Stable Formulation Research Articles

Nicotinamide Loaded Chitosan Nanocomplex Shows Improved Anticancer Potential: Molecular Docking, Synthesis, Characterization and In vitro Evaluations

Abstract: This study aimed to prepare and characterize chitosan nanoparticles encapsulating a nicotinamide derivative (Ni-CS-NP). Additionally, the therapeutic effectiveness, cytotoxicity, selectivity, and immunomodulatory properties of Ni-CS-NP were evaluated in human breast and colon cancer cell lines. Chitosan nanoparticles have shown potential as drug delivery carriers due to their biocompatibility and controlled release properties. Encapsulating a nicotinamide derivative further enhances the therapeutic potential of these nanoparticles. Computational studies were employed to validate the binding interactions, providing crucial insights into the formulation's stability and effectiveness. The primary objective was to assess the cytotoxicity and safety profiles of Ni-CS-NP in human cancer cell lines. Moreover, this study aimed to investigate the specific mechanisms underlying its cytotoxic effects, including its impact on cell cycle progression, apoptosis induction, and immunomodulation. Ni-CS-NP were synthesized using the ionic gelation method and characterized using Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and thermo gravimetric analysis. The cytotoxicity was evaluated in breast and colon cancer cell lines through the MTT assay. Selectivity indices were calculated to determine the safety profiles. The inhibition of VEGFR-2, induction of apoptosis, cell cycle disruption, and immunomodulatory effects were assessed through molecular assays. Computational analysis demonstrated favorable binding interactions through the Ni-CS-NP complex. The characterization studies confirmed the successful synthesis of Ni-CS-NP with well-defined structural and thermal properties. Ni-CS-NP exhibited remarkable cytotoxicity with a superior safety profile against MCF7 and HCT 116 cell lines showing IC50 values of 2.32 and 2.70 μM, respectively, surpassing sorafenib's efficacy (IC50 = 4.12 and 7.55 μM, respectively). Additionally, Ni-CS-NP effectively inhibited VEGFR-2, induced both early and late apoptosis, and disrupted the cell cycle progression in MCF7 cells. Notably, Ni-CS-NP demonstrated significant immunomodulatory effects by reducing TNF-α and IL-2 levels compared to dexamethasone. The encapsulation of a nicotinamide derivative within chitosan nanoparticles (Ni-CS-NP) through the ionic gelation method proved successful. Ni-CS-NP displayed potent cytotoxicity, superior safety profiles, and promising immunomodulatory effects in human breast cancer cells. These findings highlight the potential of Ni-CS-NP as a novel therapeutic agent for breast cancer treatment, warranting further investigation for clinical applications.

Evaluation of the stability and antioxidant activity of formulations with Mangifera indica L. extract

Evaluation of the stability and antioxidant activity of formulations with Mangifera indica L. extract

A Review on The Impurity Profile of Pharmaceuticals

A collection of analytical procedures known collectively as “impurity profiling” are intended to detect, identify, clarify the structure of, and quantify both organic and inorganic impurities as well as residual solvents in pharmaceutical formulations and bulk pharmaceuticals. This is the main task of contemporary drug analysis since it is the most effective approach to describe the stability and quality of pharmaceutical formulations and bulk pharmaceuticals. To keep an eye on them, specific analytical techniques must be created. When modifications are made to the synthesis, formulation, or production processes, even if they are done to improve them, new purities could be seen. The identification of impurities in Active Pharmaceutical Ingredients (APIs) and the need for purity are being emphasised by a number of regulatory bodies, including the Canadian Drug and Health Agency (CDHA), the United States Food and Drug Administration (FDA), and the International Conference on Harmonisation (ICH). Pharmaceutical products can contain impurities from a variety of sources, including reagents, heavy metals, ligands, catalysts and other materials like charcoal, filter aids, and the like. Degraded end products from hydrolysis, photolytic cleavage, oxidative degradation, decarboxylation, and other processes can also contain impurities, as can enantiomeric impurities. The various pharmacopoeias, including the Indian, American, and British pharmacopoeias, are gradually adding restrictions to the permissible concentrations of contaminants found in APIs or formulations. Capillary electrophoresis, electron paramagnetic resonance, gas-liquid chromatography, gravimetric analysis, high performance liquid chromatography, solidphase extraction techniques, liquid-liquid extraction techniques, mass spectrometry, ultraviolet spectrometry, infrared spectroscopy, supercritical fluid extraction column chromatography, nuclear magnetic resonance (NMR) spectroscopy, and RAMAN spectroscopy are some of the techniques used to isolate and characterize impurities in pharmaceuticals. Liquid Chromatography (LC)-Mass Spectroscopy (MS), GC-MS, LC-NMR, LC- NMR-MS, and LC-MS are the most frequently used hyphenated techniques for drug impurity profiling. This demonstrates the importance and range of drug impurity profiling in pharmaceutical research.

