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This study demonstrated the impact of formic acid (FAc), a common reactive impurity in pharmaceutical excipients, on the stability of mirabegron (MB). The investigation of MB‐excipient compatibility tests revealed the formation of a new degradation product, FAc‐DP, at 0.2% after 7 days of isothermal stress at 55°C. FAc‐DP was synthesized and characterized as N‐formyl MB using liquid chromatography–mass spectrometry (LC‐MS) and both 1D and 2D nuclear magnetic resonance spectroscopy (NMR). [ABSTRACT FROM AUTHOR]

Background/Objectives: Increasing drugs' stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result. [ABSTRACT FROM AUTHOR]

Abstract The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations.

Given that interactions between the active principle and formulation excipients can modify the chemical composition, stability and bioavailability of a drug, thus compromising its effectiveness, the present study aims to evaluate the compatibility of Bromopride with commonly used pharmaceutical excipients, which has been characterized by differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FTIR) and powder X-ray diffraction. For such a purpose, samples of pure drug, 10 excipients and binary drug/excipient mixtures were analyzed in a ratio of 1:1 (m/m) by DSC, FTIR and high performance liquid chromatography (HPLC). DSC results reveal a probable interaction of Bromopride with the majority of excipients under study, except for mannitol and talc. The FTIR results indicate some interaction of BROM with all studied excipients. However, HPLC results reveal that only colloidal silicon dioxide, dicalcium phosphate dihydrated, magnesium stearate and microcrystalline cellulose were incompatible with Bromopride, as content reduction ranging between 16 and 42% was reached, and chemical interactions of excipients croscarmellose sodium, hydroxypropyl-methyl-cellulose, lactose monohydrate and polyvinylpyrrolidone with the API were not confirmed by the HPLC, despite the fact that they have been pointed out by the DSC and FTIR. The present study indicates that BROM undergoes interaction/incompatibility when mixed with colloidal silicon dioxide, dicalcium phosphate dihydrate, magnesium stearate, and microcrystalline cellulose. [ABSTRACT FROM AUTHOR]

The use of lactose and cow milk protein (CMP) as potential allergens in pharmaceuticals and their ability to cause allergic reactions remains a significant concern in medicine. Lactose, a common pharmaceutical excipient due to its inert, inexpensive, and stable properties, is found in many prescription-only and over-the-counter medications. However, despite their widespread use, individuals with lactose intolerance (LI) or cow milk protein allergy (CMPA) may experience adverse reactions to these excipients. This study investigated the prevalence of lactose and other dairy-derived ingredients in pharmaceuticals marketed in Portugal. Using the Summary of Product Characteristics (SmPC) from the INFOMED database, various medications, including analgesics, antipyretics, non-steroidal anti-inflammatory drugs (NSAIDs), and antiasthmatics, were analyzed. Results showed a high prevalence of dairy-derived excipients, particularly in antiasthmatic drugs (62.6%) and NSAIDs (39%). Although CMP are not explicitly mentioned in SmPCs, the presence of lactose as an ingredient poses a risk of cross-contamination. The findings emphasize the need for healthcare professionals to be aware of potential allergens in medications and the importance of developing lactose-free alternatives to ensure the safety of patients with LI and CMPA. Further research is required to assess the safety and implications of lactose in medicines for these populations. [ABSTRACT FROM AUTHOR]

Benchtop nuclear magnetic resonance (NMR) spectrometers are being employed in a wide variety of applications from undergraduate teaching and research in academia to quality control and process monitoring in industrial settings. Incorporating benchtop NMR in some of these applications presents opportunities for new practical uses of the technology and challenges that truly test the capabilities of compact NMR spectrometers. For instance, the use of protonated solvents in manufacturing or process monitoring requires separating and quantitating the analyte signals of interest from the strong (overwhelming) response from the solvents. Furthermore, due to the lower field strength available with permanent magnet spectrometers, the NMR spectra of complex mixtures can be more difficult to analyze due to partial or complete signal overlap. To address some of these challenges and to extend the range of applications of benchtop NMR, we investigate NMR techniques that enable quantitative analysis of different components in mixtures. These pulse sequences can be used to suppress one or multiple solvent peaks, to filter out signals by spin–spin relaxation time (T2), or to separate signal components by a molecule's diffusion coefficient (NMR diffusometry). In this paper, we discuss quantitative analysis of excipients in buffers for therapeutic proteins to highlight the usefulness of these NMR pulse sequences in the analysis of complex samples with benchtop NMR spectrometers. [ABSTRACT FROM AUTHOR]

Lamellar double hydroxides (LDH) are a class of inorganic materials widely used as pharmaceutical ingredients. However, their use as excipients and mainly as drug carriers lacks specific research in pharmaceutical technology, as there are no publications capable of defining the behavior of these materials as components of a formulation in the presence of other pharmaceutical adjuvants already consolidated. The purpose of the study was to evaluate the excipient–excipient compatibility of calcium and aluminum LDH (LDH–CaAl) against other excipients, including colloidal silicon dioxide (aerosil®), soluble starch (SS), microcrystalline cellulose 101 (MCC), magnesium stearate (MS), hydroxypropyl-beta-cyclodextrin (HPβCD), lactose monohydrate (LACM), sodium starch glycollate (SSG), PVP-K30 and talc. Initially, absorption spectroscopy in the infrared region with Fourier transform (FTIR) and thermogravimetry and differential thermal analysis (TG/DTA) was performed. When signs of possible interactions were observed, X-ray diffraction (XRD) was performed as a complementary technique. At the end of the study, the FTIR spectra and the TG curves of LDH–CaAl and each of the isolated excipients were compared with the analysis of the binary mixtures, where there is compatibility between LDH–CaAl and all excipients tested. Although the XRD has been used to assess evidence of interactions in mixtures with stearate, lactose, PVP and talc, the joint analysis of the results proved to be satisfactory. All these pioneering results suggest, therefore, the acceptability and suitability of LDH–CaAl as a potentially scalable excipient for the development of safe and rational dosage forms. [ABSTRACT FROM AUTHOR]

