Advanced Pharmaceutical Research in the Czech Republic

Editors


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Guest Editor
Faculty of Chemical Technology, University of Chemistry and Technology Prague, Technická 5, 166 28 Prague, Czech Republic
Interests: dermal and transdermal application; skin barrier characterization; drug nanoformulation; drug targeting; application of biophysical techniques in pharmaceutics

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Guest Editor
Department of Pharmaceutical Technology, Pharmaceutical Faculty, Masaryk University, Palackého třída 1946/1, 61200 Brno, Czech Republic
Interests: microparticles for lung application; 2D and 3D printing of pharmaceutics; in situ forming gels; innovative processes and materials in pharmaceutical technology

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Guest Editor
Department of Pharmaceutical Technology, Pharmaceutical Faculty, Masaryk University, Palackého třída 1946/1, 61200 Brno, Czech Republic
Interests: microparticle/bead drug delivery systems; advanced drug delivery for veterinary use; biorelevant dynamic dissolution; controlled release formulation for oral drug delivery

Topical Collection Information

Dear Colleagues,

In recent decades, pharmaceutical sciences and engineering have come to represent a rapidly developing area in the Czech Republic. The aim of this regional issue is to bring an overview of the progress in this field. Researchers from both the academic and industrial spheres are welcome to submit their research or review articles focused on preformulation and formulation development, drug delivery, nanoparticulate formulation, polymer science, biopharmaceutics and pharmacokinetics, personalized medicine, or other related topics.

We intend to create a high-quality collection presenting novel results and attitudes. Moreover, we believe the issue will contribute to the discussion on these exciting topics and help to form new scientific collaborations.

Dr. Jarmila Zbytovska
Dr. Jan Gajdziok
Dr. Jakub Vysloužil
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the collection website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceutics is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • preformulation and formulation development
  • drug delivery
  • nanoparticulate formulation
  • polymer science
  • biopharmaceutics and pharmacokinetics
  • personalized medicine

Related Special Issue

Published Papers (16 papers)

2023

Jump to: 2022, 2021

26 pages, 4074 KiB  
Article
The Contest of Nanoparticles: Searching for the Most Effective Topical Delivery of Corticosteroids
by Aneta Kalvodová, Kristýna Dvořáková, Eliška Petrová, Bozena B. Michniak-Kohn and Jarmila Zbytovská
Pharmaceutics 2023, 15(2), 513; https://doi.org/10.3390/pharmaceutics15020513 - 3 Feb 2023
Cited by 3 | Viewed by 2507
Abstract
Owing to their complicated pathophysiology, the treatment of skin diseases necessitates a complex approach. Conventional treatment using topical corticosteroids often results in low effectiveness and the incidence of local or even systemic side effects. Nanoformulation of potent anti-inflammatory drugs has been selected as [...] Read more.
