Development of Chitosan Acetate Films for Transdermal Delivery of Propranolol Hydrochloride

Purpose: To formulate and evaluate chitosan acetate films designed for transdermal delivery of propranolol hydrochloride.Methods: Chitosan acetate was chemically modified with acetaldehyde and the solution was prepared with 1 % acetic acid, in which was dissolved propranolol hydrochloride, was cast as films in Petri dish and characterised by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). The films were evaluated for permeability, swelling, and in vitro drug release.Results: Drug content of propranolol hydrochloride in the films ranged from 0.9 to 1.4 mg/cm2 . Swelling was 570 % for chitosan acetate and 180 % for chitosan while drug release through chitosan acetate higher than through chitosan. Permeability coefficient was 6.12 x 10-4 and 0.97 x 10-4 g.cm2 / day for chitosan acetate and chitosan, respectively. FTIR and DSC results indicated that there was no chemical interaction between the drug and the polymers used. NMR spectra showed the appearance of specific peaks for acetate group. Differences between chitosan acetate and chitosan were significant (p < 0.05) with regard to permeability, swelling and in vitro drug release.Conclusion: The films prepared using the synthesised chitosan acetate exhibited superior physicochemical and drug release characteristics to those of chitosan. The results also indicate chitosan acetate films may be suitable for delivering propranolol hydrochloride via the transdermal route which offers some advantages over other routes.Keywords: Chitosan, Chitosan acetate, Films, Transdermal route, Propranolol hydrochloride, Permeability

Mapping geographical inequalities in access to drinking water and sanitation facilities in low-income and middle-income countries, 2000-17

Background Universal access to safe drinking water and sanitation facilities is an essential human right, recognised in the Sustainable Development Goals as crucial for preventing disease and improving human wellbeing. Comprehensive, high-resolution estimates are important to inform progress towards achieving this goal. We aimed to produce high-resolution geospatial estimates of access to drinking water and sanitation facilities. Methods We used a Bayesian geostatistical model and data from 600 sources across more than 88 low-income and middle-income countries (LMICs) to estimate access to drinking water and sanitation facilities on continuous continent-wide surfaces from 2000 to 2017, and aggregated results to policy-relevant administrative units. We estimated mutually exclusive and collectively exhaustive subcategories of facilities for drinking water (piped water on or off premises, other improved facilities, unimproved, and surface water) and sanitation facilities (septic or sewer sanitation, other improved, unimproved, and open defecation) with use of ordinal regression. We also estimated the number of diarrhoeal deaths in children younger than 5 years attributed to unsafe facilities and estimated deaths that were averted by increased access to safe facilities in 2017, and analysed geographical inequality in access within LMICs. Findings Across LMICs, access to both piped water and improved water overall increased between 2000 and 2017, with progress varying spatially. For piped water, the safest water facility type, access increased from 40.0% (95% uncertainty interval [UI] 39.4-40.7) to 50.3% (50.0-50.5), but was lowest in sub-Saharan Africa, where access to piped water was mostly concentrated in urban centres. Access to both sewer or septic sanitation and improved sanitation overall also increased across all LMICs during the study period. For sewer or septic sanitation, access was 46.3% (95% UI 46.1-46.5) in 2017, compared with 28.7% (28.5-29.0) in 2000. Although some units improved access to the safest drinking water or sanitation facilities since 2000, a large absolute number of people continued to not have access in several units with high access to such facilities (>80%) in 2017. More than 253 000 people did not have access to sewer or septic sanitation facilities in the city of Harare, Zimbabwe, despite 88.6% (95% UI 87.2-89.7) access overall. Many units were able to transition from the least safe facilities in 2000 to safe facilities by 2017; for units in which populations primarily practised open defecation in 2000, 686 (95% UI 664-711) of the 1830 (1797-1863) units transitioned to the use of improved sanitation. Geographical disparities in access to improved water across units decreased in 76.1% (95% UI 71.6-80.7) of countries from 2000 to 2017, and in 53.9% (50.6-59.6) of countries for access to improved sanitation, but remained evident subnationally in most countries in 2017. Interpretation Our estimates, combined with geospatial trends in diarrhoeal burden, identify where efforts to increase access to safe drinking water and sanitation facilities are most needed. By highlighting areas with successful approaches or in need of targeted interventions, our estimates can enable precision public health to effectively progress towards universal access to safe water and sanitation. Copyright (C) 2020 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019.