Anticancer activity of liposomal formulation co-encapsulated with coumarin and phenyl butyric acid

Anticancer treatments have poor pharmacokinetics, high toxicity to normal cells, and low bioavailability. As nanotechnology has advanced to a new level, many researchers have been motivated to develop a safer and more effective medication delivery method for the treatment of cancer. Nowadays, about 80% of the anticancer medications that have been approved recently are made from natural substances. This study aims to formulate liposomes loaded with coumarin (COM) and 4-phenylbutyric acid (PBA) and evaluate their antitumor effect in vitro. The liposomes were characterized using the dynamic light scattering instrument to determine their size, polydispersity, and charge. The formulated liposomes exhibited a particle size within the desired range of 100– 200 nm, with low polydispersity and suitable charge. Stability tests showed excellent stability of the liposomal formulations over 10 days in terms of size, charge, and polydispersity. High performance liquid chromatography analysis confirmed the successful encapsulation of COM and PBA within the liposomes, with high encapsulation efficiencies observed of 53%–25% for Lipo-PBA and Lipo-COM, respectively. Loading efficiency (LO%) was found to be 9%–5% for Lipo-PBA and Lipo-COM, respectively, which means the drugs were efficiently loaded within the liposome. In vitro cell viability studies demonstrated that the liposomes loaded with both COM and PBA exhibited the most effective inhibition on MDA-MB-231 breast cancer cells (30%) and A549 lung cancer cells (45%), while Lipo-COM showed potent inhibition on HT29 colorectal cancer cells (40%). Encapsulation of the drugs inside liposomes enhanced their cytotoxicity, potentially due to improved penetration into tumor cells. The findings suggest that the formulated liposomes have the potential for future clinical applications with high selectivity toward cancer cells.

Preparation of probiotic-loaded solid lipid nanoparticles and in vitro survival in gastrointestinal conditions

In the present study, Probiotics (Lactobacillus plantarum) loaded-solid lipid nanoparticles were prepared and characterized. Probiotics have proven to possess significant potential in addressing a range of conditions, encompassing neurodegenerative disorders, cancers, cardiovascular diseases, and inflammatory conditions. Additionally, they show efficacy in sustaining a harmonious gut microbiota ecosystem. SLNs were prepared by using solvent emulsification-diffusion technique. The size and morphology of prepared probiotic-loaded SLNs were examined by transmission electron microscopy. The activity or viability of probiotics might be compromised in the challenging gastric conditions of the stomach or in the presence of bile salts. Furthermore, they may face vulnerability to thermal or oxidative stress during preparation and storage. Hence, there is a need for stable probiotic formulations to surmount diverse physicochemical, biopharmaceutical, and biological barriers, ensuring maximal therapeutic effectiveness and clinical applicability. In vitro experiments were carried out with the aim of examining the viability of bacterial cells under gastrointestinal conditions. Encapsulation of the cells protect the cell numbers (colony forming unit) when compared to free bacteria. Nevertheless, the number of probiotic cells decreased in gastrointestinal acidic condition in contrast to free cells. Overall encapsulation of Lactobacillus plantarum in SLN’s plays an important role in enhancing viability and stability which consequently enhance the survival of bacteria against gastrointestinal environmental conditions.

