Transdermal and Buccal Delivery of Methylxanthines Through Human Tissue In Vitro

ABSTRACT

We examined the in vitro permeation of central nervous stimulants—caffeine, theophylline, and theobromine across human skin with the aid of six chemical enhancers. It was found that oleic acid was the most potent enhancer for all three methylxanthines. Further optimization studies with different solvents showed that caffeine transport could be enhanced to give flux values up to 585 μg/cm².hr^?1. Theobromine and theophylline delivery rates proved insufficient. An additional study involving a buccal tissue equivalent showed that this membrane was more permeable than skin for all model actives tested and would offer an alternate way of delivery.     

To study physical compatibility between dibasic calcium phosphate and cohesive actives using powder rheometer and thermal methods

Aim: An attempt is made to provide better understanding of the compatibility aspect of excipients with different properties of active pharmaceutical ingredient (API) using various rheological, thermal and morphological studies conducted on binary mixtures of Dibasic Calcium Phosphate anhydrous (DCP-A) and Dibasic Calcium Phosphate dihydrate (DCP-D) forms with cohesive API’s (Acetaminophen and Aspirin).

Method: Binary mixtures of DCP’s were prepared by addition of 0% w/w to 50% w/w of the API in each powder blend. Powder rheological analysis were conducted using FT4 powder rheometer, rotational shear cell and empirical approaches such as angle of repose (AOR), Hausner ratio (HR) and Carr’s index (CI). Thermal analysis was conducted using differential scanning calorimetry (DSC) and thermal effusivity. Morphological studies were conducted using Scanning Electron Microscopy (SEM) to determine the fundamental differences between powder materials.

Result/Conclusions: Powder rheometer showed distinctive understanding in the flowability behavior of binary mixtures with addition of increasing proportion of API’s than empirical approaches. Thermal approaches revealed the potential interaction of water of crystallization DCP-D while such interaction was absent in DCP-A. Binary mixtures prepared using DCP-D were better flowable while blends containing DCP-A were better in stability (physical), compressibility and permeability. This study allows the scientist to understand the powder packing of different blends with their flowability and compressibility parameter and helps selection of appropriate form of hydrate for relevant API.     

Crystallization, microstructure development and dielectric behaviour of glass ceramics in the system [SrO · TiO2]-[2SiO2 · B2O3]-La2O3

Various glasses in the system (65 – x)[SrO · TiO₂]-(35)[2SiO₂ · B₂2O₃]-(x)La₂O₃, where x = 1,5,10 (wt%) were prepared by melting in alumina crucible (1375–1575 K). Heat treatment schedules were selected from DTA plots of respective glasses. X-ray diffraction studies of glass ceramic samples containing different concentrations of La₂O₃ revealed the formation of Sr₂B₂O₅, Sr₃Ti₂O₇ and TiO₂ (rutile) phases. The addition of La₂O₃ results in the development of well formed, elongated crystallites of different phases. Results of the dielectric behaviour demonstrate higher values of dielectric constant for some of the glass ceramic samples. This can be ascribed to the relaxation polarization at the crystal-glass interface due to conductivity differences between crystalline and glassy phases.     

Co-delivery of gemcitabine and simvastatin through PLGA polymeric nanoparticles for the treatment of pancreatic cancer: in-vitro characterization,cellular uptake,and pharmacokinetic studies

Despite the ongoing extensive research, cancer therapeutics still remains an area with unmet needs which is hampered by shortfall in the development of newer medicines. The present study discusses a nano-based combinational approach for treating solid tumor. Dual-loaded nanoparticles encapsulating gemcitabine HCl (GM) and simvastatin (SV) were fabricated by double emulsion solvent evaporation method and optimized. Optimized nanoparticles showed a particle size of 258?±?2.4?nm, polydispersity index of 0.32?±?0.052, and zeta potential of ?12.5?mV. The size and the morphology of the particles wee further confirmed by transmission electron microscopy (TEM) and scanning electron microscopy, respectively of the particles. The entrapment efficiency of GM and SV in the nanoparticles was 38.5?±?4.5% and 72.2?±?5.6%, respectively. The in vitro release profile was studied for 60?h and showed Higuchi release pattern. The cell toxicity was done using MTT assay and lower IC₅₀ was obtained with the nanoparticles as compared to the pure drug. The bioavailability of GM and SV in PLGA nanoparticles was enhanced by 1.4-fold and 1.3-fold respectively, compared to drug solution. The results revealed that co-delivery of GM and SV could be used for its oral delivery for the effective treatment of pancreatic cancer.     

Investigation on Some Machinability Aspects of Inconel 825 During Dry Turning

In the current study, attempt has been made to investigate the influence of cutting speed (Vc) (51, 84, and 124 m/min) on various machining characteristics like chip morphology, chip thickness ratio, tool wear, surface, and sub-surface integrity during dry turning of Inconel 825. Comparable study was carried out using uncoated and commercially available chemical vapor deposition multilayer coated (TiN/TiCN/Al₂O₃/ZrCN) cemented carbide (ISO P30 grade) insert. Chip morphology consists of chip forms obtained at different cutting conditions. Serrated chips were observed when machining Inconel 825 with both types of tool with more serration in case of uncoated insert. The chip thickness ratio increased as cutting speed was increased. Use of multilayer coated tool also resulted in increase in chip thickness ratio. Rake and flank surfaces were examined with scanning electron microscope and optical microscope. Abrasion, adhesion, and diffusion wears were found to be dominating tool wear mechanism during dry machining of Inconel 825. The beneficial effect of coated tool over its uncoated counterpart was most prominent during machining at high cutting speed (Vc = 124 m/min). The surface and sub-surface integrity obtained with coated tool were superior to that while machining Inconel 825 with uncoated tool.     