BACKGROUND: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. METHODS: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). FINDINGS: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1-38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78-0·91) per female living with HIV in 2019, 0·99 male infections (0·91-1·10) for every female infection, and 1·02 male deaths (0·95-1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58-35·43, and a 39·66% decrease in deaths, 36·49-42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05-0·06) and the global incidence-to-mortality ratio was 1·94 (1·76-2·12). No regions met suggested thresholds for progress. INTERPRETATION: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. FUNDING: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

Development of Chitosan Acetate Films for Transdermal Delivery of Propranolol Hydrochloride

Purpose: To formulate and evaluate chitosan acetate films designed for transdermal delivery of propranolol hydrochloride.Methods: Chitosan acetate was chemically modified with acetaldehyde and the solution was prepared with 1 % acetic acid, in which was dissolved propranolol hydrochloride, was cast as films in Petri dish and characterised by Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and nuclear magnetic resonance (NMR). The films were evaluated for permeability, swelling, and in vitro drug release.Results: Drug content of propranolol hydrochloride in the films ranged from 0.9 to 1.4 mg/cm2 . Swelling was 570 % for chitosan acetate and 180 % for chitosan while drug release through chitosan acetate higher than through chitosan. Permeability coefficient was 6.12 x 10-4 and 0.97 x 10-4 g.cm2 / day for chitosan acetate and chitosan, respectively. FTIR and DSC results indicated that there was no chemical interaction between the drug and the polymers used. NMR spectra showed the appearance of specific peaks for acetate group. Differences between chitosan acetate and chitosan were significant (p < 0.05) with regard to permeability, swelling and in vitro drug release.Conclusion: The films prepared using the synthesised chitosan acetate exhibited superior physicochemical and drug release characteristics to those of chitosan. The results also indicate chitosan acetate films may be suitable for delivering propranolol hydrochloride via the transdermal route which offers some advantages over other routes.Keywords: Chitosan, Chitosan acetate, Films, Transdermal route, Propranolol hydrochloride, Permeability

Formulation of Sustained-Release Matrix Tablets Using Cross-linked Karaya Gum

Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using modified karaya gum (MK). Methods: MK was prepared by cross-linking karaya gum with tri-sodium tri-metaphosphate (STMP) which was used as a cross-linker. Matrix tablets of DTZ were prepared using varying ratios of unmodified karaya gum (K) and MK by direct compression. The matrix tablets were evaluated for pharmacotechnical properties and in vitro release, including release kinetics. The optimized formulation was compared with Dilzem SR which served as reference. MK and the formulations were also characterized by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). Results: Tablets with MK showed higher mean dissolution time (MDT) and lower dissolution efficiency than those prepared with karaya gum. Drug release was by water uptake, diffusion and erosion mechanisms. Drug release from tablets formulated with unmodified K at the end of 10 h was 99.9 %, and while for MK tablets, it was 68.2 % at the end of 12h. MK sufficiently controlled drug release unlike K which exhibited poor sustained drug release. Formulation F6 compared well with the reference, Dilzem SR (p <0.05), in terms of release characteristics. Cumulative drug release at the end of 12 h for both test and reference formulations was approx. 85 %. SEM images of the tablets before and after dissolution showed some morphological differences on their tablet surfaces while FTIR and DSC thermogram studies confirmed that there was no chemical interaction between the drug and the polymers in MK formulation. Conclusion: The results of the study demonstrate that modified karaya gum has good potentials for formulating suitable sustained-release matrix tablets of diltiazem

Preparation and Characterization of Sugar Cane Wax Microspheres Containing Indomethacin

Purpose: To formulate and characterize indomethacin (IM) microspheres prepared with sugar cane wax microsperes. Methods: Microspheres were prepared by melt-emulsified dispersion and cooling-induced solidification method. The microspheres were characterized by scanning electron microscopy (SEM) and differntial scanning calorimetry (DSC) as well as for drug loading, and in vitro and in vivo release in albino sheeps. Results: SEM images showed that the microspheres were spherical in shape and more than 98.0 % of the isolated microspheres were in the size range 345 - 360 µm. The Cmax, Tmax, AUCO - 24 and T1/2 values were 2123 ± 30 ng/ml, 3.1 h, 9734 ± 126 ng/ml h−1, and 2.68 ± 0.03 h−1 for the reference product, Microcid® SR, and 1989 ± 26 ng/ml, 3.0 h, 8013 ± 79 ng/ml h−1, and 2.79 ± 0.12 h−1, respectively, for the test formulation. Conclusion: Based on this study, it can be concluded that the developed indomethacin-loaded wax microsheres and Microcid® SR capsule are bioequivalent in terms of rate and extent of absorption

Preparation and Characterization of Sugar Cane Wax Microspheres Containing Indomethacin

Purpose: To formulate and characterize indomethacin (IM) microspheres prepared with sugar cane wax microsperes. Methods: Microspheres were prepared by melt-emulsified dispersion and cooling-induced solidification method. The microspheres were characterized by scanning electron microscopy (SEM) and differntial scanning calorimetry (DSC) as well as for drug loading, and in vitro and in vivo release in albino sheeps. Results: SEM images showed that the microspheres were spherical in shape and more than 98.0 % of the isolated microspheres were in the size range 345 - 360 µm. The Cmax, Tmax, AUCO - 24 and T1/2 values were 2123 ± 30 ng/ml, 3.1 h, 9734 ± 126 ng/ml h−1, and 2.68 ± 0.03 h−1 for the reference product, Microcid® SR, and 1989 ± 26 ng/ml, 3.0 h, 8013 ± 79 ng/ml h−1, and 2.79 ± 0.12 h−1, respectively, for the test formulation. Conclusion: Based on this study, it can be concluded that the developed indomethacin-loaded wax microsheres and Microcid® SR capsule are bioequivalent in terms of rate and extent of absorption