Hierarchical Macro-Mesoporous Silica Monolithic Tablets as a Novel Dose-Structure-Dependent Delivery System for the Release of Confined Dexketoprofen.

This study reports the application of hierarchical porous monoliths as carriers for controlled and dose-adjustable release of model pharmaceutical (dexketoprofen, DEX). The synthesis and detailed characterization of the hierarchical porous scaffolds are provided before and after the adsorption of three doses of DEX─a widely used nonsteroidal anti-inflammatory drug. The drug incorporated in the mesopores of silica was stabilized in an amorphous state, while the presence of macropores provided sufficient space for drug crystallization as we demonstrated via a combination of powder X-ray diffraction, differential scanning calorimetry, and imaging techniques (scanning electron microscopy and EDX analysis). Drug release from silica matrices was tested, and a mechanistic model of this release based on the Fick diffusion equation was proposed. The hierarchical structure of the carrier, due to the presence of micrometric macropores and nanometric mesopores, turned out to be critical for the control of the drug phase and drug release from the monoliths. It was found that at low drug content, the presence of an amorphous component in the pores promoted the rapid release of the drug, while at higher drug contents, the presence of macropores favored the crystallization of DEX, which naturally slowed down its release. Both the hierarchical porous structure and the control of the drug phase (amorphous and/or crystalline) were proven important for adjustable (fast or prolonged) release kinetics, desirable for effective pharmacotherapy and patient compliance. Therefore, the developed materials may serve as a versatile formulation platform for the smart manipulation of drug release kinetics.

The Importance of Chitosan Coatings in Dentistry.

A Chitosan is a copolymer of N-acetyl-D-glucose amine and D-glucose amine that can be easily produced. It is a polymer that is widely utilized to create nanoparticles (NPs) with specific properties for applications in a wide range of human activities. Chitosan is a substance with excellent prospects due to its antibacterial, anti-inflammatory, antifungal, haemostatic, analgesic, mucoadhesive, and osseointegrative qualities, as well as its superior film-forming capacity. Chitosan nanoparticles (NPs) serve a variety of functions in the pharmaceutical and medical fields, including dentistry. According to recent research, chitosan and its derivatives can be embedded in materials for dental adhesives, barrier membranes, bone replacement, tissue regeneration, and antibacterial agents to improve the management of oral diseases. This narrative review aims to discuss the development of chitosan-containing materials for dental and implant engineering applications, as well as the challenges and future potential. For this purpose, the PubMed database (Medline) was utilised to search for publications published less than 10 years ago. The keywords used were "chitosan coating" and "dentistry". After carefully selecting according to these keywords, 23 articles were studied. The review concluded that chitosan is a biocompatible and bioactive material with many benefits in surgery, restorative dentistry, endodontics, prosthetics, orthodontics, and disinfection. Furthermore, despite the fact that it is a highly significant and promising coating, there is still a demand for various types of coatings. Chitosan is a semi-synthetic polysaccharide that has many medical applications because of its antimicrobial properties. This article aims to review the role of chitosan in dental implantology.

Directing Crystallization Outcomes of Conformationally Flexible Molecules: Polymorphs, Solvates, and Desolvation Pathways of Fluconazole.

Control over polymorphism and solvatomorphism in API assisted by structural information, e.g., molecular conformation or associations via hydrogen bonds, is crucial for the industrial development of new drugs, as the crystallization products differ in solubility, dissolution profile, compressibility, or melting temperature. The stability of the final formulation and technological factors of the pharmaceutical powders further emphasize the importance of precise crystallization protocols. This is particularly important when working with highly flexible molecules with considerable conformational freedom and a large number of hydrogen bond donors or acceptors (e.g., fluconazole, FLU). Here, cooling and suspension crystallization were applied to access polymorphs and solvates of FLU, a widely used azole antifungal agent with high molecular flexibility and several reported polymorphs. Each of four polymorphic forms, FLU I, II, III, or IV, can be obtained from the same set of alcohols (MeOH, EtOH, isPrOH) and DMF via careful control of the crystallization conditions. For the first time, two types of isostructural channel solvates of FLU were obtained (nine new structures). Type I solvates were prepared by cooling crystallization in Tol, ACN, DMSO, BuOH, and BuON. Type II solvates formed in DCM, ACN, nPrOH, and BuOH during suspension experiments. We propose desolvation pathways for both types of solvates based on the structural analysis of the newly obtained solvates and their desolvation products. Type I solvates desolvate to FLU form I by hydrogen-bonded chain rearrangements. Type II solvates desolvation leads first to an isomorphic desolvate, followed by a phase transition to FLU form II through hydrogen-bonded dimer rearrangement. Combining solvent-mediated phase transformations with structural analysis and solid-state NMR, supported by periodic electronic structure calculations, allowed us to elucidate the interrelations and transformation pathways of FLU.

