Globule Size Research Articles

Fabrication of carotenoid enriched Crocus sativus w/o nanoemulsion: Optimization and pharmaceutical characterization

Herbal-based preparations have progressively attracted more interest nowadays due to multiple therapeutic approaches. Major concerns with the use of herbal preparations and their application as functional ingredients are about their stability, solubility, and bioaccessibility. Crocus sativus is one of the crucial nootropic traditional herbs, rich in potential phytochemicals used for the treatment of long-standing disorders. Many studies have suggested that the bioactive present in C. sativus extract may undergo enzymatic degradation in the intestine and hence less bioavailable at the site of action. A novel drug delivery approach to herbal preparation may combat the associated challenge. The present research focuses on the feasibility of developing w/o nanoemulsion incorporating the carotenoid-enriched C. sativus extract by spontaneous emulsification method. Critical process variables were optimized using 32 factorial design with Design of Expert software. The optimized formulation of w/o nanoemulsion comprising 9 mg/ml of C. sativus extracts with 12% internal phase, 21% S-mix, and 67% oil phase produced a globule size of 94.34 nm. The total content present in the nanoemulsion was 83% bioactive determined by the High Performance Liquid Chromatography- Photo Diode Array (HPLC-PDA) method. Further characterization, the Transmission Electron Microscopy (TEM) images showed the overall nanoemulsion system morphology with uniform distribution of globules of the internal phase. The in vitro release of bioactives from developed nanoemulsion showed an initial burst release of 60% at 1 hour following slow drug release. Results demonstrated that w/o nanoemulsion of C. sativus extract overcome the associated challenges and may reserve its space for medicinal application.

Prediction of globule size and globule size distribution of emulsion liquid membrane in a pulsed packed column

In this work, the emulsion globule size of an ELM system in a pulsed packed column in different surfactant concentrations was studied for the first time. The emulsion liquid membrane consists of kerosene as a diluent and Span 80 as a surfactant. The effect of surfactant concentration and hydrodynamic parameters, including pulse intensity and flow rates of the dispersed phase and continuous phase, on globule size, was investigated. Based on the results, increasing the concentration of Span 80 up to 3.5 % v/v results in 58–64 % reduction in the Sauter mean diameter (D32) and narrowing the size distribution of the globules. Operating parameters such as pulse intensity and flow rates of continuous and dispersed phases have been investigated so that the influence of flow rates was considerably smaller than the effect of pulse intensity on the globule size distribution. Also, the results showed that with increasing pulse intensity, D32 decreased by 29 %. A new empirical correlation for D32 calculation was also suggested, Featuring 4.91 % average absolute relative error (AARE). Finally, the globule size distribution was predicted using the normal probability function and the dimensionless correlations accurately predicted their parameters and the measured %AARE of α and β were 8.3 and 3.4, respectively.

Pasture feeding improves the nutritional, textural, and techno-functional characteristics of butter

There is an increasing consumer desire for pasture-derived dairy products, as outdoor pasture-based feeding systems are perceived as a natural environment for animals. Despite this, the number of grazing animals globally has declined as a result of the higher milk yields achieved by indoor TMR feeding systems, in addition to the changing climatic conditions and lower grazing knowledge and infrastructure. This has led to the development of pasture-fed standards, stipulating the necessity of pasture and its minimum requirements as the primary feed source for products advertising such claims, with various requirements depending on the region for which it was produced. This work investigates the differences in the composition and techno-functional properties of butters produced from high, medium and no pasture allowance diets during early, mid, and late lactation. Butters were produced using milks collected from 3 feeding systems: outdoor pasture grazing (high pasture allowance); indoor TMR (no pasture allowance); and a partial mixed ration (medium pasture allowance) system, which involved outdoor pasture grazing during the day and indoor TMR feeding at night. Butters were manufactured during early, mid, and late lactation. Creams derived from TMR feeding systems exhibited the highest milk fat globule size. The fatty acid profiles of butters also differed significantly as a function of diet and could be readily discriminated by partial least squares analysis. The most important fatty acids in such an analysis, as indicated by their highest variable importance projection scores, were CLA C18:2 cis-9,trans-11 (rumenic acid), C16:1n-7 trans (trans-palmitoleic acid), C18:1 trans (elaidic acid), C18:3n-3 (α-linolenic acid), and C18:2n-6 (linoleic acid). Increasing pasture allowances resulted in reduced crystallization temperatures and hardness of butters and concurrently increasing the "yellow" color. Yellow color was strongly correlated with Raman peaks commonly associated with carotenoids. The milk fat globule size of cream decreased with advancing stage of lactation and churning time of cream was lowest in early lactation. Differences in the fatty acid and triglyceride contents of butter as a result of lactation and dietary effects demonstrated significant correlations with the hardness, rheological, melting, and crystallization profiles of the butters. This work highlighted the improved nutritional profile and functional properties of butter with increasing dietary pasture allowance, primarily as a result of increasing proportions of unsaturated fatty acids. Biomarkers of pasture feeding (response in milk proportionate to the pasture allowance) associated with the pasture-fed status of butters were also identified as a result of the significant changes in the fatty acid profile with increasing pasture allowance. This was achieved through the use of 3 authentic feeding systems with varying pasture allowances, commonly operated by farmers around the world and conducted across 3 stages of lactation.

