Oral Bioavailability Enhancement Of Poorly Soluble And Poorly Permeable Drugs Using Self-Microemulsifying Drug Delivery Systems And The Effect Of Piperine

There are approximately 40% of new drug molecules discovered and some drugmolecules that are available in the market, having poor bioavailability due to poorsolubility and/or poor permeability. The present study aimed at formulating a selfmicroemulsifying drug delivery system (SMEDDS) using two BCS class IV drugs, namely sulpiride and norfloxacin. Sulpiride is a P-gp substrate and norfloxacin is a substrate of MRP2, BCRP and an unknown efflux pump

Development and Evaluation of Diagnostic Tools for Nucleopolyhedroviruses (NPVs) Infecting Major Lepidopteran Pests of Legume Crops in the Semi-Arid Tropics

The present investigation provides the insight into the evolution of baculoviruses and their hosts and may also aid in the development more effective virus strains for biological control of insects. The improvement of HaNPV-P strain for a successful introduction into biological control for legume pod borer still requires detailed knowledge of the molecular biology of this virus. This study sets the foundation for this and will serve in genetic engineering of the virus to enhance its potential as bio-control agent

Copper signaling axis as a target for prostate cancer therapeutics.

Previously published reports indicate that serum copper levels are elevated in patients with prostate cancer and that increased copper uptake can be used as a means to image prostate tumors. It is unclear, however, to what extent copper is required for prostate cancer cell function as we observed only modest effects of chelation strategies on the growth of these cells in vitro. With the goal of exploiting prostate cancer cell proclivity for copper uptake, we developed a "conditional lethal" screen to identify compounds whose cytotoxic actions were manifested in a copper-dependent manner. Emerging from this screen was a series of dithiocarbamates, which, when complexed with copper, induced reactive oxygen species-dependent apoptosis of malignant, but not normal, prostate cells. One of the dithiocarbamates identified, disulfiram (DSF), is an FDA-approved drug that has previously yielded disappointing results in clinical trials in patients with recurrent prostate cancer. Similarly, in our studies, DSF alone had a minimal effect on the growth of prostate cancer tumors when propagated as xenografts. However, when DSF was coadministered with copper, a very dramatic inhibition of tumor growth in models of hormone-sensitive and of castrate-resistant disease was observed. Furthermore, we determined that prostate cancer cells express high levels of CTR1, the primary copper transporter, and additional chaperones that are required to maintain intracellular copper homeostasis. The expression levels of most of these proteins are increased further upon treatment of androgen receptor (AR)-positive prostate cancer cell lines with androgens. Not surprisingly, robust CTR1-dependent uptake of copper into prostate cancer cells was observed, an activity that was accentuated by activation of AR. Given these data linking AR to intracellular copper uptake, we believe that dithiocarbamate/copper complexes are likely to be effective for the treatment of patients with prostate cancer whose disease is resistant to classical androgen ablation therapies

Bioavailability enhancement of sulpiride by self-microemulsifying drug delivery system

The self-microemulsifying drug delivery system (SMEDDS) was employed to improve the bioavailability of sulpiride, a drug which is poorly soluble. The mean droplet size and emulsification time of the test formulation used for in vivo study were 9.27 ± 2.02 nm and 87 ± 5 s, respectively. When compared with Reference (Dogmatil®), the test formulation exhibited faster in-vitro drug release rate. The Cmax and AUC values of the test formulation were significantly higher than those of Reference, with an enhancement of 210.64% in the extent of absorption in rabbits. In conclusion, SMEDDS could be a potential drug delivery system to enhance the bioavailability of sulpiride.Colegio de Farmacéuticos de la Provincia de Buenos Aire

Carbopol 934, 940 and Ultrez 10 as viscosity modifiers of palm olein esters based nano-scaled emulsion containing ibuprofen

Micro-emulsions and sometimes nano-emulsions are well known candidates to deliver drugs locally. However, the poor rheological properties are marginally affecting their acceptance pharmaceutically. This work aimed to modify the poor flow properties of a nano-scaled emulsion comprising palm olein esters as the oil phase and ibuprofen as the active ingredient for topical delivery. Three Carbopol ® resins: 934, 940 and Ultrez 10, were utilized in various concentrations to achieve these goals. Moreover, phosphate buffer and triethanolamine solutions pH 7.4 were used as neutralizing agents to assess their effects on the gel-forming and swelling properties of Carbopol ® 940. The addition of these polymers caused the produced nano-scaled emulsion to show a dramatic droplets enlargement of the dispersed globules, increased intrinsic viscosity, consistent zeta potential and transparent-to-opaque change in appearance. These changes were relatively influenced by the type and the concentration of the resin used. Carbopol ® 940 and triethanolamine appeared to be superior in achieving the proposed tasks compared to other materials. The higher the pH of triethanolamine solution, the stronger the flow-modifying properties of Carbopol ® 940. Transmission electron microscopy confirmed the formation of a well-arranged gel network of Carbopol ® 940, which was the major cause for all realized changes. Later in vitro permeation studies showed a significant decrease in the drug penetration, thus further modification using 10% w/w menthol or limonene as permeation promoters was performed. This resulted in in vitro and in vivo pharmacodynamics properties that are comparably higher than the reference chosen for this study

