Article
Chemistry, Multidisciplinary
Julian David Friedl, Marcel Walther, Pia Katharina Vestweber, Jana Wachter, Patrick Knoll, Arne Matteo Joergensen, Andreas Bernkop-Schnuerch, Maike Windbergs
Summary: To date, buccal administration of lipophilic drugs remains challenging due to poor solubility and limited penetration. In this study, researchers developed mucoadhesive electrospun SEDDS patches to overcome these limitations. The patches showed high encapsulation efficiency, improved drug penetration, and enhanced therapeutic effects, making them a promising approach for oromucosal delivery of lipophilic drugs.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Karin Korelc, Bjarke Strom Larsen, Mirjana Gasperlinb, Ingunn Tho
Summary: Oromucosal films and wafers are convenient solid dosage forms for drug delivery. In this study, prednisolone containing chitosan-based mucoadhesive films and wafers were developed with different chitosan types. The mucoadhesive properties, drug release rate, and permeability of the formulations were evaluated. The results showed that chitosan type, solvent, and preparation method influenced the mucoadhesive properties, drug release rate, and permeability. The mucoadhesive wafers with a slower drug release rate and stronger mucoadhesion were considered promising alternatives to films.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Cell Biology
Zhi Luo, David Klein Cerrejon, Simon Romer, Nicole Zoratto, Jean-Christophe Leroux
Summary: Biopharmaceuticals, such as proteins and peptides, have greatly improved the treatment of various diseases. However, most of these drugs need to be administered parenterally due to their large size and instability. In this study, a novel technology was developed to enhance drug absorption by combining noninvasive stretching of the buccal mucosa with permeation enhancers. The engineered suction patch achieved significantly higher bioavailability in dogs compared to a commercial tablet formulation of a peptide drug. Additionally, a first-in-human study confirmed the acceptability of this dosage form, supporting its clinical translatability.
SCIENCE TRANSLATIONAL MEDICINE
(2023)
Article
Chemistry, Medicinal
Ju-Hyun Lee, Chulhun Park, In-OK Song, Beom-Jin Lee, Chin-Yang Kang, Jun-Bom Park
Summary: The objective of this study was to design and evaluate an orodispersible film (ODF) composed of aripiprazole, prepared using a conventional solvent casting technique, and to fuse a three-dimensional (3D) printing technique with a hot-melt extrusion filament. The study showed that the 3D-printed films had faster dissolution and disintegration compared to solvent-cast films. The combination of polymer selection and 3D printing technology could innovatively design ODFs composed of aripiprazole to meet the unmet medical needs of psychiatric patients.
Article
Pharmacology & Pharmacy
Giuseppe Francesco Racaniello, Monica Pistone, Chiara Meazzini, Angela Lopedota, Ilaria Arduino, Rosanna Rizzi, Antonio Lopalco, Umberto M. Musazzi, Francesco Cilurzo, Nunzio Denora
Summary: The aim of this study is to develop and produce novel oral mucoadhesive films delivering Clobetasol propionate (CBS) through Direct Powder Extrusion (DPE) 3D printing technique for paediatric treatment of Oral Lichen Planus (OLP). Different polymeric materials, such as hydroxypropylmethylcellulose or polyethylene oxide blended with chitosan (CS), were tested to obtain suitable mucoadhesive films. Hydroxypropyl-& beta;-cyclodextrin was added to enhance CBS solubility. The DPE-printed films showed strong adhesion, improved drug characteristics, and significant drug exposure time on the mucosa.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Elisabetta Ravasi, Alice Melocchi, Alessia Arrigoni, Arianna Chiappa, Chiara Grazia Milena Gennari, Marco Uboldi, Chiara Bertarelli, Lucia Zema, Francesco Briatico Vangosa
Summary: The feasibility of using electrospinning to manufacture sildenafil-containing orodispersible films (ODFs) for pediatric patients was evaluated. A water-based formulation using pullulan as the fiber-forming agent was chosen. The electrospinning parameters for producing defect-free nanofibers at a high rate were determined and the resulting non-woven films were evaluated for their morphology, micro-structure, drug content, and interaction with aqueous fluids. The disintegration process of the electrospun ODFs was found to be the fastest, making them promising for enhancing sildenafil bioavailability and lowering dosages.
INTERNATIONAL JOURNAL OF PHARMACEUTICS
(2023)
Article
Pharmacology & Pharmacy
Anja Goebel, Joerg Breitkreutz
Summary: This paper presents a modification of the solvent casting technique to divide oral films into multiple compartments, aiming to improve handling properties, safety of application, drug release kinetics, and long-term stability. Feasibility studies showed that combination of different film-forming polymers can achieve these objectives.