Objectives: The objective of the present study was to isolate mucilage from the leaves of Phanera variegata L., to do the thermal, microscopic, elemental analysis, and physicochemical characterization of isolated mucilage. The various analytical methods were applied to mucilage and evaluated its nature, thermal stability, and structure. Materials and Methods: The mucilage was isolated and analyzed by various analytical methods like SEM, PXRD, particle size analysis, DSC, TGA, elemental analysis (CHNS), zeta potential, FTIR, and 1D (¹H and 13C) NMR spectroscopy. Results: The SEM analysis indicated that mucilage particles had irregular shapes and sizes. The PSA indicated that particles of mucilage had a particle size of nanometers. The DSC analysis observed the mucilage's glass Transitional temperature (Tg) at 95.9°C. The TGA analysis suggested the three-stage decomposition with the good thermal stability of mucilage. A complete amorphous nature of the mucilage was indicated by PXRD analysis. The specific content of CHNS was revealed by elemental analysis. FT-IR spectra identified the major functional groups include 3240 cm-1(-OH), 2848 cm-1(C-H), 1599 cm-1(C-OH), 1419 cm-1(-COO-), 1253 cm-1(C-O). 1D Hydrogen-1 and Carbon-13 NMR confirmed the presence of polysaccharides that have many similar sugar residues. Conclusion: The P. variegata mucilage was found amorphous, thermally stable, and can be used as an excellent alternative natural pharmaceutical excipient for conventional pharmaceutical drug products and novel drug delivery systems in varying concentrations. [ABSTRACT FROM AUTHOR]

Background/Objectives: Increasing drugs’ stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result.

Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host. [ABSTRACT FROM AUTHOR]

PEGylated nanomedicines have been extensively developed and applied to cancer therapy. However, the antitumor efficacy of these nanoparticles is hampered by the accelerated blood clearance (ABC) effect caused by anti-PEG antibodies in vivo. There is still limited understanding about the cause of pre-existing anti-PEG antibodies in the human body. Herein, we discovered that PEG-based pharmaceutical excipients, commonly used in clinical and daily settings, could induce anti-PEG antibodies in vivo and lead to considerable potential clinical impacts on pharmacokinetics and pharmacodynamics of PEGylated nanoparticles. Specifically, we investigated the ability of poloxamer 188 (F68) and poloxamer 407 (F127), the two most frequently used PEG-based pharmaceutical excipients, to elicit the production of anti-PEG antibodies and influence the pharmacokinetics of PEGylated nanoparticles, with PEGylated liposome nanoparticles (L-NPs) as a model. Anti-PEG IgG and IgM levels were significantly boosted 3.8- and 32.2-fold, respectively, after pre-injection with F68, leading to rapid clearance of subsequently injected L-NPs from circulation due to the capture by neutrophils and monocytes. However, pre-injection of F127 did not induce the production of anti-PEG IgG, although there was a 7.7-fold increase in IgM level, which resulted in minimal effect on circulation time of L-NPs. Furthermore, the potential clinical impacts of F68 and F127 were further inspected for PEGylated liposomal doxorubicin (PLD). It was found that administering F68 prior to treatment led to over a one-third decrease in the antitumor effectiveness of PLD, while F127 had a negligible impact. Our study elucidates the mechanism by which PEG-based pharmaceutical excipients influence the effectiveness of PEGylated nanomedicines. It also highlights the significance of considering the potential for an ABC effect induced by PEG-based pharmaceutical excipients in patients. [Display omitted] • The regular utilization of PEG-based pharmaceutical excipients may be a potential source of anti-PEG antibodies in healthy individuals. • PEG-based excipients can induce the production of anti-PEG Igs, leading to rapid clearance of subsequently injected PEGylated nanoparticles. • PEG-based pharmaceutical excipients differed in their potential to trigger the ABC effect. [ABSTRACT FROM AUTHOR]

Polymers are the major constructive material of pharmaceutical formulations that play a prime role in designing effective drug-delivery systems and releasing drugs at their sites of application. Polymers are composed of multiple repeating units of high molecular mass components with attendant properties. Most synthetic polymers are non-biocompatible, expensive, and extremely inclined to deliver adverse impacts. Meanwhile, edible polymers obtained from natural sources have gained remarkable recognition for their promising use in modern medicine. Moreover, polymers derived from natural sources are generally preferred due to certain of their unique features such as abundant availability, biocompatibility, nontoxicity, economical, safe, and effective functions that fit the purpose. Polysaccharides including starch, cellulose, hemicellulose, pectin, and mucilage are identified as a major class of naturally obtained molecules that have a substantial role as functional polymers. This review summarizes the potential role of polysaccharides derived from vegetable sources such as adhesives, anticaking agents, binders, disintegrants, emulsifiers, film-framing agents, and thickeners. This is simply an opportunity to abandon synthetic excipients that hurt our bodies and think back to nature from where we originate.

High amylose maize starch with more than 50% of amylose has unique physicochemical properties and is widely used in food, packaging, pharmaceutical, paper and textile. Compared with common, waxy maize starch, high amylose maize starch has unique thermal properties, crystalline structure as well as excellent mechanical properties, all of which make it have great application potential in the field of low glycemic index foods, active ingredient encapsulated substrates and biodegradable materials. The structural characteristics, main properties and applications of high amylose maize starch in food ingredients, food processing materials and health products are reviewed. At the same time, its development trend is also prospected, this paper may provide some theoretical reference for the future product development and application of high amylose maize starch in the food field.