Owing to their complicated pathophysiology, the treatment of skin diseases necessitates a complex approach. Conventional treatment using topical corticosteroids often results in low effectiveness and the incidence of local or even systemic side effects. Nanoformulation of potent anti-inflammatory drugs has been selected as an optimal strategy for enhanced topical delivery of corticosteroids. In order to assess the efficiency of various nanoformulations, we formulated hydrocortisone (HC) and hydrocortisone-17-butyrate (HCB) into three different systems: lipid nanocapsules (LNC), polymeric nanoparticles (PNP), and ethosomes (ETZ). The systems were characterized using dynamic light scattering for their particle size and uniformity and the morphology of nanoparticles was observed by transmission electron microscopy. The nanosystems were tested using ex vivo full thickness porcine and human skin for the delivery of HC and HCB. The skin penetration was observed by confocal microscopy of fluorescently labelled nanosystems. ETZ were proposed as the most effective delivery system for both transdermal and dermal drug targeting but were also found to have a profound effect on the skin barrier with limited restoration. LNC and PNP were found to have significant effects in the dermal delivery of the actives with only minimal transdermal penetration, especially in case of HCB administration. Full article
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16 pages, 6111 KiB  
Article
Optimization of Spray Drying Process Parameters for the Preparation of Inhalable Mannitol-Based Microparticles Using a Box-Behnken Experimental Design
by Jakub Karas, Sylvie Pavloková, Hana Hořavová and Jan Gajdziok
Pharmaceutics 2023, 15(2), 496; https://doi.org/10.3390/pharmaceutics15020496 - 2 Feb 2023
Cited by 9 | Viewed by 2950
Abstract
Inhalation is used for local therapy of the lungs and as an alternative route for systemic drug delivery. Modern powder inhalation systems try to target the required site of action/absorption in the respiratory tract. Large porous particles (LPPs) with a size >5 μm [...] Read more.
Inhalation is used for local therapy of the lungs and as an alternative route for systemic drug delivery. Modern powder inhalation systems try to target the required site of action/absorption in the respiratory tract. Large porous particles (LPPs) with a size >5 μm and a low mass density (usually measured as bulk or tapped) of <0.4 g/cm3 can avoid protective lung mechanisms. Their suitable aerodynamic properties make them perspective formulations for deep lung deposition. This experiment studied the effect of spray-drying process parameters on LPP properties. An experimental design of twelve experiments with a central point was realized using the Box–Behnken method. Three process parameters (drying temperature, pump speed, and air speed) were combined on three levels. Particles were formed from a D-mannitol solution, representing a perspective material for lung microparticles. The microparticles were characterized in terms of physical size (laser diffraction), aerodynamic diameter (aerodynamic particle sizer), morphology (SEM), and densities. The novelty and main goal of this research were to describe how the complex parameters of the spray-drying process affect the properties of mannitol LPPs. New findings can provide valuable data to other researchers, leading to the easy tuning of the properties of spray-dried particles by changing the process setup. Full article
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2022