Extraction of Sungkai (Peronema cannescens Jack) leaves, Antioxidant Activity Test and Its Nanoemulsion Formulation

Sungkai (Peronema canescens J.) is an Indonesian native plant widely distributed on the islands of Kalimantan and Sumatra. Potential of these plants is related to the presence of secondary metabolites, which can be obtained through extraction. In its application, plant extract requires a delivery system that can penetrate well into the skin and maximise the efficacy of the active ingredients, such as nanoemulsion, which has high kinetic stability due to the smaller droplet size. The research was conducted to compare the yields from the two extraction methods, the presence of active compounds in the plants related to their properties as antioxidants and then formulated into nanoemulsion. The results showed that Sungkai leaves extract contains active metabolites such as alkaloids, flavonoids, tannins and saponins. The extraction of sungkai leaves yields 15.91% and 14.71% for CE and UAE methods. The total phenolic and flavonoid values were 27.74 and 41.88 mg GAE/g extract; 17.60 and 36.02 mg QE/g extract; and IC50 values of 50.78 and 53.50, included in the strong antioxidant category. Stable nanoemulsion formulation was obtained by adding 1 gram of olive oil with a homogenisation speed of 15000 rpm, with particle size of 83.4 nm and a polydispersity index of 0.455.

Ring-opening polymerization of emulsion-templated deep eutectic system monomer for macroporous polyesters with controlled degradability.

Biodegradable polyesters with interconnected macroporosity, such as poly(l-lactide) (PLLA) and poly(ε-caprolactone) (PCL), have gained significant importance in the fields of tissue engineering and separation. This study introduces functional macroinitiators, specifically polycaprolactone triol (PCLT) and polyethylene glycol (PEG), both OH-terminated, in the solventless ring-opening polymerization (ROP) of a liquid deep eutectic system monomer (DESm) composed of LLA and CL at a 30 : 70 molar ratio, respectively. The macroinitiators selectively initiate the organocatalyzed ROP of LLA in the DESm during the first polymerization stage, thereby modifying the PLLA architecture. This results in the formation of either branched or linear PLLA copolymers depending on the macroinitiator, PCLT and PEG, respectively. In the second stage, the ROP of the CL, which is a counterpart of the DESm, produces PCL that blends with the previously formed PLLA. The insights gained into the PLLA architectures during the first stage of the DESm ROP, along with the overall molecular weight and hydrophobicity of the resulting PLLA/PCL blend in bulk, were advantageously used to design polymerizable high internal phase emulsions (HIPEs) oil-in-DESm. By incorporating a liquid mixture of DESm and macroinitiators (PCLT or PEG), stable HIPE formulations were achieved. These emulsions sustained the efficient organocatalyzed ROP of the continuous phase at 37 °C with high conversions. The resulting polymer replicas of the HIPEs, characterized by macroporous and interconnected structures, were subjected to a degradation assay in PBS at pH 7.4 and 37 °C and remained mechanically stable for at least 30 days. Notably, they exhibited the capability to sorb crude oil in a proof-of-concept test, with a rate of 2 g g-1. The macroporous and interconnected features of the polyHIPEs, combined with their inherent degradation properties, position them as promising degradable polymeric sorbents for efficient separation of hydrophobic fluids from water.

Topical Nanoemulsion Hydrogel Formulated from Supercritical Fluid Extracted Palm-Pressed Fiber Oil and Virgin Coconut Oil with Antioxidant and Antibacterial Effects.

Skincare industries are growing rapidly around the globe but most products are formulated using synthetic chemicals and organic solvent extracted plant extracts, thus may be hazardous to the users and incur higher cost for purification that eventually leads to phytonutrient degradation. Therefore, this study aimed to formulate a stable natural formulation with antioxidant and antimicrobial activities by using supercritical carbon dioxide (SC-CO 2 ) extracted palm-pressed fiber oil (PPFO) as an active ingredient with virgin coconut oil (VCO) as a formulation base. PPFO was extracted from fresh palm-pressed fiber (PPF) while VCO was from dried grated coconut copra using SC-CO 2 before being subjected to the analyses of physicochemical properties, phytonutrient content and biological activities including antioxidant and antimicrobial. The nanoemulgel formulations were then developed and examined for their stability through accelerated stability study for 3 months by measuring their pH, particle size, polydispersity index and zeta potential. The results showed that PPFO contained a high amount of phytonutrients, especially total carotenoid (1497 ppm) and total tocopherol and tocotrienol (2269 ppm) contents. The newly developed nanoemulgels maintained their particles in nano size and showed good stability with high negative zeta potentials. Sample nanoemulgel formulated with 3% PPFO diluted in VCO as effective concentration showed significantly stronger antioxidant activity than the control which was formulated from 3% tocopheryl acetate diluted in mineral oil, towards DPPH and ABTS radicals, with IC 50 values of 67.41 and 44.28 µL/mL, respectively. For the antibacterial activities, the sample nanoemulgel was found to inhibit Gram positive bacteria S. aureus and S. epidermidis growth but not the Gram negative strain E. coli. Overall, this study revealed the potential of SF-extracted PPFO as an active ingredient in the antioxidant topical formulations thus future study on in vitro skin cell models is highly recommended for validation.

