Influence of novel techniques on solubility, mechanical properties and permeability via hot melt extrusion technology

Hot melt extrusion (HME) was evaluated as a continuous processing technology for the manufacture of solid dispersions. The aim of the current research project was to study the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties of three different grades of cellulose polymers, Klucel™ ELF, EF and LF hydroxypropylcellulose (HPC) resulting from hot melt extrusion techniques, and to assess the plasticization effect of P-CO2 on the tested polymers. The physico-mechanical properties as well as the tablet characteristics of the extrudates with and without injection of P-CO2 and with non-extruded polymers were examined. P-CO2 acted as plasticizer for Klucel™ LF, EF and ELF and allofor a reduction in processing temperature during the extrusion process by 20°C as compared to the processing temperature without injecting P-CO2. Furthermore, the CO2 served as a pore former and produced foam-like structure extrudates. This morphological change resulted in an increase in bulk and tap density as well as surface area and porosity. Additionally, the hardness of the tablets of the polymers with P-CO2 was increased compared to polymer processed without P-CO2 and the non-extruded polymer. Moreover, the % friability of the tablets improved using P-CO2 processed polymer. Thus good binding properties and compressibility of the extrudates were positively influenced utilizing P-CO2 processing. The interest to incorporate a model was increased to investigate the effect of pressurized carbon dioxide (P-CO2) on the physico-mechanical properties as well as the drug release behavior. Ketoprofen (KTP), used as a model drug, was incorporated with hydroxypropylcellulose (HPC) (Klucel™ ELF, EF and LF) as a polymeric carrier to produce KTP amorphous solid dispersion using HME technique. Thermal gravimetric analysis (TGA) was used to evaluate and confirm the formulations thermal stability. Differential Scanning Calorimetery (DSC) was performed to evaluate the physical state of KTP in the extrudates. The microscopic morphology of the extrudates was changed to a foam-like structure due to expansion of the CO2 at the extrusion die. The foamy extrudates demonstrated enhanced KTP release compared to the extrudates processed without P-CO2 due to the increase in porosity and surface area of those extrudates. The moisture content of the extrudates processed with P-CO2 was slightly increased and this played a significant role in increasing KTP tablet hardness and decreasing percent friability. A concern with HME is the limitation of the drug loading due to drug-polymer miscibility. In order to solve this issue, we investigated the effect of foam like structure produced by pre P-CO2 on the drug loading and the dissolution profile of carbamazepine (CBZ) and low molecular weight hydroxypropylcellulose (HPC) matrices using HME technique. The resulted extrudates with P-CO2 injection exhibited higher surface area and porosity compared to the extrudates processed without P-CO2. Moreover, the CBZ release profile of the 20-50% drug load formulations processed with P-CO2 injection shoalmost complete drug release within 2 hours. In contrast, the drug release profiles of 20%, 30%, 40% and 50% CBZ/ Klucel™ ELF formulations processed without P-CO2 injection exhibited 90%, 86%, 80% and 73% CBZ drug release, respectively. In conclusion, HME processing assisted with P-CO2 increased the drug loading capability of CBZ in KlucelTM ELF polymeric matrix as well as optimized CBZ drug- release profiles. Drug permeability and dissolution rate are considered as key to predict the drug bioavailability. HME was used as an approach to improve solubility and permeability of the psychoactive natural product piperine. Piperine 10–40% w/w formulated in Eudragit® EPO/ Kollidon® VA 64 or Soluplus® formulation was used in this study to investigate the efficiency of various polymers to enhance the solubility and permeability of piperine via HME technique to ultimately increase its systemic absorption of the compound. Scanning electron microscopy (SEM) images shoabsence of crystals in 10% w/w piperine/Soluplus® indicating that piperine was dispersed in the Soluplus® polymer carrier in its amorphous form. However, crystals were evident in all other formulations with different ratios. Solubility of 10% and 20% piperine/Soluplus® was increased more than 160 and 45 folds in water, respectively. Furthermore, permeability studies using non- everted rat intestinal sac model demonstrated the enhancement in piperine absorption of the 10% w/w piperine/Soluplus® extrudates up to 158.9 ?g/5mL compared to 1.4 ?g/5mL in the case of pure piperine within 20 minutes

R13. Formulation development of loratadine immediate-release tablets using hot-melt extrusion coupled with 3d-printing technology

Corresponding author (Pharmaceutics and Drug delivery): Sundus Hussain Omari, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1012/thumbnail.jp

Fortification role of Curcumin against renal and testicular toxicity of synthetic food dye brilliant blue in rats

Increasing awareness has been lately paid to the toxicity of synthetic additives used in food. The main aim of this study was to survey the renal and testicular toxicity of synthetic food dye brilliant blue. Administration of the BB changed body and relative organs weights, serum creatinine, urea (BUN), uric acid and serum FSH, LH, testosterone levels. This study proved that BB induced oxidative damage as manifested by significant increase in Lipid peroxidation with disorganization in the activity of glutathione peroxidase, protein carbonyl and reactive oxygen species content. Histopathological changes include: infiltration and vacuolation in kidney. In addition; degeneration and necrosis of spermatogoneal cells lining seminiferous tubules in testis. Furthermore; BB induced appotosis via activation of casp-3. Administration of curcumin with BB attenuated the cytotoxic effects of brilliant blue on kidney and testis tissues and reducing apoptotic cell death as well as improved the redox status of kidney and testis. Keywords:  Brilliant blue dye, Curcumin, Kidney, Testis, Histopathology, Rats

