Development of a Gastroretentive Drug Delivery System based on Superporous Hydrogel

Purpose: The aim of this work was to synthesize superporous hydrogels of rosiglitazone using chitosan and to study its swelling behaviour for application as a gastroretentive drug delivery system. Methods: Chitosan superporous hydrogels were synthesized using glyoxal as a crosslinking agent by gas blowing method. The effect of pH and ionic strength on the swelling ratio was determined. Swelling reversibility studies were also carried out. Fourier transform infrared (FTIR) analysis was undertaken to characterize the superporous hydrogels while dissolution studies were carried out to assess release characteristics. Results: Swelling was highly dependent on the extent of crosslinking. The higher the amount of crosslinking agent, the lower the swelling ratio. Higher ionic strength in pH 1.2 solution led to a decrease in swelling ratio. The superporous hydrogels were highly sensitive to pH of swelling medium, and showed reversible swelling and de-swelling behaviour while still maintaining their mechanical stability. Apparent density was dependent on the volume of the superporous hydrogels and decreased with increasing crosslink density. Degradation kinetics showed that chitosan superporous hydrogels had good water retention capability. Drug release was inversely related to the amount of crosslinking agent and fitted best to the Korsmeyer-Peppas model. Conclusion: The studies showed that chitosan-based superporous hydrogels can be used as a gastroretentive drug delivery system in view of their swelling characteristics in acidic pH. Keywords: Gastroretentive, Porous hydrogels, Chitosan, Swelling, Rosiglitazon

Formulation of Sustained-Release Diltiazem Matrix Tablets Using Hydrophilic Gum Blends

Purpose: To develop sustained release matrix tablets of diltiazem hydrochloride (DTZ) using karaya gum (K) alone or in combination with locust bean gum (LB) and hydroxypropyl methylcellulose (H).Methods: Matrix tablets of DTZ were prepared at different ratios of drug:gum (1:1, 1:2, and 1:4) and of the gum blends (K, K/LB, K/H and K/LB/H) by direct compression. The matrix tablets were evaluated for hardness, friability, in vitro release and drug content. The formulations were also characterised by scanning electron microscopy (SEM), Fourier transform infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC). A commercial diltiazem hydrochloride product Dilzem SR, was used as a reference for comparison Results: Tablets with only K or K/H had the highest mean dissolution time (MDT), the least dissolution efficiency (DE, 12 %), and released drug by swelling, diffusion and erosion mechanisms. Karaya gum or combinations with locust bean gum sufficiently controlled drug release, while combinations of KH and KLBH exhibited high and low drug release efficiency, respectively. SEM images of the tablets before and after dissolution showed morphological changes on the tablet surface while FTIR and DSC studies indicate that there was no chemical interaction between the drug and the polymers. Three of the formulations compared well with the reference (p < 0.05) in terms of release characteristics. Conclusion: The results of the study demonstrate that karaya gum alone or in suitable combination with locust bean gum and hydroxypropyl methylcellulose is suitable for formulating sustained-release matrix tablets of diltiazem.Key words: Karaya gum, Locust bean gum, Diltiazem hydrochloride, Sustained release, Hydroxypropyl methylcellulos

Formulation Design and Evaluation of Hydrogel-Based Metronidazole Bioadhesive Tablet for Vaginal Candidiasis: Hydrogel based tablet for vaginal candidiasis

Hydrogel-Based Metronidazole Bioadhesive Tablet (HMBT) was prepared as a novel vaginal delivery system to achieve Controlled release of drug from the tablet for vaginal candidiasis. The highly swollen hydrogel were prepared by dissolving chitosan in acetic acid solution containing drug, followed by neutralisation with sodium hydroxide and characterized by SEM, DSC and FT-IR and evaluated for % swelling. The drug loaded hydrogels were incorporated into tablet formulation by dry granulation method using bioadhesive polymers such as HPMC, sodium CMC and guar gum in different ratios. HMBT was tested for drug content, hardness, friability, weight variation, thickness, swelling studies, in vitro drug release, bioadhesive strength, in vivo studies and antifungal activity. The FT-IR and DSC spectra’s revealed that there was no chemical interaction between drug and polymers used. SEM revealed that particles of hydrogels appeared small and irregular shaped with large numbers of pores. F3 formulation shows good in vitro release profile with highest bioadhesive strength. From the in vivo study in rabbit it was found that the HMBT hold the tablet for more than 12 hours inside the vaginal tube. It may be concluded from present study that HMBT can be used as a novel delivery system for local therapy of vaginal candidiasis which can controlled the release of drug for prolong period of time

Subnational mapping of HIV incidence and mortality among individuals aged 15–49 years in sub-Saharan Africa, 2000–18: a modelling study

Background High-resolution estimates of HIV burden across space and time provide an important tool for tracking and monitoring the progress of prevention and control efforts and assist with improving the precision and efficiency of targeting efforts. We aimed to assess HIV incidence and HIV mortality for all second-level administrative units across sub-Saharan Africa. Methods In this modelling study, we developed a framework that used the geographically specific HIV prevalence data collected in seroprevalence surveys and antenatal care clinics to train a model that estimates HIV incidence and mortality among individuals aged 15–49 years. We used a model-based geostatistical framework to estimate HIV prevalence at the second administrative level in 44 countries in sub-Saharan Africa for 2000–18 and sought data on the number of individuals on antiretroviral therapy (ART) by second-level administrative unit. We then modified the Estimation and Projection Package (EPP) to use these HIV prevalence and treatment estimates to estimate HIV incidence and mortality by second-level administrative unit. Findings The estimates suggest substantial variation in HIV incidence and mortality rates both between and within countries in sub-Saharan Africa, with 15 countries having a ten-times or greater difference in estimated HIV incidence between the second-level administrative units with the lowest and highest estimated incidence levels. Across all 44 countries in 2018, HIV incidence ranged from 2·8 (95% uncertainty interval 2·1–3·8) in Mauritania to 1585·9 (1369·4–1824·8) cases per 100 000 people in Lesotho and HIV mortality ranged from 0·8 (0·7–0·9) in Mauritania to 676·5 (513·6–888·0) deaths per 100 000 people in Lesotho. Variation in both incidence and mortality was substantially greater at the subnational level than at the national level and the highest estimated rates were accordingly higher. Among second-level administrative units, Guijá District, Gaza Province, Mozambique, had the highest estimated HIV incidence (4661·7 [2544·8–8120·3]) cases per 100 000 people in 2018 and Inhassunge District, Zambezia Province, Mozambique, had the highest estimated HIV mortality rate (1163·0 [679·0–1866·8]) deaths per 100 000 people. Further, the rate of reduction in HIV incidence and mortality from 2000 to 2018, as well as the ratio of new infections to the number of people living with HIV was highly variable. Although most second-level administrative units had declines in the number of new cases (3316 [81·1%] of 4087 units) and number of deaths (3325 [81·4%]), nearly all appeared well short of the targeted 75% reduction in new cases and deaths between 2010 and 2020. Interpretation Our estimates suggest that most second-level administrative units in sub-Saharan Africa are falling short of the targeted 75% reduction in new cases and deaths by 2020, which is further compounded by substantial within-country variability. These estimates will help decision makers and programme implementers expand access to ART and better target health resources to higher burden subnational areas