Background: As the pharmaceutical industry shifts to a patient-oriented approach, pharmaceutical education has fairly garnered increasing attention from educators, so that the teaching course centered on pharmaceutical excipients is becoming more and more popular. Purpose: The purpose of this study was to evaluate the significance of pharmaceutical excipients in clinical pharmaceutical education by a single-blind and parallel group design. Materials and Methods: The course was given in the form of small classes at Zhejiang University. The control group was taught in a traditional mode, while the intervention group mainly focused on the importance of pharmaceutical excipients in teaching. Likert five-point scale was used to analyze the test difficulty and learning effect of students in both groups. Results: Firstly, we investigated the test difficulty and learning time of the two groups of students, no significant difference was detectable between the two groups (p>0.05). Then, we investigated the learning effect of the two groups from four dimensions: accessibility of teachers' teaching concept, inspiration of the teaching methods, independence of students in the teaching process, and the extent to which the curriculum expanded student's horizons. It was found that the learning effect was much preferred in the intervention group as compared with the control group (p<0.05). Conclusion: The results showed that the emphasis on the integration of pharmaceutical excipients in pharmacy education had a positive impact on students' learning. Therefore, it is worth to reevaluate the role of pharmaceutical excipients in clinical pharmacy education. [ABSTRACT FROM AUTHOR]

Two key properties of excipients for inclusion in direct compression tablets are flowability and compactibility. Glutinous rice starch (GRS) has poor flowability, which limits its use in direct compression tablets. This study aimed to create a multifunctional direct compression excipient (filler binder disintegrant) with improved flowability from GRS by the co-precipitation method. The physicochemical and pharmaceutical properties of the co-precipitated GRS (cpGRS) were investigated. The optimum conditions for producing cpGRS (0.43 M sodium hydroxide solution, 7.09% PVP K30, 14.02% calcium carbonate, 95 min of mixing time and pH of 6.97) resulted in 68.80% yield, fair to good flowability, acceptable tablet strength, and fast disintegration. The FT-IR spectra of cpGRS showed no significant shifts in the key peaks, which indicates that there was an absence of chemical interactions within cpGRS. X-ray diffractograms also showed no significant changes, indicating that the GRS granules, calcium carbonate, and PVP K30 components remained unaltered during co-precipitation. cpGRS also demonstrated a dilution capacity of 50% when paracetamol was used as model drug. When cpGRS was combined with domperidone or propranolol hydrochloride it showed a better deformation capability than the physical mixtures. Although cpGRS was sensitive to lubricant, the hardness and tensile strength were higher than common strength for general purpose use in tablets. When compared to the physical mixture, pregelatinized starch and directly compressible calcium carbonate, the results showed that cpGRS tablets of both model drugs passed the friability test, demonstrated the best disintegration property, provided the fastest and highest drug release profile for propranolol, and improved the drug release profile for domperidone. For propranolol-cpGRS tablets, dissolution medium at different pH did not affect the dissolution profile. For domperidone-cpGRS tablets, the pH of dissolution medium did affect the dissolution profile of the tablets. This was according to the API solubility. These results reveal that cpGRS is an excellent multifunctional i.e., filler, binder, and disintegrant excipient suitable for direct compression tablets. The main component is natural. The preparation method is simple, quick, and efficient. This method does not produce harmful waste and requires only basic equipment, and affordable reactants and devices.

Many chemical modifications of starch are realized in organic (mostly methanol) phase, allowing high degrees of substitution (DS). Some of these materials are used as disintegrants. To expand the usage of starch derivative biopolymers as drug delivery system, various starch derivatives obtained in aqueous phase were evaluated with the aim to identify materials and procedures which would generate multifunctional excipients providing gastro-protection for controlled drug delivery. Chemical, structural and thermal characteristics of anionic and ampholytic High Amylose Starch (HAS) derivatives under powder (P), tablet (T) and film (F) forms were evaluated by X-ray Diffraction (XRD), Fourier Transformed Infrared (FTIR) and thermogravimetric analysis (TGA) methods and correlated with the behavior of tablets and films in simulated gastric and intestinal media. At low DS, the HAS carboxymethylation (CMHAS) in aqueous phase, generated tablets and films that were insoluble at ambient conditions. The CMHAS filmogenic solutions, with a lower viscosity, were easier to cast and gave smooth films without the use of plasticizer. Correlations were found between structural parameters and the properties of starch excipients. Compared to other starch modification procedures, the aqueous modification of HAS generated tunable multifunctional excipients that may be recommended for tablets and functional coatings for colon-targeted formulations. [ABSTRACT FROM AUTHOR]

Chemical excipients used in topical formulations may be toxic to living skin cells. Here, we compared the in vitro toxicity of some common solubilizing excipients against human melanoma cells, human keratinocytes (HaCaT) and primary skin fibroblasts (FB) as examples of cancerous, immortalized and primary human skin cells, often used as experimental models representative of in vivo conditions. Two distinct endpoint assays (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and crystal violet (CV)) were used. The mechanism of cell death after excipient exposure was assessed through Reactive Oxygen Species (ROS) production, cell membrane integrity and cell cycle progression. Results showed that the surfactants, Labrasol®, Labrafil® and Transcutol®, were less toxic than Triton X-100 (a model irritant) in all cell types whereas the oil, Labrafac®, was non-toxic. The human melanoma WM164 cell line showed the greatest sensitivity toward cytotoxicity after chemical exposure, while the other cell lines were more resistant. The relative excipient cytotoxicity responses observed in the MTT and CV assays were comparable and similar trends were seen in their estimated 50 % inhibitory concentration (IC50) values. DNA fragmentation by flow cytometry after exposing the cells to IC50 concentrations of the excipients showed negligible apoptotic populations. ROS production was increased in all cell types after toxic exposure; however, ROS elevation did not lead to apoptosis. The toxicity profiles of each excipient are not only relevant to their use in formulating safe topical products but also in the potential synergistic efficacy in the topical treatment of melanoma. [ABSTRACT FROM AUTHOR]

