Development Of Formulations Research Articles

Physicochemical and pharmacotechnical characterization of Prussian blue for future Prussian blue oral dosage forms formulation

Ferric hexacyanoferrate, Fe4 [Fe(CN)6]3 · xH2O, known as Prussian blue (PB), has proven its effectiveness as an antidote in cases of accidental poisoning or poisoning caused by radioactive materials such as cesium (Cs) and thallium (Tl); which due to their solubility in water, when absorbed by the human body, cause serious damage to vital organs. The local development of a drug with PB as an active ingredient arises as a response to the civil and military needs established within the Ministry's pharmacy request for national defense. This fact contemplates the circumstances related to public health protection in the nuclear, radiological, biological and chemical (NRBQ) of the emergency institutions in health and national security. In this paper and by using various analytical techniques, the characterization of the locally synthesized PB with pharmaceutical quality has been described, as a first step to predict its behavior in the preparation of a drug that contains it as an active ingredient.The research findings demonstrate that locally synthesized PB is suitable for use in oral dosage forms, enabling the local development of drug formulations incorporating PB, thus being able to potentially become a main resource in the treatment of Cs and Tl poisoning in any accidental or intended of the population. This development opens up the possibility of creating drug formulations that incorporate PB at a local level, making it a potentially significant resource in the treatment of Cs and Tl poisoning. The ability to locally produce and utilize PB in oral dosage forms could be crucial in addressing cases of accidental or intentional exposure within the population. This advancement not only contributes to the scientific understanding of PB but also holds promising implications for practical applications in public health and emergency situations.

Cooperative dissolution of peptidomimetic vesicles and amyloid β fibrils.

The aggregation of amyloid proteins in the brain is a significant neurotoxic event that contributes to neurodegenerative disorders. The aggregation of amyloid beta (Aβ), particularly Aβ42 monomers, into various forms such as oligomers, protofibrils, fibrils, and amyloid plaques is a key pathological feature in Alzheimer's disease. As a result, Aβ42 is a primary target and the development of molecular strategies for the dissolution of Aβ42 aggregates is considered a promising approach to mitigating Alzheimer's disease pathology. A set of pyrene-conjugated peptidomimetics derived from Aβ14-23 (AkdcPy, AkdmPy, and AkdnPy) by incorporating an unnatural amino acid [kd: cyclo(Lys-Asp)] were studied for their ability to modulate Aβ42 aggregation. AkdcPy and AkdmPy formed vesicular structures in aqueous media. The vesicles of AkdmPy loaded with the neuroprotective compound berberine (Ber), dissipated mutually in the presence of preformed Aβ42 fibrils. During this process, the active drug Ber was released. This work is expected to inspire the development of drug-loaded peptidomimetic-based therapeutic formulations to modulate disorders associated with amyloid toxicity.

Comparative Profitability and Productivity Analysis of Rice Production in Coastal and Arable Land Areas of Bangladesh

This study aims to compare the productivity and profitability of rice production in coastal and arable land areas in Bangladesh while analyzing the factors influencing productivity and profitability. It seeks to provide insights into the differences in agricultural outcomes between these two types of land, essential for policy formulation and agricultural development. The research employs a stratified random sampling method to gather primary data from six villages in Gopalganj and Khulna districts, targeting 30 farmers from each village. Cobb-Douglas profit and production function analysis is utilized to estimate the impact of various factors such as seed cost, labor cost, fertilizer cost, insecticide cost, ploughing cost, and irrigation cost on profitability. The study reveals significant differences in productivity and profitability between coastal and arable land areas for rice cultivation. It identifies key factors affecting productivity and profitability, emphasizing the importance of policy support for enhancing the quality of inputs to bridge yield gaps and improve rice crop outcomes. One limitation of this research is the focus on specific regions within Bangladesh, potentially limiting the generalizability of findings to other areas. Additionally, the study may not capture all variables influencing productivity and profitability due to data constraints. The findings provide valuable insights for policymakers, suggesting the need for targeted interventions to support farmers in improving productivity and profitability. This research contributes to the existing literature by offering empirical evidence on the productivity and profitability dynamics of rice production in coastal and arable land areas in Bangladesh.

