Article
Pharmacology & Pharmacy
Venkata Raman Kallakunta, Narendar Dudhipala, Dinesh Nyavanandi, Sandeep Sarabu, Karthik Yadav Janga, Srinivas Ajjarapu, Suresh Bandari, Michael A. Repka
Summary: The aim of this study was to develop and manufacture solid self-emulsifying drug delivery systems (HME S-SEDDS) using a single-step continuous hot-melt extrusion (HME) process. The formulation was prepared with selected excipients, and the emulsifying properties, crystallinity, stability, flow properties, and drug release characteristics were evaluated. The results showed that the prepared HME S-SEDDS had excellent flow properties, stable emulsions, and improved drug solubility. The optimized formulation exhibited a globule size of 269.6 nm and >90% drug release within 15 minutes. Stability studies were conducted for 3 months at 40 degrees C/75% RH.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Abdulmajeed A. Althobaiti, Eman A. Ashour, Mashan Almutairi, Ahmed Almotairy, Mohammed Al Yahya, Michael A. Repka
Summary: Curcumin, derived from turmeric, has various biological activities. This study successfully prepared curcumin-piperine solid dispersion using the hot-melt extrusion technique, resulting in significant improvement in the release profile of curcumin.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Polymer Science
Gilberto S. N. Bezerra, Tielidy A. de M. de Lima, Declan M. Colbert, Joseph Geever, Luke Geever
Summary: This study aimed to demonstrate the feasibility of using hot-melt extrusion to develop extended-release formulations of Fenbendazole dispersed in PEO/PCL blend-based matrices. The results showed that the drug converted to its amorphous state after thermal treatment, and the release rate of the drug could be controlled by adjusting the content of PCL in the blend.
Article
Pharmacology & Pharmacy
Phuong H. L. Tran, Beom-Jin Lee, Thao T. D. Tran
Summary: Hot-melt extrusion is a promising method for the preparation of drug delivery systems on an industrial scale, but there is still a lack of research on its recent progress and influencing factors. This review discusses the effects of hot-melt extrusion on various factors in solid dispersion systems and describes the use of molecular interactions to improve drug stability.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2021)
Article
Pharmacology & Pharmacy
Sagar Narala, Neeraja Komanduri, Dinesh Nyavanandi, Ahmed Adel Ali Youssef, Preethi Mandati, Abdullah Alzahrani, Praveen Kolimi, Nagarjuna Narala, Michael A. Repka
Summary: This study explored the use of hot-melt extrusion to develop a thermodynamically stable solid crystal suspension (SCS) for improving the solubility and dissolution rate of carbamazepine (CBZ), a BCS class II drug. The SCSs, prepared using sugar alcohols as crystalline carriers, showed significantly improved dissolution rate and solubility. Stability studies confirmed that the SCSs maintained drug content, in vitro release profiles, and thermal characteristics over 3 months.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Samuel O. Kyeremateng, Kristin Voges, Stefanie Dohrn, Ekaterina Sobich, Ute Lander, Stefan Weber, David Gessner, Rachel C. Evans, Matthias Degenhardt
Summary: This article describes the application of API-polymer phase diagrams in hot-melt extrusion (HME) technique and the development of an HME risk classification system (HCS) within AbbVie. The HCS categorizes API risks in the HME process and has been successfully applied to over 60 different APIs as a validated risk assessment and quality-by-design (QbD) tool. The classification system is based on the ability of the melt temperature to reach the API's thermodynamic solubility temperature and considers the thermal degradation regions and glass transition temperature-related dissolution kinetics limitations of API or polymer.
Article
Pharmacology & Pharmacy
Xinxin Jiang, Yanna Zhao, Qingran Guan, Shanshan Xiao, Weimiao Dong, Shipeng Lian, Huaizhen Zhang, Min Liu, Zhengping Wang, Jun Han
Summary: Amorphous solid dispersions of cyclosporine A (CsA-ASDs) were prepared using PVP K12 as a carrier via hot melt extrusion (HME) to improve CsA's oral bioavailability. The experiment indicated a potential hydrogen bond interaction between CsA and PVP K12. In vivo pharmacokinetics showed that CsA-ASD tablets significantly enhanced the drug's dissolution and absorption.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Polymer Science
Kinga Biedrzycka, Agnieszka Marcinkowska
Summary: In this study, the hot melt extrusion method was used to obtain an amorphous dispersion of an active pharmaceutical ingredient (API) that is sparingly soluble in water. The extrusion conditions included a screw rotation speed of 250 rpm, temperature above 100°C, and two mixing zones. The use of Eudragit EPO as a polymer matrix and ibuprofen as an API was investigated. The addition of the plasticizer Compritol 888 ATO improved processing parameters and modified the release profile of ibuprofen. The obtained solid dispersions showed good stability and released about 40% to 63% of the API within 180 minutes.
