Characterization of Grades of HPMCAS Spray Dried Dispersions of Itraconazole Based on Supersaturation Kinetics and Molecular Interactions Impacting Formulation Performance.

PURPOSE: The objective was to characterize hydroxypropyl methylcellulose acetate succinate (HMPCAS) grades L, M, and H to enhance itraconazole (ITZ) release and permeation from spray dried dispersions (SDDs), and to investigate underpinning molecular ITZ-HPMCAS interactions that differentiated grade performance. METHODS: ITZ or its SDDs were subjected to solution stabilization assessment, one-dimensional proton nuclear magnetic resonance (NMR) spectroscopy, saturation transfer difference NMR studies, small volume dissolution, solid state transformation studies, and in vitro dissolution/permeation flux studies. RESULTS: HPMCAS-L was the best performing grade overall and exhibited greatest ITZ supersaturation concentration, small volume dissolution, and in vitro dissolution/permeation flux. Meanwhile, H grade retarded ITZ precipitation to the greatest extent in solution stabilization studies and exhibited greater hydrophobic interaction with ITZ in NMR studies. However, this apparent advantage of H grade through hydrophobic interactions between drug-polymer appeared to limit overall dissolution/permeation performance of SDD. CONCLUSIONS: In vitro SDD studies and drug-polymer interaction studies provided insight into the performance of HPMCAS grades, as well as the relative contributions of various mechanisms that polymer can promote ITZ absorption from SDD.

Characterization and removal of microplastics in the Guheshwori Wastewater Treatment Plant, Nepal.

Contamination of river water systems by microplastic particles (MPPs) is one of the emerging global environmental concerns with potentially widespread ecological, socioeconomic, and health implications. A wastewater treatment plant (WWTP) processes and treats wastewater to remove pollutants and release safe water into the environment. There has been limited research on the characterization of microplastics and their removal in WWTP in South Asia. In this work, we report on the characterization of microplastics in wastewater and sludge samples (n = 300) from Guheshwori WWTP located on the bank of the Bagmati River in Kathmandu city, Nepal representing inlet, secondary aeration tank (SAT), outlet, and sludge from November 2021 to November 2022. On average, we detected 31.2 ± 17.3 MPPs/L, 11.2 ± 9.4 MPPs/L, 8.5 ± 5.6 MPPs/L, and 6.6 ± 4.8 MPPs/g in the samples collected from inlet, SAT, outlet, and sludge, respectively. Commonly found MPPs were in the form of fiber, fragments, foam, and pellets. Largely, MPPs were red, yellow, white, blue, and black. Among the 44 µm - 150 µm, 150 µm - 500 µm and 500 µm - 5 mm categories of size fractions, the most dominant fractions were 500 µm - 150 µm in inlet, SAT, and sludge, and 150 µm - 44 µm in the outlet sampling unit. The Guheshwori WWTP was able to remove 72.5 % of MPPs on average, that mostly occurred in the inlet. The effluent released into the river and the sludge still contained a significant number of MPPs.

Dissolution-Hollow Fiber Membrane (D-HFM) System to Anticipate Biopharmaceutics Risk of Tablets and Capsules.

A dissolution-hollow fiber membrane (D-HFM) system with relatively high area/volume ratio was previously characterized and showed favorably high percent drug absorption. Also, it's in vitro permeation constant (Kp.Ç.) was close to in vivo human permeation constant (kp). The objective of the current study was to predict the in vivo human absorption profile and biopharmaceutic performance of five drug products using the D-HFM system. Four immediate-release (IR) and one extended-release (ER) solid oral dosage form were subjected to the D-HFM system. Tablets and capsule dissolution were also measured using USP apparatus II. Drug solutions were also subjected to D-HFM testing. Predicted and observed absorption profiles in D-HFM system showed close agreement for each solid oral dosage form. Levy-Polli plots from D-HFM system successfully predicted the four IR products to be low biopharmaceutic risk due to permeation rate limited or mixed dissolution/permeation rate limited absorption, and successfully predicted metoprolol ER product to be high biopharmaceutic risk due to dissolution rate limited absorption. These observations showed potential of the in vitro D-HFM system to be utilized in biopharmaceutics risk assessment of in vivo tablet and capsule performance.