Pharmaceutical excipient soybean oil is widely used in injections. Its main components, triglycerides, are easily oxidized due to their unsaturated fatty acyls, raising safety concerns. However, it is hard to analyze those oxidized triglycerides due to their diverse compositions and low abundance. In this study, all theoretical oxidized triglycerides were predicted and a database consisting of 329 oxidized triglycerides was constructed. Then, a novel theoretical database-assisted ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF/MS) strategy was developed to finely profile and identify oxidized triglycerides in soybean oil. A total of 106 and 116 oxidized triglycerides were identified and relatively quantified in oxidized soybean oil and long-term stored soybean oil and preparations. It was found that oxidized triglycerides containing carbonyl groups were significantly more prevalent than other forms and oxidized triglycerides with two oxidized fatty acyl chains had the highest relative abundance. Fifteen markers indicating the oxidation of soybean oil were discovered. This strategy could rapidly and directly analyze the oxidized triglycerides and assign their fatty acyl compositions for the first time. This study will improve the quality control of soybean oil and its preparations. [Display omitted] • A novel theoretical database-assisted UHPLC-Q-TOF/MS strategy was developed. • The database greatly improved the efficiency and accuracy of identification. • Oxidized triglycerides in excipients were directly determined for the first time. • The oxidation characteristic and 15 markers indicated the oxidation of soybean oil. • The study provided a novel quality control method for soybean oil and preparations. [ABSTRACT FROM AUTHOR]

Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of Akkermansia muciniphila (A. muciniphila), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.

Taking curcumin as the starting point, β-cyclodextrin was introduced on both sides, and lipid-soluble curcumin was coated by acrylic resin using oil-in-water strategy. Four different types of curcumin fluorescent complexes EPO-Curcumin (EPO-Cur), L100-55-Curcumin (L100-55-Cur), EPO -Curcumin-β-cyclodextrin (EPO-Cur-β-cd) and L100-55-Curcumin-β-cyclodextrin (L100-55-Cur-β-cd) were prepared to solve their own solubility and biocompatibility issues. The prepared curcumin fluorescent complexes were characterized and tested by spectroscopy. The characteristic peaks of 3446 cm−1 (hydroxyl group), 1735cm−1(carbonyl group) and 1455 cm−1 (aromatic group) were determined in the infrared spectrum. In the fluorescence emission spectrum, it was found that the emission intensity of different curcumin fluorescent complexes in polar solvents reached hundreds of times. Through the transmission electron microscopy shows that acrylic resin tightly coats curcumin into rods or clusters. In order to observe their compatibility with tumor cells more directly, live cell fluorescence imaging was carried out, and it was found that all four kinds of curcumin fluorescence complexes had good biocompatibility. In particular, the effect of EPO-Cur-β-cd and L100-55-Cur-β-cd is better than that of EPO-Cur and L100-55-Cur.

In an ever-growing perspective of circular economy, the development of conscious, sustainable and environmental-friendly strategies to recycle the waste products is the key point. The scope of this work was to validate the waste bentonite from the grape processing industries as a precious matrix to extract polyphenols by applying a waste-to-market approach aimed at producing novel functional excipients. The waste bentonite was recovered after the fining process and opportunely pre-treated. Subsequently, both the freeze dried and the so-called "wet" bentonites were subjected to maceration. PEG200 and Propylene Glycol were selected as solvents due to their ability to dissolve polyphenols and their wide use in the cosmetic/pharmaceutical field. The extracts were evaluated in terms of yield, density, pH after water-dilution, total phenolic (Folin–Ciocalteu) and protein (Bradford) contents, antioxidant power (DPPH), amount of some representative polyphenols (HPLC-DAD), cytocompatibility and stability. Both solvents validated the bentonite as a valuable source of polyphenols and led to colored fluids characterized by an acidic pH after water-dilution. The best extract was obtained from the wet bentonite with PEG200 and highlighted the highest phenolic content and consequently the strongest antioxidant activity. Additionally, it displayed proliferative properties and resulted almost stable over time. Hence, it might be directly used as polyphenols-enriched functional novel raw material for cosmetic and pharmaceutics purposes. [ABSTRACT FROM AUTHOR]

Pharmaceutical excipients are indispensable components of drug formulations, playing critical roles in enhancing stability, improving bioavailability, and ensuring patient compliance. In pediatric and geriatric populations, the selection of these excipients becomes even more crucial due to their unique physiological and pharmacokinetic profiles, as well as age-specific formulation requirements. This review examines the functions, safety considerations, and potential adverse effects of excipients in these vulnerable groups. It addresses the challenges of drug formulation for neonates, infants, and elderly patients, including immature enzyme systems, polypharmacy, and swallowing difficulties. The impact of excipient-excipient and excipient-active pharmaceutical ingredient (API) interactions on drug stability, efficacy, and safety is also highlighted. For instance, the effects of polyethylene glycol (PEG) in patients with impaired renal function and destabilizing interactions between surfactants and protein-based APIs are analyzed. Additionally, current guidelines and safety requirements from regulatory bodies such as the FDA, EMA, and ICH are reviewed. This paper emphasizes the importance of carefully selecting excipients that balance functionality and safety to ensure therapeutic efficacy while minimizing risks for pediatric and geriatric patients. Future directions in excipient development and formulation strategies are also discussed to improve treatment outcomes for these populations.