Self-microemulsifying drug delivery system as carrier for the oral delivery of glimepiride: Formulation development, optimization, in-vitro characterization, stability assessment, ex-vivo permeation, and in-vivo antidiabetic activity in albino mice

Self-microemulsifying drug delivery system as carrier for the oral delivery of glimepiride: Formulation development, optimization, in-vitro characterization, stability assessment, ex-vivo permeation, and in-vivo antidiabetic activity in albino mice

Synergistic Formulation and Shelf Stability Evaluation of Brown Seaweed (Sargassum sp.) Infused Tisane Enhanced with Butterfly Pea Flower and Sappan Wood

Conventional seaweed beverages often concentrate solely on individual compounds, lacking the integration of complementary herbs. This study aimed to develop a functional tisane using Sargassum sp., butterfly pea flowers, and sappan wood, resulting in an antioxidant-rich tisane with favourable sensory attributes and storage stability. The research consisted of two phases: formulating the functional tisane and evaluating its quality stability. Sargassum sp. tisane contained flavonoids, saponins, phenols, and tannins. Hedonic testing revealed that the composition of Sargassum sp. significantly influenced taste and aroma preferences, with Formula F1 (ginger) achieving the highest taste score of 3.87. Formula F1 included sterols, saponins, and tannins, with an antioxidant content of 9.93 ppm. While the tisane’s pH slightly decreased during storage, importantly antioxidant activity remained consistently high until the end of storage. Microbial and other shelf-life parameters were evaluated using a combination of low-temperature storage and standard food preservatives in sterilized bottles. In conclusion, this study highlighted the potential of formulating a functional tisane using Sargassum sp., butterfly pea flowers, and sappan wood. These findings contributed to an improved comprehension of how to create appealing, stable, and bioactive-rich tisanes by utilizing a combination of marine herbs.

Navigating the challenges of lipid nanoparticle formulation: the role of unpegylated lipid surfactants in enhancing drug loading and stability.

Lipid nanoparticles have proved an attractive approach for drug delivery; however, the challenges of optimising formulation stability and increasing drug loading have limited progression. In this work, we investigate the role of unpegylated lipid surfactants (helper lipids) in nanoparticle formation and the effect of blending helper lipids with pegylated lipid surfactants on the formation and stability of lipid-based nanoparticles by nanoprecipitation. Furthermore, blends of unpegylated/pegylated lipid surfactants were examined for ability to accommodate higher drug loading formulations by means of a higher weight percentage (wt%) of drug relative to total mass of formulation components (i.e. drug, surfactants and lipids). Characterisation included evaluation of particle diameter, size distribution, drug loading and nanoformulation stability. Our findings demonstrate that the addition of unpegylated lipid surfactant (Lipoid S100) to pegylated lipid surfactant (Brij S20) enhances stability, particularly at higher weight percentages of the core material. This blending approach enables drug loading capacities exceeding 10% in the lipid nanoparticles. Notably, Lipoid S100 exhibited nucleating properties that aided in the formation and stabilisation of the nanoparticles. Furthermore, we examined the incorporation of a model drug into the lipid nanoparticle formulations. Blending the model drug with the core material disrupted the crystallinity of the core, offering additional potential benefits in terms of drug release and stability. This comprehensive investigation provides valuable insights into the interplay between surfactant properties, core material composition, and nanoparticle behaviour. The study enhances our understanding of lipid materials and offers guidance for the design and optimisation of lipid nanoparticle formulations.

