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Keywords = HPMC K4M

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13 pages, 1385 KB  
Article
Hesperetin Nanoparticle Powder as a Potential Antioxidant Nutraceutical Ingredient: Fabrication, Characterization, and Comparative Dissolution in Vegetarian and Non-Vegetarian Capsules
by Tzu-Hui Wu, Yun-Yi Lan, Huai-En Hsu, Pamela Berilyn So, Yuan-Yu Chen and Feng-Lin Yen
Pharmaceutics 2025, 17(12), 1558; https://doi.org/10.3390/pharmaceutics17121558 - 3 Dec 2025
Viewed by 455
Abstract
Background/Objectives: Hesperetin (HSP) is a bioactive flavonoid known for its strong antioxidant and anti-inflammatory properties. However, its low water solubility (1.36 ± 0.30 μg/mL) and poor oral bioavailability (~20%) greatly hinder its potential in nutraceutical applications. Methods: Using the solvent dispersion method, nanoparticles [...] Read more.
Background/Objectives: Hesperetin (HSP) is a bioactive flavonoid known for its strong antioxidant and anti-inflammatory properties. However, its low water solubility (1.36 ± 0.30 μg/mL) and poor oral bioavailability (~20%) greatly hinder its potential in nutraceutical applications. Methods: Using the solvent dispersion method, nanoparticles composed of HSP, hydroxypropyl-β-cyclodextrin (HPBCD), and polyvinylpyrrolidone K30 (PVPK30) were prepared and collectively termed HHPNP. Characterization involved particle size measurement, FTIR, XRD, SEM, and TEM. Antioxidant activity was evaluated using DPPH and ABTS+ radical scavenging assays. In vitro dissolution testing was performed at pH 1.2 and pH 6.8 to compare HHPNP with physical mixtures, and release behavior was assessed using both gelatin (non-vegetarian) and HPMC (vegetarian) capsules. Results: The optimal formulation (1:15:12) produced uniformly distributed spherical nanoparticles with a mean size of 14.87 ± 0.49 nm and achieved an 827-fold increase in water solubility compared with raw HSP. FTIR analysis indicated hydrogen bond formation, and XRD confirmed a complete transition from a crystalline to an amorphous state. In aqueous environments, HHPNP demonstrated markedly improved antioxidant activity, with DPPH and ABTS+ radical scavenging comparable to HSP solutions prepared in methanol. In vitro dissolution testing revealed rapid release at both pH 1.2 (>65% in 10 min) and at pH 6.8 (70% in 5 min). In contrast, physical mixtures only released 10–30% over two hours. T50% values at pH 1.2 were 17.8 min (gelatin) and 16.8 min (HPMC). At pH 6.8, T50% values were 17.6 min (gelatin) and 7.5 min (HPMC). Both capsule types matched the HHPNP in release at 120 min, and these comparable profiles indicate the formulation’s stability and adaptability across capsule variants. Conclusions: This nanoparticle-based delivery system, leveraging molecular inclusion and amorphization, significantly enhanced the solubility, bioactivity, and release efficiency of HSP, offering a potent platform for oral flavonoid-based dietary supplements. Full article
(This article belongs to the Special Issue Natural Bioactive Compounds in Micro- and Nanocarriers)
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19 pages, 772 KB  
Article
A Systematic Intelligent Optimization Framework for a Sustained-Release Formulation Design
by Yuchao Qiao, Yijia Wu, Mengchen Han, Hao Ren, Yu Cui, Xuchun Wang, Yiming Lou, Chongqi Hao, Quan Feng and Lixia Qiu
Pharmaceutics 2025, 17(11), 1419; https://doi.org/10.3390/pharmaceutics17111419 - 1 Nov 2025
Viewed by 630
Abstract
Objectives: This study proposes a systematic strategy for optimizing sustained-release formulations using mixture experiments. Methods: Model variables were identified and screened via LASSO regression, Smoothly Clipped Absolute Deviation (SCAD), and Minimax Concave Penalty (MCP), leading to the construction of a quadratic [...] Read more.