Problems and prospects of functional nutrition in Russia: industry and social aspect

In recent years, great importance has been attached to the preservation and strengthening of public health, the role of disease prevention and the formation of a healthy lifestyle, including the formation of a culture of healthy nutrition of the population. Prolonged improper, irrational nutrition is a factor of increased risk of developing diseases: oncological diseases, alimentary risk factors of which are the presence of carcinogenic additives in food products; diseases of the cardiovascular system; obesity; disorders of the gastrointestinal tract due to the low content of dietary fiber in food; osteoporosis is a change in the composition of bones due to the loss of calcium. The analysis of the nutrition structure of the Russian population indicates significant deviations from the recommendations on rational norms of food consumption that meet modern requirements of a healthy diet. In this paper, a matrix method of developing a formula for a fermented milk product with a high protein content is considered by enriching yogurt with vegetable components: hemp flour, jerusalem artichoke syrup and agave syrup. Using the obtained recipes, samples of fermented milk products were prepared and tasting was carried out. According to the organoleptic results, the expediency of using the matrix method of computer modeling in the development of formulations of fermented milk products is confirmed. The resulting yogurts can be recommended for use by people with diabetes and those who lead a healthy lifestyle, because the protein content in the samples has been increased to 3.7% and the introduction of sugar is excluded.

РАЗРАБОТКА РЫБОРАСТИТЕЛЬНЫХ ПИЩЕКОНЦЕНТРАТОВ (СНЕКОВ) ИЗ РЫБ ВНУТРЕННИХ ВОДОЕМОВ

Introduction. Concentrated food products are in great demand for their lengthy storage time, high nutritional value and full readiness for consumption. The range of existing concentrated food products derived from fish is limited by the presence of intermuscular bones, high rates of fish oil oxidization, and by pronounced specific taste and flavor, usually undesirable by the consumers. These reasons contribute to the relevance of the exploration of possible ways to improve marketability and consumer appeal of minced fish and the development of recipes for the mixed fish- and plant-based concentrated food products derived from it. This work is aimed at the development of formulations for the mixed fish- and plant-based concentrated food products (snacks) derived from preprocessed fish mince with improved organoleptic and rheological properties. Over the course of this research, established and currently accepted research methods have been used. Results. It has been found out that rinsing fish mince with 1 % aqueous solution (aqueous system) based on mustard powder allows for the improvement of its texture, color, flavor and taste. With the use of mathematical modeling, optimal proportions (by weight) for the main components of the mixed fish- and plant-based concentrated food products have been identified: fish mince (70–85 %), wheat bran (9–10 %), carrot powder (5 %), and beet powder (10 %). Conclusion. It has been established that 1 % aqueous solution (aqueous system) of mustard powder can be used as a rinsing solution for fish mince to ensure its fresh flavor with pleasant mustard undertones, as well as vastly improved color and texture. The optimized weight percentages of the main components (fish mince, wheat bran, powdered carrot and beet) made it possible to obtain concentrated food products with attractive organoleptic properties.

Formulation Development of Functional Oil Loaded Rizatriptan Benzoate Microemulsion: An In Vitro and Ex Vivo Insight

Formulation Development of Functional Oil Loaded Rizatriptan Benzoate Microemulsion: An In Vitro and Ex Vivo Insight

Photoresponsive 'chemo-free' phytotherapy: formulation development for the treatment of triple-negative breast cancer.

Aim: The present investigation aimed to develop a chemo-free, nanophytosomal system to treat triple-negative breast cancer (TNBC) via a phyto-photo dual treatment strategy. Method: Size, shape, surface analysis, photoprovoked release profile, photothermal stability, (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay, apoptotic assay, DNA fragmentation, in vitro cellular uptake evaluation, mitochondrial membrane potential and caspase-3 assay, andphotodynamic evaluation. Results: Biological experiments using MDA-MB-231 cells displayed dose-dependent synergistic anti-TNBC activity of PhytoS/Houttuynia cordata extract (HCE)/IR780 as compared with Phyto/HCE, PhytoS/IR780 and even more promising under laser treatment. Apoptotic assay and DNA fragmentation analysis also showed enhanced anti-TNBC effects. Investigation found that HCE acts via suppression ofmitochondrial membrane potential and inducing caspase-3 activity in cells. Conclusion: Our findings suggested that photo-empowered phytotherapy can be employed effectively and safely against TNBC.