Review
Pharmacology & Pharmacy
Jan Ferlak, Weronika Guzenda, Tomasz Osmalek
Summary: Orodispersible Films (ODFs) are drug delivery systems that can be manufactured on a large scale or for customized medicines and small-scale pharmacy. However, there are limitations to both ODFs and their fabrication methods. Pharmaceutical companies and academic research centers are collaborating to overcome these limitations and develop new formulations for a wide array of APIs. The increasing number of pending patent applications and granted patents highlights the unquestionable progress in ODF manufacturing. This review provides a summary of currently marketed and discontinued ODFs, as well as recent studies on orodispersible films and the APIs used. It also discusses the attempts to overcome limitations in ODF manufacturing methods.
Article
Pharmacology & Pharmacy
Marija Jovanovic, Natasa Tomic, Sandra Cvijic, Dusica Stojanovic, Svetlana Ibric, Petar Uskokovic
Summary: This study processed and characterized propranolol hydrochloride/gelatin mucoadhesive buccal films, finding that type A gelatin formed a physical mixture in the film, whereas type B gelatin formed a compound. Mechanical testing results showed that type A gelatin films had higher elastic modulus, tensile strength, and hardness. In terms of adhesion, type B gelatin exhibited higher adhesion strength, while type A gelatin showed higher work of adhesion.
Article
Pharmacology & Pharmacy
Sarah Teworte, Simone Aleandri, Jessica R. Weber, Marianna Carone, Paola Luciani
Summary: Gynaecological health is an overlooked area of research that requires the development of dosage forms for diseases such as endometriosis. In this study, a 3D-printed semisolid vaginal ovule containing pirfenidone, a drug candidate for endometriosis, was developed. The 3D-printed ovule showed controlled release of pirfenidone and better mucoadhesive properties compared to standard excipients. This work opens up possibilities for further preclinical and clinical studies on vaginally administered pirfenidone as a treatment for endometriosis.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Pharmacology & Pharmacy
Rasha M. Elkanayati, Walter G. Chambliss, Sundus Omari, Mashan Almutairi, Michael A. Repka, Eman A. Ashour
Summary: Polyethylene oxide-based buccal films containing adipic acid and xylitol were successfully developed using hot-melt extrusion and 3D printing. The films exhibited uniform drug release and desirable mechanical strength, making them suitable for the treatment of xerostomia.
JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY
(2022)
Article
Instruments & Instrumentation
Burcum Uzunoglu, Clive G. Wilson, Meral Sagiroglu, Selin Yuksel, Sevda Senel
Summary: A drug delivery technology using a mucoadhesive bilayered buccally anchored tablet containing natamycin was developed for controlled release of the drug into the mouth. In vitro analysis showed that the release of natamycin decreased with increasing HPMC proportion in the formulation. Volunteer study revealed variations in the distribution of the released drug in different regions of the oral cavity.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2021)
Review
Pharmacology & Pharmacy
Maram Suresh Gupta, Tegginamath Pramod Kumar, Robert Davidson, Guruprasad Rao Kuppu, Kamla Pathak, Devegowda Vishakante Gowda
Summary: Orodispersible film (ODF) formulations are promising and progressive drug delivery systems, with printed orodispersible films (POFs) being a modern and rapidly developing method. The review provides an overview of printing methods for fabricating POFs, highlighting patenting trends and future market potential.
Article
Pharmacology & Pharmacy
Elena Dinte, Dana Maria Muntean, Vlad Andrei, Bianca Adina Bosca, Cristian Mircea Dudescu, Lucian Barbu-Tudoran, Gheorghe Borodi, Sanda Andrei, Adrian Florin Gal, Vasile Rus, Luciana-Madalina Gherman, Oana Cadar, Reka Barabas, Mihaela Niculae, Aranka Ilea
Summary: This study prepared mucoadhesive films containing doxycycline hyclate for application in the oral cavity. The films exhibited good release properties and showed therapeutic effectiveness in experimental periodontitis.
Review
Pharmacology & Pharmacy
Neslihan U. Okur, Ece O. Bulbul, Ayse P. Yagcilar, Panoraia Siafaka
Summary: This article focuses on the current development of mucoadhesive gel systems used in buccal drug delivery. Various studies utilizing hydrogels, in situ gels, and nanogels as buccal gel systems were analyzed, along with mucoadhesive gel studies with mucoadhesive polymers. This review aims to provide valuable guidance to scientists in formulating buccal mucoadhesive drug delivery systems by summarizing recent findings related to buccal drug delivery, mucoadhesion, and buccal mucoadhesive gel systems.