Objectives: This study proposes a systematic strategy for optimizing sustained-release formulations using mixture experiments. Methods: Model variables were identified and screened via LASSO regression, Smoothly Clipped Absolute Deviation (SCAD), and Minimax Concave Penalty (MCP), leading to the construction of a quadratic inference function-based objective model. Using this model, three multi-objective optimization algorithms—NSGA-III, MOGWO, and NSWOA—were employed to generate a Pareto-optimal solution set. Solutions were further evaluated through the entropy weight method combined with TOPSIS to reduce subjective bias. Results: The MCP-screened model demonstrated strong fit (AIC = 19.8028, BIC = 45.2951) and suitability for optimization. Among the Pareto-optimal formulations, formulation 45, comprising HPMC K4M (38.42%), HPMC K100LV (13.51%), MgO (6.28%), lactose (17.07%), and anhydrous CaHPO4 (7.52%), exhibited superior performance, achieving cumulative release rates of 22.75%, 64.98%, and 100.23% at 2, 8, and 24 h, respectively. Compared with the original formulation, drug release was significantly improved across all time points. Conclusions: This integrated workflow effectively accounted for component interactions and repeated measurements, providing a robust and scientifically grounded approach for optimizing multi-component sustained-release formulations. Full article
(This article belongs to the Section Physical Pharmacy and Formulation)
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20 pages, 5198 KB  
Article
Expandable Gastroretentive Films Based on Anthocyanin-Rich Rice Starch for Improved Ferulic Acid Delivery
by Nattawipa Matchimabura, Jiramate Poolsiri, Nataporn Phadungvitvatthana, Rachanida Praparatana, Ousanee Issarachot and Ruedeekorn Wiwattanapatapee
Polymers 2025, 17(17), 2301; https://doi.org/10.3390/polym17172301 - 25 Aug 2025
Viewed by 1791
Abstract
Ferulic acid (FA) is a bioactive compound known for its potent antioxidant and anti-inflammatory properties; however, its poor water solubility significantly limits its bioavailability and therapeutic potential. In this study, a solid dispersion of FA (FA-SD) was developed using Eudragit® EPO via [...] Read more.
Ferulic acid (FA) is a bioactive compound known for its potent antioxidant and anti-inflammatory properties; however, its poor water solubility significantly limits its bioavailability and therapeutic potential. In this study, a solid dispersion of FA (FA-SD) was developed using Eudragit® EPO via the solvent evaporation method, achieving a 24-fold increase in solubility (42.7 mg/mL) at a 1:3 drug-to-polymer ratio. Expandable gastroretentive films were subsequently formulated using starches from Hom-Nil rice, glutinous rice, and white rice, combined with chitosan as the primary film-forming agents, via the solvent casting technique. Hydroxypropyl methylcellulose (HPMC) K100 LV was incorporated as an adjuvant to achieve controlled release. At optimal concentrations (3% w/w starch, 2% w/w chitosan, and 2% w/w HPMC), the films exhibited favorable mechanical properties, swelling capacity, and unfolding behavior. Sustained release of FA over 8 h was achieved in formulations containing HPMC with either Hom-Nil or glutinous rice starch. Among the tested formulations (R6, G6, and H6), those incorporating Hom-Nil rice starch demonstrated the most significant antioxidant (10.38 ± 0.23 μg/mL) and anti-inflammatory (9.26 ± 0.14 μg/mL) effects in murine macrophage cell line (RAW 264.7), surpassing the activities of both free FA and FA-SD. These results highlight the potential of anthocyanin-rich pigmented rice starch-based expandable films as effective gastroretentive systems for enhanced FA delivery. Full article
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20 pages, 1996 KB  
Article
Thermosensitive Mucoadhesive Intranasal In Situ Gel of Risperidone for Nose-to-Brain Targeting: Physiochemical and Pharmacokinetics Study
by Mahendra Singh, Sanjay Kumar, Ramachandran Vinayagam and Ramachandran Samivel
Pharmaceuticals 2025, 18(6), 871; https://doi.org/10.3390/ph18060871 - 11 Jun 2025
Cited by 10 | Viewed by 2702
Abstract
Background/Objectives: Non-invasive central nervous system (CNS) therapies are limited by complex mechanisms and the blood–brain barrier, but nasal delivery offers a promising alternative. The study planned to develop a non-invasive in situ intranasal mucoadhesive thermosensitive gel to deliver CNS-active risperidone via nose-to-brain targeting. [...] Read more.