Formulation and Characterization of Glucosamine Sulphate Potassium Chloride (GSPC) Loaded Emulgel for the Treatment of Osteoarthritis.

Osteoarthritis (OA) is becoming a major medical burden worldwide due to changing lifestyles and aging populations. Osteoarthritis is a disease characterized by a variety of anatomic and physiological changes to joints, including cartilage degradation, bone remodeling, and the formation of osteophytes. These changes cause pain, stiffness, swelling, and limitations in joint function. Glucosamine serves as a fundamental constituent for cartilage, the resilient connective tissue responsible for cushioning joints. Glucosamine Sulphate Potassium Chloride (GSPC) supplementation is widely employed to mitigate symptoms linked to osteoarthritis, a degenerative joint disorder hallmarked by cartilage degradation. Palliative care aims at minimizing pain and disability and improving function, performance, and quality of life. In this study, the emulgel formulation of GSPC was developed and checked for its potential. Currently, OA does not have a definitive treatment. Since conventional dosage forms cannot deliver the active drug content at a predefined target site in a predictable manner throughout the treatment period, a new carrier system is always required. Considering their reduced size, targeting potential, and site specificity, nanocarrier-based approaches could hold an answer to shortcomings associated with conventional routes. Thus, the objective of the current study was to formulate and characterize glucosamine sulphate potassium chloride-loaded emulgel for the treatment of osteoarthritis. Microemulsion of glucosamine sulphate potassium chloride was formulated using a spontaneous emulsification method comprising of oleic acid (oil phase), Tween 80, Tween 20 (surfactant) and PEG 400, Span 80 (co-surfactant), and distilled water (aqueous phase). The microemulsions were evaluated for surface morphology, globule size, poly-dispersibility index (PDI), zeta potential, and viscosity, and the final batch of microemulsions was selected. The optimized microemulsion contained 35% co-surfactant (propylene glycol), 20% surfactant (Tween 20), and 15% oil (oleic acid) and glucosamine sulphate potassium chloride in a dose of 60 mg, which has sufficient drug loading capacity with a droplet size of 182 nm for optimized formulation. The optimized microemulsion formulation was added to gel prepared by Carbopol 934 in a 1:1 (w/w) ratio, leading to the formulation of glucosamine sulphate potassium chloride- containing emulgel. The prepared emulgel was further evaluated for viscosity, drug content, pH, and in-vitro drug release. Emulgel formulation (F6) showed 88% drug release after 6 hours, and it followed the Higuchi model. Glucosamine Sulphate Potassium Chloride (GSPC) is used in the treatment of OA by increasing the production of proteoglycans, which can cause the cartilage to break down. Emulgel formulation (F3) showed 75.41% drug release, and formulation (F6) showed 88% drug release after 6 h. Therefore, it may be concluded that an emulgel of GSPC can be used as a controlled-release dosage form of the drug for local application in OA.

A New Hyaluronic Emulgel of Hesperetin for Topical Application-An In Vitro Evaluation.

