New Technology for Prolonged Drug Release

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: closed (20 May 2023) | Viewed by 25678

Special Issue Editors


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Guest Editor
Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15222 Białystok, Poland
Interests: modification of delivery systems; semisolid forms; pharmaceutical analysis; drug dosage formulations
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Department of Pharmaceutical Technology, Medical University of Białystok, Mickiewicza 2c, 15-222 Białystok, Poland
Interests: spray drying; alginates; natural polymers; microparticles; drug dosage formulations
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Prolonged drug delivery systems have become the standard in drug formulation development. The most important benefits of such dosage forms include longer duration of action, decreasing frequency of drug administration to improve patient compliance, and lower plasma concentration, which may reduce the risk of adverse effects and decrease fluctuation in plasma concentration. All these advantages promote the achievement of higher therapeutic efficacy. Innovative  technologies are applicable for an increased performance of both existing and new pharmaceutical active compounds. A sustained release profile of drug substances is obtained using various technologies. One of them is applying natural and synthetic polymers, which play an important role in preparing of gelling matrixes or coating dosage forms. Another technique used to obtain prolonged delivery system involves microencapsulation, formulating micro- or nanoparticulate systems.

This Special Issue will be a collection of full papers, short communications, and review papers focuses on recent progress in new drug delivery technologies, allowing for a sustained release profile of active substances.

Dr. Katarzyna Sosnowska
Dr. Marta Szekalska
Guest Editors

Manuscript Submission Information

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Keywords

  • prolonged drug delivery
  • sustained release
  • formulation and dosage form development
  • polymers for extended release
  • micro/nanoparticulate system
  • modification of active substances

Published Papers (8 papers)