Article
Pharmacology & Pharmacy
Jiawei Han, Mengyuan Tang, Yang Yang, Wen Sun, Zhimin Yue, Yunran Zhang, Yijun Zhu, Xiaoqian Liu, Jue Wang
Summary: This review discusses the use of solid dispersion systems as an effective formulation strategy to enhance the performance of poorly water-soluble drugs. It provides a comprehensive understanding of SD classification and highlights the most popular amorphous solid dispersions. Furthermore, it proposes a systematic design strategy for satisfactory ASDs and explores the application of hot melt extrusion as a continuous manufacturing technique.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Khater AL-Japairai, Samah Hamed Almurisi, Syed Mahmood, Thiagarajan Madheswaran, Bappaditya Chatterjee, Prasanthi Sri, Nadiatul Azra Binti Ahmad Mazlan, Turki Al Hagbani, Fawaz Alheibshy
Summary: Oral administration of drugs is preferred for being non-invasive, easy to administer, and easy to store. However, the poor solubility of drugs in oral formulations limits their effectiveness and commercial value. Amorphous solid dispersion (ASD), a method that changes the molecular structure of drugs to improve solubility, is being used with the emerging hot melt extrusion (HME) method in the pharmaceutical industry. Despite solving solubility issues, ASD also poses a risk of crystallization, requiring optimization in formulation, polymers, and HME manufacturing processes.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Hetvi Triboandas, Kendal Pitt, Mariana Bezerra, Delphine Ach-Hubert, Walkiria Schlindwein
Summary: This study successfully developed ITZ-KOL-ASD tablet formulations that meet the Quality Target Product Profile (QTPP) requirements through the production of amorphous solid dispersions using hot-melt extrusion, novel tablet formulations using inorganic salts, and design space modeling.
Article
Pharmacology & Pharmacy
Tobias Gottschalk, B. Groenniger, E. Ludwig, F. Wolbert, T. Feuerbach, G. Sadowski, M. Thommes
Summary: The manufacturing of amorphous solid dispersions via hot melt extrusion is of great interest in pharmaceutical development. In this study, a micro-scale extruder was used to process drug/polymer mixtures in different ratios, and the minimum required process temperature and residence time were determined. The phase situation was evaluated by the turbidity of the final extrudate. The results showed that the minimum required process temperature was close to solubility temperature and about three minutes were required to dissolve the drug in the polymer at these process conditions.
PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY
(2022)
Article
Medicine, Research & Experimental
Stephen A. Thompson, Daniel A. Jr Jr Davis, Chaeho Moon, Robert O. I. I. I. I. I. I. Williams
Summary: Maximizing the drug loading of pH-dependent APIs in amorphous solid dispersions (ASDs) produced by hot-melt extrusion (HME) can reduce pill burden without compromising dissolution performance. By incorporating bases to modify pH during HME, the drug loading (w/w) of telmisartan in ASDs was significantly increased from 5% to 50%. The stability of the polymer Soluplus when extruded with a strong base was also examined.
MOLECULAR PHARMACEUTICS
(2022)
Article
Pharmacology & Pharmacy
Abdullah Alshetaili, Bjad K. Almutairy, Sultan M. Alshehri, Michael A. Repka
Summary: This study aimed to develop a sustained release formulation of donepezil hydrochloride (DH) using the hot-melt extruded solid dispersion technique. By rational screening of hydrophobic carriers, the release profile of DH was successfully modified, and a preferable release pattern was obtained by optimizing the ratio of carriers and pore-forming agents as well as the extrusion temperature profile.
Article
Pharmacology & Pharmacy
Indrajeet Karnik, Ahmed Adel Ali Youssef, Poorva Joshi, Siva Ram Munnangi, Sagar Narala, Corinne Varner, Sateesh Kumar Vemula, Soumyajit Majumdar, Michael Repka
Summary: The study aimed to develop and evaluate a hot-melt extruded bioadhesive ophthalmic insert containing a fixed-dose combination of Prednisolone Sodium Phosphate (PSP) and Sulfacetamide Sodium (SA) for the treatment of ocular bacterial infections. The inserts were prepared using FDA-approved biocompatible polymers, and their physicochemical characteristics, drug release, permeation, and stability were assessed. The developed inserts showed prolonged release of the drugs and exhibited good bioadhesive strength and stability.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2023)
Article
Pharmacology & Pharmacy
Atida Selmani, Elisabeth Seibert, Carolin Tetyczka, Doris Kuehnelt, Ivan Vidakovic, Karin Kornmueller, Markus Absenger-Novak, Borna Radatovic, Ivana Vinkovic Vrcek, Gerd Leitinger, Eleonore Frohlich, Andreas Bernkop-Schnurch, Eva Roblegg, Ruth Prassl
Summary: This study aimed to design a hybrid oral liposomal delivery system for selenium nanoparticles to improve the bioavailability of selenium. Thiolated chitosan was used for surface functionalization of the liposomal nanoparticles. The thiolated liposomal nanoparticles showed good mucoadhesive properties and were stable in a simulated microenvironment of the small intestine. This study provides a promising solution for oral selenium delivery.