The present study aimed to formulate and characterize a hesperetin formulation to achieve adequate deposition and retention of hesperetin in the epidermis as a target for some cosmetic/dermatological actions. To derive the final emulgel, various formulations incorporating different proportions of Polysorbate 80 and hyaluronic acid underwent testing through a Box-Behnken experimental design. Nine formulations were created until the targeted emulgel properties were achieved. This systematic approach, following the principles of a design of experiment (DoE) methodology, adheres to a quality-by-design (QbD) paradigm, ensuring a robust and purposeful formulation and highlighting the commitment to a quality-driven design approach. The emulsions were developed using the phase inversion method, optimizing the emulgel with the incorporation of hyaluronic acid. Physically stable optimized emulgels were evaluated for their globule size, surface charge, viscosity, pH, electrical conductivity, and hesperetin content. These assays, along with the temperature swing test, were used to select the optimal formulation. It was characterized by a droplet size, d[4,3], of 4.02 μm, a Z-potential of -27.8 mV, an O/W sign, a pH of 5.2, and a creamy texture and proved to be stable for at least 2 months at room temperature. Additionally, in vitro release kinetics from the selected emulgel exhibited a sustained release profile of hesperetin. Skin assays revealed adequate retention of hesperetin in the human epidermis with minimum permeation. Altogether, these results corroborate the promising future of the proposed emulgel in cosmetic or dermatological use on healthy or diseased skin.

Administration of Momordica charantia Linnaeus Extracts for the Treatment of Hypothyroidism Induced Obesity in Mice and Study of Related Biochemical Parameters and Thyroid Histology

Background:: Hypothyroidism is marked by increased Thyroid Stimulating Hormone (TSH) levels and decreased T3 (tri-iodothyronine) and T4 (tetra-iodothyronine/thyroxine) levels. Hypothyroidism-induced obesity has been linked to various metabolism-related abnormalities like slowed down basal metabolic rate (BMR). Momordica charantia Linn. fruit has traditionally been used for reducing obesity. Objective:: Administration of Momordica charantia Linnaeus extracts for the treatment of hypothy-roidism-induced obesity in mice and study of related biochemical parameters and thyroid histology. Methods:: Hypothyroidism-induced obesity was induced by administering methimazole to the mice for 21 consecutive days and then investigating the disease reversal properties of Momordica char-antia aqueous extract, alcoholic extracts, and standard drug thyroxine following their administration to mice for 21 consecutive days. Blood sampling was done to obtain the biochemical parameters normal values, hypothyroidism-induced obesity levels, and levels after treatment with the test ex-tracts. Various biochemical parameters like thyroid profile {TSH, T3, and T4} and lipid profile {Total cholesterol (TC), total triglycerides (TGs), high-density lipoprotein (HDL), and very low-density lipoprotein (VLDL)} and physical parameters like body weight, waist circumference, and food and water intake were measured. Liver and heart were dissected from the mice of each group for oxidative stress measurement by estimation of serum Glutathione (GSH), Malondialdehyde (MDA), and Catalase levels. The thyroid gland was dissected from the mice of each group for histopathological analysis. Results:: Serum MDA levels had significantly increased (p<0.001), whereas the values of GSH and catalase had decreased significantly (0.001) in hypothyroid obese mice. The standard and test groups showed attenuation of MDA levels (p<0.0001) and elevation of GSH (p<0.0001) and cata-lase levels (p<0.0001) back toward normal measurements. After the induction of hypothyroid obe-sity, the thyroid profile and lipid profile both had disturbed significantly and the levels of TSH, TC, TGs, and VLDL elevated, whereas the levels of T3, T4 hormones, and HDL decreased significantly. After the treatment with the test plant extracts and standard drug, the levels of TSH, (p<0.0001) TC (p<0.05), TGs (0.0001), and VLDL (p<0.0001) attenuated and the levels of T3 (p<0.0001), T4 (p<0.0001), and HDL (p<0.0001) elevated back towards the normal range. Histopathological anal-ysis and the hypothyroid obese group thyroid showed significant shrinkage of thyroid globule size wise and a significant decrease in colloid levels when compared with the control group, whereas the standard and test groups showed reversal of the thyroid globule size back towards normal. Conclusion:: The plant extracts can be used as a safe herbal treatment for hypothyroid obesity.