CURRENT PHARMACEUTICAL DESIGN
(2021)
Article
Pharmacology & Pharmacy
Karin Larmene-Beld, Rommert Wijnsma, Albert Kuiper, Stefan van Berkel, Henri Robben, Katja Taxis, Henderik Frijlink
Summary: The study aimed to develop a strategy to qualify a prefillable autoclavable COP syringe as a container for multiple drug products in a hospital pharmacy setting. Different extraction studies and tests were performed on the syringes filled with various solutions, showing low levels of extractables and meeting predefined requirements for subvisible particles, sterility, and closure integrity. The 50mL syringes were found to have higher concentrations of silicon compared to the 5mL syringes.
EUROPEAN JOURNAL OF HOSPITAL PHARMACY
(2022)
Review
Immunology
Rick Heida, Wouter L. J. Hinrichs, Henderik W. Frijlink
Summary: The article discusses the current status and potential advantages of inhaled vaccines against viral pathogens, suggesting the feasibility of developing inhalable dry powder formulations. Inhalable vaccines can increase vaccine stability, facilitate mass vaccination, and provide improved protection through inducing an IgA-mediated mucosal immune response.
EXPERT REVIEW OF VACCINES
(2022)
Article
Pharmacology & Pharmacy
Renee S. van der Kooij, Rob Steendam, Henderik W. Frijlink, Wouter L. J. Hinrichs
Summary: Core-shell microspheres show promise as a drug delivery system due to their advantages over monolithic microspheres in terms of release kinetics, such as reduced initial burst release, delayed release, and dual-drug release. Various successful methods for producing these core-shell microspheres have been identified, with a focus on improving drug release efficiency through better control over particle characteristics.
EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS
(2022)
Article
Chemistry, Medicinal
Y. Tian, J. Lee, K. van der Maaden, Y. Bhide, J. J. de Vries-Idema, R. Akkerman, C. O'Mahony, W. Jiskoot, H. W. Frijlink, A. L. W. Huckriede, W. L. J. Hinrichs, J. A. Bouwstra, M. Beukema
Summary: This study demonstrates the potential of trehalose/pullulan-based dissolving-microneedle-arrays (dMNAs) as an alternative dosage form for influenza vaccination. The produced dMNAs have sufficient mechanical strength and stability to penetrate ex vivo human skin and dissolve within a short period of time to release antigens. Immunization of mice with influenza antigens via freshly prepared or stored dMNAs resulted in antibody titers comparable to intramuscularly injected mice, providing partial protection against influenza virus infection.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Gastroenterology & Hepatology
Antonius T. Otten, Hedwig H. van der Meulen, Maurice Steenhuis, Floris C. Loeff, Daan J. Touw, Jos G. W. Kosterink, Henderik W. Frijlink, Theo Rispens, Gerard Dijkstra, Marijn C. Visschedijk, Arno R. Bourgonje
Summary: A finger prick-based capillary blood self-sampling technique was validated for monitoring infliximab, vedolizumab, and C-reactive protein concentrations in patients with inflammatory bowel disease. The technique received substantial support from patients and demonstrated good tolerability and practicality.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Chemistry, Multidisciplinary
Rick Heida, Renate Akkerman, Paulo H. Jacob Silva, Anke J. Lakerveld, Daniel Ortiz, Chiara Bigogno, Matteo Gasbarri, Puck B. van Kasteren, Francesco Stellacci, Henderik W. Frijlink, Anke L. W. Huckriede, Wouter L. J. Hinrichs
Summary: Respiratory viruses, including RSV, pose a significant global health burden. Entry inhibitors, such as CD-MUS, have shown promise as antiviral drugs that can prevent infection in the respiratory tract. In this study, CD-MUS was shown to be well tolerated when administered to mice's respiratory tract and retained its activity against RSV after spray drying. This research sets the foundation for future in vivo studies on the efficacy of CD-MUS in animal models of RSV infection.
JOURNAL OF CONTROLLED RELEASE
(2023)
Article
Medicine, General & Internal
Antonius Timotheus Otten, V Peters, I Barth, C. L. Stevens, A. R. Bourgonje, H. W. Frijlink, H. J. M. Harmsen, A. Rehman, M. J. E. Campmans-Kuijpers, G. Dijkstra
Summary: This article describes a nutritional intervention trial on patients with Crohn's disease (CD) and their healthy household members, investigating the effects of an evidence-based anti-inflammatory diet and an ileocolonic-targeted capsule containing vitamin B2, B3, and C. The results of the study will provide valuable evidence for dietary recommendations for CD patients and physicians.
