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Keywords = nasal dosage form

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16 pages, 1482 KiB  
Article
Nasal Residence Depending on the Administered Dosage Form: Impact of Formulation Type on the In Vivo Nasal Retention Time of Drugs in Rats
by Daisuke Inoue, Yoshihiro Seto and Hideto To
Pharmaceutics 2025, 17(7), 863; https://doi.org/10.3390/pharmaceutics17070863 - 30 Jun 2025
Viewed by 363
Abstract
Background/Objectives: The precise control of drug absorption through the nasal mucosa following intranasal administration can be achieved through optimal formulation development that considers the nasal retention properties of the administered dosage form. This study aimed to quantitatively elucidate the effect of formulation [...] Read more.
Background/Objectives: The precise control of drug absorption through the nasal mucosa following intranasal administration can be achieved through optimal formulation development that considers the nasal retention properties of the administered dosage form. This study aimed to quantitatively elucidate the effect of formulation type on nasal residence time in vivo. Methods: The nasal residence behavior of various formulation types, including solutions, particulates, and powders, was estimated in rats. Furthermore, the effect of mucoadhesive polymers on the nasal residence time was investigated using gel and powder dosage forms of sodium alginate. Results: The nasal retention behavior of the formulation in the nasal cavity differed depending on the dosage form. The polystyrene microparticles and lactose powder, a non-adhesive powder, were quickly eliminated into the nasopharynx, whereas the solution remained in the nasal cavity longer than the other formulations. The clearance behavior of the solution was investigated, and it was found that the solution was quickly transported to the stomach without being retained in the esophagus. The disappearance of the gel and powder with the mucoadhesive polymer was different, with the powder clearing faster. This difference in clearance is thought to be due to the powder being cleared before dissolving and diffusing into the nasal mucus. Conclusions: It has been clearly shown that the nasal residence behavior differed depending on the dosage forms. The addition of mucoadhesive polymers was effective in improving the nasal residence of the drug, and more-effective formulations for nasal application can be developed by combining optimal dosage forms, such as powders and gels. Full article
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18 pages, 5904 KiB  
Article
Gellan Gum-Based In Situ Hydrogels for Nasal Delivery of Polymeric Micelles Loaded with Risperidone
by Bence Sipos, Mária Budai-Szűcs, Gábor Katona and Ildikó Csóka
Gels 2025, 11(6), 404; https://doi.org/10.3390/gels11060404 - 28 May 2025
Viewed by 469
Abstract
Nasal drug delivery faces numerous challenges related to the ineffectiveness of most nasal formulations without a mucoadhesive nature, prolonging residence time on the nasal mucosa. Another challenge is the low administrable dosage strength, which can be solved via nano-encapsulation techniques, including the utilization [...] Read more.
Nasal drug delivery faces numerous challenges related to the ineffectiveness of most nasal formulations without a mucoadhesive nature, prolonging residence time on the nasal mucosa. Another challenge is the low administrable dosage strength, which can be solved via nano-encapsulation techniques, including the utilization of polymeric micelles. In this study, gellan gum–cellulose derivative complex in situ gelling matrices were formulated to test their effect on the colloidal characteristics of polymeric micelles, their respective rheological behavior, and nasal applicability. It has been proven that these complex matrices can form gels upon contact with nasal fluid without disrupting the micellar structure. Changes in the drug release and permeation profile have been shown in a concentration-dependent manner to hinder the burst-like drug release profile of polymeric micelles. Formulations show concentration- and composition-dependent mucoadhesive features under nasal conditions. Most of the hydrogels possess a soft gel characteristic, making them suitable for nasal administration. In conclusion, this descriptive study provides useful insights for conscious, nasal dosage form design. Full article
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12 pages, 3816 KiB  
Article
Effect of Inoculation Volume on a Mouse Model of Influenza Virus Infected with the Same Viral Load
by Yali Sun, Yuwei Wei, Xuelian Han, Yuan Wang, Qi Yin, Yuhang Zhang, Tiantian Yang, Jiejie Zhang, Keyu Sun, Feimin Fang, Shuai Zhang, Kai Yuan, Min Li and Guangyu Zhao
Vaccines 2025, 13(2), 173; https://doi.org/10.3390/vaccines13020173 - 12 Feb 2025
Viewed by 1140
Abstract
Background: Influenza is a highly contagious respiratory disease that poses significant health and economic burdens. Mice are commonly used as animal models for studying influenza virus pathogenesis and the development of vaccines and drugs. However, the viral volume used for nasal inoculation varies [...] Read more.