Molecular Level Characterisation of the Surface of Carbohydrate-Functionalised Mesoporous silica Nanoparticles (MSN) as a Potential Targeted Drug Delivery System via High Resolution Magic Angle Spinning (HR-MAS) NMR Spectroscopy.

Atomistic level characterisation of external surface species of mesoporous silica nanoparticles (MSN) poses a significant analytical challenge due to the inherently low content of grafted ligands. This study proposes the use of HR-MAS NMR spectroscopy for a molecular level characterisation of the external surface of carbohydrate-functionalised nanoparticles. MSN differing in size (32 nm, 106 nm, 220 nm) were synthesised using the sol-gel method. The synthesised materials displayed narrow particle size distribution (based on DLS and TEM results) and a hexagonal arrangement of the pores with a diameter of ca. 3 nm as investigated with PXRD and N2 physisorption. The surface of the obtained nanoparticles was functionalised with galactose and lactose using reductive amination as confirmed by FTIR and NMR techniques. The functionalisation of the particles surface did not alter the pore architecture, structure or morphology of the materials as confirmed with TEM imaging. HR-MAS NMR spectroscopy was used for the first time to investigate the structure of the functionalised MSN suspended in D2O. Furthermore, lactose was successfully attached to the silica without breaking the glycosidic bond. The results demonstrate that HR-MAS NMR can provide detailed structural information on the organic functionalities attached at the external surface of MSN within short experimental times.

Ophthalmic Nanoemulsions: From Composition to Technological Processes and Quality Control.

Nanoemulsions are considered as the most promising solution to improve the delivery of ophthalmic drugs. The design of ophthalmic nanoemulsions requires an extensive understanding of pharmaceutical as well as technological aspects related to the selection of excipients and formulation processes. This Review aims at providing the readers with a comprehensive summary of possible compositions of nanoemulsions, methods for their formulation (both laboratory and industrial), and differences between technological approaches, along with an extensive outline of the research methods enabling the confirmation of in vitro properties, pharmaceutical performance, and biological activity of the obtained product. The composition of the formulation has a major influence on the properties of the final product obtained with low-energy emulsification methods. Increasing interest in high-energy emulsification methods is a consequence of their scalability important from the industrial perspective. Considering the high-energy emulsification methods, both the composition and conditions of the process (e.g., device power level, pressure, temperature, homogenization time, or number of cycles) are important for the properties and stability of nanoemulsions. It is advisible to determine the effect of each parameter on the quality of the product to establish the optimal process parameters' range which, in turn, results in a more reproducible and efficient production.

Emulsion-Based Multicompartment Vaginal Drug Carriers: From Nanoemulsions to Nanoemulgels.

In order to overcome the limitations associated with vaginal administration of drugs, e.g., the short contact time of the drug form with the mucosa or continuous carrier wash-out, the development of new carriers for gynecological use is necessary. Furthermore, high individual anatomical and physiological variability resulting in unsatisfactory therapeutic efficacy of lipophilic active substances requires application of multicompartment drug delivery systems. This manuscript provides an up-to-date comprehensive review of the literature on emulsion-based vaginal dosage forms (EVDF) including macroemulsions, microemulsions, nanoemulsions, multiple emulsions and self-emulsifying drug delivery systems. The first part of the paper discusses (i) the influence of anatomical-physiological conditions on therapeutic efficacy of drug forms after local and systemic administration, (ii) characterization of EVDF components and the manufacturing techniques of these dosage forms and (iii) methods used to evaluate the physicochemical and pharmaceutical properties of emulsion-based vaginal dosage forms. The second part of the paper presents (iv) the results of biological and in vivo studies as well as (v) clinical evaluation of EVDF safety and therapeutic efficacy across different indications.

Physicochemical and Antifungal Properties of Clotrimazole in Combination with High-Molecular Weight Chitosan as a Multifunctional Excipient.