Gastro-intestinal parasites of urban rhesus macaques (Macaca mulatta) in the Kathmandu Valley, Nepal.

Intestinal parasitic infections such as amoebiasis, ascariasis, hookworm infection, and trichuriasis are the most common infections among non-human primates (NHPs). There are always the possibilities of transmission these parasites between humans and NHPs. Multiple groups of rhesus macaques (Macaca mulatta) live in the urban area of Kathmandu Valley near human settlements, however the gastrointestinal (GI) parasitic infections in those macaques are understudied. This study aimed to explore the GI parasites in free-ranging macaques from Pashupatinath, Swayambhunath, Tripureshwor, Nilbarahi temples and a group of captive rhesus macaques in the Central Zoo, Kathmandu. Fecal samples were collected from the macaques between October 2021 to September 2022 and assessed for parasites by the both wet mount method and concentration technique. There is high prevalence of GI parasite infection; out of 121 fecal samples examined, 87.6% of samples were positive. Six species of protozoans and eight species of helminths were identified from the fecal samples including the first report of Iodamoeba butschlii in monkeys of Nepal. Among the protozoan parasites, Entamoeba coli (54.71%) showed the highest prevalence followed by Balantioides coli (44.33%), E. histolytica (19.81%), and Iodamoeba butschlii (10%). Among the helminths, Trichuris spp. (31.13%) and Strongyloides spp. (31.13%) showed the highest prevalence followed by Hookworm (24.52%), and Strongyle spp. (23.58%). The likelihood ratio test suggested that the prevalence differed significantly with the seasons for Iodamoeba butschlii, Giardia spp., Strongyles spp., Hookworm, and Trichostrongylus spp. The prevalence of E. histolytica, E. coli, Iodamoeba. butschlii, Trichuris spp., Trichostrongylus spp., and Unknown spp.1 differed with sampling localities. The high prevalence of GI parasites found in the macaques living in the densely urbanized Kathmandu presents a potential threat to humans and warrants further study as well as increased education of the public and management of the human-macaque interface in the urban landscape of the Valley.

Characterization of Dissolution-Permeation System using Hollow Fiber Membrane Module and Utility to Predict in Vivo Drug Permeation Across BCS Classes.

A dissolution-permeation system has potential to provide insight into the kinetic contributions of dissolution and permeation to overall drug absorption. The goals of the study were to characterize a dissolution-hollow fiber membrane (D-HFM) system and compare its resulting in vitro drug permeation constants (Kp') to in vivo clinical permeation constants (kp), for four drugs in various Biopharmaceutics Classification System (BCS) classes. Model predictions for D-HFM were made based on derived mixing tank (MT) and complete radial (CRM) flow models and independent measurement of membrane permeability. Experimental D-HFM studies included donor flow rate and donor volume sensitivity studies, and drug permeation profile studies. Additionally, for the four drugs, Kp'from D-HFM system was compared to (kp) from literature, as well as Kp' values from side-by-side diffusion cell and dissolution/Caco-2 system. Results show progressive D-HFM system development as a dissolution-permeation tool. Results indicated that D-HFM models using MT or CRM provided close agreement between predicted and observed drug permeation profiles. Drug permeation in D-HFM system was volume dependent, as predicted. Favorably, more drug permeated through the D-HFM system (10-20% in 60 min) compared to side-by-side diffusion cell (1%) and dissolution/Caco-2 system (0.1%). Kp' from D-HFM system was also closer to in vivo kp; the two other in vitro models showed lower Kp'. Overall, studies reflect that HFM module has potential to incorporate drug permeation into the in vitro assessment of in vivo tablet and capsule performance.

