FORMULATION OPTIMIZATION AND EVALUATION OF FLURBIPROFEN EMULGEL

Objective: The objective of the present study was to formulate flurbiprofen (FLB) emulgel, evaluation of the formulations and the selection of an optimized formulation through in vitro drug release and drug content studies. Flurbiprofen is a non-steroidal anti-inflammatory drug (NSAID) requiring frequent administration and its chronic intake can lead to systemic side effects like gastric irritation and GI bleeding. The development of a dermal drug delivery system can overcome these side effects. Methods: The emulgel formulations were produced using different combinations of oil and emulsifying agents. Carbopol 940 was used as a gelling agent. The prepared emulgels were evaluated for general appearance, pH, spreadability, extrudability, drug content, in vitro drug release, average globule size and viscosity. Results: Optimized formulation F7 showed a better in vitro drug release compared to the marketed gel preparation. The stability study for the optimized formulation was carried out at 25 °C/60 % RH for 3 mo and the emulgel was found to be stable concerning the physical appearance, pH and drug content. Conclusion: The study revolved around the formulation of emulgel containing Flurbiprofen for dermal delivery of the drug. Emulgel was formulated with the purpose to enhance the permeation of poorly water-soluble drug FLB. The study concluded that the optimized emulgel containing FLB exhibited better in vitro drug release profile compared to the marketed formulation

Anisotropic Pair Correlations and Structure Factors of Confined Hard-Sphere Fluids: An Experimental and Theoretical Study

We address the fundamental question: how are pair correlations and structure factors of hard-sphere fluids affected by confinement between hard planar walls at close distance? For this purpose, we combine x-ray scattering from colloid-filled nanofluidic channel arrays and first-principles inhomogeneous liquid-state theory within the anisotropic Percus-Yevick approximation. The experimental and theoretical data are in remarkable agreement at the pair-correlation level, providing the first quantitative experimental verification of the theoretically predicted confinement-induced anisotropy of the pair-correlation functions for the fluid. The description of confined fluids at this level provides, in the general case, important insights into the mechanisms of particle-particle interactions in dense fluids under confinement

Molybdenum nitride nanocrystals anchored on phosphorus-incorporated carbon fabric as a negative electrode for high-performance asymmetric pseudocapacitor

Pseudocapacitors hold great promise to provide high energy-storing capacity; however, their capacitances are still far below their theoretical values and they deliver much lower power than the traditional electric double-layer capacitors due to poor ionic accessibility. Here, we have engineered MoN nanoparticles as pseudocapacitive material on phosphorus-incorporated carbon fabric with enhanced ionic affinity and thermodynamic stability. This nanocomposite boosts surface redox kinetics, leading to pseudocapacitance of 400 mF/cm² (2-fold higher than that of molybdenum nitride-based electrodes) with rapid charge-discharge rates. Density functional theory simulations are used to explain the origin of the good performance of MoN@P-CF in proton-based aqueous electrolytes. Finally, an all-pseudocapacitive solid-state asymmetric cell was assembled using MoN@P-CF and RuO₂ (RuO₂@CF) as negative and positive electrodes, respectively, which delivered good energy density with low relaxation time constant (τ₀) of 13 ms (significantly lower than that of carbon-based supercapacitors).Deepak P. Dubal, Safwat Abdel-Azeim, Nilesh R. Chodankar, and Young-Kyu Ha

Multiple Scale Reorganization of Electrostatic Complexes of PolyStyrene Sulfonate and Lysozyme

We report on a SANS investigation into the potential for these structural reorganization of complexes composed of lysozyme and small PSS chains of opposite charge if the physicochemical conditions of the solutions are changed after their formation. Mixtures of solutions of lysozyme and PSS with high matter content and with an introduced charge ratio [-]/[+]intro close to the electrostatic stoichiometry, lead to suspensions that are macroscopically stable. They are composed at local scale of dense globular primary complexes of radius ~ 100 {\AA}; at a higher scale they are organized fractally with a dimension 2.1. We first show that the dilution of the solution of complexes, all other physicochemical parameters remaining constant, induces a macroscopic destabilization of the solutions but does not modify the structure of the complexes at submicronic scales. This suggests that the colloidal stability of the complexes can be explained by the interlocking of the fractal aggregates in a network at high concentration: dilution does not break the local aggregate structure but it does destroy the network. We show, secondly, that the addition of salt does not change the almost frozen inner structure of the cores of the primary complexes, although it does encourage growth of the complexes; these coalesce into larger complexes as salt has partially screened the electrostatic repulsions between two primary complexes. These larger primary complexes remain aggregated with a fractal dimension of 2.1. Thirdly, we show that the addition of PSS chains up to [-]/[+]intro ~ 20, after the formation of the primary complex with a [-]/[+]intro close to 1, only slightly changes the inner structure of the primary complexes. Moreover, in contrast to the synthesis achieved in the one-step mixing procedure where the proteins are unfolded for a range of [-]/[+]intro, the native conformation of the proteins is preserved inside the frozen core

Pivalic acid assisted Biginelli reaction for synthesis of dihydropyrimidinones and dihydrothiopyrimidinones

