Solid self microemulsification of Atorvastatin using hydrophilic carriers: a design

Context: Atorvastatin has a limited advantage to formulate oral dosage forms.

Objective: To enhance the solubility of Atorvastatin and to design the suitable solid self-microemulsifying drug delivery systems (S-SMEDDS)

Materials and methods: The clear and transparent self-microemulsifying drug delivery system (SMEDDS) were formulated using coconut oil and isopropyl myristate as lipid phases; Tween 80 as surfactant; PEG 400 and glycerin as co-surfactant at 2:1, 3:1, 1:2 and 1:3 ratio. The pseudo ternary phase diagrams were constructed to identify the microemulsion region. The SMEDDS were evaluated for zeta potential, poly dispersity index, globule size, pH, viscosity and drug release. The solid SMEDDS were developed by employing adsorption and melt granulation methods. The S-SMEDDS were evaluated for micromeritics, morphology, solid state property, reconstitution ability, drug release and stability.

Results: The micro formulations formed with particle size of 25?nm had shown a 3-folds rise in drug release. The solid SMEDDS had reconstituted to a good microemulsion rapidly in 1–3?min, with a release of 94.62% at the end of 30?min and behaved as immediate releasing capsules. Their shelf-life was found to be 1.3 years.

Discussion: The 1:3 ratio SMEDDS had shown more drug release owing to their less particle size. The solid SMEDDS had shown an increased dissolution profiles than atorvastatin. The solid state of the drug had changed in formulation inferring their enhanced solubility.

Conclusion: The solid form of atorvastatin liquid SMEDDS had been formulated successfully with enhanced shelf life and solubility.     

Modification in Surface Chemistry of the Polyetrafluoroethylene Through Chemical Graft Copolymerization for Potential Oil Contamination Control

In the present study, an attempt has been made to design an oleophobic surface through chemical graft copolymerization of methyl methacrylate (MMA) onto polytetrafluroethylene (PTFE) film. The PTFE films were grafted with MMA resulting in PTFE-g-MMA grafts using benzoyl peroxide (BPO) as initiator in aqueous media. Optimum conditions pertaining to maximum percentage of grafting were evaluated by varying time, temperature, initiator, and monomer concentration. The maximum graft yield 9.47% was obtained at [BPO] = 0.03 M, [MMA] = 10%V/V, [reaction temperature] = 50°C and [reaction time] = 120 min. Methyl iodide was used to measure the contact angle, which revealed the oleophobic nature of grafted PTFE-g-MMA film. Maximum contact angle 95.5° of PTFE-g-MMA film was observed at optimum grafting conditions. The surface morphology of PTFE-g-MMA films was studied by Field emission scanning electron microscopy (FE-SEM) and x-ray diffraction (XRD) analysis confirmed the change in structure of PTFE after MMA grafting.     

Antioxidant-Rich Extract from Dehydrated Seabuckthorn Berries by Supercritical Carbon Dioxide Extraction

Seabuckthorn (Hippophae rhamnoides L.) berry oil having high nutraceutical, cosmeceutical, and therapeutic activity has been extracted from dried seabuckthorn (SBT) whole berry powder using supercritical carbon dioxide (SC-CO₂), a green process for extraction of bioactives. The SC-CO₂ process was optimized using Box?CBehnken design. Three SC-CO₂ parameters namely extracting pressure, extracting temperature, and time of extraction were examined. The optimal SC-CO₂ conditions were determined, and the quadratic response surfaces were drawn from the mathematical models. A maximum recovery of 85.12% tocopherol, 71.73% carotene, and an EC₅₀ of 29.02?mg/ml (from DPPH assay) was obtained after SC-CO₂ extraction at 44?°C, 345?bar, and run time of 80?min. Use of methanol as an entrainer at 30% v/w of SBT berry at optimized conditions further increased the extraction efficiency and the potency. This extract can be used for varied nutraceutical, cosmeceutical, and pharmaceutical applications.     

Investigation of platelet activation and calcium store release by a topical hemostatic xerogel dressing for improved blood clotting

Adequate topical hemostatic dressings are required as first-line approach for reduction of uncontrolled hemorrhage, a leading cause of mortalities. Platelets play a major role during blood clotting to prevent hemorrhage during injuries. Here, we demonstrate the mechanisms activated through protease activating receptor 1 (PAR1), a platelet membrane protein in response to a porous composite xerogel dressing incorporating SiNPs (size 122 ± 10 nm) and calcium (2.5 mM), characterized by scanning electron microscopy–energy dispersive x-ray spectroscopy and Fourier transform infrared spectroscopy. The composite displayed 13.9-fold improved blood clotting index in comparison to commercial dressing. The composite displayed increased platelet aggregation due to development of well-formed pseudopodia as compared to bare xerogel, SFLLRN (a thrombin mimic), adenosine di-phosphate (a platelet activator), and heparin (a thrombin inhibitor). Further, PAR1 gene was significantly upregulated in model A549 epithelial cell line (1.2-fold) and human platelets (1.4-fold). The composite enhanced calcium release and its extrusion in A549 cells. Upregulation of PAR1 on the platelet surface and calcium release are crucial for platelet shape change and aggregation. The data indicate that xerogel composite containing SiNPs and calcium enhanced blood clotting through activation of PAR1. Such dressings can provide a potential hemostatic solution to reduce blood loss, disability, and mortality during surgery and trauma care.     