Background/Objectives: Non-invasive central nervous system (CNS) therapies are limited by complex mechanisms and the blood–brain barrier, but nasal delivery offers a promising alternative. The study planned to develop a non-invasive in situ intranasal mucoadhesive thermosensitive gel to deliver CNS-active risperidone via nose-to-brain targeting. Risperidone, a second-generation antipsychotic, has shown efficacy in managing both psychotic and mood-related symptoms. The mucoadhesive gel formulations help to prolong the residence time at the nasal absorption site, thereby facilitating the uptake of the drug. Methods: The poloxamer 407 (18.0% w/v), HPMC K100M and K15M (0.3–0.5% w/v), and benzalkonium chloride (0.1% v/v) were used as thermosensitive polymers, a mucoadhesive agent, and a preservative, respectively, for the development of in situ thermosensitive gel. The developed formulations were evaluated for various parameters. Results: The pH, gelation temperature, gelation time, and drug content were found to be 6.20 ± 0.026–6.37 ± 0.015, 34.25 ± 1.10–37.50 ± 1.05 °C, 1.65 ± 0.30–2.50 ± 0.55 min, and 95.58 ± 2.37–98.03 ± 1.68%, respectively. Furthermore, the optimized F3 formulation showed satisfactory gelling capacity (9.52 ± 0.513 h) and an acceptable mucoadhesive strength (1110.65 ± 6.87 dyne/cm2). Diffusion of the drug through the egg membrane depended on the formulation’s viscosity, and the F3 formulation explained the first-order release kinetics, indicating concentration-dependent drug diffusion with n < 0.45 (0.398) value, indicating the Fickian-diffusion (diffusional case I). The pharmacokinetic study was performed with male Wistar albino rats, and the F3 in situ thermosensitive risperidone gel confirmed significantly (p < 0.05) ~5.4 times higher brain AUC0–∞ when administered intranasally compared to the oral solution. Conclusions: Based on physicochemical, in vitro, and in vivo parameters, it can be concluded that in situ thermosensitive gel is suitable for administration of risperidone through the nasal route and can enhance patient compliance through ease of application and with less repeated administration. Full article
(This article belongs to the Section Pharmaceutical Technology)
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17 pages, 2228 KB  
Article
Formulation and In Vitro Characterization of Cellulose-Based Propranolol Hydrochloride Sustained Release Matrix Tablets
by Aashish Khadka, Bhupendra Raj Giri, Rishiram Baral, Shailendra Shakya and Ashwinee Kumar Shrestha
BioChem 2025, 5(2), 14; https://doi.org/10.3390/biochem5020014 - 30 May 2025
Cited by 1 | Viewed by 2465
Abstract
Background/Objectives: Propranolol HCl (PPH), a nonselective beta-adrenergic receptor blocker, is employed as an anti-hypertensive, anti-anginal, anti-arrhythmic, and anti-migraine agent. Given its utility in chronic conditions, developing a sustained-release dosage form becomes imperative to optimize therapeutic outcomes while enhancing patient adherence and minimizing side [...] Read more.
Background/Objectives: Propranolol HCl (PPH), a nonselective beta-adrenergic receptor blocker, is employed as an anti-hypertensive, anti-anginal, anti-arrhythmic, and anti-migraine agent. Given its utility in chronic conditions, developing a sustained-release dosage form becomes imperative to optimize therapeutic outcomes while enhancing patient adherence and minimizing side effects. In this study, we employed a widely adopted matrix-based system to develop PPH sustained-release (PPH-SR) matrix tablets, ensuring the uniform dispersion of the drug within the polymeric matrix to regulate its release rate. Methods: Utilizing cellulose-based polymers, specifically HPMC K100M and ethyl cellulose (EC), as matrix formers, nine different formulations were prepared at varying drug-to-polymer ratios. We employed a wet granulation method, followed by compression of the dried granules, to fabricate round-shaped biconvex PPH-SR tablets. Results: Among these different formulations, formulation 2 (F2), comprising 40 mg PPH and 50 mg HPMC K100M (along with other excipients), showed excellent flowability, as evidenced by Carr’s index and angle of repose values of 12.50 and 28.50, respectively. Additionally, the mechanical properties of F2 tablets showed a hardness of 12.34 ± 0.91 KP, an average weight of 200.45 ± 1.87 mg, with a friability of 0.20%, and a content uniformity of 98.36%. Moreover, in vitro release characteristics of F2 tablets demonstrated a sustained-release behavior, with 94.3 ± 10.2% drug release over 24 h. A comparative analysis with marketed tablets yielded similarity and dissimilarity factors of 64 and 8, respectively. Furthermore, the release profile of F2 exhibited a high degree of linearity with the Korsmeyer–Peppas model (R2 of 0.977), showcasing its reliability and predictability. Conclusions: In essence, this in-house developed PPH sustained-release formulation can improve patient adherence, reduce side effects, and improve therapeutic outcomes. These results align with our objective of enhancing the therapeutic efficacy of PPH and affirm the broader relevance of innovative formulation strategies in addressing the challenges of chronic disease management. Full article
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21 pages, 4835 KB  
Article
Development of Glycerosomal pH Triggered In Situ Gelling System to Ameliorate the Nasal Delivery of Sulpiride for Pediatric Psychosis
by Mona M. Shahien, Alia Alshammari, Somaia Ibrahim, Enas Haridy Ahmed, Hanan Abdelmawgoud Atia, Hemat A. Elariny and Marwa H. Abdallah
Gels 2024, 10(9), 608; https://doi.org/10.3390/gels10090608 - 23 Sep 2024
Cited by 6 | Viewed by 2269
Abstract
Sulpiride (Sul) is a medication that blocks dopamine D2 receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim [...] Read more.
