Modeling, the Optimization of the Composition of Emulgels with Ciclopirox Olamine, and Quality Assessment.

The design and development of pharmaceutical products require specific knowledge, time, and investment. Response surface methodology (RSM) is a widely used technique in the design of experiments (DoE) to optimize various processes and products. The aim of this study was to model and produce experimental emulgels containing 1% ciclopirox olamine and to evaluate their physical, rheological, and mechanical properties and their ability to release ciclopirox olamine. The objective was to optimize the composition of the experimental emulgel containing 1% ciclopirox olamine by applying a central composite design based on selected criteria. The surfactant (polysorbate 80) had the greatest influence on the physical, rheological, and mechanical properties of the emulgels, as well as on the release of ciclopirox olamine from these systems. During the optimization process, an emulgel of optimal composition was generated containing 38.27% mineral oil, 6.56% polysorbate 80, and 55.17% hydrogel containing 1% ciclopirox olamine, meeting specified criteria (dependent variables) including the maximum flux of ciclopirox olamine, the minimum sol-gel transition temperature (Tsol/gel), and the minimum particle size of the oil phase. The oil phase particle size (D50) of this emulgel was determined to be 0.337 µm, the system Tsol/gel was 9.1 °C, and the flux of ciclopirox olamine from this gel matrix was calculated to be 1.44 mg/cm2. This emulgel of optimal composition could be used to treat fungal skin diseases.

Technological Functionalisation of Microencapsulated Genistein and Daidzein Delivery Systems Soluble in the Stomach and Intestines.

Encapsulating antioxidant-rich plant extracts, such as those found in red clover, within microcapsules helps protect them from degradation, thus improving stability, shelf life, and effectiveness. This study aimed to develop a microencapsulation delivery system using chitosan and alginate for microcapsules that dissolve in both the stomach and intestines, with the use of natural and synthetic emulsifiers. The microcapsules were formed using the extrusion method and employing alginate or chitosan as shell-forming material. In this study, all selected emulsifiers formed Pickering (ß-CD) and traditional (white mustard extract, polysorbate 80) stable emulsions. Alginate-based emulsions resulted in microemulsions, while chitosan-based emulsions formed macroemulsions, distinguishable by oil droplet size. Although chitosan formulations with higher red clover extract (C1) concentrations showed potential, they exhibited slightly reduced firmness compared to other formulations (C2). Additionally, both alginate and chitosan formulations containing ß-CD released bioactive compounds more effectively. The combined use of alginate and chitosan microcapsules in a single pill offers an innovative way to ensure dual solubility in both stomach and intestinal environments, increasing versatility for biomedical and pharmaceutical applications.

Nutmeg Essential Oil, Red Clover, and Liquorice Extracts Microencapsulation Method Selection for the Release of Active Compounds from Gel Tablets of Different Bases.

The current study presents the most suitable method for encapsulating nutmeg essential oil with liquorice and red clover. Two widely used methods, spray-drying and freeze-drying, were employed to find the most suitable for essential oil volatile compounds' protection. Results showed that freeze-dried capsules (LM) had a higher yield (85.34%) compared to the exact formulation of spray-dried microcapsules (SDM)-45.12%. All the antioxidant and total phenolic compounds' results obtained with the LM sample were significantly higher compared with SDM. LM microcapsules were incorporated in two different bases with no additional sugar (gelatin and pectin) for targeted release. Pectin tablets had firmer and harder texture properties, while gelatin tablets had a more elastic texture. There was a significant impact on texture changes caused by microcapsules. Microencapsulated essential oil with extracts can be used alone or in a gel base (pectin or gelatin, depending on user preferences). It could be an effective product to protect the active volatile compounds and regulate the release of active compounds and give a pleasant taste.

Application of Antiviral, Antioxidant and Antibacterial Glycyrrhiza glabra L., Trifolium pratense L. Extracts and Myristica fragrans Houtt. Essential Oil in Microcapsules.

Viruses and bacteria can disrupt normal human functions; therefore, ways to use the beneficial properties of plants to promote health are constantly being researched. Plant materials that accumulate biologically active compounds can be used to create a new pharmaceutical form. This study aimed to investigate the biological activity of selected plant extracts and essential oil and to produce microcapsules. The main compounds in extracts and essential oil were determined using chromatographic methods, antioxidant activity was evaluated spectrophotometrically, antimicrobial activity was assessed by monitoring the growth of nine pathogens, and the antiviral effect on infected bird cells with coronavirus was evaluated. Trifolium pratense L. extract had the highest antioxidant (26.27 ± 0.31 and 638.55 ± 9.14 µg TE/g dw by the DPPH and ABTS methods, respectively) and antiviral activity (56 times decreased titre of virus). Liquorice extract expressed antibacterial activity against Gram-positive pathogens and the highest antioxidant activity using the FRAP method (675.71 ± 4.61 mg FS/g dw). Emulsion stability depended on excipients and their amount. Microcapsules with extracts and essential oil were 1.87 mm in diameter, and their diameter after swelling was increased more than two times in intestinal media, while less than 0.5 times in gastric media.