Structural and physical characteristics of Au2O3-doped sodium antimonate glasses – Part II electrical characteristics

In continuation of our earlier investigations on structural and physical characteristics of Au₂O₃-doped sodium antimonate glass-ceramics (Part-1), in this part we have investigated the influence of gold ions on electrical characteristics of the Na₂O–Sb₂O₃: Au₂O₃ glass-ceramics. The study contains the results of quantitate investigations on dielectric properties, impedance spectra and A.C. conductivity in larger ranges of continuous frequencies (4 Hz-8 MHz) and temperatures (300-630 K). The variations exhibited by dielectric parameters with temperature and also with frequency were discussed in terms of various polarization mechanisms. The observed dielectric relaxation effects were analyzed using pseudo Cole-Cole plot method and the analysis indicated spreading of relaxation times for dipoles. A.c. conductivity and also d.c. conductivity were found to decrease (to three orders of magnitude) with increase in Au₂O₃ concentration upto 0.1 mol%. The decrement is ascribed to the increasing concentration of Sb⁵⁺ ions that were predicted to participate in the glass network forming with SbO₄ units. Even though, both ionic and polaronic contributions are possible for conduction in the studied material, quantitative analysis of these results indicated that the polaronic conduction (due to intervalence transfer between Sb³⁺ ↔ Sb⁵⁺ and Au⁰ ↔ Au³⁺) is prevalent. The results have also suggested that there is a gradual decrement in the ionic component with increase in Au₂O₃ concentration. Variation in σ_ac in the low-temperature region could satisfactorily be explained using quantum mechanical tunneling (QMT) model. Analysis of the results of d.c. conductivity indicated that the small polaron hoping (SPH) model is valid, especially in a high-temperature region while the low temperature part of d.c. conductivity is analyzed based on variable range hopping (VRH) model. Overall, the increase in Au₂O₃ dopant concentration in the studied glass-ceramics caused a decrement in the magnitude of the conductivity or increase in the insulating strength of the material.     

EP/AW performance evaluation of some zinc alkyl/dialkyl/alkylaryl‐dithiocarbamates in four‐ball tests

Tribochemistry, the chemistry of interacting surfaces under the influence of a lubricant, helps in the appropriate selection of suitable lubricant additives for specific uses. Modern lubricants are usually formulated from a range of petroleum base oils or synthetic fluids incorporating a variety of chemical additives for performance enhancement. Extreme‐pressure (EP) and anti‐wear (AW) additives are used extensively in lubricants for hypoid gears and metal cutting and forming operations to reduce wear, modify friction, and prevent scuffing of moving metallic parts. The present paper includes the synthesis and the evaluation of the tribological properties of 0.5% (w/v) solutions of some zinc bis‐(alkyl/dialkyl/alkylaryldithiocarbamates) in paraffin oil using 12.7 mm diameter steel bearing ball specimens in four‐ball tests. All the synthesised zinc dithiocarbamate additives in general, and zinc bis‐(morpholinodithio‐carbamate) (A₄) in particular, exhibited good AW, EP, and friction‐reducing properties. Additive A₄ especially gave low values of wear‐scar diameter and coefficient of friction at higher loads and higher values of load wear index and flash temperature parameter during EP tests (ASTM D 2783) and afforded lower values of wear‐scar diameter in a one‐hour wear test (ASTM D 2266–67). The surface topography of the wear‐scar matrix of the used ball specimens was investigated by scanning electron microscopy.     

The Effect of Early Life Stress on Emotional Behaviors in GPR37KO Mice

GPR37 is an orphan G-protein-coupled receptor, a substrate of parkin which is linked to Parkinson’s disease (PD) and affective disorders. In this study, we sought to address the effects of early life stress (ELS) by employing the paradigm of limited nesting material on emotional behaviors in adult GPR37 knockout (KO) mice. Our results showed that, while there was an adverse effect of ELS on various domains of emotional behaviors in wild type (WT) mice in a sex specific manner (anxiety in females, depression and context-dependent fear memory in males), GPR37KO mice subjected to ELS exhibited less deteriorated emotional behaviors. GPR37KO female mice under ELS conditions displayed reduced anxiety compared to WT mice. This was paralleled by lower plasma corticosterone in GPR37KO females and a lower increase in P-T286-CaMKII by ELS in the amygdala. GPR37KO male mice, under ELS conditions, showed better retention of hippocampal-dependent emotional processing in the passive avoidance behavioral task. GPR37KO male mice showed increased immobility in the forced swim task and increased P-T286-CaMKII in the ventral hippocampus under baseline conditions. Taken together, our data showed overall long-term effects of ELS—deleterious or beneficial depending on the genotype, sex of the mice and the emotional context.     

GERT analysis of a two-unit warm standby system with repair

A two-unit warm standby system has been modelled and analysed through GERT approach. A general concept of system utilization factor and availability curve have been introduced.