Formulasi Dan Stabilitas Fisik Krim Ekstrak Daun Kelor (Moringa Oleifera Lamk) Dengan Perbedaan Humektan

One of the medicinal plants used as traditional medicine is kelor (Moringa oleifera Lamk). Moringa leaves are rich in vitamin C and antioxidants which can increase collagen production to prevent and slow down premature aging. The effect of humectants on cream preparations is to obtain creams that have good physical characteristics during storage. This study aims to determine the formulation and physical stability of moringa leaf extract cream preparations (Moringa oliefera Lamk) that meet the requirements. The variations of humectants used in this study include propylenglycol-glycerin (FI), glycerin (FII) and propylenglycol (FIII). Stearic acid, cetyl alcohol (oil phase) were melted on a water bath, TEA, methylparaben, propylparaben, glycerol and distilled water (water phase) were heated. The two phases gradually and grind to form a creamy mass and add the extract. Test the physical quality of the cream for 1 week, namely organoleptic test, homogeneity test, pH test, spreadability test and viscosity test. The results of the cream spreadability test of Moringa leaf extract (Moringa oleifera Lamk) in formula I did not meet the requirements, formula II produced cream preparations that met the requirements with a spreadability range of 5-6 cm, formula III did not meet the requirements. The results of the viscosity test on the formula I, II, III are in the range of 22000-30000 cPs. Based on the results of research on formula II with the addition of the humectant glycerin, it produces a good cream preparation.

Formulation development and stability studies of quinine sulphate suppositories for paediatric use Quinine sulphate suppositories for paediatric use

Rectal administration is preferred to oral and parenteral routes in paediatric population because it is relatively painless while avoiding nausea, vomiting and first pass metabolism. With emergence of chloroquine resistance, quinine is still one of the accepted chemotherapeutic agents against Plasmodium falciparum. The aim of this study is to develop paediatric suppositories of quinine sulphate using FattibaseTM to aid stability, adequate release, ease of administration and affordability. Physical appearance, weight uniformity, hardness, melting range, liquefaction time, drug content uniformity, FTIR and release profile of the suppositories were determined at 27.0±2.0 ᵒC and 4.0±0.5 ᵒC after 0, 1, 4 and 8 weeks. Statistical analysis was done using two-way ANOVA.  FTIR analysis revealed no significant modification occurred in the chemical structure of quinine throughout storage. For suppositories stored at 27.0±2.0 ᵒC, hardness and liquefaction time increased significantly with time. Release of quinine from the fattibaseTM was sustained (quantity released at 120 min, Q120 = 52.16 - 71.16%). Storage time had significant influence (p< 0.05) on all the parameters while storage temperature significantly influenced hardness, liquefaction time, Q120 and drug content. Quinine sulphate suppositories made with fattibaseTM were stable throughout the period of study and will be suitable for peadiatric use

Development and characterization of Tinospora cordifolia extract-loaded SLNs for the treatment of autoimmune hepatitis

Solid Lipid Nanoparticles (SLNs) have emerged as promising drug delivery systems with the potential to enhance the therapeutic efficacy of bioactive compounds. In this study, T. Cordifolia extract-loaded SLNs were developed and characterized for their application in the treatment of autoimmune hepatitis. T. Cordifolia, known for its immunomodulatory and anti-inflammatory properties, was chosen as the active ingredient. The formulations were systematically evaluated for drug-excipient compatibility, particle size, zeta potential, drug loading efficiency, drug release kinetics, encapsulation efficiency, in-vitro release, and stability. The results indicated "No Change" in drug-excipient compatibility, ensuring the formulation's stability. The SLNs exhibited nanoscale particle sizes (159.30 nm to 172.12 nm) with narrow size distributions, facilitating consistent drug delivery. Negative zeta potentials (-28.28 mV to -35.44 mV) indicated colloidal stability. High drug loading efficiencies (up to 32.23%) and controlled drug release kinetics were observed, suggesting the potential for sustained and targeted drug delivery. Encapsulation efficiencies of up to 83.41% highlighted efficient drug loading within the SLNs. In-vitro release studies revealed that SLN2 and SLN4 exhibited superior drug release profiles compared to other formulations. These findings indicate the potential of these formulations for controlled drug delivery. In-vivo efficacy studies in murine models of autoimmune hepatitis are recommended to assess the therapeutic benefits of T. Cordifolia extract-loaded SLNs. Additionally, stability studies demonstrated the maintenance of critical parameters, such as particle size, zeta potential, and drug loading efficiency, under different storage conditions.