A pilot scale study on the effects of various temperature and time conditions on milk quality using direct and indirect heating systems

Effects of various heating temperatures (124, 129, 134, 140 or 143 °C) and holding times (1 and 4 s) on milk quality using direct and indirect heating systems at pilot scale were investigated. Vitamin degradation was observed for both direct and indirect heating and the degradation increased with increasing temperature and holding time, however, no difference could be seen between heating systems. Slight increase in pH and decrease in ionic calcium for direct heating occurred. An increase in fat globule size and aggregate formation were noted for direct heating with more pronounced effects with increasing temperature. Physical stability of milk was unaffected on day of production; however, after 28 days of storage instability was more apparent for indirect heating. No effect of heating system was observed on colour. This suggests that heating may influence milk quality, however, no clear differences between direct and indirect heating were observed for the quality parameters investigated.

Formulation and Evaluation of Idebenone Microemulsion as a Potential Approach for the Transmucosal Drug Delivery Systems

Idebenone, a synthetic analogue of ubiquinone (Co-Q10), is used for the treatment of Leiber’s hereditary optic neuropathy. Although it is almost completely absorbed from GIT, its extensive rate of metabolism makes its oral bioavailability less than 1%. This study aims to formulate the poorly water-soluble drug as nanoemulsion (NE) to increase drug solubility as well as transmucosal permeation and circumventing hepatic biodegradation by using transmucosal routes of administration such as intranasal rout to enhance drug bioavailability. Nanoemulsion components were selected through screening of the preferential solubility of IDB in several oils and emulsifying agents and subsequent formulation optimization through screening for their best miscibility through phase study. Lemongrass oil showed superior characteristics to represent the oil phase in which the drug was dissolved while Cremophor EL® and Transcutol-P® represented the surfactant system. The method of spontaneous-emulsification was used to prepare twelve NE formulas (F1-F12) which were subjected to several characterization tests. Out of four successful formulas, F-11 showed the best globule size (45.6nm), PDI (0.19) zeta-potential (-2.8 mV), low viscosity and suitable pH (5.9). Using sheep nasal mucosa as model, (F-11) was subjected to ex-vivo transmucosal permeation study against plain drug oil dispersion with pronounced enhanced permeation due to formulation as NEs. Permeation kinetic parameters were obtained such as permeation rate 40.9 µg/h/cm2, lag time 15min, permeability coefficient 40.9x10-4 cm/h and enhancement ratio 39. The outcome of this study indicates the possibility of incorporation of this formula into a suitable carrier for finalizing its formulation as non-enteral dosage form with enhanced IDB bioavailability.

Formulation Development and Evaluation of Microemulsion Loaded Hydrogel Systems with Plant Bioactives in Combination for Treatment of Psoriasis

Psoriasis is an autoimmune, long-lasting skin disorder affecting about 1 to 3% of the world’s population. Plant bio-actives like flavonoids, alkaloids, glycosides, terpenoids, phenolic acids, peptides, tannins, etc., are considered as the best alternative over synthetic drugs, especially for the topical treatment of such chronic skin ailments to avoid side effects of such synthetic agents. The present study aims at the formulation and characterization of novel topical carrier systems for the incorporation of plant bioactive molecules from the class of alkaloids and flavonoids so as to enhance the therapeutic efficacy, bypass the side effects of synthetic drugs, and improve drug localization in the diseased skin to achieve site-specific action. This work created oil, surfactant, and co-surfactant formulations of plant bio-actives using oleic acid, polysorbate 80, and propylene glycol. Different batches of microemulsions with surfactant: Cosurfactant composition ranging from 25 to 34.8% were prepared and were embedded in a hydrogel system containing gelling agents like sodium alginate and carbapol 940 to get ease of topical application in the treatment of psoriasis. These developed micro-emulates (microemulsion loaded hydrogels) were evaluated for various parameters like viscosity, spreadability, content uniformity, microscopic examination, globule size, zeta potential, polydispersibility index, centrifugation test, dilution test, dye test, percent transmittance, conductivity test, etc. The developed formulations were pharmaceutically stable and efficient.

High mobility group box 1 cytokine targeted topical delivery of resveratrol embedded nanoemulgel for the management of atopic dermatitis.