Lentiform fork sign: Uremia alone or multifactorial causation?

Neurological complications are common in patients with acute or chronic renal failure, especially when there is marked reduction in the glomerular filtration rate (GFR). One such clinical syndrome, uremic encephalopathy (UE), occurs due to widespread dysfunction of central nervous system (CNS). It manifests with myriad clinical features and usually is suggested by bedside elicitation of asterixis (flapping tremor). Symptomatic involvement of the basal ganglia manifesting as choreoathetosis and clinical and radiological resolution with hemodialysis has been reported in the medical literature, but only rarely. The present report details such a case.     

Photocatalytic degradation of azo dyes using Au:TiO2, gamma-Fe2O3:TiO2 functional nanosystems

We report photocatalytic degradation studies on Navy Blue HE2R (NB) dye on significant details as a representative from the class of azo dyes using functional nanosystems specifically designed to allow a strong photocatalytic activity. A modified sol-gel route was employed to synthesize Au and gamma-Fe2O3 modified TiO2 nanoparticles (NPs) at low temperature. The attachment strategy is better because it allows clear surface of TiO2 to remain open for photo-catalysis. X-ray diffraction, Raman and UV-VIS spectroscopy studies showed the presence of gold and iron oxide phases along-with the anatase TiO2 phase. TEM studies showed TiO2 nanocomposite particles of size approximately 10-12 nm. A detailed investigation on heterogeneous photocatalytic performance for Navy Blue HE2R dye was done using the as-synthesized catalysts Au:TiO2 and gamma-Fe2O3:TiO2 in aqueous suspension under 8 W low-pressure mercury vapour lamp irradiation. Also, the photocatalytic degradation of Amranth and Orange G azo dyes were studied. The surface modified TiO2 NPs showed significantly improved photocatalytic activity as compared to pure TiO2. Exposure of the dye to the UV light in the presence of pure and gold NPs attached TiO2 catalysts caused dye degradation of about approximately 20% and approximately 80%, respectively, in the first couple of hours. In the presence of gamma-Fe2O3 NPs attached TiO2, a remarkable approximately 95% degradation of the azo dye was observed only in the first 15 min of UV exposure. The process parameters for the optimum catalytic activity are established which lead to a complete decoloration and substantial dye degradation, supported by the values of the Chemical Oxygen Demand (COD) approximately 93% and Total Organic Carbon (TOC) approximately 65% of the treated dye solution after 5 hours on the employment of the UV/Au:TiO2/H2O2 photocatalytic process.     

Synthesis, structure and impedance spectroscopic analysis of [(Pb x Sr1?x )·OTiO2]–[(2SiO2·B2O3)]–7[BaO]–3[K2O] glass ceramic system doped with La2O3

Various compositions of glasses were prepared by melt quenching method in the glass ceramic 64[(Pb _x Sr_1?x )OTiO₂]–25[(2SiO₂·B₂O₃)]–7[BaO]–3[K₂O]–1[La₂O₃] (0.5?≤?x?≤?1) system doped with La₂O₃. Dielectric constant, ε_r versus temperature, T, plots revealed diffused peaks, while dielectric loss, D, versus T plots showed shifting in the peaks toward the higher temperature side similar to relaxor-like ceramics. Curie temperature was found to change systematically with changing the concentration of SrO. Impedance spectroscopy results indicated the contributions of polarization process relaxing in low frequency region attributed to polarizations at the crystal to glass interface and the glassy region.     

Gold nanorods mediated controlled release of doxorubicin: nano-needles for efficient drug delivery

Use of cysteamine hydrochloride (Cys-HCl) protected gold nanorods (GNRs) as efficient carrier of widely used anti-cancer drug doxorubicin using folic acid as navigational molecule is presented in this work. GNRs were found to have excellent drug loading capacity of >97 %. A detailed comprehension of in vitro drug release profile under ideal physiological condition was found to obey 1st order kinetics at pH 6.8, 5.3 and 7.2, an ideal milieu for drug delivery to solid tumours.     

Conduction mechanism and dielectric properties of BiFeO3–BaTiO3 solid solutions

The first measurements are reported for the frequency-dependent conductivity of (1?x)BiFeO₃–xBaTiO₃ (x = 0.10, 0.15 and 0.30) solid solutions in the frequency range of 10⁰–10⁶ Hz and in the temperature range of 50–300 °C. Powder X-ray diffraction confirms the formation of solid solutions. The dielectric properties were seen to improve with increasing BaTiO₃ (BT) content. The conductivity (AC and DC) measurements reveal an inverse variation of the frequency exponent ‘s’ with temperature, high density of states and thermally activated process. The calculated density of states was found to be N(E_f) = 80.2 × 10³² eV^?1 cm^?1 at 1 kHz and 50 °C for BiFeO₃–10 % BaTiO₃ (BFO–10 % BT) solid solution. The impedance spectroscopy analysis confirms the presence of grain and grain boundary affecting the conductivity. Our results provide the first unambiguous evidence of conduction in crystallite BFO–BT solid solutions through correlated-barrier-hopping model.