Effect of Implementation of COVID-19 Guidelines on the Lives of Haemophilia Patients Registered with the Haemophilia Treatment Centre, Rawalpindi

Introduction: The development of isolation strategies to prevent spread of COVID -19 could affect the lives of Haemophilia patients beyond the risk of infection. In order to prevent this, the Haemophilia Treatment Centre, Rawalpindi, adopted additional combat strategies including the use of telephonic and video consultations, dispensing medicine at home and single day treatments.Objective: To assess the impact of COVID -19 pandemic and associated lockdown and changes in Standard Operating Procedures (SOPs) on the working of Haemophilia Treatment Centre, Rawalpindi and on the lives of its registered patients.Methods: An observational study was carried out at the Haemophilia Treatment Centre, Rawalpindi, between September, 2019 and August, 2020. Written records of frequency of virtual/physical visits to the Centre, treatment compliance, bleeding episodes, musculoskeletal health, psychosocial health, pain, disability and inhibitor status were obtained from six months pre pandemic and followed prospectively six months into the pandemic.Results: The Haemophilia Treatment remained open and functional throughout the study period. All staff members followed specially developed Haemophilia Treatment Centre guidelines vigilantly. Since telemedicine was encouraged , a rise in telephonic consultations was observed and therefore, no difference in overall visits was observed among the Pre- and Intra- Pandemic eras. The option of at-home dispensing of medicine via courier was available, and therefore, all patients remained treatment compliant. Among patients on Low Dose Prophylaxis (LDP) regimen, no difference in musculoskeletal health, bleeding episodes, inhibitor status, psychosocial health and nutritional status was observed among the two time periods. None of the staff members or patients were affected by the Covid-19.Conclusion: Our study shows that timely anticipation of potential impact of a pandemic and prompt development of modified mechanisms can indeed make the working of a Health Care Centre successful and prevent side effects on the lives of its patients

Establishment of a continuous sonocrystallization process for lactose in an oscillatory baffled crystallizer

Crystallization at production scale (>10 kg) is typically a poorly understood unit operation with limited application of first-principles understanding of crystallization to routine design, optimization, and control. In this study, a systematic approach has been established to transfer an existing batch process enabling the implementation of a continuous process in an oscillatory baffled crystallizer (OBC) using ultrasound. Process analytical technology (PAT) was used to understand and monitor the process. Kinetic and thermodynamic parameters have been investigated for lactose sonocrystallization using focused beam reflectance measurement (FBRM) (Mettler Toledo) and mid-infrared spectroscopy (mid-IR) (ABB) in a multiorifice batch oscillatory baffled crystallizer (Batch-OBC). This platform provides an ideal mimic of the mixing, hydrodynamics and operating conditions of the continuous oscillatory flow crystallizer (COBC) while requiring only limited material. Full characterization of the hydrodynamics of the COBC was carried out to identify conditions that deliver plug-flow behavior with residence times of 1–5 h. The results show that continuous crystallization offers significant advantages in terms of process outcomes and operability, including particle size distribution (mean particle size <1500 μm) of alpha lactose monohydrate (ALM), as well as reduced cycle time (4 h compared to the 13–20 h in a batch process). Continuous sonocrystallization was performed for the first time at a throughput of 356 g·h–1 for 12–16 h. During the run at near plug flow, with supersaturation and controlled nucleation using sonication, no issues with fouling or agglomeration were observed. This approach has demonstrated the capability to provide close control of particle attributes at an industrially relevant scale

Development and characterisation of a cascade of moving baffle oscillatory crystallisers (CMBOC)

