Tyloxapol niosomes as prospective drug delivery module for antiretroviral drug nevirapine.

With the aim of assuring more patient compliant pharmacotherapy for acquired immuno deficiency syndrome, a formulation of the first line anti-retroviral drug, nevirapine (NVP), has been developed by encapsulating it within niosomes. Biocompatible niosomes were fabricated using a biological surfactant, tyloxapol, with variable cholesterol concentrations. Formulation with surfactant/cholesterol molar ratio 1:0.1 exhibits maximum stability and optimum hydrophobicity. Thus, it is most suitable for the entrapment of NVP and has high entrapment efficiency of 94.3%. FTIR and DSC results indicate that NVP has sufficient compatibility with the excipients of the formulation. Photoluminescence quenching measurements were employed to elucidate the position of drug molecules in niosome bilayer along with the partition coefficient. Dissolution results indicate that the efflux of drug is sustained which creates a depot effect and decreases the fluctuations in drug release. Such a versatile and improved formulation of NVP is expected to increase its therapeutic index and alleviate toxic systemic side effects while improving the quality of life and duration of survival of the patients.

Hindi translation and validation of the English version of the gastrointestinal symptom rating scale questionnaire: An observational study.

BACKGROUND: The gastrointestinal symptom rating scale (GSRS) is a questionnaire in English language which is designed to assess the clinical symptoms in patients with irritable bowel syndrome (IBS) and peptic ulcer disease. This validated scale has questions on around 15 items and has been validated in patients with dyspepsia and IBS. AIM: To translate and validate the English version of the GSRS questionnaire to the Hindi version. METHODS: The purpose of the present work was to create a Hindi version of this questionnaire for use in the Indian population. The process involved various steps as per the World Health Organization methodology including initial forward translation, backward translation, and assessment by an expert committee. Initial pilot testing was followed by testing in healthy and diseased individuals. RESULTS: The Hindi translation was pilot tested in 20 individuals and further validated in healthy controls (n = 30, 15 females) and diseased individuals (n = 72, 27 females). The diseased group included patients with functional dyspepsia and IBS. Cronbach's alpha for internal consistency on the final translated GSRS questionnaire was 0.715 which is considered adequate. Twelve questions significantly differentiated the diseased population from the healthy population (P value < 0.05) in the translated Hindi version of the GSRS. CONCLUSION: The translated Hindi GSRS can be used to evaluate gastrointestinal function in clinical trials and community surveys in Hindi speaking populations.

Nanotechnology-assisted treatment of pharmaceuticals contaminated water.

The presence of pharmaceutical compounds in wastewater due to an increase in industrialization and urbanization is a serious health concern. The demand for diverse types of pharmaceutical compounds is expected to grow as there is continuous improvement in the global human health standards. Discharge of domestic pharmaceutical personal care products and hospital waste has aggravated the burden on wastewater management. Further, the pharmaceutical water is toxic not only to the aquatic organism but also to terrestrial animals coming in contact directly or indirectly. The pharmaceutical wastes can be removed by adsorption and/or degradation approach. Nanoparticles (NPs), such as 2D layers materials, metal-organic frameworks (MOFs), and carbonaceous nanomaterials are proven to be more efficient for adsorption and/or degradation of pharmaceutical waste. In addition, inclusion of NPs to form various composites leads to improvement in the waste treatment efficacy to a greater extent. Overall, carbonaceous nanocomposites have advantage in the form of being produced from renewable resources and the nanocomposite material is biodegradable either completely or to a great extent. A comprehensive literature survey on the recent advancement of pharmaceutical wastewater is the focus of the present article.

Nanostructures derived from expired drugs and their applications toward sensing, security ink, and bactericidal material.

In this research, a facile and economical route is introduced for the transformation of pharmaceutical waste (i.e., expired medicines) into value-added fluorescent carbon quantum dots (pharmaceutically derived CQDs abbreviated as 'P-CQDs'). The synthesized P-CQDs were identified to have surface functionalities of -OH, C=O, and C=C with an average size of ~2-3 nm and a high quantum yield of 35.3%. The photoluminescence of P-CQDs recorded a maximum optical emission intensity at 2.8 eV (425 nm). The binding of Cu (II) ions by -COOH functionalities on the surface of P-CQDs led to its fluorescence quenching (turn-off) over a wide Cu (II) concentration range of 0.25-50 ppm. The P-CQDs exhibited the detection limit of 0.66 ppm (well below the WHO permissible limit of 2 ppm). The fluorescence intensity of the P-CQDs-Cu (II) complex was recovered from NaHCO3.Hence, their "off-on" behavior was also explored for security ink applications for information encryption and decryption. Moreover, the rich oxygenated groups on the surface of the P-CQDs were utilized for green synthesis of plasmonic Ag@P-CQDs nanostructures, which were also demonstrated to have enhanced potential as bactericidal materials (e.g., against both E. coli and S. aureus). The overall results of this study are demonstrated to help create new and diverse routes for converting expired drugs into value-added nanostructures.