Sulpiride (Sul) is a medication that blocks dopamine D2 receptors. It is used to treat gastrointestinal disturbances and has antipsychotic effects depending on the dose given. Sulpiride is subject to P-glycoprotein efflux, resulting in limited bioavailability and erratic absorption. Hence, the aim of this study was to generate a glycerosomal in situ gel of sulpiride for intranasal administration, specifically targeting children with schizophrenia who may have difficulty swallowing traditional solid medications, for enhancing its bioavailability. This study aimed to demonstrate the efficacy of intranasal administration of glycerin-encapsulated lipid-nanovesicles (glycerosomes) mixed with in situ gels for prolonged release of anti-psychotic medication. A Box–Behnken design was utilized to create sulpiride-loaded glycerosomes (Sul-GMs), with the lipid amount (A), glycerin concentration (B), and sonication time (C) acting as independent variables. Their impact on the entrapment efficiency, EE% (Y1), and in vitro drug release (Y2) were evaluated. The sulpiride EE% showed an increase when the glycerin concentration was raised to 25% v/v. Nevertheless, when the glycerin concentration was raised to 40% v/v, there was a notable decrease in the EE%. The optimized glycerosome was added to pH triggered carbopol 974P in situ gel formulations including HPMC K15M with different concentrations. The in situ gel formulation (G3) comprising 0.6% carbopol 974P and 0.6% hydroxypropyl methyl cellulose-K15M (HPMC K15M) demonstrated suitable pH, viscosity, desired gel strength, spreadability, and mucoadhesive strength. Consequently, it was selected for in vitro study, ex vivo permeation investigation, and in vivo evaluations. The glycerosomal in situ gel exhibited favorable ex vivo permeability of SU when applied to the nasal mucosa. The pharmacokinetic investigation revealed that the optimized Sul-loaded glycerosomal in situ gel exhibited a significant fourfold and twofold enhancement in systemic bioavailability compared to both the control gel and the commercially available formulation. Finally, the intranasal administration of Sul-loaded glycerosomal in situ gel is a promising alternative to oral treatment for pediatric patients with psychosis. Full article
(This article belongs to the Special Issue Functional Gels Applied in Drug Delivery)
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13 pages, 2912 KB  
Article
Effect of Cremophor RH40, Hydroxypropyl Methylcellulose, and Mixing Speed on Physicochemical Properties of Films Containing Nanostructured Lipid Carriers Loaded with Furosemide Using the Box–Behnken Design
by Pakorn Kraisit, Namon Hirun, Premjit Limpamanoch, Yongthida Sawaengsuk, Narumol Janchoochai, Ornpreeya Manasaksirikul and Sontaya Limmatvapirat
Polymers 2024, 16(11), 1605; https://doi.org/10.3390/polym16111605 - 5 Jun 2024
Cited by 7 | Viewed by 3207
Abstract
This study aimed to examine the characteristics of H-K4M hydroxypropyl methylcellulose (HPMC) films containing nanostructured lipid carriers (NLCs) loaded with furosemide. A hot homogenization technique and an ultrasonic probe were used to prepare and reduce the size of the NLCs. Films were made [...] Read more.