Jump to: 2023, 2021

19 pages, 2874 KiB  
Article
Development and Comparison of Various Coated Hard Capsules Suitable for Enteric Administration to Small Patient Cohorts
by Nicole Fülöpová, Sylvie Pavloková, Ivan DeBono, David Vetchý and Aleš Franc
Pharmaceutics 2022, 14(8), 1577; https://doi.org/10.3390/pharmaceutics14081577 - 29 Jul 2022
Cited by 12 | Viewed by 3743
Abstract
Pharmaceutical technology offers several options for protecting substances from acidic environments, such as encapsulation in enteric capsules or dosage form with enteric coating. However, commercial enteric capsules do not always meet limits for pharmacopeial delayed release, and the coating process is generally challenging. [...] Read more.
Pharmaceutical technology offers several options for protecting substances from acidic environments, such as encapsulation in enteric capsules or dosage form with enteric coating. However, commercial enteric capsules do not always meet limits for pharmacopeial delayed release, and the coating process is generally challenging. Preparing small enteric batches suitable for clinical use is, therefore, an unsolved problem. This experiment offers a simple coating process of DRcapsTM capsules based on hypromellose (HPMC) and gellan gum to achieve small intestine administration. In addition, DRcapsTM capsules were compared to hard gelatin capsules to evaluate the suitability of the coating method. Both capsules were immersed in dispersions of Eudragit® S 100, Acryl-EZE®, and Cellacefate at concentrations of 10.0, 15.0, and 20.0% and dried. Coated capsules were evaluated by electron microscopy, disintegration, and dissolution test with a two-step pH change (from 1.2 to 6.8, then to 7.5) to simulate passage through the digestive tract. DRcapsTM capsules coated with Eudragit® S and Cellacefate achieved acid resistance. While samples coated with Eudragit® S released their contents within 360 min at pH 6.8 (small intestine), regardless of polymer concentration, capsules with 15.0 and 20.0% coatings of Cellacefate released content at pH 7.5 (colon) within 435 and 495 min, respectively. Full article
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21 pages, 4798 KiB  
Article
Rational Design of Self-Emulsifying Pellet Formulation of Thymol: Technology Development Guided by Molecular-Level Structure Characterization and Ex Vivo Testing
by Jan Macku, Katerina Kubova, Martina Urbanova, Jan Muselik, Ales Franc, Gabriela Koutna, Miroslava Pavelkova, David Vetchy, Josef Masek, Eliska Maskova and Jiri Brus
Pharmaceutics 2022, 14(8), 1545; https://doi.org/10.3390/pharmaceutics14081545 - 25 Jul 2022
Cited by 3 | Viewed by 2495
Abstract
The growing need for processing natural lipophilic and often volatile substances such as thymol, a promising candidate for topical treatment of intestinal mucosa, led us to the utilization of solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for the rational design of enteric pellets with [...] Read more.
The growing need for processing natural lipophilic and often volatile substances such as thymol, a promising candidate for topical treatment of intestinal mucosa, led us to the utilization of solid-state nuclear magnetic resonance (ss-NMR) spectroscopy for the rational design of enteric pellets with a thymol self-emulsifying system (SES). The SES (triacylglycerol, Labrasol®, and propylene glycol) provided a stable o/w emulsion with particle size between 1 and 7 µm. The ex vivo experiment confirmed the SES mucosal permeation and thymol delivery to enterocytes. Pellets W90 (MCC, Neusilin®US2, chitosan) were prepared using distilled water (90 g) by the M1–M3 extrusion/spheronisation methods varying in steps number and/or cumulative time. The pellets (705–740 µm) showed mostly comparable properties—zero friability, low intraparticular porosity (0–0.71%), and relatively high density (1.43–1.45%). They exhibited similar thymol release for 6 h (burst effect in 15th min ca. 60%), but its content increased (30–39.6 mg/g) with a shorter process time. The M3-W90 fluid-bed coated pellets (Eudragit®L) prevented undesirable thymol release in stomach conditions (<10% for 3 h). A detailed, ss-NMR investigation revealed structural differences across samples prepared by M1–M3 methods concerning system stability and internal interactions. The suggested formulation and methodology are promising for other lipophilic volatiles in treating intestinal diseases. Full article
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18 pages, 2069 KiB  
Article
Comparative Study of Powder Carriers Physical and Structural Properties
by Klára Kostelanská, Barbora Blahová Prudilová, Sylva Holešová, Jakub Vlček, David Vetchý and Jan Gajdziok
Pharmaceutics 2022, 14(4), 818; https://doi.org/10.3390/pharmaceutics14040818 - 8 Apr 2022
Cited by 16 | Viewed by 3776
Abstract
High specific surface area (SSA), porous structure, and suitable technological characteristics (flow, compressibility) predetermine powder carriers to be used in pharmaceutical technology, especially in the formulation of liquisolid systems (LSS) and solid self-emulsifying delivery systems (s-SEDDS). Besides widely used microcrystalline cellulose, other promising [...] Read more.