Assessment of Physical, Mechanical, Biopharmaceutical Properties of Emulgels and Bigel Containing Ciclopirox Olamine.

Emulsions are thermodynamically unstable systems and it is difficult to produce biphasic formulations with large amounts of oil. The aim of our study was to prepare biphasic formulations containing 1% ciclopirox olamine and to determine the influence of the method of oil incorporation (without and with emulsifier and gelifier) on the physical (pH, particle size, rheological properties), mechanical, and biopharmaceutical properties of the formulations. It was found that the use of a poloxamer 407 gel as the hydrophase could result in a stable formulation when an oil with (EPG) or without an emulsifier (APG) or oleogel (OPG) was used as the oily phase. The results of the studies showed that the addition of an emulsifier (polysorbate 80) led to a decrease in the sol-gel temperature, a slower release of ciclopirox olamine, and a higher stability in the freeze-thaw test. However, regardless of the way the oil is incorporated, the particles are distributed in the same range and the antifungal activity against T. rubrum is the same. It is possible to create a biphasic formulation with a large amount of oil and poloxamer gel, but for greater stability, it is recommended to include an emulsifier in the composition.

Development of Innovative Chewable Gel Tablets Containing Nutmeg Essential Oil Microcapsules and Their Physical Properties Evaluation.

Chewable gel tablets are a dosed pharmaceutical form, which can have an active substance, pharmacological effect, or value of nutrition. The texture of these tablets is soft, springy, flexible, and elastic-this is influenced by the chosen ingredients. The aim of this study was to prepare chewable gel tablets with nutmeg essential oil-loaded microcapsules and determine the volatile compounds released from this pharmaceutical form. Gel tablets were prepared by using gelatin as basis, nutmeg essential oil as active compound, and natural ingredients: thyme-sugar syrup, thyme extract, and citric acid as taste and color additives. Texture properties were measured by a texture analyzer. The release of volatile compounds from nutmeg essential oil and gel tablets were analyzed by headspace-gas chromatography with mass spectroscopy in control and artificial saliva conditions in vitro. Nutmeg essential oil microcapsules had influence on the gel tablet's physical properties (p < 0.05, by comparing tablets without glycerol and relative sample with glycerol); glycerol protects the tablets from the formation of sugar crystals on top and keeps good physical parameters (p < 0.05). A total of 12 volatile compounds were identified in nutmeg essential oil, and the six compounds with the highest amounts were selected as controls. Gel tablets prolong the release time of volatile compounds and reduce the amount of the compounds compared to the microcapsules (p < 0.05).

The Effect of Myristica fragrans on Texture Properties and Shelf-Life of Innovative Chewable Gel Tablets.

Chewable gel tablets are an underdeveloped subject, even though there are many simple chewable tablets and gummy candies in the food and pharmaceutical industries. Chewable gel tablets are not as sweet, they can have an active substance, pharmacological effect, and a value of nutrition. The aim of this study was to prepare gelatin-based chewable tablets with Myristica fragrans as a preservative and to determine the shelf-life variability depending on storage conditions, and to evaluate texture changes. Firmness and springiness of gel tablets were measured by a texture analyzer and compared between different storage conditions and the shelf-life of tablets was established by mold growing time. Chewable gel tablets were prepared by using silicone form. Mold was most likely to grow on tablets that have been packaged in squeezable bags (after 14 days 60% of all formulations had a mold, p < 0.05). The most stable tablets (over 180 days) were in sealed boxes and contained nutmeg essential oil or its solution, or ethanolic nutmeg extract. The gel tablets' firmness increased about 4 times when they were stored in opened plastic boxes and their springiness decreased about 1.65 times after 28 days in the mentioned conditions, p < 0.05. Nutmeg hydrolat had the highest influence on texture variation (p < 0.05).

The effect of nutmeg essential oil constituents on Novikoff hepatoma cell viability and communication through Cx43 gap junctions.

Essential oils from plants are a potential source of molecules having anti-inflammatory, anticancer, cardiotropic, and other activities. However, most of these effects lack mechanistic explanations and structure-activity relationship testing. In the present study, we: 1) identified the nutmeg essential oil (NEO) composition; 2) using molecular docking, we determined the putative regulatory binding sites on the connexin 43 (Cx43) that is responsible for gap junction-dependent intercellular communication (GJIC) in the majority of tissues; 3) examined the effect of NEO and its three constituents - sabinene, α-pinene, and α-copaene - on GJ conductance and gating in Novikoff cells expressing endogenous Cx43; and 4) verified whether NEO effects on GJIC correlated with its action on Novikoff cell viability, proliferation, and colony formation capability. Our results revealed NEO and its constituents as potent and efficient Cx43 GJ inhibitors acting by slow gating mechanism. In addition, NEO reduced Novikoff hepatoma cell viability, proliferation, and colony formation capability; however, this was achieved at higher doses and was unrelated to its effects on GJIC.