Resveratrol is a polyphenolic compound showing anti-inflammatory activity by inhibition of high mobility group box 1 cytokine responsible for the activation of nuclear factor-κB pathway in atopic dermatitis. To evaluate the efficacy of resveratrol through topical route we have developed resveratrol-loaded nanoemulgel for the effective management of atopic dermatitis in mice model. The resveratrol-loaded nanoemulsion (0.5%, 0.75% and 1% w/w) was optimized by spontaneous nano-emulsification. The optimized resveratrol-loaded nanoemulsions showed average globule size in the 180-230nm range and found to be monodispersed. The resveratrol nanoemulgel was prepared with a SEPINEO™ P 600 gel base and propylene glycol. Ex vivo permeation and retention study resulted in significantly higher skin retention of resveratrol from resveratrol-loaded nanoemulgel than free resveratrol-loaded gel. Preclinical efficacy of resveratrol nanoemulgel displayed promising therapeutic outcomes where, western blotting of skin tissues disclosed a significant reduction in the relative expression of high mobility group box 1, the receptor for advanced glycation end products, toll-like receptor-4 and phosphorylated nuclear factor-κB. Further, real-time polymerase chain reaction also disclosed a significant reduction in pro-inflammatory cytokines such as thymic stromal lymphopoietin, interleukin-4, interleukin-13, interleukin-31, tumor necrosis factor-α and interleukin-6. The histopathological examination of skin sections showed improvement in the skin condition. Collectively, the findings from our study showcased the significant improvement in the atopic dermatitis skin condition in mice model after topical application of resveratrol loaded nanoemulgel.

Microfiltration of milk fat globules for particle size affects key sensory parameters of Cheddar cheese

AbstractDescriptive sensory analysis discriminated between the appearance, aroma, flavor, taste and texture of Cheddar cheese samples prepared from milk varying in fat globule size; small milk fat globule milk (SMM, d4,3 = 2.76 ± 0.07 μm), large milk fat globule milk (LMM, d4,3 = 5.07 ± 0.06 μm) and Control (d4,3 = 3.91 ± 0.09 μm), over a six‐month maturation period. Significant differences were measured between SMM, LMM and the Control as each cheese matured, where SMM was the most different across all parameters examined. SMM was lowest in color intensity (34.6 < 38.8–47.0), firmness (29.4 < 36.1–47.7), and fracturability (24.5 < 28.8–30.7), and highest in cohesiveness (57.0 > 39.8–45.8), adhesiveness (52.9 > 39.0–45.4), and smoothness (50.4 > 37.9–44.0). Moreover, SMM was more intense than the Control in cultured odor (34.9 > 29.6–30.6) and flavor (45.5 > 34.9–36.2), rancid (23.3 > 16.0–18.6) and metallic (17.7 > 14.3) flavor, salty taste (45.7 > 40.3–40.5) and aftertaste (38.5 > 34.9–35.8), sour (36.3 > 28.9) and umami taste (19.6 > 16.4); attributes that align with the degree of maturation. LMM showed similar differences to the Control, but was firmer (36.1 > 29.4), less cohesive (45.8 < 57.0), adhesive (45.4 < 52.9) and smooth (44.0 < 50.4) and had a less intense cultured odor (31.5 < 34.9) than SMM. An increase in salty taste was associated with a decrease in cheese firmness (−0.91, p < 0.0001). These results could provide process‐driven solutions that allow the dairy industry to decrease maturation time or create differentiated cheese products to meet specific consumer tastes or function.

Formulation and optimisation of Ozenoxacin topical nano-emulgel including a comprehensive methodology to qualify and validate the critical parameters of an in-vitro release test method and ex-vivo permeation test

Objective The purpose of this study was to formulate, optimize Ozenoxacin topical nano-emulsion using factorial design followed by to prepare and evaluate nano-emulgel using validated in-vitro release testing (IVRT) technique for determination of Ozenoxacin release rate along with ex-vivo permeation testing (EVPT). Significance: Nano-emulgel is a proven delivery system for poorly soluble substances works by enhancing the solubility and bioavailability. Factorial design provides a systematic and efficient means to study the effect of multiple factors on responses. IVRT is an USP compendia technique utilized for performance analysis of semi-solid formulations. Methods Nano-emulsion formulation optimization was done with factorial design, evaluated for globule size and % entrapment efficiency (EE). Nano-emulgels were characterized for assay, organic impurities, rheological behavior, IVRT, EVPT, and skin retention studies. IVRT validation was executed using vertical diffusion cells (VDCs). Results Ozenoxacin nano-emulsion was optimized with 1:1 ratio of Oil: Smix, 3:1 ratio of Surfactant:Co-Surfactant, and 15000 RPM of homogenization speed which resulted 414.6 ± 5.2 nm globule size and 92.8 ± 2.1% entrapment efficiency. Results confirmed that IVRT and Reversed Phase – High Performance Liquid Chromatographic techniques were validated as per regulatory guidelines. In-vitro, ex-vivo drug release, and skin retention from the optimized nano-emulgel formulation was comparatively higher (∼1.5 times) than that from the innovator (OZANEXTM) formulation. Conclusions Based on these results, Ozenoxacin nano-emulgel can be considered an effective alternative and was found to be stable at 40 °C/75% RH and 30 °C/75% RH storage condition for 6 months.