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

Formulation of Mild Shampoos and Investigation of Possible Prebiotic Effects

Background: Recently, there has been a significant increase in the application of prebiotics in cosmetic products. Thus, this investigation aims to create two mild shampoo compositions, containing inulin; a distinguished prebiotic, and a reference shampoo. As a further step, the efficacy of formulations against strains of Staphylococcus aureus and Staphylococcus epidermidis bacteria, as well as mixed cultures of these two bacteria, was assessed.
 Materials and Methods: After formulation development, physicochemical (physical appearance, pH, percentage of solid contents, viscosity, density and stability studies) and biological evaluations (challenge test, MIC (Minimum inhibition concentration), MBC (Minimum Bactericidal Concentration) were carried out. 
 Results: The results showed that the hair and body shampoo formulas displayed good stability and maintained their physicochemical properties under different conditions over time. Furthermore, they were microbiologically safe according to the challenge test and instrumental analysis. Microbial assays indicated that Shampoo-A promoted the growth of Staphylococcus epidermidis while inhibiting the growth of Staphylococcus aureus in the presence of prebiotic active, whereas Shampoo-B inhibited the growth of both bacteria. 
 Conclusions: Although further research is required to declare the microbiome-related claims, the development of these products holds promise for positive effects on skin health and microbiome.

Unveiling the Power of Burhâni Epistemology in Reshaping Islamic Economic Law for a Fair Financial Landscape

This study aims to explain the concept of burhâni epistemology and its implementation in the development of Islamic economic law formulation. The method used in the research is a literature review (library research) with qualitative descriptive analysis based on empirical normative data to ensure the consistency of the research data. The result of this research is that burhâni epistemology as a logical method or argumentative rationale can be applied to the reality or context analysis of interest-based finance. The practice of imposing interest in the conventional financial system indicates an addition (ziayadah) that can harm one of the parties to the contract (bathil). In addition, the implementation of the burhani method must include the bayani method in the formulation of Islamic economic law because the reasoning process of the concept of interest must be linked to the concept of usury in the text (nash), which must be read and understood textually and contextually. The application of these findings is to review the reality of interest practices in the banking system as a home base in the formulation of Islamic economic laws by eliminating aspects of usury and interest in the financial system. The Burhani method is used to explain banking interest and contractual agreements that incorporate falsehoods like gharar (uncertainty) and injustice (mistreatment) against the parties.

Pharmaceutical Cocrystals: A Novel Systematic Approach for the Administration of Existing Drugs in New Crystalline Form

ABSTRACT: Poor physicochemical properties like solubility, dissolution profile, stability, etc. of drugs remain as an obstacle to formulation development. In the last two decades, pharmaceutical cocrystal gaining lots of interest from researchers as these physicochemical, mechanical, and pharmacokinetic properties can be altered without compromising the therapeutic effect. The multi-component systems wherein one component is essentially the Active Pharmaceutical Ingredient and another may be either one more drug or coformer are termed as pharmaceutical cocrystal. Cocrystal is a novel, promising, and emerging approach to encountering such problems and improving the performance of pharmaceuticals. The present article describes the types, rationale of design, synthesis methods, and characterization of pharmaceutical cocrystals. In addition to this, challenges before and after synthesizing cocrystal along with currently approved formulations based on the pharmaceutical cocrystal approach and cocrystals under clinical investigation are highlighted.

Nose-to-Brain (N2B) Delivery: An Alternative Route for the Delivery of Biologics in the Management and Treatment of Central Nervous System Disorders.