A novel four stage Cascade of Moving Baffle Oscillatory Crystallisers (CMBOC) is developed, characterised and implemented for continuous crystallisation of pharmaceuticals. The platform was fully automated with pressure controlled slurry transfer and process analytical tools (PAT) to support process monitoring and control. Model predictive control was used to achieve precise temperature control during operation of crystallisations. Mixing and flow characterisation for liquids and slurries was performed confirming near-ideal mixing performance for mean residence times in the range 20 – 90 min. Heat transfer characteristics were determined and shown to be well suited to the demands of cooling crystallisation processes. Heat transfer efficiency increased with increasing oscillatory Reynolds number (Reo). This cascade is shown to provide the advantages of more uniform mixing and efficient heat transfer performance compared to a traditional cascade of stirred tank crystallisers. Continuous crystallisations of both alpha lactose monohydrate (ALM) and paracetamol (PCM) were carried out in which the target size, form, agglomeration and encrustation were controlled. For ALM, the products showed a narrow particle size distribution (PSD) with dv50 = 65 ± 5 μm and a span of 1.4 ± 0.2, and achieved a yield of 70%. The continuous crystallisation of paracetamol in the CMBOC produced non-agglomerated product with dv50 = 398 ± 20μm with a span of 1.5 ± 0.2 and achieved an 85% yield. No fouling or encrustation in the vessels or transfer lines were observed during the processes. The flexible configuration and operation of the platform coupled with well characterised shear rate distribution, residence time distributions and heat transfer shows that this platform is well suited to a range of crystallisation modes including seeded, antisolvent, cooling or reactive processes, where careful control of crystal attributes is required

Foot-and-Mouth Disease Virus (FMDV) and Its Treatment with Plant Extracts

Foot-and-mouth disease (FMD) is a contagious viral infection which is caused by foot-and-mouth disease virus (FMDV). The disease appears in cloven-footed animals. Symptoms of the disease are abrupt manifestation of sores on the mouth, nose, feet, etc. Nowadays the control and treatment of FMDVare becoming a worldwide economic problem and challenge for the society. Currently, there is no particular treatment available for FMDV, as well as the limitations and disadvantages in the use of vaccines divert the focus of researchers toward natural sources like plant extracts which possess potential antiviral activity. Various researches documented in the literature demonstrated various plant extracts with antiviral potency against FMDV. In the current chapter, we discussed about FMDV and its possible treatment with plant extracts

Enabling precision manufacturing of active pharmaceutical ingredients: workflow for seeded cooling continuous crystallisations

Continuous manufacturing is widely used for the production of commodity products. Currently, it is attracting increasing interest from the pharmaceutical industry and regulatory agencies as a means to provide a consistent supply of medicines. Crystallisation is a key operation in the isolation of the majority of pharmaceuticals and has been demonstrated in a continuous manner on a number of compounds using a range of processing technologies and scales. Whilst basic design principles for crystallisations and continuous processes are known, applying these in the context of rapid pharmaceutical process development with the associated constraints of speed to market and limited material availability is challenging. A systematic approach for continuous crystallisation process design is required to avoid the risk that decisions made on one aspect of the process conspire to make a later development step or steps, either for crystallisation or another unit operation, more difficult. In response to this industry challenge, an innovative system-wide approach to decision making has been developed to support rapid, systematic, and efficient continuous seeded cooling crystallisation process design. For continuous crystallisation, the goal is to develop and operate a robust, consistent process with tight control of particle attributes. Here, an innovative system-based workflow is presented that addresses this challenge. The aim, methodology, key decisions and output at each at stage are defined and a case study is presented demonstrating the successful application of the workflow for the rapid design of processes to produce kilo quantities of product with distinct, specified attributes suited to the pharmaceutical development environment. This work concludes with a vision for future applications of workflows in continuous manufacturing development to achieve rapid performance based design of pharmaceuticals

Correlation of Iron Status between Pregnant Women and their Corresponding Newborns

Background: To determine correlation of iron status between pregnant women and their corresponding newborns using a combination of hematological and biochemical parameters.Methods: In this cross-sectional study venous blood samples from fifty pregnant women, with single fetus at term 37-42 weeks of gestation, having uneventful vaginal casearation section delivery, and their corresponding umbilical cord samples were obtained. C-reactive protein, blood complete picture, serum iron, serum ferritin, serum total iron binding capacity and serum transferrin saturation were performed. Pregnant women were divided into non-iron deficient, iron deficient and anemic with iron deficiency. Newborns with and without maternal anemia were placed in separate groups. Statistical analysis included descriptive analysis, Pearson’s correlation coefficient and one way ANOVA.Results: Among pregnant women, twenty two percent were iron deficient but without anemia and forty six percent were anemic (forty percent iron deficient and six percent non-iron deficient). Significant difference was observed in the mean values of hemoglobin and hematocrit between newborns with and without maternal anemia (p &lt; 0.01). Significant association was observed between newborn and maternal iron parameters (p &lt; 0.01).Conclusion: Iron related parameters are correlated between pregnant women and their corresponding newborns meaning that iron is transported from mother to fetus in direct proportion with the levels found in the maternal circulation