Development of New Formula Microcapsules from Nutmeg Essential Oil Using Sucrose Esters and Magnesium Aluminometasilicate.

Essential oils are volatile liquids which evaporate and lose their pharmacological effect when exposed to the environment. The aim of this study is to protect nutmeg essential oil from environmental factors by encapsulation (shell material, sodium alginate) and determine the influence of crosslinker concentration (2%, 5% calcium chloride), different emulsifiers (polysorbate 80, sucrose esters), and magnesium aluminometasilicate on microcapsule physical parameters, encapsulation efficiency (EE), swelling index (SI), and other parameters. Nutmeg essential oil (NEO)-loaded calcium alginate microcapsules were prepared by extrusion. The swelling test was performed with and without enzymes in simulated gastric, intestinal, and gastrointestinal media. This study shows that the crosslinker concentration has a significant influence on EE, with 2% calcium chloride solution being more effective than 5%, and capsules being softer with 2% crosslinker solution. Using sucrose esters, EE is higher when polysorbate 80 is used. The swelling index is nearly three times higher in an intestinal medium without enzymes than in the medium with pancreatin. Microcapsule physical parameters depend on the excipients: the hardest capsules were obtained with the biggest amount of sodium alginate; the largest with magnesium aluminometasilicate. Sucrose esters and magnesium aluminometasilicate are new materials used in extrusion.

The Essential Oil and Hydrolats from Myristica fragrans Seeds with Magnesium Aluminometasilicate as Excipient: Antioxidant, Antibacterial, and Anti-inflammatory Activity.

Nutmeg (Myristica fragrans) essential oil has antimicrobial, antiseptic, antiparasitic, anti-inflammatory, and antioxidant properties. We have recently demonstrated that hydrodistillation of nutmeg essential oil by applying magnesium aluminometasilicate as an excipient significantly increases both the content and amount of bioactive substances in the oil and hydrolats. In this study, we aimed to compare the antioxidant, antimicrobial, and anti-inflammatory activity of hydrolats and essential oil obtained by hydrodistillation in the presence and absence of magnesium aluminometasilicate as an excipient. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging method revealed that magnesium aluminometasilicate did not significantly improved antioxidant activity of both essential oil and hydrolat. Antibacterial efficiency was evaluated by monitoring growth of 15 bacterial strains treated by a range of dilutions of the essential oil and the hydrolats. Essential oil with an excipient completely inhibited the growth of E. faecalis, S. mutans (referent), and P. multocida, whereas the pure oil was only efficient against the latter strain. Finally, the anti-inflammatory properties of the substances were assessed in a fibroblast cell culture treated with viral dsRNR mimetic Poly I:C. The essential oil with an excipient protected cells against Poly I:C-induced necrosis more efficiently compared to pure essential oil. Also, both the oil and the hydrolats with aluminometasilicate were more efficient in preventing IL-6 release in the presence of Poly I:C. Our results show that the use of magnesium aluminometasilicate as an excipient might change and in some cases improve the biological activities of nutmeg essential oil and hydrolats.

GC-MS Analysis of the Composition of the Extracts and Essential Oil from Myristica fragrans Seeds Using Magnesium Aluminometasilicate as Excipient.

Myristica fragrans (f. Myristicaceae) seeds are better known as a spice, but their chemical compounds may have a pharmacological effect. The yield of their composition of extracts and essential oils differs due to different methodologies. The aim of this study was to evaluate an excipient material-magnesium aluminometasilicate-and to determine its influence on the qualitative composition of nutmeg extracts and essential oils. Furthermore, we wanted to compare the yield of essential oil. The extracts were prepared by maceration (M) and ultrasound bath-assisted extraction (UAE), and the essential oil-by hydrodistillation (HD). Conventional methods (UAE, HD) were modified with magnesium aluminometasilicate. The samples were analyzed by gas chromatography-mass spectrometry (GC-MS) method. From 16 to 19 chemical compounds were obtained using UAE with magnesium aluminometasilicate, while only 8 to 13 compounds were obtained using UAE without an excipient. Using our conditions and plant material, for the first time eight new chemical compounds in nutmeg essential oil were identified. Two of these compounds (γ-amorphene and cis-α-bergamotene) were obtained with the use of excipient, the other six (ß-copaene, bergamotene, citronellyl decanoate, cubebol, cubenene, orthodene) by conventional hydrodistillation. Magnesium aluminometasilicate significantly increased the quantity of sabinene (from 6.53% to 61.42%) and limonene (from 0% to 5.62%) in essential oil. The yield of the essential oil from nutmeg seeds was significantly higher using magnesium aluminometasilicate; it increased from 5.25 ± 0.04% to 10.43 ± 0.09%.