High specific surface area (SSA), porous structure, and suitable technological characteristics (flow, compressibility) predetermine powder carriers to be used in pharmaceutical technology, especially in the formulation of liquisolid systems (LSS) and solid self-emulsifying delivery systems (s-SEDDS). Besides widely used microcrystalline cellulose, other promising materials include magnesium aluminometasilicates, mesoporous silicates, and silica aerogels. Clay minerals with laminar or fibrous internal structures also provide suitable properties for liquid drug incorporation. This work aimed at a comparison of 14 carriers’ main properties. Cellulose derivatives, silica, silicates, and clay minerals were evaluated for flow properties, shear cell experiments, SSA, hygroscopicity, pH, particle size, and SEM. The most promising materials were magnesium aluminometasilicates, specifically Neusilin® US2, due to its proper flow, large SSA, etc. Innovative materials such as FujiSil® or Syloid® XDP 3050 were for their properties evaluated as suitable. The obtained data can help choose a suitable carrier for formulations where the liquid phase is incorporated into the solid dosage form. All measurements were conducted by the same methodology and under the same conditions, allowing a seamless comparison of property evaluation between carriers, for which available company or scientific sources do not qualify due to different measurements, conditions, instrumentation, etc. Full article
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15 pages, 2923 KiB  
Article
Formulation and Evaluation of Novel Film Wound Dressing Based on Collagen/Microfibrillated Carboxymethylcellulose Blend
by Kateřina Tenorová, Ruta Masteiková, Sylvie Pavloková, Klára Kostelanská, Jurga Bernatonienė and David Vetchý
Pharmaceutics 2022, 14(4), 782; https://doi.org/10.3390/pharmaceutics14040782 - 3 Apr 2022
Cited by 13 | Viewed by 4096
Abstract
Collagen is essential as a physiological material in wound healing, so it is often used in wound management, mainly as a lyophilisate. Collagen also has excellent film-forming properties; unfortunately, however, its utilisation as a film wound dressing is limited because of its weak [...] Read more.
Collagen is essential as a physiological material in wound healing, so it is often used in wound management, mainly as a lyophilisate. Collagen also has excellent film-forming properties; unfortunately, however, its utilisation as a film wound dressing is limited because of its weak mechanical properties, especially in its wet state. For this reason, modifications or combinations with different materials are investigated. The combination of collagen with partially modified microfibrillar carboxymethylcellulose (CMC), which has not previously been described, provided a new possibility for strengthening collagen films and was the aim of this work. The collagen–CMC films based on three types of collagens, two plasticizers and two collagen. Plasticiser ratios were prepared using the solvent casting method; partially modified CMC served here as both a film-forming agent and a filler, without compromising the transparency of the films. The presence of microfibrils was confirmed microscopically by SEM. Organoleptic and physicochemical evaluation, especially in terms of practical application on wounds, demonstrated that all the samples had satisfactory properties for this purpose even after wetting. All the films retained acidic pH values even after 24 h, with a maximum of 6.27 ± 0.17, and showed a mild degree of swelling, with a maximum of about 6 after 24 h. Full article
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12 pages, 543 KiB  
Article
Effects of Various Drying Times on the Properties of 3D Printed Orodispersible Films
by Natália Janigová, Jan Elbl, Sylvie Pavloková and Jan Gajdziok
Pharmaceutics 2022, 14(2), 250; https://doi.org/10.3390/pharmaceutics14020250 - 21 Jan 2022
Cited by 14 | Viewed by 2757
Abstract
Orodispersible films are an innovative dosage form. Their main advantages are the application comfort and the possibility of personalization. This work aimed to evaluate the influence of different drying times on the properties of orodispersible films of various thicknesses, prepared in two different [...] Read more.
Orodispersible films are an innovative dosage form. Their main advantages are the application comfort and the possibility of personalization. This work aimed to evaluate the influence of different drying times on the properties of orodispersible films of various thicknesses, prepared in two different semisolid extrusion 3D printing setups. In the first experiment, drying times were dependent on the overall print time of each batch. In the second setup, the drying time was set equal according to the longest one. The evaluated parameters were films’ weight uniformity, thickness, moisture content, surface pH, disintegration time, hardness, and tensile strength. Upon statistical comparison, significant differences in the moisture content were found, subsequently affecting the disintegration time. Moreover, statistically significant differences in films’ mechanical properties (hardness, tensile strength) were also described, proving that moisture content simultaneously affects film plasticity and related properties. In conclusion, a mutual comparison of the manufactured orodispersible films showed that the drying time affects their physical and mechanical properties. The in-process drying setup was proved to be sufficient while allowing quicker manufacturing. Full article