Background: Influenza is a highly contagious respiratory disease that poses significant health and economic burdens. Mice are commonly used as animal models for studying influenza virus pathogenesis and the development of vaccines and drugs. However, the viral volume used for nasal inoculation varies substantially in reported mouse influenza infection models, and the appropriate viral dose is crucial for reproducing experimental results. Methods: Mice were inoculated with mouse lung-adapted strains of influenza virus A/Puerto Rico/8/34 (H1N1) via intranasal administration of 10 μL, 20 μL, and 40 μL at doses of 200 plaque-forming units (PFU) and 2000 PFU. This study investigated the impact of varying viral inoculum volumes on murine outcomes at identical doses and assessed the disparities across diverse dosage levels. Results: Regarding weight change trajectories, mortalities, lung tissue viral titers, and pathological manifestations, the group that received the 40 μL inoculation volume within the low-dose infection mice (200 PFU) manifested a statistically significant divergence from those inoculated with both the 10 μL and 20 μL volumes. Within the context of high-dose infections (2000 PFU), groups that received inoculation volumes of 20 μL and 40 μL exhibited marked disparities when compared to those receiving the 10 μL volume. Conclusions: Disparities in inoculation volume, even under uniform infection dosages, engender differential outcomes in pathogenicity. Of particular note, the viral replication efficacy at a 20 μL inoculation volume demonstrates conspicuous fluctuations across diverse infection dose regimens. Full article
(This article belongs to the Special Issue Viral Infections, Host Immunity and Vaccines)
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51 pages, 2274 KiB  
Review
Evaluation of Drug Permeation Enhancement by Using In Vitro and Ex Vivo Models
by Johan D. Steyn, Anja Haasbroek-Pheiffer, Wihan Pheiffer, Morné Weyers, Suzanne E. van Niekerk, Josias H. Hamman and Daniélle van Staden
Pharmaceuticals 2025, 18(2), 195; https://doi.org/10.3390/ph18020195 - 31 Jan 2025
Cited by 3 | Viewed by 3130
Abstract
Drugs administered by means of extravascular routes of drug administration must be absorbed into the systemic circulation, which involves the movement of the drug molecules across biological barriers such as epithelial cells that cover mucosal surfaces or the stratum corneum that covers the [...] Read more.
Drugs administered by means of extravascular routes of drug administration must be absorbed into the systemic circulation, which involves the movement of the drug molecules across biological barriers such as epithelial cells that cover mucosal surfaces or the stratum corneum that covers the skin. Some drugs exhibit poor permeation across biological membranes or may experience excessive degradation during first-pass metabolism, which tends to limit their bioavailability. Various strategies have been used to improve drug bioavailability. Absorption enhancement strategies include the co-administration of chemical permeation enhancers, enzymes, and/or efflux transporter inhibitors, chemical changes, and specialized dosage form designs. Models with physiological relevance are needed to evaluate the efficacy of drug absorption enhancement techniques. Various in vitro cell culture models and ex vivo tissue models have been explored to evaluate and quantify the effectiveness of drug permeation enhancement strategies. This review deliberates on the use of in vitro and ex vivo models for the evaluation of drug permeation enhancement strategies for selected extravascular drug administration routes including the nasal, oromucosal, pulmonary, oral, rectal, and transdermal routes of drug administration. Full article
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22 pages, 7402 KiB  
Article
Development of Nanocomposite Microspheres for Nasal Administration of Deferiprone in Neurodegenerative Disorders
by Radka Boyuklieva, Plamen Katsarov, Plamen Zagorchev, Silviya Abarova, Asya Hristozova and Bissera Pilicheva
J. Funct. Biomater. 2024, 15(11), 329; https://doi.org/10.3390/jfb15110329 - 5 Nov 2024
Cited by 1 | Viewed by 1624
Abstract
Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the [...] Read more.
Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood–brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity. Full article
(This article belongs to the Special Issue Medical Application of Functional Biomaterials (2nd Edition))
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14 pages, 3150 KiB  
Article
Comparative Study of TPGS and Soluplus Polymeric Micelles Embedded in Poloxamer 407 In Situ Gels for Intranasal Administration
by Bence Sipos, Frézia Földes, Mária Budai-Szűcs, Gábor Katona and Ildikó Csóka
Gels 2024, 10(8), 521; https://doi.org/10.3390/gels10080521 - 9 Aug 2024
Cited by 3 | Viewed by 2224
Abstract
This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic [...] Read more.
This study aims to highlight the importance of choosing the appropriate co-polymer or co-polymer mixed combinations in order to design value-added nasal dosage forms. Local therapy of upper respiratory tract-related infections, such as nasal rhinosinusitis is of paramount importance, thus advanced local therapeutic options are required. Dexamethasone was encapsulated into three different polymeric micelle formulations: Soluplus or TPGS-only and their mixed combinations. Dynamic light scattering measurements proved that the particles have a micelle size less than 100 nm in monodisperse distribution, with high encapsulation efficiency above 80% and an at least 7-fold water solubility increase. Tobramycin, as an antimicrobial agent, was co-formulated into the in situ gelling systems which were optimized based on gelation time and gelation temperature. The sol–gel transition takes place between 32–35 °C, which is optimally below the temperature of the nasal cavity in a quick manner below 5 min, a suitable strategic criterion against the mucociliary clearance. In vitro drug release and permeability studies confirmed a rapid kinetics in the case of the encapsulated dexamethasone accompanied with a sustained release of tobramycin, as the hydrophilic drug. Full article
(This article belongs to the Section Gel Analysis and Characterization)
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16 pages, 2533 KiB  
Article
Development and Optimization of Nasal Composition of a Neuroprotective Agent for Use in Neonatology after Prenatal Hypoxia
by Igor Belenichev, Olena Aliyeva, Bogdan Burlaka, Kristina Burlaka, Oleh Kuchkovskyi, Dmytro Savchenko, Valentyn Oksenych and Oleksandr Kamyshnyi
Pharmaceuticals 2024, 17(8), 990; https://doi.org/10.3390/ph17080990 - 26 Jul 2024
Cited by 2 | Viewed by 1611
Abstract
The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system (CNS), bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs [...] Read more.
The intranasal route of drug administration is characterized by high bioavailability and is considered promising for rapid delivery of drugs with systemic action to the central nervous system (CNS), bypassing the blood-brain barrier. This is particularly important for the use of neuroprotective drugs in the treatment of brain tissue damage in infants caused by the effects of intrauterine hypoxia. The creation of new dosage forms for neonatology using mathematical technologies and special software in pharmaceutical development allows for the creation of cerebroprotective drugs with controlled pharmaco-technological properties, thus reducing time and resources for necessary research. We developed a new nasal gel formulation with Angiolin using a Box-Behnken experiment design for the therapy of prenatal CNS damage. It was found that the consistency characteristics of the nasal gel were significantly influenced by the gelling agent and mucoadhesive component—sodium salt of carboxymethylcellulose. We optimized the composition of nasal gel formulation with Angiolin using the formed models and relationships between the factors. The optimized nasal gel composition demonstrated satisfactory thixotropic properties. The 1% gel for neuroprotection with Angiolin, developed for intranasal administration, meets all safety requirements for this group of drug forms, showing low toxicity and no local irritant or allergic effects. Full article
(This article belongs to the Section Pharmaceutical Technology)
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14 pages, 737 KiB  
Review
A Review of the Literature on Episodes of Acute Fentanyl Intoxication in Pediatric Age and Toxicological Applications
by Matteo Antonio Sacco, Saverio Gualtieri, Alessandro Pasquale Tarallo, Lucia Tarda, Maria Cristina Verrina, Andrea Costa and Isabella Aquila
Toxics 2024, 12(8), 534; https://doi.org/10.3390/toxics12080534 - 24 Jul 2024
Cited by 3 | Viewed by 3397
Abstract
Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability [...] Read more.
