 nicotinamide (UQ-NC). Compared to the marketed ubiquinol form, the cocrystal exhibited an excellent stability, improved dissolution properties, and higher bioavailability. The cocrystal remained stable for a long period, even when stored under stressed conditions. In the dissolution experiments, the cocrystal generated 12.6 (in SIF) and 38.3 (in SGF) times greater maximum ubiquinol concentrations above that of the marketed form. In addition, in the PK studies, compared to the marketed form, the cocrystal exhibited a 2.2 times greater maximum total coenzyme Q10 concentration and a 4.5 times greater AUC than that of the marketed form. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Figure 1

Review

Jump to: Research

34 pages, 1507 KiB

Open AccessEditor’s ChoiceReview

Process Simulation of Twin-Screw Granulation: A Review

by Tony Bediako Arthur and Nejat Rahmanian

Pharmaceutics 2024, 16(6), 706; https://doi.org/10.3390/pharmaceutics16060706 - 24 May 2024

Cited by 1 | Viewed by 3619

Abstract

Twin-screw granulation has emerged as a key process in powder processing industries and in the pharmaceutical sector to produce granules with controlled properties. This comprehensive review provides an overview of the simulation techniques and approaches that have been employed in the study of twin-screw granulation processes. This review discusses the major aspects of the twin-screw granulation process which include the fundamental principles of twin-screw granulation, equipment design, process parameters, and simulation methodologies. It highlights the importance of operating conditions and formulation designs in powder flow dynamics, mixing behaviour, and particle interactions within the twin-screw granulator for enhancing product quality and process efficiency. Simulation techniques such as the population balance model (PBM), computational fluid dynamics (CFD), the discrete element method (DEM), process modelling software (PMS), and other coupled techniques are critically discussed with a focus on simulating twin-screw granulation processes. This paper examines the challenges and limitations associated with each simulation approach and provides insights into future research directions. Overall, this article serves as a valuable resource for researchers who intend to develop their understanding of twin-screw granulation and provides insights into the various techniques and approaches available for simulating the twin-screw granulation process. Full article

(This article belongs to the Special Issue Pharmaceutical Solids: Advanced Manufacturing and Characterization)

► Show Figures

Journal Menu

Journal Browser

Pharmaceutical Solids: Advanced Manufacturing and Characterization

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Benefits of Publishing in a Special Issue

Published Papers (9 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI