EFFECT OF CHEMICAL ENHANCERS ON THE RELEASE OF GLIPIZIDE IN A MATRIX DISPERSION TRANSDERMAL SYSTEM

Glipizide is one of the most commonly prescribed drugs for treatment of type 2 diabetes.   Oral therapy with Glipizide comprises problems of bioavailability fluctuations and may be associated with severe hypoglycaemia and gastric disturbances. As a potential for convenient, safe and effective antidiabetic therapy, the rationale of this study is to develop a transdermal delivery system for Glipizide in order to improve its therapeutic efficacy.  In the preparation of films, chitosan was used as polymer. Inclusion complex of glipizide with β-Cyclodextrin was formed. The role of different permeation enhancers in the formulation was also studied. The films were characterized for thickness, tensile strength, drug content, moisture uptake, moisture content, and drug release. In vivo and skin irritation studies were performed for the optimized film. Formulation F12 containing Chitosan (1.5percent w/v) and combination of permeation enhancers (Oleic acid: ethanol 1:1.5) showed the highest drug content 99.95percent and the drug release was 99.39percent in a period of 24 hours. The release data fitted into kinetic equations, yielded Higuchi plot and diffusion mechanism of drug release. The physical evaluation indicated the formation of smooth, flexible and translucent films. No skin irritation occurred on rat skin and the infrared studies showed the compatibility of the drug with the formulation excipients. The ex vivo study revealed a constant permeation of drug for long periods. The best permeation enhancer was F12 (Oleic acid: ethanol 1:1.5). The obtained results indicated the feasibility for transdermal delivery of Glipizide using Chitosan. Key words:Glipizide, Diabetes, Transdermal Drug Delivery, β-cyclodextrin, Chitosan, in vitro permeationÂ

Profile of Pediatric Kidney Transplantation at a Tertiary Care Centre in Southern India

Introduction: Renal transplantation offers the best chance of survival to children with End Stage Renal Disease (ESRD). Patient survival and growth are superior in children with a renal allograft compared to dialysis. The aim of the study was to evaluate the outcomes of pediatric transplants done at a tertiary care hospital in Kochi, India over the study period.Materials and Methods: In this retrospective study, the data of children who underwent renal transplantation at Amrita Institute of Medical Sciences from 2002 to 2016 Kochi were analyzed.Results: Thirty-four children underwent renal transplantation over a 14-year period. Thirty-three underwent live related transplant whereas one underwent deceased donor transplantation. The mean age and weight of the recipients at transplantation was 14.3 years and 35.7 kg, respectively. Fourteen children were boys and twenty were girls. Thirty-one patients underwent hemodialysis prior to transplant, 2 were taken up preemptively, and 1 patient was on continuous ambulatory peritoneal dialysis. There were 5 documented urinary tract infections. No surgical complications were noted in the immediate post-transplant period. There were 5 episodes of acute rejection (14.7%). Two cases experienced Delayed Graft Function and the patient survival rate was 100%.Conclusions: Renal transplantation is a viable option to manage children with ESRD with satisfactory long term results and can be done in a developing nation’s set-up. Keywords: Kidney transplantation; India; Child

An evaluation of tocotrienol ethosomes for transdermal delivery using Strat-M® membrane and excised human skin

Tocotrienol (TRF) ethosomes were developed and evaluated in vitro for potential transdermal delivery against melanoma. The optimised TRF ethosomal size ranged between 64.9 ± 2.2 nm to 79.6 ± 3.9 nm and zeta potential (ZP) between −53.3 mV to −62.0 ± 2.6 mV. Characterisation of the ethosomes by ATR-FTIR indicated the successful formation of TRF-ethosomes. Scanning electron microscopy (SEM) images demonstrated the spherical shape of ethosomes, and the entrapment efficiencies of all the formulations were above 66%. In vitro permeation studies using full-thickness human skin showed that the permeation of gamma-T3 from the TRF ethosomal formulations was significantly higher (p < 0.05) than from the control. The cumulative amount of gamma-T3 permeated from TRF ethosome after 48 hours was 1.03 ± 0.24 µg cm−2 with a flux of 0.03 ± 0.01 µg cm−2 h−1. Furthermore, the flux of gamma-T3 across the Strat-M ® and the epidermal membrane was significantly higher than that across full-thickness human skin (p < 0.05). In vitro cytotoxicity studies on HaCat cells showed significantly higher cell viability than the pure drug solution (p < 0.05). The enhanced skin permeation and high cell viability associated with this formulation suggest a promising carrier for transdermal delivery.The present work was funded by the University of Nottingham Malaysia (UNM) and through the open access funding provided by the Qatar National Library. The authors are grateful to ExcelVite Sdn. Bhd. (Perak, Malaysia) for providing TRF and tocotrienol standards

Cigarette smoking dose-response and suicidal ideation among young people in Nepal: a cross-sectional study

Background: Worldwide, tobacco smoking is a major risk factor for morbidity and early mortality among adult population. The present study aimed to find out the association between current smoking and suicidal ideation among young people in Nepal. Materials and Methods: A cross-sectional questionnaire-based survey was carried out among 452 youths from Pokhara, Nepal. The present study included both genders (age 18-24 years) who were smokers as well as non-smokers. Results: Across the study period, 452 participants were identified after matching for age, and sex (226 in the smoking group and 226 in the non-smoking group). The mean age of participants was 21.6±1.2 years and 58.8% were males. The overall rate of suicidal ideation in our cohort was 8.9%. Smokers were slightly more likely to report suicidal ideation than non-smokers (aOR 1.12). The risk of developing suicidal ideation was 3.56 (95% CI 1.26-10.09) times more in individuals who smoked greater than 3.5 cigarettes per week (p=0.01). Conclusion: The rate of suicidal ideation was slightly higher among smokers and a dose-response relationship was identified with the number of cigarettes smoked per week. Being aware of the link between smoking and suicidal ideation may help health care professionals working with young people to address more effectively the issues of mental well-being and thoughts about suicide

An evaluation of crude palm oil (CPO) and tocotrienol rich fraction (TRF) of palm oil as percutaneous permeation enhancers using full-thickness human skin

The drawbacks associated with chemical skin permeation enhancers such as skin irritation and toxicity necessitated the research to focus on potential permeation enhancers with a perceived lower toxicity. Crude palm oil (CPO) is obtained by direct compression of the mesocarp of the fruit of the oil palm belonging to the genus Elaeis. In this research, CPO and tocotrienol-rich fraction (TRF) of palm oil were evaluated for the first time as skin permeation enhancers using full-thickness human skin. The in vitro permeation experiments were conducted using excised human skin mounted in static upright ‘Franz-type’ diffusion cells. The drugs selected to evaluate the enhancing effects of these palm oil derivatives were 5-fluorouracil, lidocaine and ibuprofen: compounds covering a wide range of Log p values. It was demonstrated that CPO and TRF were capable of enhancing the percutaneous permeation of drugs across full-thickness human skin in vitro. Both TRF and CPO were shown to significantly enhance the permeation of ibuprofen with flux values of 30.6 µg/cm2 h and 23.0 µg/cm2 h respectively, compared to the control with a flux of 16.2 µg/cm2 h. The outcome of this research opens further scope for investigation on the transdermal penetration enhancement activity of pure compounds derived from palm oil

Assessment of core capacities for the International Health Regulations (IHR[2005]) – Uganda, 2009

<p>Abstract</p> <p>Background</p> <p>Uganda is currently implementing the International Health Regulations (IHR[2005]) within the context of Integrated Disease Surveillance and Response (IDSR). The IHR(2005) require countries to assess the ability of their national structures, capacities, and resources to meet the minimum requirements for surveillance and response. This report describes the results of the assessment undertaken in Uganda.</p> <p>Methods</p> <p>We conducted a descriptive cross-sectional assessment using the protocol developed by the World Health Organisation (WHO). The data collection tools were adapted locally and administered to a convenience sample of HR(2005) stakeholders, and frequency analyses were performed.</p> <p>Results</p> <p>Ugandan national laws relevant to the IHR(2005) existed, but they did not adequately support the full implementation of the IHR(2005). Correspondingly, there was a designated IHR National Focal Point (NFP), but surveillance activities and operational communications were limited to the health sector. All the districts (13/13) had designated disease surveillance offices, most had IDSR technical guidelines (92%, or 12/13), and all (13/13) had case definitions for infectious and zoonotic diseases surveillance. Surveillance guidelines were available at 57% (35/61) of the health facilities, while case definitions were available at 66% (40/61) of the health facilities. The priority diseases list, surveillance guidelines, case definitions and reporting tools were based on the IDSR strategy and hence lacked information on the IHR(2005). The rapid response teams at national and district levels lacked food safety, chemical and radio-nuclear experts. Similarly, there were no guidelines on the outbreak response to food, chemical and radio-nuclear hazards. Comprehensive preparedness plans incorporating IHR(2005) were lacking at national and district levels. A national laboratory policy existed and the strategic plan was being drafted. However, there were critical gaps hampering the efficient functioning of the national laboratory network. Finally, the points of entry for IHR(2005) implementation had not been designated.</p> <p>Conclusions</p> <p>The assessment highlighted critical gaps to guide the IHR(2005) planning process. The IHR(2005) action plan should therefore be developed to foster national and international public health security.</p

Orally administered amphotericin B nanoformulations:Physical properties of nanoparticle carriers on bioavailability and clinical relevance

Amphotericin B is an effective polyene antifungal considered as a &ldquo;gold standard&rdquo; in the management of fungal infections. Currently, it is administered mainly by IV due to poor aqueous solubility, which precludes its delivery orally. Paradoxically, IV administration is akin to side effects that have not been fully eliminated even with more recent IV formulations. Thus, the need for alternative formulations/route of administration for amphotericin B remains crucial. The oral route offers the possibility of delivering amphotericin B systemically and with diminished side effects; however, enterocyte permeation remains a constraint. Cellular phagocytosis of submicron particles can be used to courier encapsulated drugs. In this regard, nanoparticulate delivery systems have received much attention in the past decade. This review examines the trajectory of orally delivered amphotericin B and discusses key physical factors of nanoformulations that impact bioavailability. The review also explores obstacles that remain and gives a window into the possibility of realizing an oral nanoformulation of amphotericin B in the near future

A Validated Reverse-Phase High Performance Liquid Chromatography (RP-HPLC) Method for the Quantification of Gamma-Tocotrienol in Tocotrienol Rich Fractions of Crude Palm Oil

Background: Palm oil and its constituents have wide applications in food, cosmet-ics and pharmaceutical industries. The tocotrienol-rich fractions of crude palm oil have drawn greater research interest in recent years due to their potent health benefits. Therefore, reliable and validated analytical methods are essential for the quantification of tocotrienols. Objective: This study aimed to develop a simple and economical RP-HPLC method for the quantification of gamma-tocotrienol in tocotrienol-rich fractions of crude palm oil. Methods: An Agilent HPLC system supplied with a Diode Array detector and an auto-injector system was used for the method development, and the wavelength was set 295 nm. A reversed-phase C18 column maintained at 30 °C using a mobile phase composition of methanol: water (95:05) at a flow rate of 1 mL/min was used for the analysis. The developed method was validated according to ICH guidelines. Results and Discussion: A symmetrical peak of gamma-tocotrienol was observed at 8.7 minutes with minimal peak tailing (between 0.76 and 0.78), and an acceptable resolution above 2.0. Excellent linearity was evident with R2 values 0.9996 and 0.9991 for intra-day and inter-day, respectively. The method demonstrated a high precision (%RSD values ≤ 5.8%) and accu-racy (%RE<9.6%). The LOD and LOQ of gamma-tocotrienol were determined as 1.4 μg/mL and 4.2 μg/mL, respectively. The system suitability studies indicate that the chromatographic parameters are well within the acceptable limit. Conclusion: In conclusion, the developed RP-HPLC method is rapid, precise, stable and economical for the quantification of gamma-tocotrienol.The paper has recieved funding from the Faculty of Sci-ence, University of Nottingham Malaysia, for the financial support provided to this research project