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Research

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11 pages, 1502 KiB  
Article
Systems Biology and Peptide Engineering to Overcome Absorption Barriers for Oral Peptide Delivery: Dosage Form Optimization Case Study Preceding Clinical Translation
by Puneet Tyagi, Chandresh Patel, Kimberly Gibson, Fiona MacDougall, Sergei Y. Pechenov, Sarah Will, Jefferson Revell, Yue Huang, Anton I. Rosenbaum, Kemal Balic, Umar Maharoof, Joseph Grimsby and J. Anand Subramony
Pharmaceutics 2023, 15(10), 2436; https://doi.org/10.3390/pharmaceutics15102436 - 09 Oct 2023
Viewed by 1215
Abstract
Oral delivery of peptides and biological molecules promises significant benefits to patients as an alternative to daily injections, but the development of these formulations is challenging due to their low bioavailability and high pharmacokinetic variability. Our earlier work focused on the discovery of [...] Read more.
Oral delivery of peptides and biological molecules promises significant benefits to patients as an alternative to daily injections, but the development of these formulations is challenging due to their low bioavailability and high pharmacokinetic variability. Our earlier work focused on the discovery of MEDI7219, a stabilized, lipidated, glucagon-like peptide 1 agonist peptide, and the selection of sodium chenodeoxycholate (Na CDC) and propyl gallate (PG) as permeation enhancer combinations. We hereby describe the development of the MEDI7219 tablet formulations and composition optimization via in vivo studies in dogs. We designed the MEDI7219 immediate-release tablets with the permeation enhancers Na CDC and PG. Immediate-release tablets were coated with an enteric coating that dissolves at pH ≥ 5.5 to target the upper duodenal region of the gastrointestinal tract and sustained-release tablets with a Carbopol bioadhesive polymer were coated with an enteric coating that dissolves at pH ≥ 7.0 to provide a longer presence at the absorption site in the gastrointestinal tract. In addition to immediate- and enteric-coated formulations, we also tested a proprietary delayed release erodible barrier layer tablet (OralogiKTM) to deliver the payload to the target site in the gastrointestinal tract. The design of tablet dosage forms based on the optimization of formulations resulted in up to 10.1% absolute oral bioavailability in dogs with variability as low as 26% for MEDI7219, paving the way for its clinical development. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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20 pages, 3649 KiB  
Article
Enhanced Cellular Uptake and Transport of Bovine Lactoferrin Using Pectin- and Chitosan-Modified Solid Lipid Nanoparticles
by Xudong Yao, Craig Bunt, Mengyang Liu, Siew-Young Quek, John Shaw, Jillian Cornish and Jingyuan Wen
Pharmaceutics 2023, 15(8), 2168; https://doi.org/10.3390/pharmaceutics15082168 - 21 Aug 2023
Cited by 2 | Viewed by 1263
Abstract
Aim: The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport. Methods: Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid [...] Read more.
Aim: The aim of this project is to use pectin- and chitosan-modified solid lipid nanoparticles for bovine lactoferrin to enhance its cellular uptake and transport. Methods: Solid lipid particles containing bovine lactoferrin (bLf) were formulated through the solvent evaporation technique, incorporating stearic acid along with either chitosan or pectin modification. bLf cellular uptake and transport were evaluated in vitro using the human adenocarcinoma cell line Caco-2 cell model. Results and Discussion: The bLf-loaded SLPs showed no significant effect on cytotoxicity and did not induce apoptosis within the eight-hour investigation. The use of confocal laser scanning microscopy confirmed that bLf follows the receptor-mediated endocytosis, whereas the primary mechanism for the cellular uptake of SLPs was endocytosis. The bLf-loaded SLPs had significantly more cellular uptake compared to bLf alone, and it was observed that this impact varied based on the time, temperature, and concentration. Verapamil and EDTA were determined to raise the apparent permeability coefficients (App) of bLf and bLf-loaded SLPs. Conclusion: This occurred because they hindered efflux by interacting with P-glycoproteins and had a penetration-enhancing influence. These findings propose the possibility of an additional absorption mechanism for SLPs, potentially involving active transportation facilitated by the P-glycoprotein transporter in Caco-2 cells. These results suggest that SLPs have the potential to be applied as effective carriers to improve the oral bioavailability of proteins and peptides. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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14 pages, 1014 KiB  
Article
In Vivo Evaluation of Thiamine Hydrochloride with Gastro-Retentive Drug Delivery in Healthy Human Volunteers Using Gamma Scintigraphy
by Li-Ying Kam, Jia-Woei Wong and Kah-Hay Yuen
Pharmaceutics 2023, 15(2), 691; https://doi.org/10.3390/pharmaceutics15020691 - 17 Feb 2023
Cited by 2 | Viewed by 1515
Abstract
A floating tablet system containing thiamine hydrochloride, a model drug with a narrow absorption window, was evaluated. The tablet was found to have a floating lag time of less than 30 s with a sustained drug release over 12 h during in vitro [...] Read more.