Background: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. Methods: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. Results: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1β, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. Conclusions: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs' therapeutic efficiency outcome. [ABSTRACT FROM AUTHOR]

Over the years, the selection of excipients that are key ingredients of the pharmaceutical formulation has always been challenging tasks from a formulation scientist to the manufacturer. Their inherent properties along with unique characteristics make them suitable for successful dosage form globally. Various rules for selection at the laboratory scale with rock bottom criteria for the number and concentration of excipients have been proposed in relation to the pharmacological class of API. However, their compatibility, regulatory requirements and manufacturer or supplier criteria are always under prospective consideration due to the unavailability of harmonized guidelines. This review discusses these challenges in-depth and suggests the novel steps to be followed during pre-formulation studies to industrial scale. [ABSTRACT FROM AUTHOR]

The limited time indorsed to face the COVID-19 emergency and large number of deaths across the globe, poses an unrelenting challenge to find apt therapeutic approaches. However, lead candidate selection to phase III trials of new chemical entity is a time-consuming procedure, and not feasible in pandemic, such as the one we are facing. Drug repositioning, an exploration of existing drug for new therapeutic use, could be an effective alternative as it allows fast-track estimation in phase II–III trials, or even forthright compassionate use. Although, drugs repurposed for COVID-19 pandemic are commercially available, yet the evaluation of their safety and efficacy is tiresome and painstaking. In absence of any specific treatment the easy alternatives such as over the counter products, phytotherapies and home remedies have been largely adopted for prophylaxis and therapy as well. In recent years, it has been demonstrated that several pharmaceutical excipients possess antiviral properties making them prospective candidates against SARS-CoV-2. This review highlights the mechanism of action of various antiviral excipients and their propensity to act against SARs-CoV2. Though, repurposing of pharmaceutical excipients against COVID-19 has the edge over therapeutic agents in terms of safety, cost and fast-track approval trial burdened, this hypothesis needs to be experimentally verified for COVID-19 patients. [ABSTRACT FROM AUTHOR]

Many chemical modifications of starch are realized in organic (mostly methanol) phase, allowing high degrees of substitution (DS). Some of these materials are used as disintegrants. To expand the usage of starch derivative biopolymers as drug delivery system, various starch derivatives obtained in aqueous phase were evaluated with the aim to identify materials and procedures which would generate multifunctional excipients providing gastro-protection for controlled drug delivery. Chemical, structural and thermal characteristics of anionic and ampholytic High Amylose Starch (HAS) derivatives under powder (P), tablet (T) and film (F) forms were evaluated by X-ray Diffraction (XRD), Fourier Transformed Infrared (FTIR) and thermogravimetric analysis (TGA) methods and correlated with the behavior of tablets and films in simulated gastric and intestinal media. At low DS, the HAS carboxymethylation (CMHAS) in aqueous phase, generated tablets and films that were insoluble at ambient conditions. The CMHAS filmogenic solutions, with a lower viscosity, were easier to cast and gave smooth films without the use of plasticizer. Correlations were found between structural parameters and the properties of starch excipients. Compared to other starch modification procedures, the aqueous modification of HAS generated tunable multifunctional excipients that may be recommended for tablets and functional coatings for colon-targeted formulations.

This study examined three different surface tension measurement methods and compared them using statistical theory to determine the most suitable measurement method for different kinds of pharmaceutical excipients. [Display omitted] Surface tension is a crucial functional indicator for various classes of pharmaceutical excipients, as highlighted in both the Pharmacopoeia of the People's Republic of China (ChP) < 9601 Guidelines for Functionality-related Characteristics of Pharmaceutical Excipients > and the United States Pharmacopoeia (USP) < 1059 Excipient Performance >. However, there are few systematic studies on surface tension measurement of pharmaceutical excipients, resulting in a lack of stable parameter support in practical applications. In this study, we aim to fill this gap by exploring three different methods for measuring surface tension. These methods were carefully developed taking into account the actual measurement process and statistical theory, thus ensuring their applicability and reliability. Through comparative analyses, we have identified the most suitable measurement methods for different classes of pharmaceutical excipients. In addition, this paper describes the surface adsorption behavior of various excipients. Therefore, this study provides valuable guidance for the determination of surface tension and the study of surface adsorption behavior, which lays the foundation for further comprehensive research in the field of surface tension of pharmaceutical excipients and the improvement of general pharmacopoeia specification. [ABSTRACT FROM AUTHOR]

Background: Various potential effect of drugs on alleviating diseases by regulating intestinal microbiome as well as the pharmaceutical excipients on gut microbiota has been revealed. However, the interaction between them is rarely investigated. Methods: Histological analysis, immunohistochemistry analysis, enzyme-linked immunosorbent assay (ELISA) analysis, RT-qPCR, and 16S rRNA analysis were utilized to explore the effect mechanism of the five excipients including hydroxypropyl methylcellulose (HPMC) F4M, Eudragit (EU) S100, chitosan (CT), pectin (PT), and rheum officinale polysaccharide (DHP) on berberine (BBR) to cure UC. Results: The combined BBR with PT and DHP group exhibited better therapeutic efficacy of UC with significantly increased colon length, and decreased hematoxylin-eosin (H&E) scores than other groups. Furthermore, the expression of tight junction ZO-1 and occludin in colon tissue were upregulated, and claudin-2 was downregulated. Ultimately, the serum content of tumor necrosis (TNF)-α, interleukin (IL)-1β, and IL-6 was decreased. Moreover, the combined BBR with PT significantly promoted the restoration of gut microbiota. The relative abundance of Firmicutes and Lactobacillus was significantly increased by the supplement of PT and DHP, and the relative abundance of Proteobacteria was downregulated. Conclusions: Our study may provide a new perspective that the selection of pharmaceutical excipients could be a crucial factor affecting the drugs’ therapeutic efficiency outcome.