This study aimed to examine the characteristics of H-K4M hydroxypropyl methylcellulose (HPMC) films containing nanostructured lipid carriers (NLCs) loaded with furosemide. A hot homogenization technique and an ultrasonic probe were used to prepare and reduce the size of the NLCs. Films were made using the casting technique. This study used a Box–Behnken design to evaluate the influence of three key independent variables, specifically H-K4M concentration (X1), surfactant Cremophor RH40 concentration (X2), and mixing speed (X3), on the physicochemical properties of furosemide-loaded NLCs and films. The furosemide-loaded NLCs had a particle size ranging from 54.67 to 99.13 nm, and a polydispersity index (PDI) ranging from 0.246 to 0.670. All formulations exhibited a negative zeta potential, ranging from −7.05 to −5.61 mV. The prepared films had thicknesses and weights ranging from 0.1240 to 0.2034 mm and 0.0283 to 0.0450 g, respectively. The drug content was over 85%. Film surface wettability was assessed based on the contact angle, ranging from 32.27 to 68.94°. Film tensile strength varied from 1.38 to 7.77 MPa, and their elongation at break varied from 124.19 to 170.72%. The ATR-FTIR analysis confirmed the complete incorporation of the drug in the film matrix. Therefore, the appropriate selection of values for key parameters in the synthesis of HPMC films containing drug-loaded NLCs is important in the effective development of films for medical applications. Full article
(This article belongs to the Special Issue Smart and Bio-Medical Polymers)
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16 pages, 2927 KB  
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 10 | Viewed by 2985
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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26 pages, 4744 KB  
Article
Tailoring Risperidone-Loaded Glycethosomal In Situ Gels Using Box–Behnken Design for Treatment of Schizophrenia-Induced Rats via Intranasal Route
by Marwa H. Abdallah, Hemat El-Sayed El-Horany, Hanan M. El-Nahas and Tarek M. Ibrahim
Pharmaceutics 2023, 15(11), 2521; https://doi.org/10.3390/pharmaceutics15112521 - 24 Oct 2023
Cited by 14 | Viewed by 2319
Abstract
Schizophrenic patients often face challenges with adherence to oral regimens. The study aimed to highlight the potentiality of intranasal ethanol/glycerin-containing lipid-nanovesicles (glycethosomes) incorporated into in situ gels for sustaining anti-psychotic risperidone (RS) release. The Box–Behnken Design (BBD) was followed for in vitro characterization. [...] Read more.
Schizophrenic patients often face challenges with adherence to oral regimens. The study aimed to highlight the potentiality of intranasal ethanol/glycerin-containing lipid-nanovesicles (glycethosomes) incorporated into in situ gels for sustaining anti-psychotic risperidone (RS) release. The Box–Behnken Design (BBD) was followed for in vitro characterization. Glycethosomal-based in situ gels were examined by physical, ex vivo, and in vivo investigations. The ethanol impact on minimizing the vesicle size (VS) and enhancing the zeta potential (ZP) and entrapment efficiency (EE%) of nanovesicles was observed. Glycerin displayed positive action on increasing VS and ZP of nanovesicles, but reduced their EE%. After incorporation into various mucoadhesive agent-enriched poloxamer 407 (P407) in situ gels, the optimized gel containing 20% P407 and 1% hydroxypropyl methyl cellulose-K4M (HPMC-K4M) at a 4:1 gel/glycethosomes ratio showed low viscosity and high spreadability with acceptable pH, gel strength, and mucoadhesive strength ranges. The ethanol/glycerin mixture demonstrated a desirable ex vivo skin permeability of RS through the nasal mucosa. By pharmacokinetic analysis, the optimized gel showed eight-fold and three-fold greater increases in RS bioavailability than the control gel and marketed tablet, respectively. Following biochemical assessments of schizophrenia-induced rats, the optimized gel boosted the neuroprotective, anti-oxidant, and anti-inflammatory action of RS in comparison to other tested preparations. Collectively, the intranasal RS-loaded glycethosomal gel offered a potential substitute to oral therapy for schizophrenic patients. Full article
(This article belongs to the Special Issue Hydrogel Systems for Efficient Drug Delivery)
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11 pages, 4476 KB  
Article
Study on the Leaching Kinetics of Weathered Crust Elution-Deposited Rare Earth Ores by Hydroxypropyl Methyl Cellulose
by Huifang Yang, Aoyang Sha, Zhengyan He, Chenjie Wu, Yuanlai Xu, Jingjing Hu, Zhigao Xu and Ruan Chi
Minerals 2023, 13(9), 1156; https://doi.org/10.3390/min13091156 - 31 Aug 2023
Cited by 3 | Viewed by 1633
Abstract
In the process of the in situ leaching of weathered crust elution-deposited rare earth ores (WCE-DREOs), there are many problems in the conventional leaching agent, such as a slow leaching rate, low leaching yield and long leaching period. In order to solve the [...] Read more.