A floating tablet system containing thiamine hydrochloride, a model drug with a narrow absorption window, was evaluated. The tablet was found to have a floating lag time of less than 30 s with a sustained drug release over 12 h during in vitro dissolution studies. The gastro-retentive property of the tablet in relation to the bioavailability of thiamine was determined in healthy human volunteers using gamma scintigraphy under fasted and fed conditions. The gastro-retentive time of the floating tablet could be prolonged up to 10 h under the fed state, compared to about 1.8 h in the fasted state. The prolonged gastric retention under the fed state resulted in a 2.8-fold increase in oral bioavailability of thiamine compared to that of the fasted state. There was also a 1.4-fold increase in thiamine absorption compared to that of a conventional immediate release tablet in the fed state. In the fasted state, the extent of thiamine absorption from the floating tablet was only about 70% of that absorbed from the immediate release tablet. Thus, to achieve a better performance, such floating tablet systems should be administered under a fed condition, to prolong the gastric retention time. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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22 pages, 8653 KiB  
Article
MUPS Tableting—Comparison between Crospovidone and Microcrystalline Cellulose Core Pellets
by Daniel Robin Thio, Paul Wan Sia Heng and Lai Wah Chan
Pharmaceutics 2022, 14(12), 2812; https://doi.org/10.3390/pharmaceutics14122812 - 15 Dec 2022
Cited by 5 | Viewed by 1924
Abstract
Multi-unit pellet system (MUPS) tablets were fabricated by compacting drug-loaded pellets of either crospovidone or microcrystalline cellulose core. These pellets were produced by extrusion-spheronization and coated with ethylcellulose (EC) for a sustained drug release function. Coat damage due to the MUPS tableting process [...] Read more.
Multi-unit pellet system (MUPS) tablets were fabricated by compacting drug-loaded pellets of either crospovidone or microcrystalline cellulose core. These pellets were produced by extrusion-spheronization and coated with ethylcellulose (EC) for a sustained drug release function. Coat damage due to the MUPS tableting process could undermine the sustained release function of the EC-coated pellets. Deformability of the pellet core is a factor that can impact the extent of pellet coat damage. Thus, this study was designed to evaluate the relative performance of drug-loaded pellets prepared with either microcrystalline cellulose (MCC) or crospovidone (XPVP) as a spheronization aid and were comparatively evaluated for their ability to withstand EC pellet coat damage when compacted. These pellets were tableted at various compaction pressures and pellet volume fractions. The extent of pellet coat damage was assessed by the change in drug release after compaction. The findings from this study demonstrated that pellets spheronized with XPVP had slightly less favorable physical properties and experienced comparatively more pellet coat damage than the pellets with MCC. However, MUPS tablets of reasonable quality could successfully be produced from pellets with XPVP, albeit their performance did not match that of vastly mechanically stronger pellets with MCC at higher compaction pressure. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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17 pages, 3294 KiB  
Article
Engineering and Evaluation of Forcespun Gelatin Nanofibers as an Isorhamnetin Glycosides Delivery System
by Elsy J. García-Valderrama, Narsimha Mamidi, Marilena Antunes-Ricardo, Janet A. Gutiérrez-Uribe, Karina Del Angel-Sanchez and Alex Elías-Zúñiga
Pharmaceutics 2022, 14(6), 1116; https://doi.org/10.3390/pharmaceutics14061116 - 24 May 2022
Cited by 7 | Viewed by 1949
Abstract
Opuntia ficus-indica (L.) Mill (OFI) is considered a natural source of bioactive phytochemicals, mainly isorhamnetin glycosides (IRGs). These compounds have demonstrated antioxidant, anti-inflammatory, and anticancer activities, among others. The development of a suitable delivery system for these compounds is needed to improve their [...] Read more.
Opuntia ficus-indica (L.) Mill (OFI) is considered a natural source of bioactive phytochemicals, mainly isorhamnetin glycosides (IRGs). These compounds have demonstrated antioxidant, anti-inflammatory, and anticancer activities, among others. The development of a suitable delivery system for these compounds is needed to improve their chemical and biological stability. This study aimed to evaluate the feasibility of fabrication and characterization of IRG-loaded gelatin (GL) forcespun fibers and crosslinking with glutaraldehyde (GTA). Two different percentages (25% and 30% w/v) of GL were evaluated with 12% (w/v) OFI flour to obtain nanofibers GL/OFI1 and GL/OFI2, respectively. The morphology and physicochemical properties of the fibers were investigated. The results indicated that the diameters of the fibers were on the nanoscale. The amount of IRGs was determined using high-performance liquid chromatography (HPLC). The IRGs release and the cytocompatibility of the nanofibers were also evaluated. GL concentration significantly affected the IRG release. Among both nanofibers, the GL/OFI2 nanofiber achieved a cumulative IRGs release of 63% after 72 h. Both fibers were shown to be biocompatible with human skin/fibroblast cells. Specifically, GL/OFI1 nanofibers exhibited favorable features for their application as an extract-coupled release system. The IRGs-embedded GL nanofiber mats may become a good alternative for the delivery of phytochemicals for the health sector and biomedical applications. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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Review