The aim of this study was to characterize and evaluate the compatibility of the dry extract (DE) of leaves of Annona muricata L. with pharmaceutical excipients usually used in the manufacturing of medicines. Characterization of the DE and binary mixtures of the extract and excipients was carried out using scanning electron microscopy (SEM), differential scanning calorimetry, thermogravimetry (TG) and Fourier transform infrared attenuated total reflection spectroscopy. Spray drying technique produced extract to form spherical and hollow particles revealed by SEM, with four stages of mass loss in the TG curve. Pre-formulation study showed compatibility between the extract and microcrystalline cellulose, lactose, croscarmellose sodium and sodium starch glycolate. New medicines containing herbal drugs enter the market every year, and our study demonstrates that thermoanalytical techniques can be used in the development and quality control of herbal medicines. [ABSTRACT FROM AUTHOR]

The aim of present study was to investigate the effect of pharmaceutical excipients and other active substances on antimicrobial efficacy of standard antibiotic against resistant and susceptible microorganisms. Pharmaceutical excipients (sodium lauryl sulfate [SLS], Tween-80, citric acid, NaOH, NaCl) and active substances (fusidic acid, sorbic acid) were investigated to check in-vitro efficacy and their effect on the efficacy of standard antibiotic. Clindamycin was selected as standard antibiotic. Clindamycin was found to be ineffective against methicillin-resistant Staphylococcus aureus (MRSA). Fusidic acid and SLS showed concentration dependent effect against MRSA. Other tested substances were also ineffective against MRSA, and also failed to improve the susceptibility of MRSA towards clindamycin. The clindamycin + fusidic acid (0.05 μg, 0.1 μg), and clindamycin + SLS (0.5 mg, 1 mg) showed concentration dependent effect on Staphylococcus epidermidis (S. epidermidis). Clindamycin combinations with fusidic acid or SLS showed better inhibition of S. epidermidis, than individual substance. At lower concentration of clindamycin (2 μg), the sorbic acid (25 μg) improves its effectiveness. SLS (0.5 mg, 1 mg) and clindamycin (4 μg, 10 μg) showed almost equal zone of inhibition against S. epidermidis, respectively. Present findings showed that certain pharmaceutical excipients (e.g. SLS) are effective against resistant and susceptible microbes, and suggested that more excipients should be screened for their antimicrobial potential and their ability to improve the efficacy of standard antibiotics. [ABSTRACT FROM AUTHOR]

An anti-diabetic approach of inhibiting α-amylase i.e. carbohydrate hydrolyzing enzymes results in decreased gastrointestinal glucose absorption and production. Gums belonging to natural sources are used as pharmaceutical excipients in several dosage forms. The present comparative study investigated the effect and efficiency of such gums i.e. guar gum(Cyamompsis tetraganolobus), gum acacia (Acacia arabica) and gum tragacanth (Astragalus gummifer) on α-amylase inhibition activity. Various aqueous concentrations (10-100 mg/mL) of all the three gums were made to examine the effects. In vitro α-amylase inhibition activities of these gums were examined spectrophotometrically using dinitrosalicylic acid - starch azure method. The inhibition of α-amylase by guar gum, gum acacia and gum tragacanth were significant with the IC50 value of 28.4, 61.9 and 66.5 µg/mL, on an individual basis, when compared to standard acarbose. The inhibition activity report says that Guar gum was the most potent candidate among all the gums and further developing a dosage formwould be the future interest. [ABSTRACT FROM AUTHOR]

Pharmaceutical cellulosic polymers will inevitably reach natural water systems if they are not removed after entering wastewater. Biodegradation of organic chemicals in sewage or in the aquatic environment is an important removal mechanism. In this study, we investigated the environmental biodegradation of 14 cellulose derivatives commonly utilized as pharmaceutical excipients using three different test systems that are based on the closed bottle test (OECD 301D) and the manometric respirometry test (OECD 301F). For the different cellulose derivatives tested, we observed varying degrees of biodegradation ranging from 0 to 20.4 % chemical oxygen demand (COD). However, none met the criteria for classification as 'readily biodegradable'. In addition, 10 out of 14 cellulose derivatives and/or their possible transformation products formed during the experiments, may exhibit possible toxic inhibitory effects on the inoculum. This includes one or several derivatives of hydroxy propyl methyl cellulose, hydroxy propyl cellulose, methyl cellulose, ethyl cellulose, and hydroxy ethyl cellulose. Based on the results obtained, we have developed a graded classification score ('traffic light system') for excipient biodegradation. This could help streamline the assessment and classification of cellulose derivatives concerning risk of persistence and potential adverse environmental effects, thereby assisting in the prioritization of more favorable compounds. In the long term, however, excipients should be designed from the very beginning to be biodegradable and mineralizable in the environment ('benign by design'). [Display omitted] • First systematic study on biodegradation of 14 cellulose-based pharmaceutical excipients using OECD 301 standard methods. • None of the tested cellulose derivatives met the criteria for 'readily biodegradable' classification. • Identification of potential inhibitory effects on inoculum respiration for 10 compounds. • Development of a 'traffic light system' for grouping the substances, highlighting structure-biodegradability relationships. [ABSTRACT FROM AUTHOR]