Prediction of zinc extraction from aqueous solution using iron oxide nanoparticles embedded formulation for tuning emulsion liquid membrane stability

The contamination of industrial wastewater with heavy metals poses a threat to both aquatic and human life. In this study, emulsion liquid membrane (ELM) as a great potential process was applied to remove and recover zinc (Zn) from industrial wastewater. However, the instability of ELM continues to hinder their commercialization. Consequently, this research focuses on studying the stability of water-in-oil-in-water (W/O/W) emulsion in ELM with the aid of nanoparticles in the formulation. The emulsion stability measurement based on volume and pH were applied. Additionally, a digital microscope with a camera is utilized to assess emulsion stability in terms of globule size. ELM formulation with incorporation of iron (III) oxide (Fe2O3) nanoparticles, and blended surfactant (Span 80 and Tween 80) were employed. The research investigates the optimal process parameters for W/O/W emulsion stability. This includes varying parameters such as nanoparticle concentration (0–0.08 % w/v), treat ratio (1:3 – 1:7), agitation speed (200–600 rpm), and time (1 – 5 min). The W/O/W emulsion with the highest stability was achieved at Fe2O3 concentration of 0.04 % (w/v), a treat ratio of 1:3, agitation speed, and time of 300 rpm and 3 min, respectively. Under these stable conditions, Zn extraction was predicted by simulation using a mathematical boundary breakage model of the process. The effects of the treat ratio, concentrations of synergist carrier (D2EHPA and Cyanex 302), stripping agent (acidic thiourea), and external feed phase were examined. The result showed that almost 100 % of Zn was extracted within 3 min at a 1:3 treat ratio, 0.03 M synergist carrier, and 1.37 M acidic thiourea for 50 ppm Zn concentration in the feed phase. This research highlights the tremendous potential of nanoparticle presence in enhancing emulsion stability and improving Zn extraction.

Formulation and Characterization of Self-Microemulsifying Drug Delivery System (SMEDDS) of Sertraline Hydrochloride.

Sertraline hydrochloride is the most widely used selective serotonin reuptake inhibitor (SSRI) for the treatment of several depressive disorders. Its applicability is limited due to extensive metabolism and poor oral bioavailability of 44 %. The current research focused on improving the solubility and oral bioavailability of Sertraline by using microemulsions developed by a self-micro emulsifying drug delivery system (SMEDDS) for significant antidepressant action. SMEDDS were developed by selecting appropriate proportions of oil, surfactant, and co-solvents and out of them isopropyl myristate, tween 80 and propylene glycol were identified as best. The emulsification zone was demonstrated by a ternary phase diagram, and compatibility was confirmed with Fourier-transformed infrared spectroscopy (FT-IR). The formulated SMEDDS were characterized for robustness to dilution, globule size (GS), polydispersity index (PDI), viscosity, in-vitro dissolution and diffusion study, and drug release kinetics study. All the batches (A1-A9) passes the test and A3 was selected as an optimized batch that doesn't show phase separation, precipitation with globule size (101 nm), PDI (0.319), drug content (99.14±0.35 %), viscosity (10.71±0.02 mPa), self-emulsification time (46 sec), in-vitro drug release (98.25±0.22 %) within 8 h, release kinetics (Higuchi) and effective antidepressant in in-vitro diffusion studies. An optimized batch A3 observed circular in shape estimated by Transmission electron microscopy (TEM) and passes all the thermodynamic stability testing with loss of 0.271 mg of the drug after 90 days and showed marked antidepressant action with higher stability.