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26 pages, 4800 KiB  
Review
Solid Lipid Nanoparticles (SLN) and Nanostructured Lipid Carriers (NLC) Prepared by Microwave and Ultrasound-Assisted Synthesis: Promising Green Strategies for the Nanoworld
by Karla L. López, Andrea Ravasio, José Vicente González-Aramundiz and Flavia C. Zacconi
Pharmaceutics 2023, 15(5), 1333; https://doi.org/10.3390/pharmaceutics15051333 - 25 Apr 2023
Cited by 6 | Viewed by 2432
Abstract
Many pharmaceutically active molecules are highly lipophilic, which renders their administration and adsorption in patients extremely challenging. Among the countless strategies to overcome this problem, synthetic nanocarriers have demonstrated superb efficiency as drug delivery systems, since encapsulation can effectively prevent a molecules’ degradation, [...] Read more.
Many pharmaceutically active molecules are highly lipophilic, which renders their administration and adsorption in patients extremely challenging. Among the countless strategies to overcome this problem, synthetic nanocarriers have demonstrated superb efficiency as drug delivery systems, since encapsulation can effectively prevent a molecules’ degradation, thus ensuring increased biodistribution. However, metallic and polymeric nanoparticles have been frequently associated with possible cytotoxic side effects. Solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), which are prepared with physiologically inert lipids, therefore emerged as an ideal strategy to bypass toxicities issues and avoid the use of organic solvents in their formulations. Different approaches to preparation, using only moderate amounts of external energy to facilitate a homogeneous formation, have been proposed. Greener synthesis strategies have the potential to provide faster reactions, more efficient nucleation, better particle size distribution, lower polydispersities, and furnish products with higher solubility. Particularly microwave-assisted synthesis (MAS) and ultrasound-assisted synthesis (UAS) have been utilized in the manufacturing of nanocarrier systems. This narrative review addresses the chemical aspects of those synthesis strategies and their positive influence on the characteristics of SLNs and NLCs. Furthermore, we discuss the limitations and future challenges for the manufacturing processes of both types of nanoparticles. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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58 pages, 7296 KiB  
Review
Metal–Organic Frameworks and Their Biodegradable Composites for Controlled Delivery of Antimicrobial Drugs
by Tayah C. Livesey, Lila A. M. Mahmoud, Maria G. Katsikogianni and Sanjit Nayak
Pharmaceutics 2023, 15(1), 274; https://doi.org/10.3390/pharmaceutics15010274 - 12 Jan 2023
Cited by 15 | Viewed by 4444
Abstract
Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition [...] Read more.
Antimicrobial resistance (AMR) is a growing global crisis with an increasing number of untreatable or exceedingly difficult-to-treat bacterial infections, due to their growing resistance to existing drugs. It is predicted that AMR will be the leading cause of death by 2050. In addition to ongoing efforts on preventive strategies and infection control, there is ongoing research towards the development of novel vaccines, antimicrobial agents, and optimised diagnostic practices to address AMR. However, developing new therapeutic agents and medicines can be a lengthy process. Therefore, there is a parallel ongoing worldwide effort to develop materials for optimised drug delivery to improve efficacy and minimise AMR. Examples of such materials include functionalisation of surfaces so that they can become self-disinfecting or non-fouling, and the development of nanoparticles with promising antimicrobial properties attributed to their ability to damage numerous essential components of pathogens. A relatively new class of materials, metal–organic frameworks (MOFs), is also being investigated for their ability to act as carriers of antimicrobial agents, because of their ultrahigh porosity and modular structures, which can be engineered to control the delivery mechanism of loaded drugs. Biodegradable polymers have also been found to show promising applications as antimicrobial carriers; and, recently, several studies have been reported on delivery of antimicrobial drugs using composites of MOF and biodegradable polymers. This review article reflects on MOFs and polymer–MOF composites, as carriers and delivery agents of antimicrobial drugs, that have been studied recently, and provides an overview of the state of the art in this highly topical area of research. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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37 pages, 8782 KiB  
Review
Poly(Lactic Acid)-Based Microparticles for Drug Delivery Applications: An Overview of Recent Advances
by Antonios Vlachopoulos, Georgia Karlioti, Evangelia Balla, Vasileios Daniilidis, Theocharis Kalamas, Myrika Stefanidou, Nikolaos D. Bikiaris, Evi Christodoulou, Ioanna Koumentakou, Evangelos Karavas and Dimitrios N. Bikiaris
Pharmaceutics 2022, 14(2), 359; https://doi.org/10.3390/pharmaceutics14020359 - 04 Feb 2022
Cited by 78 | Viewed by 9420
Abstract
The sustained release of pharmaceutical substances remains the most convenient way of drug delivery. Hence, a great variety of reports can be traced in the open literature associated with drug delivery systems (DDS). Specifically, the use of microparticle systems has received special attention [...] Read more.
The sustained release of pharmaceutical substances remains the most convenient way of drug delivery. Hence, a great variety of reports can be traced in the open literature associated with drug delivery systems (DDS). Specifically, the use of microparticle systems has received special attention during the past two decades. Polymeric microparticles (MPs) are acknowledged as very prevalent carriers toward an enhanced bio-distribution and bioavailability of both hydrophilic and lipophilic drug substances. Poly(lactic acid) (PLA), poly(lactic-co-glycolic acid) (PLGA), and their copolymers are among the most frequently used biodegradable polymers for encapsulated drugs. This review describes the current state-of-the-art research in the study of poly(lactic acid)/poly(lactic-co-glycolic acid) microparticles and PLA-copolymers with other aliphatic acids as drug delivery devices for increasing the efficiency of drug delivery, enhancing the release profile, and drug targeting of active pharmaceutical ingredients (API). Potential advances in generics and the constant discovery of therapeutic peptides will hopefully promote the success of microsphere technology. Full article
(This article belongs to the Special Issue New Technology for Prolonged Drug Release)
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