Pharmaceutical excipients (PEs) are substances included in drug formulations. Recent studies have revealed that some PEs can affect the activity of metabolic enzymes and drug transporters; however, the effects of PEs on CYP2C8 and its interaction potential with drugs remain unclear. In this study, we evaluated the effects of Tween 80 and EL−35 on CYP2C8 in vitro and further investigated their impacts on the PK of paclitaxel (PTX) in rats after single or multiple doses. The in vitro study indicated that Tween 80 and EL−35 inhibited CYP2C8 activity in human and rat liver microsomes. EL−35 also decreased the expression of CYP2C8 in HepG2 cells. In the in vivo study, Tween 80 did not alter the PK of PTX after single or multiple doses, whereas EL−35 administered for 14 days significantly increased the AUC and MRT of PTX. Further analysis indicated that multiple-dose EL−35 reduced the expression of Cyp2c22 and production of 6-OH-PTX in the rat liver. Our study suggested that short-term exposure to both PEs did not affect the PK of PTX in rats, but multiple doses of EL−35 increased the AUC and MRT of PTX by downregulating the hepatic expression of Cyp2c22. Such effects should be taken into consideration during drug formulation and administration.

The aim of this study was to characterize the interaction between the binary systems of albendazole (ABZ)—cyclodextrins (CDs) with pharmaceutical excipients. Hydroxyl-propyl-beta-cyclodextrin (HPBCD) and random methyl-beta-cyclodextrin (RAMEB) were used as cyclodextrins and magnesium stearate, mannitol, polyvinylpyrrolidone K30 (PVP K30), colloidal silica, starch, and talc were used as excipients. The utilized investigation techniques were attenuated total reflection Fourier transform infrared spectroscopy (ATR-FTIR), powder X-ray diffractometry (PXRD) and thermoanalytical techniques: thermogravimetry (TG)/derivative thermogravimetry (DTG)/heat flow (HF) and differential scanning calorimetry (DSC). The ATR-FTIR analysis clearly suggested interactions under ambient conditions between ABZ-HPBCD with PVP K30 and SiO2 and between ABZ-RAMEB with SiO2 and talc. The PXRD patterns indicated the formation of less crystalline mixtures but with no clear indication of interactions, since no peaks appeared nor disappeared. The modifications on the DSC curves suggested an interaction between ABZ-HPBCD and PVP K30 and SiO2 respectively, and in case of ABZ-RAMEB was observed an interaction with talc. Thermal analysis (TG/DTG/HF) carried out in open crucibles in dynamic air atmosphere suggested that at temperatures over 40 °C dehydration of samples occurred, later followed by thermolysis and appearance of interactions in all studied cases. Our study concludes by recommending precautionary measures in elaborating new solid formulations containing ABZ, HPBCD and PVP K30/SiO2 and for the ones containing ABZ, RAMEB and Talc/SiO2, due to the present interactions under ambient conditions. [ABSTRACT FROM AUTHOR]

Sorbitol is a popular sugar alcohol which has been used as an excipient in formulations of various drugs. Although from a safety perspective the presence of sorbitol in drug formulations does not raise a concern, reports have emerged and these suggest that sorbitol in drug formulations may alter oral absorption and bioavailability of certain drugs. The focus of this article was to review the published literature of various drugs where pharmacokinetic data has been reported for the drug alone versus drug administered with sorbitol and provide perspectives on the pharmacokinetic findings. Interestingly, for BCS class I drugs such as theophylline, metoprolol, the oral absorption, and bioavailability were generally not affected by sorbitol. However, theophylline oral absorption and bioavailability were decreased when sustained release formulation was used in place of immediate release formulation. For drugs such as risperidone (BCS class II) and lamivudine and ranitidine (BCS class III), the solution formulations showed diminished oral bioavailability in presence of sorbitol, whereas cimetidine and acyclovir (BCS class III), did not show any changes in pharmacokinetic profiles due to sorbitol. Finally, the presence of activated charcoal with sorbitol showed different pharmacokinetic outcome for BCS class I and II drugs. [ABSTRACT FROM AUTHOR]

Abstract An alternative method for the determination of total chlorine content in hydroxypropyl cellulose (HPC) was applied, combining a recently developed system based on a combustion step followed by pyrohydrolysis reaction. Using this approach it the determination of total chlorine by inductively coupled plasma optical emission spectrometry (ICP-OES) without interferences was feasible. It overcame the limitations of European Pharmacopoeia (EP) method for HPC analysis regarding to the inability to determine total chlorine in HPC, once some chlorine compounds (e.g., chloroform) that can not be identified by the official method (EP). The following parameters of combustion and pyrohydrolysis were evaluated: absorbing solution, sample mass, the use of powdered silica as retardant of combustion, oxygen flow rate and reaction time. Reference values for total chlorine were obtained after digestion using microwave-induced combustion and determination by ion chromatography (IC). Microwave-assisted extraction (MAE) was also investigated for Cl extraction. The accuracy of the proposed method was also evaluated by analyte recovery tests (agreement of 95–103%), as well as by the analysis of certified reference materials (CRMs). The agreement with the certified values was higher than 95% and the limit of quantification (LOQ) was 50 µg g−1. Up to 500 mg of sample were efficiently digested by the proposed method in 5 min (dissolved carbon in digests was below 50 mg L−1). Total chlorine content in samples of modified cellulose ranged from 284 to 576 µg g−1. Despite the relatively high chlorine content in all samples, the concentration was lower than the maximum limit allowed by the EP for HPC (0.5%). Graphical abstract fx1 Highlights • The proposed sample preparation method overcomes the limitation of the official method proposed by official pharmacopoeias. • Chlorine determination was possible in HPC excipient by ICP-OES. • Up to 500 mg of HPC were efficiently digested in 5 min. • The LOQ was 50 µg g−1, allowing the determination of chlorine in pharmaceutical excipients. • Higher digestion efficiency was achieved (>99%). [ABSTRACT FROM AUTHOR]