Employing Hot-Melt Extrusion Technology to Enhance the Solubility of Cannabidiol (CBD)

Corresponding author (Pharmaceutics and Drug Delivery): Iman Taha, [email protected]://egrove.olemiss.edu/pharm_annual_posters_2022/1020/thumbnail.jp

D04. Department of Pharmaceutics and Drug Delivery

Corresponding author (Pharmaceutics and Drug Delivery): Eman Ashour, [email protected]://egrove.olemiss.edu/pharm_annual_posters/1026/thumbnail.jp

Antifungal activity of Streptomyces canescens MH7 isolated from mangrove sediment against some dermatophytes

The main objective of this study is to isolate actinobacteria has antifungal activity against some dermatophytes, Epidermophyton floccosum, Trichophyton rubrum, Microsporum canis, and Candida albicans, evaluation, and optimization of various cultural and nutritional conditions for maximum antifungal metabolite production. Total 64 actinobacteria were isolated from various localities in Egypt and screened for their antifungal activity against the tested fungi. Out of 64 isolates, the identified Streptomyces canescens MH7 has a good antifungal activity and inhibits the growth of the tested fungi. This isolate was capable of producing glucanase, lipase, and amylase enzymes which are important hydrolytic enzyme in the lysis of the fungal cell wall. Several growth factors were optimized to maximize the production of antifungal metabolites. Streptomyces canescens MH7 had the best antifungal activity in starch casein broth media supplemented with starch as a carbon source, potassium nitrate as a nitrogen source, salinity of 3% (w/v), pH8, incubation temperature at 30°C, incubation for 7 days, and shaking at 180 rpm

Risk of severe SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in Qatar: a cohort matched study

Background: It remains unclear whether patients with autoimmune rheumatic diseases (ARDs) are at a higher risk of poor outcomes from a SARS-CoV-2 infection. We evaluated whether patients with an ARDs infected with SARS-CoV-2 were at a higher risk of a poorer outcome than those without an ARDs. Methods: Patients with an ARDs infected with SARSCoV-2 were matched to control patients without a known ARDs. Matching was performed according to age (6 years) and sex at a case-to-control ratio of 1:3. Demographic and clinical data were extracted from the databases and were compared between the two groups. Severe SARS-CoV-2 infection was the primary outcome and was defined as the requirement for oxygen therapy support, the need for invasive or noninvasive mechanical ventilation, or the use of glucocorticoids. Results: A total of 141 patients with an ARDs were matched to 398 patients who formed the control group. The mean ages (SD) of the ARDs and nonARDs groups were 44.4 years (11.4) and 43.4 years (12.2). Women accounted for 58.8% of the ARDs group and 56.3% of the control group (p = 0.59). Demographics and comorbidities were balanced between the groups. ARDs included connective tissue disease in 43 (30.3%) patients, inflammatory arthritis in 92 (65.2%), and other ARDs in 8 (5.7%). ARDs medications included biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARDs) in 28 (15.6%) patients, conventional synthetic DMARDs in 95 (67.4%), and immunosuppressive antimetabolites in 13 (9.2%). The ARDs group had more respiratory and gastrointestinal symptoms related to SARS-CoV-2 infection than the control group (24.8% and 20.6% vs. 10% and 5.3%, respectively; p, 0.001 for both). Severe SARS-CoV2 infection was more common in the ARDs group than in the control group (14.9% vs. 5.8%; p, 0.001). Conclusions: In this single-center matched cohort study, patients with an ARDs experienced more respiratory and gastrointestinal symptoms related to SARS-CoV-2 infection and had more severe infection than those from the control group. Therefore, patients with an ARDs require close observation during the coronavirus disease 2019 pandemic

K-variant BCHE and pesticide exposure: Gene-environment interactions in a case-control study of Parkinson's disease in Egypt

Pesticide exposure is associated with increased risk of Parkinson's disease (PD). We investigated in Egypt whether common variants in genes involved in pesticide detoxification or transport might modify the risk of PD evoked by pesticide exposure. We recruited 416 PD patients and 445 controls. Information on environmental factors was collected by questionnaire-based structured interviews. Candidate single-nucleotide polymorphisms (SNPs) in 15 pesticide-related genes were genotyped. We analyzed the influence of environmental factors and SNPs as well as the interaction of pesticide exposure and SNPs on the risk of PD. The risk of PD was reduced by coffee consumption [OR = 0.63, 95% CI: 0.43-0.90, P = 0.013] and increased by pesticide exposure [OR = 7.09, 95% CI: 1.12-44.01, P = 0.036]. The SNP rs1126680 in the butyrylcholinesterase gene BCHE reduced the risk of PD irrespective of pesticide exposure [OR = 0.38, 95% CI: 0.20-0.70, P = 0.002]. The SNP rs1803274, defining K-variant BCHE, interacted significantly with pesticide exposure (P = 0.007) and increased the risk of PD only in pesticide-exposed individuals [OR = 2.49, 95% CI: 1.50-4.19, P = 0.0005]. The K-variant BCHE reduces serum activity of butyrylcholinesterase, a known bioscavenger for pesticides. Individuals with K-variant BCHE appear to have an increased risk for PD when exposed to pesticides

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London