In the process of the in situ leaching of weathered crust elution-deposited rare earth ores (WCE-DREOs), there are many problems in the conventional leaching agent, such as a slow leaching rate, low leaching yield and long leaching period. In order to solve the above problems, 2.0 wt% ammonium sulfate was mixed with hydroxypropyl methyl cellulose (HPMC). The effects of the HPMC concentration, temperature, pH and flow rate on the leaching kinetics of rare earth (RE) and aluminum (Al) were investigated. The results showed that when the concentration of HPMC was 0.05 wt%, the leaching equilibrium time of RE and Al was about 60% shorter than that of single ammonium sulfate. With an increase in the leaching temperature, the leaching equilibrium time of RE and Al decreased, and the apparent activation energy of RE and Al was 23.13 kJ/mol and 17.31 kJ/mol, respectively. The leaching process was in line with the internal diffusion kinetic control model. When the pH of the leaching agent was 4.02~8.01, the leaching yield of RE and Al was basically the same, but the leaching yield of Al was greatly increased at pH 2.0 due to a large amount of adsorbed hydroxy-Al in the RE ore eluded. The leaching yield reached the maximum when the flow rate was 0.7 mL/min. The leaching time and the leaching cost of RE can be saved by the composite leaching agent. The results provide theoretical guidance for the development and industrial application of the new composite leaching agent. Full article
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20 pages, 5422 KB  
Article
Comparative Evaluation of the Powder and Tableting Properties of Regular and Direct Compression Hypromellose from Different Vendors
by Nihad Mawla, Maen Alshafiee, John Gamble, Mike Tobyn, Lande Liu, Karl Walton, Barbara R. Conway, Peter Timmins and Kofi Asare-Addo
Pharmaceutics 2023, 15(8), 2154; https://doi.org/10.3390/pharmaceutics15082154 - 17 Aug 2023
Cited by 6 | Viewed by 3661
Abstract
Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can [...] Read more.
Hypromellose, a widely used polymer in the pharmaceutical industry, is available in several grades, depending on the percentage of substitution of the methoxyl and hydroxypropyl groups and molecular weight, and in various functional forms (e.g., suitable for direct compression tableting). These differences can affect their physicomechanical properties, and so this study aims to characterise the particle size and mechanical properties of HPMC K100M polymer grades from four different vendors. Eight polymers (CR and DC grades) were analysed using scanning electron microscopy (SEM) and light microscopy automated image analysis particle characterisation to examine the powder’s particle morphology and particle size distribution. Bulk density, tapped density, and true density of the materials were also analysed. Flow was determined using a shear cell tester. Flat-faced polymer compacts were made at five different compression forces and the mechanical properties of the compacts were evaluated to give an indication of the powder’s capacity to form a tablet with desirable strength under specific pressures. The results indicated that the CR grades of the polymers displayed a smaller particle size and better mechanical properties compared to the DC grade HPMC K100M polymers. The DC grades, however, had better flow properties than their CR counterparts. The results also suggested some similarities and differences between some of the polymers from the different vendors despite the similarity in substitution level, reminding the user that care and consideration should be given when substitution is required. Full article
(This article belongs to the Collection Feature Papers in Pharmaceutical Technology)
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26 pages, 17953 KB  
Article
Bulk Flow Optimisation of Amorphous Solid Dispersion Excipient Powders through Surface Modification
by Danni Suhaidi, Yao-Da Dong, Paul Wynne, Karen P. Hapgood and David A. V. Morton
Pharmaceutics 2023, 15(5), 1447; https://doi.org/10.3390/pharmaceutics15051447 - 9 May 2023
Cited by 3 | Viewed by 3555
Abstract
Particulate amorphous solid dispersions (ASDs) have been recognised for their potential to enhance the performance of various solid dose forms, especially oral bioavailability and macromolecule stability. However, the inherent nature of spray-dried ASDs leads to their surface cohesion/adhesion, including hygroscopicity, which hinders their [...] Read more.