Robson's Group 2 Criteria among Total Caesarean Sections in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Globally, there is a dramatic rise in cesarean section rate which has increased the maternal morbidity and adverse effects in a subsequent pregnancy. Robson's classification will aid in the optimization of the cesarean section use, assessment of the strategies aimed to decrease the cesarean section rate and thus improve the clinical practices and quality of care in various health care facilities. The main aim of this study is to find out the prevalence of caesarean section for Robson's group 2 among total caesarean sections done in a tertiary care hospital. METHODS: A descriptive cross-sectional study was carried out at a tertiary care centre in Nepal from August 2020 to January 2021. Ethical approval was taken from the institutional review committee (reference number: 1607202003) and data were entered using Robson's criteria. The convenient sampling technique was used. Data was analyzed using Microsoft Excel. Point estimate at 95% Confidence Interval was calculated along with frequency and percentage for binary data. RESULTS: According to Robson's group 10 classification, among 380 caesarean sections, 110 (28.94%) (24.38-33.50 at 95% Confidence Interval) cases were in Robson's group number 2. CONCLUSIONS: This study showed that the prevalence of caesarean section which lies in Robson's group 2 in our study is higher than the standard of World Health Organization. It showed that Robson's group 2 was one of the significant contributors to the greater caesarean section rate. Improved case selection, standardization, and protocol for induction of labour as well as regular audit could also reduce caesarean section rates.

Anxiety among Pregnant Women about Corona Virus Infections during COVID-19 Pandemic at a Tertiary Care Center in Nepal: A Descriptive Cross-sectional Study.

INTRODUCTION: COVID-19 is a beta coronavirus that is transmitted by physical interaction or close contact. This Coronavirus Pandemic has also created stress and anxiety among pregnant women all over the world. The disease was first identified in Wuhan city, China, in late December 2019 and was declared pandemic by the World Health Organization on 11th March 2020. Concern and stress in pregnancy are associated with pre-eclampsia, intrauterine growth restriction, preterm labour, depression etc. Pregnancy is an immune-compromised state and poses a high risk to this risk. This study aims to identify anxiety about the coronavirus infection among pregnant women visiting a tertiary care centre in Kathmandu, Nepal, during this COVID-19 pandemic. METHODS: This is a descriptive cross-sectional study conducted at Kathmandu Medical College and Teaching Hospital from 15th July 2020 to 30th July 2020 after taking the ethical clearance from the Institutional Review Committee of Kathmandu Medical College (reference no. 207202002). Convenient sampling method was used. All the data were entered in Statistical Package for the Social Sciences data 20.0 and analyzed. Data was presented in frequencies, charts and percentage. RESULTS: Among the total 273 cases, only 2 (0.73%) cases had a score between 25-30 corresponding to moderate to severe anxiety, 21 (7.69%) had a score between 18-24, which corresponds to mild to moderate anxiety and 250 (91.57%) had score 0-17 which corresponds mild status. CONCLUSIONS: Most of the participants in the study reported a mild status of anxiety. Very few participants reported moderate to severe anxiety.

Similarity of dissolution profiles from biorelevant media: Assessment of interday repeatability, interanalyst repeatability, and interlaboratory reproducibility using ibuprofen and ketoconazole tablets.

Biorelevant media are increasingly being employed as dissolution media in drug development, including in smaller volumes than 900ml and under non-sink conditions. The objectives were to assess interday repeatability, interanalyst repeatability, and interlaboratory reproducibility of dissolution profiles from biorelevant media, as well as to assess the impacts of biorelevant media production method and biorelevant medium volume on dissolution profiles. Ibuprofen and ketoconazole tablets were subjected to dissolution testing in 500ml, 300ml, and 40ml of fasted state simulated gastric fluid (FaSSGF), fed state simulated gastric fluid (FeSSGF), fasted state simulated intestinal fluid version 2 (FaSSIF-V2), and fed state simulated intestinal fluid version 2 (FeSSIF-V2). f2 was used to assess repeatability and reproducibility of dissolution profiles. Results indicate favorable interday repeatability (83 of 88 comparisons were similar), favorable interanalyst repeatability (19 of 21 comparisons were similar), and favorable interlaboratory reproducibility (10 of 14 comparisons were similar) of dissolution profiles from biorelevant media, with commercial media showing greater interlaboratory reproducibility than 'from scratch' media. However, biorelevant medium production had low impact on profiles when one analyst conducted all medium preparations and study procedures at one location. Additionally, biorelevant media detected differences when products were not similar. Overall, biorelevant media showed favorable repeatability and reproducibility performance.