In recent years, there have been a growing number of small and large molecules that could be used to treat diseases of the central nervous system (CNS). Nose-to-brain delivery can be a potential option for the direct transport of molecules from the nasal cavity to different brain areas. This review aims to provide a compilation of current approaches regarding drug delivery to the CNS via the nose, with a focus on biologics. The review also includes a discussion on the key benefits of nasal delivery as a promising alternative route for drug administration and the involved pathways or mechanisms. This article reviews how the application of various auxiliary agents, such as permeation enhancers, mucolytics, in situ gelling/mucoadhesive agents, enzyme inhibitors, and polymeric and lipid-based systems, can promote the delivery of large molecules in the CNS. The article also includes a discussion on the current state of intranasal formulation development and summarizes the biologics currently in clinical trials. It was noted that significant progress has been made in this field, and these are currently being applied to successfully transport large molecules to the CNS via the nose. However, a deep mechanistic understanding of this route, along with the intimate knowledge of various excipients and their interactions with the drug and nasal physiology, is still necessary to bring us one step closer to developing effective formulations for nasal-brain drug delivery.

Formulation development and characterization of galantamine hydrobromide extended-release capsules (8mg)

The aim of the present work is to develop extended-release capsules of Galantamine HBr (8mg) and compare them with the reference listed drug (Reminyl or Razadyne). The capsules were prepared using Pelletization technique and evaluated for preformulation characteristics, physical, and chemical parameters. The In-vitro dissolution studies were conducted using USP type II (paddle apparatus) in 900 ml of pH 6.5 phosphate buffer. Among all the formulations, F7 was found to be pharmaceutically equivalent to reference listed drug due to its similarity factor (f2= 96) in drug release profile. The F7 formulation was loaded for stability study and no change was observed, which indicates that the optimized F7 formulation was stable.

Development and Evaluation of an Eco-Friendly Hand Sanitizer Formulation Valorized from Fruit Peels.

Hand sanitizer usage has proven to be a common and practical method for reducing the spread of infectious diseases which can be caused by many harmful pathogens. There is a need for alcohol-free hand sanitizers because most hand sanitizers on the market are alcohol-based, and regular use of them can damage the skin and can be hazardous. India is the world's largest producer of fruits and one of the major problems after fruit consumption is their peels, causing waste management problems and contributing to the formation of greenhouse gases leading to air pollution and adding to the problem of climate change. Valorization of such wastes into other value-added products and their incorporation into formulations of eco-friendly alcohol-free hand sanitizers would solve these issues, save the environment, benefit the society, and help in achieving the sustainable development goals. Thus, this research focuses on formulating an effective natural alcohol-free hand sanitizer that harnesses the antimicrobial properties of the various types of bioactive components found in fruit peels of pomegranate, sweet lime, and lemon. The peel extracts and the formulated sanitizer proved considerable antimicrobial activity against the pathogenic Escherichia coli and hand microflora. Molecular docking was also applied to examine ligand-protein interaction patterns and predict binding conformers and affinity of the sanitizer phytocompounds towards target proteins in COVID-19, influenza, and pneumonia viruses. The binding affinities and the protein-ligand interactions virtual studies revealed that the sanitizer phytocompounds bind with the amino acids in the target proteins' active sites via hydrogen bonding interactions. As a result, it is possible to formulate a natural, alcohol-free hand sanitizer from fruit peels that is effective against pathogenic germs and viruses using the basic structure of these potential findings.

Flexible Manufacturing with Starch-based Excipient Blends for Early-Stage Drug Product Development