Enhancing lymphatic uptake of Darunavir Ethanolate through TPGS-enriched lipid nanocarriers for oral delivery

Darunavir ethanolate (DRVE) is a promising molecule against wild-type protease inhibitors in human immunodeficiency virus (HIV) infection. It has a 37% oral bioavailability. In this study, the d-alpha-Tocopheryl Polyethylene Glycol 1000 Succinate (TPGS)-decorated DRVE-loaded lipid nanocarriers (DRVE-TPGS-LNCs) were optimized via central composite rotatable design using a modified solvent emulsification method. Various characteristic features of DRVE-TPGS-LNCs, such as globule size, polydispersity index, zeta potential, % entrapment efficiency, and % drug loading, were determined and found to be 116.5 ± 2.52 nm, 0.269 ± 0.0221, −10.8 ± 0.265 mV, 94.31% ± 10.75%, and 8.79% ± 0.937%, respectively. The spherical shape was evaluated by cryo-transmission electron microscopy. In-vitro study demonstrated % cumulative drug release of 81.70% ± 7.35% at pH 1.2 and 73.03% ± 7.17% at pH 6.8 after 12 h of drug release study. Moreover, the intestinal permeation and confocal microscope studies revealed approximately two-fold increased permeation in optimized nanoformulation across the gut sac compared to a drug suspension, and the inhibition of p-glycoprotein efflux was also confirmed by obtaining a minimum efflux ratio (0.253) of the optimized formulation compared to a drug suspension. The pharmacokinetic study demonstrated that the relative bioavailability of TPGS-DRVE-LNCs and drug suspension were found to be 19.85 ± 1.75 and 8.72 ± 0.753 μg.h/mL, respectively, which is approximately 2.25-fold more than the drug suspension which means approximately threefold increase in oral bioavailability compared to the drug suspension. The increased bioavailability in optimized DRVE-TPGS-LNCs was due to improved lymphatic uptake and p-glycoprotein efflux inhibition. Thus, the improved bioavailability of DRVE can meet the need to reduce the high dose of antiretroviral drugs to minimize the peripheral adverse reactions associated with the dose-related burden.

Formulation Development of Solid Self-Nanoemulsifying Drug Delivery Systems of Quetiapine Fumarate via Hot-Melt Extrusion Technology: Optimization Using Central Composite Design.

Quetiapine fumarate (QTF) was approved for the treatment of schizophrenia and acute manic episodes. QTF can also be used as an adjunctive treatment for major depressive disorders. QTF oral bioavailability is limited due to its poor aqueous solubility and pre-systemic metabolism. The objective of the current investigation was the formulation development and manufacturing of solid self-nanoemulsifying drug delivery system (S-SNEDDS) formulation through a single-step continuous hot-melt extrusion (HME) process to address these drawbacks. In this study, Capmul® MCM, Gelucire® 48/16, and propylene glycol were selected as oil, surfactant, and co-surfactant, respectively, for the preparation of S-SNEDDS. Soluplus® and Klucel™ EF (1:1) were selected as the solid carrier. Response surface methodology in the form of central composite design (CCD) was utilized in the current experimental design to develop the S-SNEDDS formulations via a continuous HME technology. The developed formulations were evaluated for self-emulsifying properties, particle size distribution, thermal behavior, crystallinity, morphology, physicochemical incompatibility, accelerated stability, and in vitro drug release studies. The globule size and emulsification time of the optimized SNEDDS formulation was 92.27 ± 3.4 nm and 3.4 ± 3.38 min. The differential scanning calorimetry (DSC) and powder X-ray diffraction (PXRD) studies revealed the amorphous nature of the drug within the formulation. There were no drug-excipient incompatibilities observed following the Fourier transform infrared (FTIR) spectroscopy. The optimized formulation showed an extended-release profile for 24 h. The optimized formulation was stable for three months (last time-point tested) at 40 °C/75% RH. Therefore, the developed S-SNEDDS formulation could be an effective oral delivery platform for QTF and could lead to better therapeutic outcomes.

Evaluation of the Stability of Newborn Hospital Parenteral Nutrition Solutions.