Article
Biochemistry & Molecular Biology
R. Jeitler, C. Glader, C. Tetyczka, S. Zeiringer, M. Absenger-Novak, A. Selmani, E. Froehlich, E. Roblegg
Summary: Lipid-based nanosystems can effectively deliver drugs to oral cavity cells for the treatment of local diseases. Through quality design and predictive modeling, we have demonstrated the stability of solid lipid nanoparticles and nanostructured lipid carriers, enabling reliable drug release in the oral cavity.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2022)
Article
Pharmacology & Pharmacy
Daniela Fiedler, Carolina Alva, Joana T. Pinto, Martin Spoerk, Ramona Jeitler, Eva Roblegg
Summary: This study investigated a flexible method for the production of biologics using inkjet printing and vacuum drying to stabilize the products. The addition of a surfactant was found to improve the printability and stability of the formulations. The investigated formulations showed no significant protein aggregation after drying and achieved the targeted dose after reconstitution.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2022)
Article
Biochemistry & Molecular Biology
Sebastian P. Nischwitz, Julia Fink, Marlies Schellnegger, Hanna Luze, Vladimir Bubalo, Carolin Tetyczka, Eva Roblegg, Christian Holecek, Martin Zacharias, Lars-Peter Kamolz, Petra Kotzbeck
Summary: Persistent inflammation during wound healing is identified as a precipitating factor in the development of hypertrophic scars. However, lack of standardized models and limited evidence for therapeutic approaches hinder research progress. This study aimed to investigate scar formation mechanisms and develop a method for generating standardized hypertrophic scars through prolonged inflammation.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, Research & Experimental
Adrian Rump, Carolin Tetyczka, Eva Littringer, Marie-Luise Kromrey, Robin Buelow, Eva Roblegg, Werner Weitschies, Michael Grimm
Summary: Gastroretentive dosage forms, which can release drugs inside the stomach for a prolonged period, offer advantages such as improved pharmacokinetics/bioavailability and reduced intake frequency, leading to better patient adherence. However, there are currently no gastroretentive products with proven efficacy in humans. One effective approach is the use of mucoadhesive properties to prevent gastric emptying. The adhesion time of minitablets containing Carbopol 71G NF was significantly longer compared to non-adhesive minitablets, resulting in delayed gastric emptying. However, further improvement is needed to achieve clinical benefits, and variations in gastric residence time were observed.
MOLECULAR PHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Christina Winter, Manuel Zettl, Jerome Mantanus, Eftychios Hadjittofis, Gerd Leitinger, Dagmar Kolb, Wen-Kai Hsiao, Martin Spoerk, Amrit Paudel, Eva Roblegg, Joana T. Pinto
Summary: The study successfully demonstrated the production of engineered microparticles with defined structures using inkjet printing technology, showing promising potential for future drug development and delivery approaches.
PHARMACEUTICAL RESEARCH
(2023)
Review
Medicine, Research & Experimental
Filipa Leal, Scarlett Zeiringer, Ramona Jeitler, Pedro F. F. Costa, Eva Roblegg
Summary: Orally administered drugs are processed in the gastrointestinal tract, absorbed in the small intestine, and metabolized in the liver. Animal models, while commonly used, are not suitable for studying drug-tissue interactions and making accurate predictions due to significant differences in absorption, distribution, metabolism, and excretion between humans and animals. In vitro cell culture systems used for preclinical drug screening often do not accurately replicate the native characteristics of biological barriers. Dynamic microfluidic models, such as single- and multi-tissue micro-bioreactors, offer in vivo-like cell phenotypes and functionalities, allowing for better safety and efficacy prediction.