INTRODUCTIONStarch-based excipients have gained attention in early-stage drug product development due to their unique properties and process flexibility. Studies have demonstrated their use in various manufacturing techniques, such as roller compaction, wet granulation, direct compression, and fluid bed granulation (Svačinová, P et al., 2021). These excipients have been shown to improve the compressibility, tabletability, and strength of the final drug product. By conducting laboratory-based compaction analysis early within the formulation and process development may de-risk tablet development (Stewart, S et al, 2021).MATERIALS AND METHODSStarch 1500®  and StarTab® were supplied by Colorcon Ltd, mannitol was obtained from Roquette microcrystalline cellulose (MCC) was provided by IMCD Ltd,and magnesium carbonate (surrogate API) was procured from Scora S.A.S. Blends for direct compression and roller compaction were prepared by mixing the ingredients in a Turbula blender for 10 minutes. The granulation process utilized both fluid bed and high shear granulation techniques, involving the application of water and subsequent drying. The resulting granules/blends were lubricated with 0.5% w/w magnesium stearate and analysed for compaction using a Gamlen™ D-Series compaction analyser.RESULTS AND DISCUSSIONTable 1 shows the formulations of multifunctional excipients like Starch 1500® and StarTab®, combined with plastically deforming MCC and brittle deforming mannitol. These excipient blends were selected to strike the right balance between tablet strength and disintegration, making them suitable for immediate-release drug products.Figure 1 displays tabletability profiles of different formulations from Table 1, produced using various manufacturing processes. The results show that fluidized bed granulation generated the strongest tablets (tensile strength ≥ 1.8 MPa) at all compaction pressures.Roller compaction produced weaker, yet acceptable tablets. Surprisingly, the wet-granulation process, intended to enhance tablet hardness, showed similar tabletability to the DC StarTab® blend. This suggests that high tensile strength tablets can be achieved using the direct compression grade of Starch(StarTab®).Figure 2 presents compressibility profiles(compaction pressure vs solid fraction) of the different processes. The data shows that all combinations have a solid fraction of ≤0.9 at a nominal compression pressure of 200 MPa, indicating minimal risk of over compression.This finding is crucial as over compression can cause undesirable outcomes like capping and lamination. Figure 3 illustrates compactability profiles (solid fraction vs tensile strength) of the blends. The results indicate that the fluid bed granulation process generates the highest tensile strength at similar solid fraction levels. This is likely due to starch activation with water,which acts as a binder and increases compact hardness. Additionally, the fluid bed granulation process promotes granule formation and uniform mixing of excipients, resulting in a more homogenous blend and higher tensile strength.CONCLUSIONSThe study concludes that starch-based powder blends offer process flexibility and compatibility with different manufacturing techniques in the pharmaceutical industry. The results suggest that fluid bed granulation is a more suitable technique for achieving strong tablet blends compared to roller compaction.REFERENCESSvačinová, P., Mužíková, J., & Ondrejček, P.(2021). Comparison of compressibility, compactability, and lubricant sensitivity of two partially pregelatinized starches. Starch/Stärke, 73(1-2),2000166. Stewart, S., Dean, I. L., Lawlor, M. &Lawrence, S., (2022) The Use of Compaction Simulation as a Tool to Aid Successful Tablet Formulation, British Journal of Pharmacy 7(2).

Application of Design of Experiment for development of orally disintegrating tablets

The current work presents the formulation development methodology for Orally Disintegrating Tablets (ODTs) using Design of Experiment (DoE). The statistical software JMP was used to design the experiments and analyse the data for producing sodium Ibuprofen freeze-dried ODTs. In the first stage, several pure excipients (polymers, amino acids, and polyols) were freeze-dried and the quality attributes of the cakes were evaluated. Four critical quality attributes (CQAs) were determined based on the target profile: disintegration time, mechanical strength, moisture uptake, appearance. In the second stage, the placebo tablets comprising sodium alginate, alanine, and mannitol (working as a matrix shape-former and lyo-/cryo-protectors), were designed using Mixture DoE, freeze-dried and characterized to identify the optimal combination of the excipients. In the third stage, the ODTs containing sodium Ibuprofen were designed within a reduced design space to optimize the formulation. The wettability and dissolution of the ODTs were studied. The proposed methodology enabled the estimation of working design space and facilitated the production of freeze-dried ODTs with the required quality attributes. Sodium alginate was identified as the key excipient in the formulation, affecting all CQAs. The optimal combination of sodium alginate, alanine and mannitol corresponding to the desirable target profile was found (30%:40%:30%).

Probing the Protein-Excipient Interaction in the Orally Delivered Protein by Solid-State Hydrogen-Deuterium Exchange Mass Spectrometry and Molecular Dynamics.