Characterization directed to evaluate health care usefulness of kaolinitic samples from various deposits from the south of Venezuela exploited used as raw materials in ceramics have been done Identity, purity and richness in mineral phases and presence of chemical impurities were compared to pharmaceutical grade kaolins and correlated to international requirements described in pharmacopoeias. Color parameters and textural analysis were used as a complementary characterization of the suitability of the samples as a diluent for pharmaceutical oral dosage forms. Most of the samples would require purification before considering their use as health care ingredients. In particular, treatment to eliminate quartz as a mineral impurity or Pb as metallic impurity would be advisable for some of the studied kaolins. Nevertheless, at least seven of the studied samples could be used directly, as they are comparable to commercial kaolin used as excipients or cosmetic ingredients. • Health care usefullness of fourteen Venezuelan kaolins have been determined. • Kaolinite content in seven of the samples was higher or similar to pharmaceutical kaolins. • The presence of heavy metals or other impurities limit the possibilities of some high purity kaolinitic samples. • Some samples comply with identity and safety quality requirements to be used as health care ingredients. [ABSTRACT FROM AUTHOR]

Mucilage is the thick, gluey substances produced by nearly all plant and some microorganisms. Okra mucilage is extracted from the plant of the malavaceae [A. esculantus]. Which is originally from Egypt, but it also in cropped in southern Asia elsewhere for nutritional purposes. Their use as potential reinforcement in polymer composites requires the understanding of their microstructure and mechanical properties. This work investigates the extraction methods, solubility behavior, TLC, loss on drying, ash value, FTIR spectra, surface tension, organoleptic properties. Extracted mucilage is soluble in warm water while insoluble in organic solvents. This can shows that it safely used in dosage form without causing any adverse effect. [ABSTRACT FROM AUTHOR]

Graphical abstract Abstract Therapeutic peptides are facing an increasing interest as drugs for the treatment of many diseases. The challenge in the administration of such drugs, due to inherent properties of these peptides, is to make them bioavailable. Self-emulsifying drug delivery systems (SEDDS) are considered a suitable and promising strategy to deliver the peptides and increase their bioavailability. However, to enter into the SEDDS nanodroplets, the peptides must be made hydrophobic by complexation with surfactants (formation of hydrophobic ion pair, HIP). The aim of this work is to assess the possibility to quantify the amount of released peptides and of the remaining docusate/peptide HIP in the nanodroplets by Taylor Dispersion Analysis (TDA) on two therapeutic peptides (leuprorelin and desmopressin). It also clearly demonstrates that the log P value of the peptide has a strong influence on the extent of HIP inside of the SEDDS nanodroplets. For instance leuprorelin-docusate complex (log P = 3) was 100% inside of the nanodroplets at low ionic strength, while for desmopressin-docusate complex (log P = 0.5) only 30% were able to enter the nanodroplets. It was also shown that an increase in the ionic strength of the release media allowed to increase the amount of released peptide up to 80% for leuprorelin and 100% for desmopressin, at physiological ionic strength. TDA experiments allowed to determine the partitioning coefficient, log D value, of the peptide between the SEDDS and continuous aqueous phases. In conclusion, this work demonstrates that TDA is a rapid, straightforward and useful technique for developing SEDDS formulations. [ABSTRACT FROM AUTHOR]

Omega-3 fatty acid plays a role in protecting cells in the human body, maintaining the structure of the cell, and helping smooth metabolism. Also, it inhibits the formation of blood clotting and is effective in enhancing the formation of bone. However, the instability due to fatty acid oxidation and a fishy smell are the reasons it is avoided by people. In this study, we tried to obtain the omega-3 powder through spray-drying method using a variety of binders and surfactants for improving the limit of omega-3 fatty acid. First of all, an olive oil was used instead of omega-3 for optimization of the preparation of spray-dried omega-3 powder. Through the screening of binders and surfactants, γ-cyclodextrin and hydrogenated lecithin were chosen as a binder and a surfactant, respectively. Omega-3-loaded spray-dried powder was obtained, eventually. The morphology of omega-3-loaded spray-dried powder was spherical of 310 nm and the DHA amount was 98%. This study suggested that the transformation of omega-3 fatty acid into solid state by spray-drying using a binder and a surfactant was successively performed. [ABSTRACT FROM AUTHOR]

The topical delivery route is proposed as an alternative or adjunctive approach to melanoma treatment, since the target site for melanoma treatment—the epidermal basal layer—is potentially accessible by this route. Microemulsion systems are effective delivery vehicles for enhanced, targeted skin delivery. This work investigated the effect of Rose Bengal (RB) and RB-loaded self-emulsifying microemulsions (SEMEs) on growth inhibition of human melanoma and normal skin cell monolayers, the safety of the excipients incorporated in SEMEs on human cell lines, and the in-vitro human skin penetration of RB delivered in SEMEs and control solution. Cellular toxicity was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and the growth inhibitory mechanism of RB was investigated by flow cytometry using PI staining. Unloaded SEMEs caused reduced cellular toxicity compared to the surfactant excipient, Labrasol®. RB-loaded SEMEs increased cell growth inhibition compared to the RB aqueous solution. Flow cytometry revealed apoptotic cells after treatment with RB-loaded SEMEs, indicating that apoptosis may be one of the mechanisms of cell death. Preliminary results of multiphoton microscopy with fluorescence lifetime imaging (MPM-FLIM) analysis showed deeper penetration with greater skin concentrations of RB delivered from SEMEs compared to the RB aqueous solution. This study highlights the enhanced skin penetration and antimelanoma effects of RB loaded in a SEME system.