(1) Background: parenteral nutrition (PN) solutions are an extremely complex mixture. It is composed of a multitude of chemical elements that can give rise to a large number of interactions that condition its stability and safety. The aim of this study was to evaluate the stability of PN solutions for preterm infants. (2) Methods: eight samples were prepared according to the protocol for prescribing PN in preterm infants. Samples PN1-PN7 had the normal progression of macronutrients and standard amounts of micronutrients for a 1 kg preterm infant. The PN8 sample had a high concentration of electrolytes, with the idea of forcing stability limits. Samples were stored both at room temperature and under refrigeration. Measurements of globule size, pH, density, and viscosity were performed in both storage protocols on different days after processing. (3) Results: the changes in the composition of the samples did not affect the evolution of the stability at the different measurement times and temperatures. Viscosity was affected by the compositional changes made in the PN samples, but no alterations due to time or temperature were observed. Density and pH remained stable, without significant changes due to time, storage temperature, or different composition. (4) Conclusion: all samples remained stable during the study period and did not undergo significant alterations due to compositional changes or different experimental conditions.

Enhanced in vitro and ex vivo transdermal permeation of microemulsion gel of tapentadol hydrochloride

Aim of the current study is to develop a microemulsion gel for transdermal delivery of tapentadol hydrochloride. Microemulsion was developed using phase diagram and subjected to assay, globule size, PDI, zeta potential, TEM and in vitro drug release studies. The optimized microemulsion was converted into gel using carbopol 934 NF and evaluated for viscosity, spreadability, in vitro, ex vivo, FTIR, DSC, stability and skin irritation studies. The mean globule size, PDI, zeta potential and in vitro drug release of microemulsion were found 247.3 nm, 0.298, –17.6 mV and 98.42% respectively. In vitro and ex vivo drug release of gel was found 92.2% and 88.6% in 24 h. Viscosity and spreadability results indicated ease of application and no incompatibility was observed from FTIR studies. The skin irritation studies showed absence of erythema. Key findings from the current research concluded that microemulsion gel was suitable for effective transdermal delivery.

Effects of spans on whipping capabilities of aerated emulsions: Reinforcement of fat crystal-membrane interactions

Poor whipping capabilities of anhydrous milkfat based aerated emulsions pose a fresh challenge to food industrial production, limiting their potential applications in tea drinks, coffee, cakes, and desserts. In this study, the effects of high melting- and low melting-Spans on whipping compatibilities of the aerated emulsions were investigated from view of fat crystal-membrane interactions. With an increase in Spans concentration, there was a corresponding decrease in both fat globule size and interfacial protein. However, in comparison with low melting-Span 20 and Span 80, Span 40 and Span 60 with higher melting points have been found to improve anhydrous milkfat crystal matrix in terms of dense (Df > 1.8) and spot-like crystals (5–10 μm). The interfacial film strength was reduced in this case as both long chain-saturated Spans competitively absorb at the membrane, and elasticity-dominant interfacial membrane was further obtained as their crystallization effects. Occurrence and development of partial coalescence of fat globules (>80% at more than 0.5% addition) were therefore promoted with such fat crystal-membrane interactions during whipping, contributing to a significant improvement in whipping capabilities and heat-stable stabilities of foam structures. A mechanism on the effects of Spans on improving whipping capabilities of aerated emulsions was therefore proposed based on the fat crystal-membrane interactions, which will provide guidance to produce high-quality whipped structures for aerated emulsions.

Research of Maillard reaction and stability of liquid infant formulas during storage

SummaryThis study investigated the Maillard reaction (MR) and the stability of liquid infant formulas (LIFs) stored at 5 °C, 25 °C and 40 °C for 6 months. With the increase in storage temperature, the concentrations of 2‐furoylmethyl‐ε‐lysine (furosine) increased from 60.72 to 109.60 mg/100 g protein and Nɛ‐ Carboxy methyl lysine (CML) increased 106.82 to 197.04 mg/100 g protein. Colour became darker, yellower and redder, and pH values decreased. Negative charges increased during the first 3 months and decreased during the last 3 months. Fat globule sizes increased and particle size distribution (PSD) regressed, and the accumulation of fat was clearly observed by confocal laser scanning microscopy (CLSM). Shear thickened with the increase in shear rate, and the turbiscan stability index (TSI) values increased. In summary, these results indicated that lower storage temperature (5 °C) inhibits the MR and reduces unstable changes of LIF during storage period; thus, the nutritional value of LIF can be largely preserved.