Development and biological evaluation of 99mTc-sulfonamide derivatives for in? vivo visualization of CA IX as surrogate tumor hypoxia markers

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Study of Pseudoternary Phase Diagram Behaviour and the Effect of Several Tweens and Spans on Palm Oil Esters Characteristics

Palm oil esters are high molecular weight esters oil that has been newly synthesized by University Putra Malaysia researchers. It has received a lot of attention for its pharmaceutical and chemical application. The aim of this study is to study the effects of the palm oil esters with different HLB surfactant mixture on the ternary diagrams behaviour and to confine the various systems resulted from these combinations. These systems include traditional emulsion, gel area, transpernat micro-emulsion area, O/W and W/O emulsions. In this study, pseudoternary phase diagrams of water, POEs and non-ionic surfactant mixture of several HLB values were constructed using water titration method. The resultant mixtures collected after each addition and mixing of water were analysed visually, along with conductivity, dilution in water and dye test (methylene blue) to classify them as O/W emulsion (transparent and opaque) or W/O (opaque) and liquid or gel. As a conclusion, palm oil esters were found to be suitable for the formulation of different types of emulsion. Additionally, different HLB value of non-ionic surfactant(s) exhibited different pseudoternary phase diagram characteristics.Keywords: palm oil esters, Tween, Span, Pseudoternary phase diagram, O/W emulsio

Modification and Validation of an HPLC Method for Quantification of Piroxicam

Piroxicam is a NSAID that is widely used in the treatment of joint pain and osteoarthritis. The objectives of the study were to modify and validate HPLC method so as to obtain an accurate, sensitive and precise method to quantify piroxicam concentrations without interference from the other ingredients presence in the formulation. The method published by Owen et al. was adapted and modified to suit the above requirements. The modification was carried out on the mobile phase as the mobile phase used by the authors was not able to separate the drug peak from the interference of the formulation excipients. The modified mobile phase consisted of 5 mM of disodium hydrogen phosphate adjusted to pH 3 with concentrated ortho phosphoric acid, methanol, acetonitrile and glacial acetic acid at ratios of 27:20:52:1 respectively. The method was validated and found to be specific, precise, accurate and reproducible even when run at different times of the same day or on different times on different days. The limit of detection and quantification were determined to be 0.035 μg/ml and 0.0625 μg/ml respectively. It could be concluded that this method could be used to determine piroxicam concentration in the samples collected from in vitro study of permeability through the synthetic membrane and excised rat skin.Keywords: Piroxicam, HPLC, Quantification analysis, Modification

Stability Studies of Nano-Scaled Emulsions Containing Ibuprofen for Topical Delivery

Biphasic systems, like emulsions and nano-scaled emulsions, are naturally unstable. The extent and rate of the destabilization process differ from system to another. The stability of such systems upon storage is an important aspect to ensure their abilities to exert the expected effects and consequently render them pharmaceutically acceptable. In the present study, the stability of the nano-scaled emulsion containing newly synthesized palm oil esters (POEs) was assessed under different storage conditions and over specified durations. Three nano-scaled emulsion formulae were chosen for this investigation. They basically comprised ibuprofen as the active ingredient, triethanolamine aqueous solution pH 7.4 as the external phase, POEs as the oil phase, Tween 80 as an emulsifier, Carbopol® 940 as the rheology modifier and menthol or limonene as penetration promoters. The evaluation processes were carried out at several temperatures (4, 25 and 40 °C) with factors, such as droplets size, electrical conductivity, drug content, pH and flow properties were relatively held constant. The data collectively showed that all formulations were stable over an observation period of three months.Keywords: Ibuprofen, nano-scaled emulsion, palm oil esters, stabilit

Stability Studies of Nano-Scaled Emulsions Containing Ibuprofen for Topical Delivery

Biphasic systems, like emulsions and nano-scaled emulsions, are naturally unstable. The extent and rate of the destabilization process differ from system to another. The stability of such systems upon storage is an important aspect to ensure their abilities to exert the expected effects and consequently render them pharmaceutically acceptable. In the present study, the stability of the nano-scaled emulsion containing newly synthesized palm oil esters (POEs) was assessed under different storage conditions and over specified durations. Three nano-scaled emulsion formulae were chosen for this investigation. They basically comprised ibuprofen as the active ingredient, triethanolamine aqueous solution pH 7.4 as the external phase, POEs as the oil phase, Tween 80 as an emulsifier, Carbopol® 940 as the rheology modifier and menthol or limonene as penetration promoters. The evaluation processes were carried out at several temperatures (4, 25 and 40 °C) with factors, such as droplets size, electrical conductivity, drug content, pH and flow properties were relatively held constant. The data collectively showed that all formulations were stable over an observation period of three months.Keywords: Ibuprofen, nano-scaled emulsion, palm oil esters, stabilit