Nevirapine loaded Poloxamer 407/Pluronic P123 mixed micelles: Optimization of formulation and in vitro evaluation.

An attempt has been made to develop polymeric mixed micelle delivery system using Poloxamer 407 and Pluronic P123 for the encapsulation of an antiretroviral drug, Nevirapine. The stability of formulated mixed micellar system at different ratios (1:2, 1:1 and 2:1) and standard thermodynamic parameters of micellization have been determined from the temperature dependence of the critical micelle concentration. The process of micellization of Poloxamer 407/Pluronic P 123 system has been found to be entropy dominant at low temperatures and enthalpy driven at high temperatures. The amity of the different components of mixed micelles has been explored using Fourier transform infrared spectroscopy, Differential scanning calorimeter and X-ray diffraction studies, which rule out the possibility of any interactions between the drug and excipients. Micropolarity measurements infer that the drug is solubilized in the inner core of mixed micelles. In addition, dialysis method has been employed to determine the entrapment efficiency of all the three formulations. The formulation at 1:1 ratio exhibits high entrapment efficiency along with sustained release of the drug.

Pharmacy resident publication success: factors of success based on abstracts from a regional meeting.

OBJECTIVE: To determine the publication rate among pharmacy resident research projects in a region of the United States and to compare characteristics of published and unpublished projects. METHODS: Research project abstracts from the Great Lakes Pharmacy Residency Conference in 2003, 2005, and 2007 were reviewed. Two independent investigators collected all study data. Data on residency year, state, institution, study design, and whether results were reported were extracted from available abstracts. Publication rate was determined systematically using a search algorithm within the following databases: Scopus, International Pharmaceutical Abstracts (IPA), and MEDLINE (PubMed). Kappa-statistic was used to determine inter-rater variability. Descriptive statistics were used to analyze nominal and continuous data. Univariate and multivariate regression analyses were used to determine characteristics of publication success. Sensitivity analysis was performed on projects that were successfully published. RESULTS: Information was extracted from 655 abstracts in which 76 abstracts were published (11.4%). Publication rate trended down over the three years analyzed (2003=12.9%, 2005=12.2%, 2007=9.9%; p=0.57). Study design (interventional, observational, cross-sectional, or service development, p=0.115), direction of inquiry (prospective or retrospective; p=0.146), intervention of interest (drug, human, or other; p=0.096), results in abstract (p=0.096), and institution type (university-affiliated, veterans affairs, community-hospital, or retail; p=0.001) were entered into the multivariate model. Cross-sectional design (odds ratio (OR) 3.6), human (OR 1.9) and other (OR 2.1) interventions, as well as university-affiliated residency (OR 2.6) remained significant for publication success. The mean time to publication from abstract to presentation was 24.5 months, and 83% of projects were published within pharmacy journals. CONCLUSION: Publication rate of pharmacy resident research projects presented at the Great Lakes Pharmacy Residency Conference is low, but it is consistent with other regions of the United States. Study design and study outcomes may influence chance of project publication as well as institution-type, which may have unique research resources, training, and mentorship.

Non-traumatic ileal perforation: a retrospective study.

OBJECTIVE: To determine clinical features, operative findings and post-operative complications in patients operated for non-traumatic ileal perforation and to discuss the role of typhoid vaccination. MATERIALS AND METHODS: A retrospective study was carried out from 2009-2010. Seven patients were admitted through casualty as cases of acute abdomen. Underlying conditions were typhoid ulcers (4 patients) and non-specific etiology (3 patients). Diagnosis was made on clinical grounds, laboratory investigations, radiology and operative findings. Exploratory laporotomy was done. Different variables studied post-operatively were wound infection, residual abscess, recurrence and delayed post-operative complications. RESULTS: Tenderness, distension and rigidity were found in maximum patients. Gases under diaphragm and air fluid levels were common radiological findings. However, widal test and blood culture for S. typhi was positive in four patients. Six patients had single perforation and one patient had two perforations, all being on antimesentric border of ileum. Maximum patients had peritoneal collection of less than 1000 ml. In five patients simple closure of perforation was done and in remaining two resection with end to side ileotransverse anatomosis was required. Wound infection and residual intraabdominal abscess were found in one patient each. CONCLUSION: Management criteria remain same in typhoid and non-specific perforations. Commonest cause of ileal perforation is typhoid fever in our country, so immunization against typhoid beyond 18 years of age is recommended.