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20 pages, 7196 KiB  
Article
Technology of Processing Plant Extracts Using an Aluminometasilicate Porous Carrier into a Solid Dosage Form
by Klára Kostelanská, Slavomír Kurhajec, Sylvie Pavloková, David Vetchý, Jan Gajdziok and Aleš Franc
Pharmaceutics 2022, 14(2), 248; https://doi.org/10.3390/pharmaceutics14020248 - 21 Jan 2022
Cited by 6 | Viewed by 2485
Abstract
A method of preparing tablets called liquisolid technique is currently emerging. In these formulations, an important role is played by porous carriers, which are the basic building blocks of liquisolid systems (LSSs). The most common are microcrystalline cellulose (MCC), magnesium aluminometasilicates, silica aerogels, [...] Read more.
A method of preparing tablets called liquisolid technique is currently emerging. In these formulations, an important role is played by porous carriers, which are the basic building blocks of liquisolid systems (LSSs). The most common are microcrystalline cellulose (MCC), magnesium aluminometasilicates, silica aerogels, mesoporous silicates, clays, etc. In this study, magnesium aluminometasilicate is used to prepare modified LSS formulations with plant extracts as model drugs dissolved in water (W) or ethanol (E). The modification involves drying tablets in a microwave (MW) and hot air dryer (HA) for a specified period. Powder blends and tablets were evaluated for physical properties, and their antioxidant activity (AA) was measured in a modified dissolution by ferric reducing antioxidant power assay (FRAP). PLS and ANOVA were used to compare tablets properties depending on the composition and technology. The experiment is based on a previous one, in which the plant extracts were processed into tablets using a similar method. Therefore, extending the study to include more plants and the robust statistical evaluation and comparison of the products was a procedure to justify the suitability of the presented method for a wide range of liquid plant extracts. As a result, we obtained tablets with excellent physical properties, including a short disintegration and dissolution, which is problematic in tableted extracts. Full article
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18 pages, 3848 KiB  
Article
Exploration of Neusilin® US2 as an Acceptable Filler in HPMC Matrix Systems—Comparison of Pharmacopoeial and Dynamic Biorelevant Dissolution Study
by Tomáš Bílik, Jakub Vysloužil, Martina Naiserová, Jan Muselík, Miroslava Pavelková, Josef Mašek, Drahomíra Čopová, Martin Čulen and Kateřina Kubová
Pharmaceutics 2022, 14(1), 127; https://doi.org/10.3390/pharmaceutics14010127 - 5 Jan 2022
Cited by 2 | Viewed by 2568
Abstract
Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We [...] Read more.
Modern pharmaceutical technology still seeks new excipients and investigates the further use in already known ones. An example is magnesium aluminometasilicate Neusilin® US2 (NEU), a commonly used inert filler with unique properties that are usable in various pharmaceutical fields of interest. We aimed to explore its application in hypromellose matrix systems (HPMC content 10–30%) compared to the traditionally used microcrystalline cellulose (MCC) PH 102. The properties of powder mixtures and directly compressed tablets containing individual fillers NEU or MCC, or their blend with ratios of 1.5:1, 1:1, and 0.5:1 were investigated. Besides the routine pharmaceutical testing, we have enriched the matrices’ evaluation with a biorelevant dynamic dissolution study and advanced statistical analysis. Under the USP apparatus 2 dissolution test, NEU, individually, did not provide advantages compared to MCC. The primary limitations were the burst effect increase followed by faster drug release at the 10–20% HPMC concentrations. However, the biorelevant dynamic dissolution study did not confirm these findings and showed similarities in dissolution profiles. It indicates the limitations of pharmacopoeial methods in matrix tablet development. Surprisingly, the NEU/MCC blend matrices at the same HPMC concentration showed technologically advantageous properties. Besides improved flowability, tablet hardness, and a positive impact on the in vitro drug dissolution profile toward zero-order kinetics, the USP 2 dissolution data of the samples N75M50 and N50M50 showed a similarity to those obtained from the dynamic biorelevant apparatus with multi-compartment structure. This finding demonstrates the more predictable in vivo behaviour of the developed matrix systems in human organisms. Full article
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2021

Jump to: 2023, 2022

16 pages, 5984 KiB  
Article
N-Alkylmorpholines: Potent Dermal and Transdermal Skin Permeation Enhancers
by Kristýna Dvořáková, Petr Štěpánek, Jiřina Kroupová and Jarmila Zbytovská
Pharmaceutics 2022, 14(1), 64; https://doi.org/10.3390/pharmaceutics14010064 - 28 Dec 2021
Cited by 10 | Viewed by 2244
Abstract
Transdermal drug delivery is an attractive non-invasive method offering numerous advantages over the conventional routes of administration. The main obstacle to drug transport is, however, the powerful skin barrier that needs to be modulated, for example, by transdermal permeation enhancers. Unfortunately, there are [...] Read more.
Transdermal drug delivery is an attractive non-invasive method offering numerous advantages over the conventional routes of administration. The main obstacle to drug transport is, however, the powerful skin barrier that needs to be modulated, for example, by transdermal permeation enhancers. Unfortunately, there are still only a few enhancers showing optimum properties including low toxicity and reversibility of enhancing effects. For this reason, we investigated a series of new N-alkylmorpholines with various side chains as potential enhancers in an in vitro permeation study, using three model permeants (theophylline, indomethacin, diclofenac). Moreover, electrical impedance, transepidermal water loss, cellular toxicity and infrared spectroscopy measurements were applied to assess the effect of enhancers on skin integrity, reversibility, toxicity and enhancers’ mode of action, respectively. Our results showed a bell-shaped relationship between the enhancing activity and the hydrocarbon chain length of the N-alkylmorpholines, with the most efficient derivatives having 10–14 carbons for both transdermal and dermal delivery. These structures were even more potent than the unsaturated oleyl derivative. The best results were obtained for indomethacin, where particularly the C10-14 derivatives showed significantly stronger effects than the traditional enhancer Azone. Further experiments revealed reversibility in the enhancing effect, acceptable toxicity and a mode of action based predominantly on interactions with stratum corneum lipids. Full article
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27 pages, 7432 KiB  
Article
3D-Printed Coating of Extended-Release Matrix Tablets: Effective Tool for Prevention of Alcohol-Induced Dose Dumping Effect
by Barbora Skalická, Kevin Matzick, Alena Komersová, Roman Svoboda, Martin Bartoš and Luděk Hromádko
Pharmaceutics 2021, 13(12), 2123; https://doi.org/10.3390/pharmaceutics13122123 - 9 Dec 2021
Cited by 11 | Viewed by 3656
Abstract
Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of [...] Read more.
Tablets used for extended drug release commonly contain large amounts of drugs. The corresponding drug release mechanism thus has to be well-known and invariable under numerous conditions in order to prevent any uncontrolled drug release. Particularly important is the stability and invariability of the release mechanism in the presence of alcohol due to the possible occurrence of the dose dumping effect. The effect of 3D printing (3DP) coating on the drug release mechanism and the drug release rate was studied as a possible tool for the prevention of the alcohol-induced dose dumping effect. Three types of matrix tablets (hydrophilic, lipophilic, and hydrophilic-lipophilic) were prepared by the direct compression method and coated using 3DP. The commercial filament of polyvinyl alcohol (PVA) and the filament prepared from hypromellose by hot melt extrusion (HME) were used as coating materials. Both coating materials were characterized by SEM, DSC, Raman spectroscopy, and PXRD during particular stages of the processing/coating procedure. The dissolution behavior of the uncoated and coated tablets was studied in the strongly acidic (pH 1.2) and alcoholic (40% of ethanol) dissolution media. The dissolution tests in the alcoholic medium showed that the Affinisol coating was effective in preventing the dose dumping incidence. The dissolution tests in the acidic dissolution media showed that the Affinisol coating can also be useful for the delayed release of active substances. Full article
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21 pages, 7276 KiB  
Article
Systematic Study of the Effects of High Shear Granulation Parameters on Process Yield, Granule Size, and Shape by Dynamic Image Analysis
by Oliver Macho, Ľudmila Gabrišová, Peter Peciar, Martin Juriga, Róbert Kubinec, Pavol Rajniak, Petra Svačinová, Tereza Vařilová and Zdenka Šklubalová
Pharmaceutics 2021, 13(11), 1894; https://doi.org/10.3390/pharmaceutics13111894 - 8 Nov 2021
Cited by 3 | Viewed by 2555
Abstract
The aim of the work was to analyze the influence of process parameters of high shear granulation on the process yield and on the morphology of granules on the basis of dynamic image analysis. The amount of added granulation liquid had a significant [...] Read more.