Herein is provided an alternate, simple, multigram scale, efficient route for Biginelli reaction for synthesis of dihydropyrimidinones using urea, ethylacetatoacetate, and benzaldehyde with pivalic acid

Pivalic acid assisted Biginelli reaction for synthesis of dihydropyrimidinones and dihydrothiopyrimidinones

677-681Herein is provided an alternate, simple, multigram scale, efficient route for Biginelli reaction for synthesis of dihydropyrimidinones using urea, ethylacetatoacetate, and benzaldehyde with pivalic acid

Nanostructure-specific X-ray tomography reveals myelin levels, integrity and axon orientations in mouse and human nervous tissue

Myelin insulates neuronal axons and enables fast signal transmission, constituting a key component of brain development, aging and disease. Yet, myelin-specific imaging of macroscopic samples remains a challenge. Here, we exploit myelin’s nanostructural periodicity, and use small-angle X-ray scattering tensor tomography (SAXS-TT) to simultaneously quantify myelin levels, nanostructural integrity and axon orientations in nervous tissue. Proof-of-principle is demonstrated in whole mouse brain, mouse spinal cord and human white and gray matter samples. Outcomes are validated by 2D/3D histology and compared to MRI measurements sensitive to myelin and axon orientations. Specificity to nanostructure is exemplified by concomitantly imaging different myelin types with distinct periodicities. Finally, we illustrate the method’s sensitivity towards myelin-related diseases by quantifying myelin alterations in dysmyelinated mouse brain. This non-destructive, stain-free molecular imaging approach enables quantitative studies of myelination within and across samples during development, aging, disease and treatment, and is applicable to other ordered biomolecules or nanostructures

E-cadherin expression and bromodeoxyuridine incorporation during development of ovarian inclusion cysts in age-matched breeder and incessantly ovulated CD-1 mice

BACKGROUND: Female CD-1/Swiss Webster mice subjected to incessant ovulation for 8 months and 12-month breeder mice both developed ovarian inclusion cysts similar to serous cystadenomas. The majority of cysts appeared to be dilated rete ovarii tubules, but high ovulation number resulted in more cortical inclusion cysts. We hypothesized that comparison of inclusion cyst pathology in animals of the same age, but with differences in total lifetime ovulation number, might allow us to determine distinguishing characteristics of the two types of cyst. METHODS: Ovaries from breeder mice (BR) or females subjected to incessant ovulation (IO) were compared at 6-, 9- and 12-months of age. Ovaries were serially sectioned and cysts characterized with regard to location and histology, E-cadherin immunoreactivity and rates of BrdU incorporation. RESULTS: Inclusion cysts developed with age in BR and IO ovaries. The majority of cysts were connected to the ovarian hilus. Two cortical inclusion cysts were observed in ten IO ovaries and one in ten BR ovaries. Low or no E-cadherin immuno-staining was seen in the OSE of all mice studied. Conversely, strong membrane immuno-staining was observed in rete ovarii epithelial cells. Variable E-cadherin immunoreactivity was seen in cells of hilar inclusion cysts, with strong staining observed in cuboidal ciliated cells and little or no staining in flat epithelial cells. Two of the three cortical cysts contained papillae, which showed E-cadherin immuno-staining at the edge of cells. However hilar and cortical cysts were not distinguishable by morphology, cell type or E-cadherin immunoreactivity. BrdU incorporation in cyst cells (1.4% [95% CI: 1.0 to 2.1]) was greater than in OSE (0.7% [95% CI: 0.4 to 1.2]) and very few BrdU-labeled cells were observed in rete ovarii at any age. Incessant ovulation significantly increased BrdU incorporation in OSE of older animals. CONCLUSION: These experiments confirm ovarian inclusion cysts develop with age in the CD-1 mouse strain, irrespective of total ovulation burden. We conclude longer periods of incessant ovulation do not lead to significant changes in inclusion cyst formation or steroidogenesis in CD-1 mice and inclusion cyst type can not be distinguished by morphology, cell proliferation rate or E-cadherin immunoreactivity

Expression of Activated PIK3CA in Ovarian Surface Epithelium Results in Hyperplasia but Not Tumor Formation

activation is one of the early genetic events in ovarian cancer. However, its role in malignant transformation of ovarian surface epithelium (OSE) is largely unclear..

Optimisaton techniques: a futuristic approach for formulating and processing of pharmaceuticals

Designing and formulating an ideal pharmaceutical product is a very tedious job for a formulator as it comprises of multiple objectives. The traditional method followed for years is not only expensive and time consuming but it also needs lot of effort to be put in and in spite of that at times it proves to be unfavourable and unpredictable too.The recent approach to optimise i.e. to achieve the best combination of product and process characteristics under the given conditions is by using Design of Experiment (DoE).Design of Experiment (DoE) is an organised approach to determine the relationship between the factors (Xs) affecting a process and the output of that process (Ys).The recent optimisation methodologies include various approaches that come under the 2 main categories namely, simultaneous optimisation and sequential optimisation. Nowadays there are various software available to carry out the optimisation of pharmaceutical products