Chitosans represent a group of multifunctional drug excipients. Here, we aimed to estimate the impact of high-molecular weight chitosan on the physicochemical properties of clotrimazole-chitosan solid mixtures (CL-CH), prepared by grinding and kneading methods. We characterised these formulas by infrared spectroscopy, differential scanning calorimetry, and powder X-ray diffractometry, and performed in vitro clotrimazole dissolution tests. Additionally, we examined the antifungal activity of clotrimazole-chitosan mixtures against clinical Candida isolates under neutral and acid conditions. The synergistic effect of clotrimazole and chitosan S combinations was observed in tests carried out at pH 4 on Candida glabrata strains. The inhibition of C. glabrata growth reached at least 90%, regardless of the drug/excipient weight ratio, and even at half of the minimal inhibitory concentrations of clotrimazole. Our results demonstrate that clotrimazole and high-molecular weight chitosan could be an effective combination in a topical antifungal formulation, as chitosan acts synergistically with clotrimazole against non-albicans candida strains.

Development of the rectal dosage form with silver-coated glass beads for local-action applications in lower sections of the gastrointestinal tract.

CONTEXT: Recent findings indicating the anti-inflammatory action of silver preparations through modulation of the gut microbiota and apoptosis of inflammatory cells predestine silver use in inflammatory bowel disease (IBD). OBJECTIVE: The aim of our study was to validate the possibility of effective silver release from silver-coated glass beads for anti-inflammatory local application in the lower sections of the gastrointestinal (GI) tract. MATERIALS AND METHODS: Silver-coated glass beads were prepared using magnetron method. Release of silver from the silver-coated glass bead surface was carried out in BIO-DIS reciprocating cylinder apparatus. Erosion of silver coating and indirect estimation of the silver release dynamics was assessed using scanning electron microscope. Rectal suppositories containing silver-coated glass beads were prepared using five different methods (M1-M5) and X-ray scanned for their composition. RESULTS AND DISCUSSION: The XR microanalysis and the chemical composition analysis evidenced for a rapid (within 30 min) release of nearly 50% of silver from the coating of the glass beads, which remained stable up to 24 h of incubation. The most homogeneous distribution of beads in the entire volume of the suppository was obtained for formulation M5, where the molten base was poured into mold placed in an ice bath, and the beads were added after 10 s. CONCLUSIONS: Our study is the first to present the concept of enclosing silver-coated glass beads in the lipophilic suppository base to attenuate inflammation in the lower GI tract and promises efficient treatment with reduced side effects.

PROSPECTS FOR DEVELOPMENT OF PHARMACY IN POLAND UNTIL THE YEAR 2030. THE DOCUMENT OF THE NATIONAL SECTION OF PHARMACEUTICAL CARE OF THE POLISH PHARMACEUTICAL SOCIETY.

Modern society expects pharmacists to be more involved in monitoring and supervising pharmacotherapy. International documents clearly define pharmacists as guardians of the safety and effectiveness of pharmacotherapy, not coincidentally putting safety matters first. With regard to this issue, the National Section of Pharmaceutical Care of the Polish Pharmaceutical Society hereby presents its own proposal for the development of modern pharmaceutical practice in Poland. The purpose of the proposed actions is to increase the involvement of pharmacists from generally accessible pharmacies in ensuring the safety and effectiveness of pharmacotherapy applied outside of hospitals and improving health indicators within society over the next ten to twenty years.

A review of polymers as multifunctional excipients in drug dosage form technology.

In the article, groups of multifunctional polymers used in drug dosage form technology were classified and evaluated. These compounds, in addition to their basic function as excipients, may have additional properties, e.g. stimuli sensitivity, enzyme inhibition, intestinal epithelium penetration enhancement, efflux pump inhibition, taste-masking, pharmacological activity and the ability to interact with enzymes responsible for drug metabolism. While classifying specific groups of multifunctional polymers, special emphasis was placed on the advantages of using them when designing new drug. Such advantages include, i.a., increasing substance bioavailability, improving substance stability during formulation and the possibility of obtaining forms of controlled or localized release to a specific site in the organism.

SELECTED ASPECTS OF TERAHERTZ SPECTROSCOPY IN PHARMACEUTICAL SCIENCES.