Fentanyl is an opioid with powerful analgesic effects and a high speed of action. Due to its pharmacological properties, this molecule has therapeutic application as an anesthetic in surgery or as palliative therapy for cancer patients. Unfortunately, in recent years, the easy availability of this substance, the low cost and the illegal online market have favored the large-scale diffusion of fentanyl. Fentanyl is available in different forms, including nasal spray, oral patches, soluble capsules, aerosol or the new version of fentanyl mixed with other drugs, making its use very widespread. Subjects of various ages are involved in fentanyl consumption, including minors that have not yet reached adolescence. In this work, we performed a literature review using the search engines PubMed NCBI and SCOPUS regarding episodes of acute fentanyl intoxication occurring in those of a pediatric age using the Mesh Terms “fentanyl” AND “overdose” AND “children”. The inclusion criteria were English papers published in the last 10 years regarding the cases of children under the age of 10. We evaluated the most frequent methods of intake and the circumstances of such episodes. In cases of death, we analyzed the autopsy, the toxicological findings and the investigations carried out. The review results show that in this age group (under < 10 y.o. s), it is possible to identify the risk factors for fentanyl intake, such as the presence of this molecule within the family unit due to drug addiction or medical therapy. The results also demonstrate a significant risk of underestimation of this phenomenon, since the molecule is often not investigated through adequate toxicological analysis. These results, therefore, suggest always carrying out toxicological investigations in the case of suspected fentanyl intoxication, both on patients or cadavers. The investigations must always include a urinary screening for opiates, and the request for a second level analysis with molecule dosage in cases of positivity or in cases of strong suspicion for assumption. In cases of intoxication in a family context of drug addiction, it is necessary to investigate the chronicity of the intake through hair analysis and evaluate the possible co-administration of other drugs. In conclusion, we suggest a protocol, applicable both on patients or cadavers, which can be useful for physicians and forensic pathologists in order to promptly identify these cases and allow for the reporting of them to the judicial authorities with the adoption of strict prevention and control measures. Full article
(This article belongs to the Section Drugs Toxicity)
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16 pages, 2927 KiB  
Article
Optimization of Pramipexole-Loaded In Situ Thermosensitive Intranasal Gel for Parkinson’s Disease
by Rushi Trivedi, Vahid Vikram Minglani, Ahmed M. El-Gazzar, Gaber El-Saber Batiha, Mohamed H. Mahmoud, Mitesh Patel and Meenakshi Patel
Pharmaceuticals 2024, 17(2), 172; https://doi.org/10.3390/ph17020172 - 29 Jan 2024
Cited by 6 | Viewed by 2311
Abstract
The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson’s disease. Preliminary studies were performed to select formulation components and identify [...] Read more.