Formulasi Dan Evaluasi Sediaan Salep Luka Bakar Basis Hidrokarbon Ekstrak Etanol Daun Katang-Katang (Ipomoea Pescaprae L.) Asal Desa Seith Tahun 2023

Background: Ointment is a semisolid preparation used as a topical medicine, which has direct access to the skin tissues. Katang-katang is one of the medicinal plants traditionally used to treat various types of wounds. Objective: The aim of this study is to identify the secondary metabolite content of katang-katang leaves (Ipomoea pescaprae L.), create and evaluate a good and stable ointment formulation pharmaceutically, and test the irritation of the ointment for burn wounds using ethanol extract of katang-katang leaves (Ipomoea pescaprae L.). Method: The method used is experimental research, the ointment formulation is made using three formulations with different concentrations of active ingredients, with a ratio of FI 20%, FII 25%, and FIII 30%. Result: The results of the study indicate that katang-katang leaves contain flavonoids, tannins, and steroids. The study determined the formulation of a burn ointment from ethanol extract of katang-katang leaves (Ipomoea pescaprae L.). The organoleptic test results of FI, FII, and FIII showed good and stable color, odor, and shape, as well as homogeneity after one week of storage. The pH values measured were 7 for all formulations even after one week of storage. The spreading power of FI was (5.52 cm), FII was (5.88 cm), and FIII was (7.23 cm), which met the standards for good formulation. The irritation tests for all three formulas were categorized as safe. Conclusion: Based on the identification test results, the katang-katang leaves were found to contain flavonoids, tannins, and steroids. The evaluation test results for the three formulations using a hydrocarbon base showed that a good and stable burn ointment could be made from the ethanol extract of katang-katang leaves (Ipomoea pescaprae L.) without causing skin irritation.

Investigation of Oil in Water Emulsion properties depending on the change of Emulsifiers combinations

Oil in water emulsion formulations as dosage forms for topical application are intended to produce the therapeutic effect in the skin. Their quality features mainly depend on the choice of emulsifying combination composition. This work aimed at establishing a mixture of oil phase, water and combinations of different kinds of emulsifiers to screen factors that affect the quality features of oil in water emulsion cream`s formulations. Eleven formulations were prepared with different ratio of different kinds of emulsifiers by a high temperature method. The emulsions were prepared with oil phase having calculated HLB value range 10.96 and emulsifiers having HLB values ranged from 0.20 to 14.60. The formulated oil in water emulsion compositions were evaluated for physical stability, rheological properties, colloidal and thermodynamic stability, microscopy observation. The results showed that not all formulations were physically stable after 24h storage period. Stable formulations were subjected to rheological properties studies. Some of samples presented the flow which was close to the Newtonian fluid, others showed pseudo-plastic flow type. The results of colloidal and thermodynamic stability evaluations allowed to establish the regularities between the type of the flow and formulations` stability. When varying the ratio of emulsifiers, the total HLB range of the mixture changed, which also affected the dispersion properties of emulsion systems. With certain ratios of emulsifiers the dispersion of the system increased.

Development of Topical Formulations Containing 20% of Coated and Uncoated Zinc Oxide Nanoparticles: Stability Assessment and Penetration Evaluation by Reflectance Confocal Laser Microscopy

The introduction of zinc oxide nanoparticles (ZnOn) in sunscreens solved the issue of poor spreadability of these formulations, which often left a white film on the skin. However, safety concerns have arisen regarding the topical application of ZnOn. Some studies employed commercial sunscreens to address the safety issues of the topical application of ZnOn; however, commercial formulations are often complex and contain a wide range of ingredients that could attenuate the potential damage caused by the ZnOn. Therefore, in this study we aimed to develop a simple stable formulation containing 20% of coated and uncoated ZnOn, characterize the formulations and the nanoparticles, and assess the skin penetration in a Franz diffusion cell. The Feret’s diameter for the uncoated and coated ZnOn was 137 nm and 134 nm, respectively. For the uncoated ZnOn the hydrodynamic size in water was 368 nm and for the coated ZnOn, the average hydrodynamic size in ethyl acetate was 135 nm. The incorporation of ZnOn led to formulations more consistent and easier to spread, as suggested by the lower work of shear and higher values of firmness, cohesiveness, consistency and index of viscosity compared with the vehicle. The stability assessment at 45 °C suggested that the formulations containing the ZnOn were stable for 30 days and the vehicle was stable for 90 days. The assessment of the skin penetration by reflectance confocal laser microscopy indicated that the ZnOn did not permeate into the deepest layers of the skin, but accumulated on the skin furrows, hair and hair follicles.

Potency and Powder X-ray Diffraction (PXRD) Evaluation of Levothyroxine Sodium Tablets under Ambient, Accelerated, and Stressed Conditions.