THz-TDS techniques are applied to investigate selected pharmaceutical samples. Investigations were performed on selected pharmaceutical samples with active pharmaceutical ingredients (API)--famotidine, ranitidine, fenofibrate, lovastatin, simvastatin, aspirin, ketoconazole, acyclovir (hydrated and non-hydrated), on excipients--lactose, glucose (hydrated and non-hydrated), Pluronic 127, and on mixtures of selected compounds. Pseudo-polymorphism effects are considered as well. Examples of the terahertz imaging technique are also given. APIs and excipients can be easily recognized in the terahertz band by their specific "fingerprints" as individual components and in mixtures. The hydration process as a variety of polymorphism can also be easily monitored using the THz technique. Moreover, terahertz light can be useful for the penetration of tablets, giving clear pictures of possible defects in tablet coatings.

Ophthalmic drug dosage forms: characterisation and research methods.

This paper describes hitherto developed drug forms for topical ocular administration, that is, eye drops, ointments, in situ gels, inserts, multicompartment drug delivery systems, and ophthalmic drug forms with bioadhesive properties. Heretofore, many studies have demonstrated that new and more complex ophthalmic drug forms exhibit advantage over traditional ones and are able to increase the bioavailability of the active substance by, among others, reducing the susceptibility of drug forms to defense mechanisms of the human eye, extending contact time of drug with the cornea, increasing the penetration through the complex anatomical structure of the eye, and providing controlled release of drugs into the eye tissues, which allows reducing the drug application frequency. The rest of the paper describes recommended in vitro and in vivo studies to be performed for various ophthalmic drugs forms in order to assess whether the form is acceptable from the perspective of desired properties and patient's compliance.

Stability Studies of Amorphous Ibrutinib Prepared Using the Quench-Cooling Method and Its Dispersions with Soluplus®.

The successful development of an amorphous form of a drug demands the use of process conditions and materials that reduce their thermodynamic instability. For the first time, we have prepared amorphous ibrutinib using the quench-cooling method with very high process efficiency. In the presented study, different formulations of amorphous active pharmaceutical ingredient (API) with Soluplus (SOL) in various weight ratios 1:9, 3:7, and 1:1 were prepared. The obtained samples were stored under long-term (25 ± 2 °C/60%RH ± 5% RH, 12 months) and accelerated (40 ± 2 °C/75%RH ± 5% RH, 6 months) storage conditions. The physical stability of amorphous ibrutinib and ibrutinib-Soluplus formulations was analyzed using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), powder X-ray diffraction analysis (XRPD), Fourier transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM). The lack of significant interactions between the ingredients of the formulation was confirmed by FTIR analysis. An increase in moisture content with an increasing SOL weight ratio was observed under accelerated aging and long-term conditions. Additionally, a slight increase in the moisture content of the stored sample compared to that at the initial time was observed. The results revealed the physical strength of the polymeric systems in the presence of high humidity and temperature. The observed high thermal stability allows the use of various technological processes without the risk of thermal degradation.

PVA-based formulations as a design-technology platform for orally disintegrating film matrices.

In the majority of pharmaceutical applications, polymers are employed extensively in a diverse range of pharmaceutical products, serving as indispensable components of contemporary solid oral dosage forms. A comprehensive understanding of the properties of polymers and selection the appropriate methods of characterization is essential for the design and development of novel drug delivery systems and manufacturing processes. Orally disintegrating film (ODF) formulations are considered to be a potential substitute to traditional oral dosage forms and an alternative method of drug administration for children and uncooperative adult patients, including those with swallowing difficulties. A multitude of pharmaceutical formulations with varying mechanical and biopharmaceutical properties have emerged from the modification of the original polymeric bulk. Here we propose different formulation approaches, i.e. solvent casting (SC), 3D printing (3DP), electrospinning (ES), and lyophilization (LP) that enabled us to adjust the disintegration time and the release profile of poorly water soluble haloperidol (HAL, BCS class II) from PVA (polyvinyl alcohol) based polymer films while maintaining similar hydrogel composition. In this study, the solubility of haloperidol in aqueous solution was improved by the addition of lactic acid. The prepared films were evaluated for their morphology (SEM, micro-CT), physicochemical and biopharmaceutical properties. TMDSC, TGA and PXRD were employed for extensive thermal and structural analysis of fabricated materials and their stability. These results allowed us to establish correlations between preparation technology, structural characteristics and properties of PVA films and to adapt the suitable manufacturing technique of the ODFs to achieve appropriate HAL dissolution behaviour.