The objective of the present work was to develop and optimize an intranasal in situ gel of Pramipexole dihydrochloride for enhanced drug delivery, better patient acceptability, and possible proper treatment of Parkinson’s disease. Preliminary studies were performed to select formulation components and identify key variables affecting the formulation. The optimization of the in situ gelling system of Pramipexole dihydrochloride was achieved by applying 32 full factorial design using Design-Expert® software (Stat-Ease 9.0.6 version) and taking concentrations of Poloxamer 407 (X1) and HPMC K4M (X2) as independent variables. The gelling temperature, gel strength, and percentage of drug diffused after 8 h were taken as dependent variables. The software provided an optimized formulation, with 16.50% of X1 and 0.2% of X2 with the highest desirability. An in vivo drug retention time study was performed for the optimized formulation in Wistar rats. The results of the optimization process demonstrated that the selected gel formulation exhibited desirable characteristics, including gelation near body temperature, good gel strength, suitable viscosity, and sustained drug release. The optimized formulation displayed significantly higher drug retention, lasting about 5 h, versus the plain poloxamer gel formulation. Hence, it was concluded that the optimized formulation will remain affixed at the site of application for a significant time after intranasal administration and consequently sustain the release of the drug. The optimized formulation was found to be stable during the stability studies. The developed dosage form may improve patient compliance, enhance nasal drug residence, and offer sustained drug release. However, further clinical studies are necessary to validate these findings. Full article
(This article belongs to the Section Pharmaceutical Technology)
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12 pages, 3673 KiB  
Systematic Review
The Anti-Nociceptive Effects of Nicotine in Humans: A Systematic Review and Meta-Analysis
by Yujia Luo, Yating Yang, Carl Schneider and Thomas Balle
Pharmaceuticals 2023, 16(12), 1665; https://doi.org/10.3390/ph16121665 - 30 Nov 2023
Cited by 2 | Viewed by 3335
Abstract
Background: Pain can have a serious impact on a patient’s physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical [...] Read more.
Background: Pain can have a serious impact on a patient’s physical, mental, and social health, often causing their quality of life to decline. Various nicotine dosage forms, such as nicotine patches and nasal spray, have been developed and used as analgesics in clinical settings. However, there is controversy over the anti-nociceptive effects of nicotine among different clinical trials. The purpose of this meta-analysis is to quantify the analgesic effect of nicotine patches, nicotine nasal spray, and tobacco smoking on pain in humans. Methods: Relevant articles published in English prior to July 2023 were identified using the PubMed, Cochrane Library, and Embase online databases in accordance with PRISMA (2020) guidelines. Two reviewers independently screened and selected studies, extracted data, and assessed the quality of the included studies using version 2 of the Cochrane risk-of-bias tool for randomized trials (RoB 2). RStudio was used for data synthesis, heterogeneity assessment, sensitivity analysis, publication bias assessment, trim-and-fill analyses, and generating forest plots. Results: Sixteen eligible articles, including k = 5 studies of pain tolerance (n = 210), k = 5 studies of pain threshold (n = 210), and k = 12 studies of pain scores (N = 1249), were included for meta-analysis. Meta-analytic integration for pain threshold (Hedges’ g = 0.28, 95% CI = 0–0.55, Z = 1.99, p = 0.05) and pain tolerance (Hedges’ g = 0.32, 95% CI = 0.05–0.59, Z = 2.30, p = 0.02) revealed that nicotine administered via tobacco smoke generated acute analgesic effects to thermal stimuli. Meta-analytic integration for pain scores revealed that nicotine had a weak anti-nociceptive effect on postoperative pain of −0.37 (95% CI = −0.77 to 0.03, Z = −1.80) but with no statistical significance (p = 0.07). In addition, a limited number of included studies revealed that long-term smoking produced hyperalgesia that may be characterized as small to medium in magnitude (Hedges’ g = 0.37, 95% CI = 0.29–0.64, Z = 5.33, p < 0.01). Conclusion: These results help to clarify the mixed outcomes of trials and may ultimately inform the treatment of pain. We observed that acute nicotine administration prolonged the laboratory-induced pain threshold and tolerance time and may mildly relieve postoperative pain. In addition, long-term tobacco smoking may have a nociceptive effect on different types of chronic pain. More research is needed to determine the anti-nociceptive effects of nicotine in humans, and to understand the optimal timing, dose, and method of delivery of nicotine. Full article
(This article belongs to the Section Pharmacology)
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23 pages, 9470 KiB  
Article
Solid Lipid Nanoparticles Containing Dopamine and Grape Seed Extract: Freeze-Drying with Cryoprotection as a Formulation Strategy to Achieve Nasal Powders
by Elvira De Giglio, Udo Bakowsky, Konrad Engelhardt, Antonello Caponio, Matteo La Pietra, Stefania Cometa, Stefano Castellani, Lorenzo Guerra, Giuseppe Fracchiolla, Maria Luana Poeta, Rosanna Mallamaci, Rosa Angela Cardone, Stefano Bellucci and Adriana Trapani
Molecules 2023, 28(23), 7706; https://doi.org/10.3390/molecules28237706 - 22 Nov 2023
Cited by 7 | Viewed by 2142
Abstract
(1) Background: DA-Gelucire® 50/13-based solid lipid nanoparticles (SLNs) administering the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) have been prepared by us in view of a possible application for Parkinson’s disease (PD) treatment. To develop powders constituted [...] Read more.