Particulate amorphous solid dispersions (ASDs) have been recognised for their potential to enhance the performance of various solid dose forms, especially oral bioavailability and macromolecule stability. However, the inherent nature of spray-dried ASDs leads to their surface cohesion/adhesion, including hygroscopicity, which hinders their bulk flow and affects their utility and viability in terms of powder production, processing, and function. This study explores the effectiveness of L-leucine (L-leu) coprocessing in modifying the particle surface of ASD-forming materials. Various contrasting prototype coprocessed ASD excipients from both the food and pharmaceutical industries were examined for their effective coformulation with L-leu. The model/prototype materials included maltodextrin, polyvinylpyrrolidone (PVP K10 and K90), trehalose, gum arabic, and hydroxypropyl methylcellulose (HPMC E5LV and K100M). The spray-drying conditions were set such that the particle size difference was minimised, so that it did not play a substantial role in influencing powder cohesion. Scanning electron microscopy was used to evaluate the morphology of each formulation. A combination of previously reported morphological progression typical of L-leu surface modification and previously unreported physical characteristics was observed. The bulk characteristics of these powders were assessed using a powder rheometer to evaluate their flowability under confined and unconfined stresses, flow rate sensitivities, and compactability. The data showed a general improvement in maltodextrin, PVP K10, trehalose and gum arabic flowability measures as L-leu concentrations increased. In contrast, PVP K90 and HPMC formulations experienced unique challenges that provided insight into the mechanistic behaviour of L-leu. Therefore, this study recommends further investigations into the interplay between L-leu and the physico-chemical properties of coformulated excipients in future amorphous powder design. This also revealed the need to enhance bulk characterisation tools to unpack the multifactorial impact of L-leu surface modification. Full article
(This article belongs to the Special Issue Recent Advances in Secondary Processing of Pharmaceutical Powders)
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18 pages, 6774 KB  
Article
Study on Preparation and Rheological Properties of 3D Printed Pre-Foaming Concrete
by Yanan Gao, Sudong Hua and Hongfei Yue
Appl. Sci. 2023, 13(9), 5303; https://doi.org/10.3390/app13095303 - 24 Apr 2023
Cited by 11 | Viewed by 3220
Abstract
The high fluidity and low yield stress of fresh foam concrete affect the shape stability and buildability of foam concrete in the printing process, which is quite a challenge to its application in digital construction. Therefore, this article proposes the preparation and characteristics [...] Read more.
The high fluidity and low yield stress of fresh foam concrete affect the shape stability and buildability of foam concrete in the printing process, which is quite a challenge to its application in digital construction. Therefore, this article proposes the preparation and characteristics of 3D printed pre-foaming concrete (3DFC). The rheological properties proved that the addition of 0.1 wt.% Hydroxypropyl methyl cellulose (HPMC) to 3DFCs weakens the fluidity but increases the static yield stress and apparent viscosity, thus enhancing the buildability. More importantly, the influences of surfactant on the rheological property, compressive strength, pore structure and thermal conductivity of 3DFCs were evaluated. Analysis results show that the static yield stress of 3DFCs decreases from 1735 to 687 Pa with surfactant dosage from 0 to 2 wt.%. Moreover, the addition of surfactant significantly reduced the apparent viscosity of 3DFCs (especially at low shear rates), but its viscosity recovery rate was basically unchanged, which is good for buildability. Thanks to the increase of porosity, the volume density of 3DFCs decreased from 2211 to 1159 kg/m3, but the compressive strength of 3DFCs also decreased slightly. The thermal conductivity of 3DFCs shows good thermal insulation performance in the range of 0.2254–0.2879 W/m·K, which is also due to the increase in porosity of 3DFCs. Finally, in order to verify the practical application value of 3DFCs, an industrial printing product with more than 30 layers during the field application is displayed. Full article
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29 pages, 3584 KB  
Article
Lyophilized Nasal Inserts of Atomoxetine HCl Solid Lipid Nanoparticles for Brain Targeting as a Treatment of Attention-Deficit/Hyperactivity Disorder (ADHD): A Pharmacokinetics Study on Rats
by Mahmoud H. Teaima, Merhan Taha El-Nadi, Raghda Rabe Hamed, Mohamed A. El-Nabarawi and Rehab Abdelmonem
Pharmaceuticals 2023, 16(2), 326; https://doi.org/10.3390/ph16020326 - 20 Feb 2023
Cited by 13 | Viewed by 5507
Abstract
The study aims to investigate the ability of lyophilized nasal inserts of nanosized atomoxetine HCl solid lipid nanoparticles (ATM-SLNs) to transport atomoxetine (ATM) directly to the brain and overcome the first-pass metabolism. In this case, 16 formulae of (ATM-SLNs) were prepared using hot [...] Read more.