Article
Engineering, Biomedical
Andreia M. M. Goncalves, Filipa Leal, Anabela Moreira, Tobias Schellhorn, Veronika Hefka Blahnova, Scarlett Zeiringer, Karolina Vocetkova, Carolin Tetyczka, Aiva Simaite, Matej Buzgo, Eva Roblegg, Pedro F. F. Costa, Peter Ertl, Eva Filova, Yvonne Kohl
Summary: This study presents intestinal, skin, and pulmonary in vitro tissue models based on electrospun membranes of poly(epsilon-caprolactone) (PCL) and cellulose derivatives. The physicochemical characterization and biocompatibility of the scaffolds are evaluated using different cell types. The results show that the fibrous meshes prepared are biocompatible and have the potential to be used as substrates for in vitro epithelial tissue modeling and toxicity screening.
ADVANCED NANOBIOMED RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Manuel Zettl, Christina Winter, Jerome Mantanus, Eftychios Hadjittofis, Sandrine Rome, Gerd Leitinger, Wen-Kai Hsiao, Eva Roblegg, Joana T. Pinto, Martin Spoerk
Summary: Active pharmaceutical ingredients (APIs) with challenging shapes and reduced bioavailability can be effectively processed and improved by inkjet printing. This technique offers benefits such as maintaining particle properties, scalability, and co-processing options with excipients to enhance bioavailability. This study successfully demonstrates the optimization of particle shapes through inkjet printing, producing spherical lacosamide particles with improved flow properties compared to the bulk material. The particle size can be easily adjusted by controlling the ink volume and printing cycles.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2023)
Article
Chemistry, Multidisciplinary
Atida Selmani, Ramona Jeitler, Michael Auinger, Carolin Tetyczka, Peter Banzer, Brian Kantor, Gerd Leitinger, Eva Roblegg
Summary: Biocompatible gold nanoparticles have been utilized in wound healing due to their radical scavenging activity. An acidic microenvironment is also found to promote wound healing through cell proliferation and inhibit bacterial growth. Combining these two approaches shows promising results for wound healing.
Article
Chemistry, Multidisciplinary
Claudia Meindl, Markus Absenger-Novak, Ramona Jeitler, Eva Roblegg, Eleonore Froehlich
Summary: The toxicity of inhaled nanoparticles was assessed using air-liquid interface cultures of respiratory cells and reconstructed bronchial and alveolar tissues. The results showed no significant adverse effects on the bronchial and alveolar models when exposed to nanoparticles at doses corresponding to the maximum estimated lifetime exposure of workers, except for a slight increase in interleukin 6 secretion in the alveolar model.
Article
Pharmacology & Pharmacy
Daniela Fiedler, Elisabeth Fink, Isabella Aigner, Gerd Leitinger, Walter Keller, Eva Roblegg, Johannes G. Khinast
Summary: This study proposes a new material-efficient multi-step machine learning approach for the development of a design space for spray drying proteins. By comparing the ML and DoE model predictions to protein-based validation runs, the suitability of using a surrogate material and ML for the development of a design space was investigated with demonstrated advantages.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Chemistry, Analytical
Laura Wiltschko, Eva Roblegg, Reingard Raml, Thomas Birngruber
Summary: The importance of plasma protein binding in drug development is recognized. However, validated methods for assessing protein binding in physiological fluids such as dermal interstitial fluid (dISF) are currently missing. This study successfully validated small volume rapid equilibrium dialysis (RED) for low protein samples, providing a tool to directly examine drug-protein binding in the biological fluid at the site of action. Small volume RED was applied to assess the effects of interstitial parameters on protein-bound drug fraction using surrogate dISF samples.
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
(2023)
Article
Medicine, Research & Experimental
Scarlett Zeiringer, Laura Wiltschko, Christina Glader, Martin Reiser, Markus Absenger-Novak, Eleonore Froehlich, Eva Roblegg
Summary: In vitro intestinal models are used to investigate biological processes, drug absorption, and cytotoxicity. Synthetic hydrogel Vitrogel is found to be the best material for cell proliferation and differentiation in the model.
MOLECULAR PHARMACEUTICS
(2023)
Article
Materials Science, Multidisciplinary
Simone Eder, Lisa Kuchler, Matthias Katschnig, Bianca Brandl, Matthias Wolfgang, Ioannis Koutsamanis, Lukas Hentschel, Florian Arbeiter, Eva Roblegg, Martin Spoerk
Summary: This study demonstrates the fabrication of 3D-printed vaginal inserts made of EVA28. By optimizing viscosity, employing 3D-printer adaptations, and carefully selecting printing parameters, customized vaginal inserts can be successfully produced. This research has significant implications for the application of customized vaginal inserts.
ADVANCED MATERIALS TECHNOLOGIES
(2023)