(1) Background: DA-Gelucire® 50/13-based solid lipid nanoparticles (SLNs) administering the neurotransmitter dopamine (DA) and the antioxidant grape-seed-derived proanthocyanidins (grape seed extract, GSE) have been prepared by us in view of a possible application for Parkinson’s disease (PD) treatment. To develop powders constituted by such SLNs for nasal administration, herein, two different agents, namely sucrose and methyl-β-cyclodextrin (Me-β-CD), were evaluated as cryoprotectants. (2) Methods: SLNs were prepared following the melt homogenization method, and their physicochemical features were investigated by Raman spectroscopy, Scanning Electron Microscopy (SEM), atomic force microscopy (AFM) and X-ray Photoelectron Spectroscopy (XPS). (3) Results: SLN size and zeta potential values changed according to the type of cryoprotectant and the morphological features investigated by SEM showed that the SLN samples after lyophilization appear as folded sheets with rough surfaces. On the other hand, the AFM visualization of the SLNs showed that their morphology consists of round-shaped particles before and after freeze-drying. XPS showed that when sucrose or Me-β-CD were not detected on the surface (because they were not allocated on the surface or completely absent in the formulation), then a DA surfacing was observed. In vitro release studies in Simulated Nasal Fluid evidenced that DA release, but not the GSE one, occurred from all the cryoprotected formulations. Finally, sucrose increased the physical stability of SLNs better than Me-β-CD, whereas RPMI 2650 cell viability was unaffected by SLN-sucrose and slightly reduced by SLN-Me-β-CD. (4) Conclusions: Sucrose can be considered a promising excipient, eliciting cryoprotection of the investigated SLNs, leading to a powder nasal pharmaceutical dosage form suitable to be handled by PD patients. Full article
(This article belongs to the Special Issue Lipid Chains: Supramolecular Behavior and Biological Applications)
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22 pages, 3071 KiB  
Article
Development of Lyophilised Eudragit® Retard Nanoparticles for the Sustained Release of Clozapine via Intranasal Administration
by Rosamaria Lombardo, Marika Ruponen, Jarkko Rautio, Carla Ghelardini, Lorenzo Di Cesare Mannelli, Laura Calosi, Daniele Bani, Riikka Lampinen, Katja M. Kanninen, Anne M. Koivisto, Elina Penttilä, Heikki Löppönen and Rosario Pignatello
Pharmaceutics 2023, 15(5), 1554; https://doi.org/10.3390/pharmaceutics15051554 - 21 May 2023
Cited by 11 | Viewed by 2733
Abstract
Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the [...] Read more.