Formulation of Tyloxapol niosomes for encapsulation, stabilization and dissolution of anti-tubercular drugs.

The present study delineates the formulation of niosomes from biocompatible surfactant Tyloxapol and their potential as drug delivery system for anti-tuberculosis drugs. Drug loaded niosomes have a size of 150 nm with a loading efficiency of 97.95±0.2, 98.89±0.2 and 99.50±0.2% for rifampicin (RIF), isoniazid (INH), pyrazinamide (PZA), respectively. Fourier transform infrared spectroscopic studies infer that the drugs are in harmony with the fabricated niosomes since no visible interactions between the drug and niosomes have been detected. The prepared formulations are quite stable as assessed using absorption spectroscopy. TEM images and photoluminescence results reveal that RIF and INH are located in the film bilayer whereas PZA is adsorbed mainly on the surface head groups. In vitro dissolution studies at physiological conditions have been undertaken to compare the release behavior of drugs from the prepared niosomes. Sustained release has been achieved for hydrophilic drugs and an acceptable release in case of RIF. Comparison of regression coefficients of different kinetic models reveal that INH release follows Fickian diffusion mechanism whereas RIF and PZA, a non-Fickian release mechanism. Such a versatile system is expected to reduce dose-related drug toxicity and reach the atelectatic areas.

Mixed micelles of Lecithin-Tyloxapol as pharmaceutical nanocarriers for anti-tubercular drug delivery.

The equimolar mixed micellar system of Lecithin-Tyloxapol has been explored using physicochemical and spectroscopic measurements. Thermodynamic parameters have been computed for the prepared mixed micellar system. Interaction parameter, ß, suggests synergistic interactions in the mixed systems. This has been further examined for the solubilization of anti-tuberculosis drugs (ATDs). In addition, the entrapment efficiency of the formulation has been evaluated for three ATDs. Micropolarity measurements indicate location of all the three drugs inside the mixed micellar systems. Fourier transform infrared spectroscopic and differential scanning calorimetric studies infer that the drugs are in harmony with the excipients since no visible interactions between the drugs and mixed micelles have been detected. In vitro release analyses exhibit sustained release of drugs from the formulation. Comparison of regression coefficients of different kinetic models reveal that release of ATDs from mixed micellar system follows first order exponential decay.

Stability of presynaptic vesicle pools and changes in synapse morphology in the amygdala following fear learning in adult rats.

Changes in synaptic strength in the lateral amygdala (LA) that occur with fear learning are believed to mediate memory storage, and both presynaptic and postsynaptic mechanisms have been proposed to contribute. In a previous study we used serial section transmission electron microscopy (ssTEM) to observe differences in dendritic spine morphology in the adult rat LA after fear conditioning, conditioned inhibition (safety conditioning), or naïve control handling (Ostroff et al. [2010] Proc Natl Acad Sci U S A 107:9418-9423). We have now reconstructed axons from the same dataset and compared their morphology and relationship to the postsynaptic spines between the three training groups. Relative to the naïve control and conditioned inhibition groups, the ratio of postsynaptic density (PSD) area to docked vesicles at synapses was greater in the fear-conditioned group, while the size of the synaptic vesicle pools was unchanged. There was significant coherence in synapse size between neighboring boutons on the same axon in the naïve control and conditioned inhibition groups, but not in the fear-conditioned group. Within multiple-synapse boutons, both synapse size and the PSD-to-docked vesicle ratio were variable between individual synapses. Our results confirm that synaptic connectivity increases in the LA with fear conditioning. In addition, we provide evidence that boutons along the same axon and even synapses on the same bouton are independent in their structure and learning-related morphological plasticity.

Quantitative investigation, stability and in vitro release studies of anti-TB drugs in Triton niosomes.

The highly stable innocuous niosomes composed of four components (Triton X 100, polyethylene glycol 2000, water, Span 80) have been prepared successfully and characterized using particle size analyzer, transmission and scanning electron microscopy. The mean size has been found to be in the range 200-300 nm. The optimization of niosomes has been carried out using fluorescence spectroscopy. An attempt has been made to incorporate anti-tuberculosis drugs (ATD's) in the prepared niosomes. The stability and encapsulation efficiency of these drugs in the niosome have also been assessed and high encapsulation efficiency is observed. Such high encapsulation efficiency will serve as an advantage to solve the problem of multi-drug resistance in case of tuberculosis. Release studies and kinetics have been carried out to investigate the release behavior of drugs from the prepared niosomes. Fickian or diffusional release has been observed for rifampicin and isoniazid and a non-Fickian release mechanism for pyrazinamide. Fluorescence probe quenching technique has been used to determine the location and distribution coefficient of the ATD's in niosome/water system.