Levothyroxine tablets, although highly prescribed in the United States, have been one of the most frequently recalled products. Because of the importance of the medication, several efforts have been put in place by the United States Food and Drug Administration (US FDA) to control the quality of levothyroxine tablets available to patients using the drug. The choice of excipients used in the formulation has been shown to impact the hygroscopicity and microenvironment, and ultimately the stability of the levothyroxine tablets formulations. Based on information generated from the US FDA Enforcement Report database, one of the main reasons for recalls is the low potency of different batches of the product. The yearly product recall trends for levothyroxine formulations were determined using the FDA Enforcement Report database. Three brands of levothyroxine tablets were selected with excipient lists similar to those products that have been historically recalled. The samples were placed at ambient (~23 °C), accelerated stability (40 °C/75% RH), and stress (50 °C/75% RH) conditions for up to 6 months. Sample potencies were determined at 0, 1.5, 3, and 6 months using the methods for assay and impurities in the United States Pharmacopeia (USP) monograph for levothyroxine tablets. Additional sample monitoring was conducted by overlaying the initial powder X-ray diffractograms (PXRD) of the samples from 0 months with the patterns generated thereafter. There has been a decline in the number of levothyroxine tablets recalled over the years. The highest numbers of recalls were recorded in the years 2013 [33] and 2020 [23]; no recalls occurred in the years 2019 and 2022. All of the brands evaluated met the USP 95.0-105.0% assay requirements at 1.5 months under accelerated conditions; only one of the brands complied at 3 months. Under ambient conditions, two brands were stable at 6 months, with borderline assay results. For stability, levothyroxine was found in microgram quantities in the formulations and PXRD could not detect changes at these low levels. However, we found some distinguishing data for samples under stress conditions.

PEtOxylated polyesteramide nanoparticles for the delivery of anti-inflammatory drugs

Poly(ester amide)s (PEAs) consisting of l-valine (Val), glycolic acid (G), and l-isoleucine (Ile), i.e., PValG and PIleG, and various poly(2-ethyl-2-oxazoline)-block-poly(ester amide) copolymers (PEtOx-b-PEA) were investigated for their suitability as particle-based delivery systems for the anti-inflammatory drugs BRP-187 and BRP-201. A small-scale, high-throughput formulation approach was utilized to evaluate the nanoparticle properties in dependence of the composition of mixtures of PEA homo- and copolymers. Atomistic molecular dynamics simulations of PValG and PIleG with the active ingredients indicated thermodynamic compatibility of the PEAs with the drugs. Drug encapsulation studies confirmed the formation of stable formulations, and the enzymatic degradation of the nanoparticles was also demonstrated. The nanoparticles exhibited no cytotoxicity and were able to efficiently deliver the active pharmaceutical ingredients, i.e., BRP-187 and BRP-201 into macrophages and HEK293 cells. All nanoparticle systems displayed anti-inflammatory effectiveness as they were able to suppress cellular 5-lipoxygenase activity. The most promising effects were obtained with the block copolymer-based PEtOx-b-PEA nanoparticles, which revealed an enhanced performance compared to the control PLGA nanoparticles.

Design, Development, and Characterization of Lyophilized Posaconazole-Loaded Mixed Micelles for Improved Fungal Treatment and Stability

Posaconazole, a BCS class II drug with poor solubility, hampers its absorption in the body, leading to suboptimal drug levels and reduced treatment effectiveness. To address this issue, this research aimed to develop a lyophilized powder of posaconazole-loaded mixed micelles (POS-MMs) using pluronic F68 and soluplus to enhance fungal treatment and stability. A 32 factorial design optimized the POS-MMs formulation by varying PF68 and soluplus concentrations. Various characterization techniques were employed, including particle size analysis, zeta potential measurement, FTIR, DSC, and XRPD. In vitro drug release studies indicated sustained release with 79.4% released within 24 hrs, while in vitro hemolysis studies confirmed biocompatibility. Lyophilization with lactose as a cryoprotectant was successful, yielding a stable formulation over three months. The optimized POS-MMs exhibited a particle size of 66.30 ± 2.10 nm, a high % entrapment efficiency of 94.88 ± 2.4%, and a desirable zeta potential of -25.3±2.8 mV. These findings highlight the potential of POS-MMs to enhance the therapeutic outcomes of posaconazole in the treatment of fungal infections. In addition, lyophilized powder is a promising technique for improving the stability of POS-MMs.