Clozapine (CZP) is the only effective drug in schizophrenia resistant to typical antipsychotics. However, existing dosage forms (oral or orodispersible tablets, suspensions or intramuscular injection) show challenging limitations. After oral administration, CZP has low bioavailability due to a large first-pass effect, while the i.m. route is often painful, with low patient compliance and requiring specialised personnel. Moreover, CZP has a very low aqueous solubility. This study proposes the intranasal route as an alternative route of administration for CZP, through its encapsulation in polymeric nanoparticles (NPs) based on Eudragit® RS100 and RL100 copolymers. Slow-release polymeric NPs with dimensions around 400–500 nm were formulated to reside and release CZP in the nasal cavity, where it can be absorbed through the nasal mucosa and reach the systemic circulation. CZP-EUD-NPs showed a controlled release of CZP for up to 8 h. Furthermore, to reduce mucociliary clearance and increase the residence time of NPs in the nasal cavity to improve drug bioavailability, mucoadhesive NPs were formulated. This study shows that the NPs already exhibited strong electrostatic interactions with mucin at time zero due to the presence of the positive charge of the used copolymers. Furthermore, to improve the solubility, diffusion and adsorption of CZPs and the storage stability of the formulation, it was lyophilised using 5% (w/v) HP-β-CD as a cryoprotectant. It ensured the preservation of the NPs’ size, PDI and charge upon reconstitution. Moreover, physicochemical characterisation studies of solid-state NPs were performed. Finally, toxicity studies were performed in vitro on MDCKII cells and primary human olfactory mucosa cells and in vivo on the nasal mucosa of CD-1 mice. The latter showed non-toxicity of B-EUD-NPs and mild CZP-EUD-NP-induced tissue abnormalities. Full article
(This article belongs to the Special Issue Polymer-Based Micro- and Nanocarriers for Drug Delivery and Targeting)
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28 pages, 1446 KiB  
Review
Formulation Strategies of Nanosuspensions for Various Administration Routes
by Sıla Gülbağ Pınar, Ayşe Nur Oktay, Alptuğ Eren Karaküçük and Nevin Çelebi
Pharmaceutics 2023, 15(5), 1520; https://doi.org/10.3390/pharmaceutics15051520 - 17 May 2023
Cited by 55 | Viewed by 8755
Abstract
Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and [...] Read more.
Nanosuspensions (NSs), which are nanosized colloidal particle systems, have recently become one of the most interesting substances in nanopharmaceuticals. NSs have high commercial potential because they provide the enhanced solubility and dissolution of low-water-soluble drugs by means of their small particle sizes and large surface areas. In addition, they can alter the pharmacokinetics of the drug and, thus, improve its efficacy and safety. These advantages can be used to enhance the bioavailability of poorly soluble drugs in oral, dermal, parenteral, pulmonary, ocular, or nasal routes for systemic or local effects. Although NSs often consist mainly of pure drugs in aqueous media, they can also contain stabilizers, organic solvents, surfactants, co-surfactants, cryoprotectants, osmogents, and other components. The selection of stabilizer types, such as surfactants or/and polymers, and their ratio are the most critical factors in NS formulations. NSs can be prepared both with top-down methods (wet milling, dry milling, high-pressure homogenization, and co-grinding) and with bottom-up methods (anti-solvent precipitation, liquid emulsion, and sono-precipitation) by research laboratories and pharmaceutical professionals. Nowadays, techniques combining these two technologies are also frequently encountered. NSs can be presented to patients in liquid dosage forms, or post-production processes (freeze drying, spray drying, or spray freezing) can also be applied to transform the liquid state into the solid state for the preparation of different dosage forms such as powders, pellets, tablets, capsules, films, or gels. Thus, in the development of NS formulations, the components/amounts, preparation methods, process parameters/levels, administration routes, and dosage forms must be defined. Moreover, those factors that are the most effective for the intended use should be determined and optimized. This review discusses the effect of the formulation and process parameters on the properties of NSs and highlights the recent advances, novel strategies, and practical considerations relevant to the application of NSs to various administration routes. Full article
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16 pages, 3316 KiB  
Article
Combination of Cellulose Derivatives and Chitosan-Based Polymers to Investigate the Effect of Permeation Enhancers Added to In Situ Nasal Gels for the Controlled Release of Loratadine and Chlorpheniramine
by Prasanth Viswanadhan Vasantha, Sheri Peedikayil Sherafudeen, Mohamed Rahamathulla, Sam Thomarayil Mathew, Sandhya Murali, Sultan Alshehri, Faiyaz Shakeel, Prawez Alam, Ala Yahya Sirhan and Bhageerathy Anantha Narayana Iyer
Polymers 2023, 15(5), 1206; https://doi.org/10.3390/polym15051206 - 27 Feb 2023
Cited by 9 | Viewed by 2464
Abstract
The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as [...] Read more.