Pluronic F-127 Enhances the Antifungal Activity of Fluconazole against Resistant Candida Strains.

Candida strains as the most frequent causes of infections, along with their increased drug resistance, pose significant clinical and financial challenges to the healthcare system. Some polymeric excipients were reported to interfere with the multidrug resistance mechanism. Bearing in mind that there are a limited number of marketed products with fluconazole (FLU) for the topical route of administration, Pluronic F-127 (PLX)/FLU formulations were investigated in this work. The aims of this study were to investigate (i) whether PLX-based formulations can increase the susceptibility of resistant Candida strains to FLU, (ii) whether there is a correlation between block polymer concentration and the antifungal efficacy of the FLU-loaded PLX formulations, and (iii) what the potential mode of action of PLX assisting FLU is. The yeast growth inhibition upon incubation with PLX formulations loaded with FLU was statistically significant. The highest efficacy of the azole agent was observed in the presence of 5.0 and 10.0% w/v of PLX. The upregulation of the CDR1/CDR2 genes was detected in the investigated Candida strains, indicating that the efflux of the drug from the fungal cell was the main mechanism of the resistance.

Technological Aspects and Evaluation Methods for Polymer Matrices as Dental Drug Carriers.

The development of polymer matrices as dental drug carriers takes into account the following technological aspects of the developed formulations: the composition and the technology used to manufacture them, which affect the properties of the carriers, as well as the testing methods for assessing their behavior at application sites. The first part of this paper characterizes the methods for fabricating dental drug carriers, i.e., the solvent-casting method (SCM), lyophilization method (LM), electrospinning (ES) and 3D printing (3DP), describing the selection of technological parameters and pointing out both the advantages of using the mentioned methods and their limitations. The second part of this paper describes testing methods to study the formulation properties, including their physical and chemical, pharmaceutical, biological and in vivo evaluation. Comprehensive in vitro evaluation of carrier properties permits optimization of formulation parameters to achieve prolonged retention time in the dynamic oral environment and is essential for explaining carrier behavior during clinical evaluation, consequently enabling the selection of the optimal formulation for oral application.

Assessment of the Prescribing Pharmacist's Role in Supporting Access to Prescription-Only Medicines-Metadata Analysis in Poland.

In 2020, pharmacists in Poland received additional authority to prescribe drugs. In this study, we analyzed prescribing after the implementation of this new responsibility. We assessed how the new regulation works in practice and what it means for the healthcare system in the area of access to prescription-only medicines. Data analysis included information on the prescriptions written, the type of substance according to the ATC classification, and data on the prescribing pharmacists. The study used over 2.994 million e-prescriptions written by pharmacists in Poland, which were made available by the e-Health Center. The largest group of drugs prescribed were drugs used in the treatment of cardiovascular diseases, accounting for 25% of all prescribed medications during the time of the analysis. The next prescription groups were for drugs used in gastrointestinal diseases and metabolic disorders, and those acting on the central nervous system, the respiratory system, and the musculoskeletal system. Among pharmaceutical prescriptions, 73% were pharmaceutical prescriptions issued in pharmacies at full price to the patient. The results indicate that pharmacists are eager to use their permission to prescribe drugs in authority situations. Almost three million records showed improved patient access to medicines in the healthcare system (approximately 5% of repeat prescriptions for all patients during the study period). These data confirm the possibility of cooperation between physicians and pharmacists in strengthening the efficiency of the patient healthcare system. An important conclusion from this work is the need to create the possibility for the pharmacist to access the information resources of the implemented Internet Patient Account system, including therapeutic indications for the drugs used.

Screening of Fenofibrate-Simvastatin Solid Dispersions in the Development of Fixed-Dose Formulations for the Treatment of Lipid Disorders.

The combination of statins and fibrates in the treatment of lipid abnormalities effectively regulates individual lipid fraction levels. In this study, the screening and assessment of the physicochemical properties of simvastatin-fenofibrate solid dispersions were performed. Fenofibrate and simvastatin were processed using the kneading method in different weight ratios, and the resulting solid dispersions were assessed using differential scanning calorimetry (DSC), X-ray powder diffractometry (XRPD), Fourier-transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), contact angle, as well as dissolution tests. The obtained results confirmed the formation of a simple eutectic phase diagram, with a eutectic point containing 79 wt% fenofibrate and 21 wt% simvastatin, lack of chemical interactions between the ingredients, and simvastatin impact on improving fenofibrate dissolution profile, due to the formation of crystalline solid dispersions by the kneading method.