Review
Pharmacology & Pharmacy
Primawan Putra Nugrahadi, Wouter L. J. Hinrichs, Henderik W. Frijlink, Christian Schoneich, Christina Avanti
Summary: In recent decades, there has been a significant increase in the use of therapeutic peptides. However, peptides are often unstable in aqueous solutions, which affects their stability and bioactivity. This literature review provides an overview of the degradation pathways and formulation strategies to stabilize therapeutic peptides in aqueous solutions. The most practical approaches to peptide stabilization are pH optimization and selecting the appropriate type of buffer, along with other strategies such as co-solvency, air exclusion, viscosity enhancement, PEGylation, and the use of polyol excipients.
Article
Pharmacology & Pharmacy
Renee S. van der Kooij, Martin Beukema, Anke L. W. Huckriede, Johan Zuidema, Rob Steendam, Henderik W. Frijlink, Wouter L. J. Hinrichs
Summary: Although vaccination is important for public health, the increase in vaccination coverage has slowed down. Single-injection vaccines could solve the problem of multiple injections. Researchers developed injectable microspheres that released bovine serum albumin (BSA) over several weeks. In vitro and in vivo studies showed successful sustained release and immunization.
Article
Pharmacology & Pharmacy
Aisha A. Ahmed, Antonius T. Otten, Bahez Gareb, Judith E. Huijmans, Anko C. Eissens, Ateequr Rehman, Gerard Dijkstra, Jos G. W. Kosterink, Henderik W. Frijlink, Reinout C. A. Schellekens
Summary: The development of capsules containing riboflavin, nicotinic acid, and ascorbic acid covered with a pH-sensitive coating (ColoVit) was described to achieve site-specific release in the ileocolon. The capsules met the required specifications and had a lag-time in drug release of 277-283 min, which meets the requirements for ileocolonic release. The production process of the ColoVit formulation was validated and reproducible, and the vitamin blend was stable during the production process and in the finished coated product. ColoVit is intended as an innovative treatment approach for beneficial microbiome modulation and optimization of gut health.
Article
Pharmacology & Pharmacy
Sohaib Mahri, Tobias Wilms, Paul Hagedorm, Marie-Julie Guichard, Kevin Vanvarenberg, Mireille Dumoulin, Henderik Frijlink, Rita Vanbever
Summary: In this study, the effects of PEGylation on the thermodynamic stability of rhDNase were investigated. PEGylation destabilized rhDNase upon denaturation and ethanol exposure, but PEG30-rhDNase remained stable enough to withstand aerosolization stresses. High aerosol output and excellent aerosol characteristics were achieved while preserving protein integrity and enzymatic activity.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2023)
Article
Microbiology
Rick Heida, Henderik Frijlink, Wouter Hinrichs
Summary: The pulmonary route of administration plays an important role in the treatment of respiratory virus infections, as it can induce a broader immune response and improve drug bioavailability.
Article
Pharmacology & Pharmacy
Rick Heida, Paul Hagedoorn, Melle C. van Meel, Jurrie E. R. Prins, Frederike S. Simonis, Renate Akkerman, Anke L. W. Huckriede, Henderik W. Frijlink, Anne H. de Boer, Wouter L. J. Hinrichs
Summary: A challenge in developing dry powder formulations for inhalation is the poor reproducibility of administration to small laboratory animals. Current devices for delivering dry powder formulations to small rodents often fail to function optimally due to the use of the same puff of air for both powder dispersion and aerosol delivery. A novel aerosol generator was introduced, allowing the administration of a pre-generated aerosol to mice lungs, with controlled powder delivery. Although the emitted aerosol showed favorable size range for lung deposition and reproducibility, in vivo fluorescent imaging revealed significant differences in dose deposition and powder distribution among mice, suggesting inevitable biological variation in lung deposition.
Article
Pharmacology & Pharmacy
Khanh T. T. Nguyen, Daan Zillen, Franca F. M. van Heijningen, Kjeld J. C. van Bommel, Renz J. van Ee, Henderik W. Frijlink, Wouter L. J. Hinrichs
Summary: This study demonstrates the successful production of PBP tablets with smooth surfaces that can be directly coated with the ColoPulse coating, while preserving the stability of the encapsulated biopharmaceutical, BIAP.
Article
Multidisciplinary Sciences
Y. A. de Reus, P. Hagedoorn, M. G. G. Sturkenboom, F. Grasmeijer, M. S. Bolhuis, I Sibum, H. A. M. Kerstjens, H. W. Frijlink, O. W. Akkerman
Summary: This study assessed the local tolerability, safety, and pharmacokinetic parameters of inhaled HCQ using a dry powder inhaler. The results showed that single doses of inhaled dry powder HCQ up to 20 mg are safe and well tolerated, without significant adverse effects.