The purpose of the study is to develop and assess mucoadhesive in situ nasal gel formulations of loratadine and chlorpheniramine maleate to advance the bioavailability of the drug as compared to its conventional dosage forms. The influence of various permeation enhancers, such as EDTA (0.2% w/v), sodium taurocholate (0.5% w/v), oleic acid (5% w/v), and Pluronic F 127 (10% w/v), on the nasal absorption of loratadine and chlorpheniramine from in situ nasal gels containing different polymeric combinations, such as hydroxypropyl methylcellulose, Carbopol 934, sodium carboxymethylcellulose, and chitosan, is studied. Among these permeation enhancers, sodium taurocholate, Pluronic F127 and oleic acid produced a noticeable increase in the loratadine in situ nasal gel flux compared with in situ nasal gels without permeation enhancer. However, EDTA increased the flux slightly, and in most cases, the increase was insignificant. However, in the case of chlorpheniramine maleate in situ nasal gels, the permeation enhancer oleic acid only showed a noticeable increase in flux. Sodium taurocholate and oleic acid seems to be a better and efficient enhancer, enhancing the flux > 5-fold compared with in situ nasal gels without permeation enhancer in loratadine in situ nasal gels. Pluronic F127 also showed a better permeation, increasing the effect by >2-fold in loratadine in situ nasal gels. In chlorpheniramine maleate in situ nasal gels with EDTA, sodium taurocholate and Pluronic F127 were equally effective, enhancing chlorpheniramine maleate permeation. Oleic acid has a better effect as permeation enhancer in chlorpheniramine maleate in situ nasal gels and showed a maximum permeation enhancement of >2-fold. Full article
(This article belongs to the Special Issue Chitosan, Chitin, and Cellulose Nanofiber Biomaterials II)
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16 pages, 1898 KiB  
Article
Development of In Vitro Evaluation System for Assessing Drug Dissolution Considering Physiological Environment in Nasal Cavity
by Daisuke Inoue, Ayari Yamashita and Hideto To
Pharmaceutics 2022, 14(11), 2350; https://doi.org/10.3390/pharmaceutics14112350 - 31 Oct 2022
Cited by 3 | Viewed by 3103
Abstract
Estimating the dissolution behavior of a solid in the nasal mucus is challenging for solid dosage forms designed for the nasal application as the solid dissolves into nasal mucus and permeates through the mucosa. In the current study, the dissolution behavior of powders [...] Read more.
Estimating the dissolution behavior of a solid in the nasal mucus is challenging for solid dosage forms designed for the nasal application as the solid dissolves into nasal mucus and permeates through the mucosa. In the current study, the dissolution behavior of powders in the artificial nasal fluid was investigated using a 3D-printed chamber system to establish in vitro evaluation system for the dissolution of solid formulations that can simulate the intranasal environment in vivo. The dissolution rates of the five model drugs correlated with their solubility (r2 = 0.956, p < 0.01). The permeation rate of drugs across the Calu-3 cell layers after powder application depends on the membrane permeability of the drug. An analysis of membrane permeability considering the dissolution of powders showed the possibility of characterizing whether the drug in the powder was dissolution-limited or permeation-limited. This suggests that critical information can be obtained to understand which mechanism is more effective for the improvement of drug absorption from powders. This study indicates that the elucidation of drug dissolution behavior into nasal mucus is an important factor for the formulation of nasal powders and that the in vitro system developed could be a useful tool. Full article
(This article belongs to the Special Issue Advances and Challenges in Nasal Formulation Developments)
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