The aim of the work was to analyze the influence of process parameters of high shear granulation on the process yield and on the morphology of granules on the basis of dynamic image analysis. The amount of added granulation liquid had a significant effect on all monitored granulometric parameters and caused significant changes in the yield of the process. In regard of the shape, the most spherical granules with the smoothest surface were formed at a liquid to solid ratio of ≈1. The smallest granules were formed at an impeller speed of 700 rpm, but the granules formed at 500 rpm showed both the most desirable shape and the highest process yield. Variation in the shape factors relied not only on the process parameters, but also on the area equivalent diameter of the individual granules in the batch. A linear relationship was found between the amount of granulation liquid and the compressibility of the granules. Using response surface methodology, models for predicting the size of granules and process yield related to the amount of added liquid and the impeller speed were generated, on the basis of which the size of granules and yield can be determined with great accuracy. Full article
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15 pages, 3304 KiB  
Article
Utilization of Pharmaceutical Technology Methods for the Development of Innovative Porous Metasilicate Pellets with a Very High Specific Surface Area for Chemical Warfare Agents Detection
by Jiří Zeman, Sylvie Pavloková, David Vetchý, Adam Staňo, Zdeněk Moravec, Lukáš Matějovský and Vladimír Pitschmann
Pharmaceutics 2021, 13(11), 1860; https://doi.org/10.3390/pharmaceutics13111860 - 4 Nov 2021
Cited by 4 | Viewed by 2744
Abstract
Pharmaceutical technology offers various dosage forms that can be applied interdisciplinary. One of them are spherical pellets which could be utilized as a carrier in emerging second-generation detection tubes. This detection system requires carriers with high specific surface area (SSA), which should allow [...] Read more.
Pharmaceutical technology offers various dosage forms that can be applied interdisciplinary. One of them are spherical pellets which could be utilized as a carrier in emerging second-generation detection tubes. This detection system requires carriers with high specific surface area (SSA), which should allow better adsorption of toxic substances and detection reagents. In this study, a magnesium aluminometasilicate with high SSA was utilized along with various concentrations of volatile substances (menthol, camphor and ammonium bicarbonate) to increase further the carrier SSA after their sublimation. The samples were evaluated in terms of physicochemical parameters, their morphology was assessed by scanning electron microscopy, and the Brunauer–Emmett–Teller (BET) method was utilized to measure SSA. The samples were then impregnated with a detection reagent o-phenylenediamine-pyronine and tested with diphosgene. Only samples prepared using menthol or camphor were found to show red fluorescence under the UV light in addition to the eye-visible red-violet color. This allowed the detection of diphosgene/phosgene at a concentration of only 0.1 mg/m3 in the air for samples M20.0 and C20.0 with their SSA higher than 115 m2/g, thus exceeding the sensitivity of the first-generation DT-12 detection tube. Full article
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12 pages, 1474 KiB  
Article
A Critical Overview of FDA and EMA Statistical Methods to Compare In Vitro Drug Dissolution Profiles of Pharmaceutical Products
by Jan Muselík, Alena Komersová, Kateřina Kubová, Kevin Matzick and Barbora Skalická
Pharmaceutics 2021, 13(10), 1703; https://doi.org/10.3390/pharmaceutics13101703 - 15 Oct 2021
Cited by 54 | Viewed by 6719
Abstract
A drug dissolution profile is one of the most critical dosage form characteristics with immediate and controlled drug release. Comparing the dissolution profiles of different pharmaceutical products plays a key role before starting the bioequivalence or stability studies. General recommendations for dissolution profile [...] Read more.
A drug dissolution profile is one of the most critical dosage form characteristics with immediate and controlled drug release. Comparing the dissolution profiles of different pharmaceutical products plays a key role before starting the bioequivalence or stability studies. General recommendations for dissolution profile comparison are mentioned by the EMA and FDA guidelines. However, neither the EMA nor the FDA provides unambiguous instructions for comparing the dissolution curves, except for calculating the similarity factor f2. In agreement with the EMA and FDA strategy for comparing the dissolution profiles, this manuscript provides an overview of suitable statistical methods (CI derivation for f2 based on bootstrap, CI derivation for the difference between reference and test samples, Mahalanobis distance, model-dependent approach and maximum deviation method), their procedures and limitations. However, usage of statistical approaches for the above-described methods can be met with difficulties, especially when combined with the requirement of practice for robust and straightforward techniques for data evaluation. Therefore, the bootstrap to derive the CI for f2 or CI derivation for the difference between reference and test samples was selected as the method of choice. Full article