The study aims to investigate the ability of lyophilized nasal inserts of nanosized atomoxetine HCl solid lipid nanoparticles (ATM-SLNs) to transport atomoxetine (ATM) directly to the brain and overcome the first-pass metabolism. In this case, 16 formulae of (ATM-SLNs) were prepared using hot melt emulsification, stirring and ultrasonication method technique. A full factorial design was established with 24 trials by optimization of four variables; lipid type (Compritol 888 ATO or stearic acid) (X1), lipid to drug ratio [(1:2) or (2:1)] (X2), span 60: Pluronic f127 ratio [(1:3) or (3:1)] (X3) and probe sonication time (five or ten minutes) (X4). The prepared SLNs were characterized for entrapment efficiency (EE%), in-vitro drug release after 30 min (Q30min), particle size (PS), zeta potential (ZP) and polydispersity index (PDI). Design Expert® software was used to select the optimum two formulae. The morphological examination for the optimum two formulae was carried out using a transmission electron microscope (TEM). Furthermore, eight lyophilized nasal inserts were prepared by using a 23 full factorial design by optimization of three variables: type of (ATM-SLNs) formula (X1), type of polymer (NOVEON AA1 or HPMC K100m) (X2) and concentration of polymer (X3). They were evaluated for nasal inserts’ physicochemical properties. The two optimum inserts were selected by Design Expert® software. The two optimum insets with the highest desirability values were (S4 and S8). They were subjected to DSC thermal stability study and in-vivo study on rats. They were compared with atomoxetine oral solution, atomoxetine (3 mg/kg, intraperitoneal injection) and the pure atomoxetine solution loaded in lyophilized insert. (ATM-SLNs) showed EE% range of (41.14 mg ± 1.8% to 90.6 mg ± 2.8%), (Q30min%) of (27.11 ± 5.9% to 91.08 ± 0.15%), ZP of (−8.52 ± 0.75 to −28.4 ± 0.212% mV), PS of (320.9 ± 110.81% nm to 936.7 ± 229.6% nm) and PDI of (0.222 ± 0.132% to 0.658 ± 0.03%). Additionally, the two optimum (ATM-SLNs) formulae chosen, i.e., F7 and F9 showed spherical morphology. Nasal inserts had assay of drug content of (82.5 ± 2.5% to 103.94 ± 3.94%), Q15min% of (89.9 ± 6.4% to 100%) and Muco-adhesion strength of (3510.5 ± 140.21 to 9319.5 ± 39.425). DSC results of S4 and S8 showed compatibility of (ATM) with the other excipients. S8 and S4 also showed higher trans-nasal permeation to the brain with brain targeting efficiency of (211.3% and 177.42%, respectively) and drug transport percentages of (52.7% and 43.64%, respectively). To conclude, lyophilized nasal inserts of (ATM-SLNs) enhanced (ATM) trans-nasal drug targeting permeation and brain targeting efficiency. Full article
(This article belongs to the Special Issue Brain Theranostics: Focus on Drug Delivery and Outcomes)
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18 pages, 2657 KB  
Article
Clarithromycin and Pantoprazole Gastro-Retentive Floating Bilayer Tablet for the Treatment of Helicobacter Pylori: Formulation and Characterization
by Ghufran Ullah, Asif Nawaz, Muhammad Shahid Latif, Kifayat Ullah Shah, Saeed Ahmad, Fatima Javed, Mulham Alfatama, Siti Aisyah Abd Ghafar and Vuanghao Lim
Gels 2023, 9(1), 43; https://doi.org/10.3390/gels9010043 - 4 Jan 2023
Cited by 11 | Viewed by 6227
Abstract
Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs [...] Read more.
Bilayer/multilayer tablets have been introduced to formulate incompatible components for compound preparations, but they are now more commonly used to tailor drug release. This research aimed to formulate a novel gastro-retentive tablet to deliver a combination of a fixed dose of two drugs to eliminate Helicobacter pylori (H. pylori) in the gastrointestinal tract. The bilayer tablets were prepared by means of the direct compression technique. The controlled-release bilayer tablets were prepared using various hydrophilic swellable polymers (sodium alginate, chitosan, and HPMC-K15M) alone and in combination to investigate the percent of swelling behavior and average drug release. The weight of the controlled-release floating layer was 500 mg, whereas the weight of the floating tablets of pantoprazole was 100 mg. To develop the most-effective formulation, the effects of the experimental components on the floating lag time, the total floating time, T 50%, and the amount of drug release were investigated. The drugs’ and excipients’ compatibilities were evaluated using ATR-FTIR and DSC. Pre-compression and post-compression testing were carried out for the prepared tablets, and they were subjected to in vitro characterization studies. The pantoprazole layer of the prepared tablet demonstrated drug release (95%) in 2 h, whereas clarithromycin demonstrated sustained drug release (83%) for up to 24 h (F7). The present study concluded that the combination of sodium alginate, chitosan, and HPMC polymers (1:1:1) resulted in a gastro-retentive and controlled-release drug delivery system of the drug combination. Thus, the formulation of the floating bilayer tablets successfully resulted in a biphasic drug release. Moreover, the formulation (F7) offered the combination of two drugs in a single-tablet formulation containing various polymers (sodium alginate, chitosan, and HPMC polymers) as the best treatment option for local infections such as gastric ulcers. Full article
(This article belongs to the Special Issue Engineering Hydrogel for Biomedical Applications)
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