Oral Wound Healing Potential of Polygoni Cuspidati Rhizoma et Radix Decoction-In Vitro Study.

Polygoni Cuspidati Rhizoma et Radix (syn. rhizomes of Reynoutria japonica Houtt.) is a pharmacopoeial raw material in Europe and China. In traditional medicine, one of the applications for Reynoutria japonica rhizomes is wound healing. In a recent in vitro study, we demonstrated that ethanol and acetone extracts from this herbal drug have the potential to heal oral gum wounds. However, considering that a majority of herbal medicines have been traditionally administered as water decoctions, in the present study, a decoction of Reynoutria japonica rhizomes was prepared and detailed tests to determine its in vitro gingival wound healing activity were conducted. We used the primary human gingival fibroblasts (HGF) incubated with a decoction to determine cell viability (MTT assay), cell proliferation (the confocal laser scanning microscope-CLSM), and cell migration (wound healing assay). Moreover, the collagen type III expression was examined using immunocytochemical staining. The studied decoction was qualitatively and quantitatively characterized using the validated HPLC/DAD/ESI-HR-QTOF-MS method. The Folin-Ciocalteu assay was used to determine the total phenols and tannins content. Additionally, HPLC-RI analysis of decoction and the previously obtained ethanol and acetone extracts was used to determine the composition of saccharides. Low concentration (from 50 to 1000 µg/mL) of decoction after 24 h incubation caused a significant increase in HGF cell viability. No cytotoxic effect was observed at any tested concentration (up to 2000 µg/mL). The lowest active concentration of decoction (50 µg/mL) was selected for further experiments. It significantly stimulated human gingival fibroblasts to proliferate, migrate, and increase the synthesis of collagen III. Phytochemical analysis showed significantly fewer polyphenols in the decoction than in the ethanol and acetone extracts tested earlier. In contrast, high levels of polysaccharides were observed. In our opinion, they may have a significant effect on the oral wound healing parameters analyzed in vitro. The results obtained encourage the use of this raw material in its traditional, safe form-decoction.

The Effect of High-Pressure Homogenization Conditions on the Physicochemical Properties and Stability of Designed Fluconazole-Loaded Ocular Nanoemulsions.

The growing interest in high-energy emulsification is a result of its scalability, which is important from an industrial perspective and allows for a more reproducible and efficient production of pharmaceutical formulations. The aim of this study was to evaluate the effect of composition, mainly a fixed surfactant/cosurfactant (Smix) ratio, their concentration, and the parameters of high-pressure homogenization (HPH) processing on the quality and stability of ophthalmic fluconazole-loaded nanoemulsions. After a physicochemical analysis of nanoemulsions containing 20% w/w of oil, as optimal conditions for the HPH process, three cycles at a pressure of 1000 bar were established, obtaining formulations with an average droplet diameter size in the range of 80.63-129.68 nm and PDI values below 0.25. While it was expected that an increasing cosurfactant concentration decreased the droplet size, in the case of formulations containing Tween 20 and 10% w/w of cosurfactants, "over-processing" was observed, identified by the droplet size and polydispersity index increase. Consecutively, the selected formulations were evaluated for in vitro drug release in Franz's cell, antifungal activity, and 30-day stability using NMR spectroscopy. An antifungal activity test showed no significant difference in the antifungal activity between optimal fluconazole-loaded nanoemulsions and a 0.3% aqueous drug solution, but previously, research showed that prepared formulations were characterized by a higher viscosity and satisfactory prolonged release compared to a control. In a 30-day stability study, it was observed that higher HLB values of the used surfactants decreased the stability of the formulations in the following order: Kolliphor EL, Tween 80, Tween 20. The NMR spectra confirmed that Kolliphor EL-based formulations ensured the higher stability of the nanoemulsion composition in comparison to Tween 80 and a better stabilizing effect of propylene glycol as a cosurfactant in comparison to PEG 200. Therefore, the optimization of HPH technology should be focused on the selection of Smix and the Smix:oil ratio in order to prepare stable formulations of high quality.