The oral administration of protein therapeutics in solid dosage form is gaining popularity due to its benefits, such as improved medication adherence, convenience, and ease of use for patients compared to traditional parental delivery. However, formulating oral biologics presents challenges related to pH barriers, enzymatic breakdown, and poor bioavailability. Therefore, understanding the interaction between excipients and protein therapeutics in the solid state is crucial for formulation development. In this Letter, we present a case study focused on investigating the role of excipients in protein aggregation during the production of a solid dosage form of a single variable domain on a heavy chain (VHH) protein. We employed solid-state hydrogen-deuterium exchange coupled with mass spectrometry (ssHDX-MS) at both intact protein and peptide levels to assess differences in protein-excipient interactions between two formulations. ssHDX-MS analysis revealed that one formulation effectively prevents protein aggregation during compaction by blocking β-sheets across the VHH protein, thereby preventing β-sheet-β-sheet interactions. Spatial aggregation propensity (SAP) mapping and cosolvent simulation from molecular dynamics (MD) simulation further validated the protein-excipient interaction sites identified through ssHDX-MS. Additionally, the MD simulation demonstrated that the interaction between the VHH protein and excipients involves hydrophilic interactions and/or hydrogen bonding. This novel approach holds significant potential for understanding protein-excipient interactions in the solid state and can guide the formulation and process development of orally delivered protein dosage forms, ultimately enhancing their efficacy and stability.

Data-driven development of an oral lipid-based nanoparticle formulation of a hydrophobic drug.

Due to its cost-effectiveness, convenience, and high patient adherence, oral drug administration normally remains the preferred approach. Yet, the effective delivery of hydrophobic drugs via the oral route is often hindered by their limited water solubility and first-pass metabolism. To mitigate these challenges, advanced delivery systems such as solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) have been developed to encapsulate hydrophobic drugs and enhance their bioavailability. However, traditional design methodologies for these complex formulations often present intricate challenges because they are restricted to a relatively narrow design space. Here, we present a data-driven approach for the accelerated design of SLNs/NLCs encapsulating a model hydrophobic drug, cannabidiol, that combines experimental automation and machine learning. A small subset of formulations, comprising 10% of all formulations in the design space, was prepared in-house, leveraging miniaturized experimental automation to improve throughput and decrease the quantity of drug and materials required. Machine learning models were then trained on the data generated from these formulations and used to predict properties of all SLNs/NLCs within this design space (i.e., 1215 formulations). Notably, formulations predicted to be high-performers via this approach were confirmed to significantly enhance the solubility of the drug by up to 3000-fold and prevented degradation of drug. Moreover, the high-performance formulations significantly enhanced the oral bioavailability of the drug compared to both its free form and an over-the-counter version. Furthermore, this bioavailability matched that of a formulation equivalent in composition to the FDA-approved product, Epidiolex®.

Ph-Responsive Drug Delivery System Based on Polymeric Prodrug for Efficient Antitumor Therapy

Ph-responsive micellar nanoparticles in nuclear endosomes were prepared by self-assembling amphiphilic poly (ethylene glycol)-Schiff-doxorubicin (PEG-Schiff-DOX, PSD) predrugs. Self-assembly of an amphiphilic poly (ethylene glycol)-Schiff-doxorubicin (PEG-Schiff-DOX, PSD) prodrug was adopted to prepare endosomal pH-responsive micellar nanoparticles, and the encapsulation of free DOX could be made in the hydrophobic core of the nanoparticles by Schiff base bond. These nanoparticles showed great storage steadiness for above 1 week under normal circumstances but disassembled rapidly to answer faintly acidic environment. Thus, we are able to obtain a simple nano-polymer prodrug material that enables efficient and accurate delivery of tumor drugs and can maintain stability in neutral environments and rapidly degrade in the acidic context of tumor cells. In addition, it benefits from the good stability of PSD with high drug loading concentration and long drug release behavior. According to CCK-8 assays, the nanoparticle showed great antitumor activity over free DOX against HeLa tumor cells. These prodrug-based nanomedicines show excellent potential for the development of translational DOX formulations for cancer therapy.

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.