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22 pages, 3561 KiB  
Article
Comparison of Flow and Compression Properties of Four Lactose-Based Co-Processed Excipients: Cellactose® 80, CombiLac®, MicroceLac® 100, and StarLac®
by Martin Dominik, Barbora Vraníková, Petra Svačinová, Jan Elbl, Sylvie Pavloková, Barbora Blahová Prudilová, Zdeňka Šklubalová and Aleš Franc
Pharmaceutics 2021, 13(9), 1486; https://doi.org/10.3390/pharmaceutics13091486 - 16 Sep 2021
Cited by 9 | Viewed by 5263
Abstract
The utilization of co-processed excipients (CPEs) represents a novel approach to the preparation of orally disintegrating tablets by direct compression. Flow, consolidation, and compression properties of four lactose-based CPEs—Cellactose® 80, CombiLac®, MicroceLac® 100, and StarLac®—were investigated using [...] Read more.
The utilization of co-processed excipients (CPEs) represents a novel approach to the preparation of orally disintegrating tablets by direct compression. Flow, consolidation, and compression properties of four lactose-based CPEs—Cellactose® 80, CombiLac®, MicroceLac® 100, and StarLac®—were investigated using different methods, including granulometry, powder rheometry, and tablet compaction under three pressures. Due to the similar composition and the same preparation technique (spray drying), the properties of CPEs and their compacts were generally comparable. The most pronounced differences were observed in flowability, undissolved fraction after 3 min and 24 h, energy of plastic deformation (E2), ejection force, consolidation behavior, and compact friability. Cellactose® 80 exhibited the most pronounced consolidation behavior, the lowest values of ejection force, and high friability of compacts. CombiLac® showed excellent flow properties but insufficient friability, except for compacts prepared at the highest compression pressure (182 MPa). MicroceLac® 100 displayed the poorest flow properties, lower ejection forces, and the best mechanical resistance of compacts. StarLac® showed excellent flow properties, the lowest amounts of undissolved fraction, the highest ejection force values, and the worst compact mechanical resistance. The obtained results revealed that higher compression pressures need to be used or further excipients have to be added to all tested materials in order to improve the friability and tensile strength of formed tablets, except for MicroceLac® 100. Full article
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19 pages, 2002 KiB  
Article
Structural Changes of Sodium Warfarin in Tablets Affecting the Dissolution Profiles and Potential Safety of Generic Substitution
by Jan Muselík, Martina Urbanova, Eva Bartoníčková, Jakub Palovčík, David Vetchý, Jiří Czernek, Larisa Janisova, Nadiia Velychkivska, Aleš Franc and Jiří Brus
Pharmaceutics 2021, 13(9), 1364; https://doi.org/10.3390/pharmaceutics13091364 - 30 Aug 2021
Cited by 2 | Viewed by 3988
Abstract
At present, the risk of generic substitutions in warfarin tablets is still being discussed. The aim of this study was to assess whether API interactions with commonly used excipients may affect the safety of generic replacement of warfarin sodium tablets. These interactions were [...] Read more.
At present, the risk of generic substitutions in warfarin tablets is still being discussed. The aim of this study was to assess whether API interactions with commonly used excipients may affect the safety of generic replacement of warfarin sodium tablets. These interactions were observed during an accelerated stability study, and the effect of the warfarin solid phase (crystalline/amorphous form) as well as the API particle size distribution was studied. Commercial tablets and prepared tablets containing crystalline warfarin or amorphous warfarin were used. In addition, binary mixtures of warfarin with various excipients were prepared. The structural changes before and after the stability study were monitored by dissolution test in different media, solid-state NMR spectroscopy and Raman microscopy. During the stability study, the conversion of the sodium in warfarin to its acid form was demonstrated by some excipients (e.g., calcium phosphate). This change in the solid phase of warfarin leads to significant changes in dissolution, especially with the different particle sizes of the APIs in the tablet. Thus, the choice of suitable excipients and particle sizes are critical factors influencing the safety of generic warfarin sodium tablets. Full article
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