Formulation Strategies Research Articles

Quality by Design in Pharmaceuticals: A Review of its Impact on Regulatory Compliance and Product Quality.

The pharmaceutical industry has embraced the quality-by-design (QbD) approach as a promising development, formulation and manufacturing strategy. QbD provides a systematic and science-based framework for designing and producing high-quality products, with a particular focus on identifying, assessing and controlling risks throughout the development process. This review aims to assess the benefits of implementing QbD in pharmaceutical processes, evaluate its impact on regulatory compliance and explore its potential to enhance drug product quality. The primary objective of this review is to evaluate the influence of QbD on pharmaceutical development and manufacturing processes. It also seeks to examine the regulatory requirements associated with the implementation of QbD and highlight the advantages of this approach in terms of product quality and cost-effectiveness. Additionally, the review aims to explore the potential of QbD in improving the safety and efficacy of drug products. The QbD approach holds tremendous potential to revolutionize the pharmaceutical industry by optimizing drug development & manufacturing processes, reducing costs and enhancing product quality and consistency. However, implementing QbD requires a comprehensive understanding of the underlying science, as well as strict adherence to regulatory requirements in drug development and manufacturing. In conclusion, by embracing the QbD approach, the pharmaceutical industry can ensure the production of safe, effective and regulation-compliant products while simultaneously improving process efficiency. This strategic shift toward QbD represents a pivotal step in advancing pharmaceutical research and manufacturing capabilities, ultimately benefiting both the industry and more importantly, patients worldwide.

Exploring street vendors’ entrepreneurial potential and gender disparities in an eastern cape port city, South Africa

This study examines the entrepreneurial potential of informal traders, specifically focusing on street vendors operating in East London, a prominent port city in the Eastern Cape, South Africa. Entrepreneurship, characterised by its dynamic nature entailing visionary foresight and astute exploitation of opportunities, requires agility and fervent dedication in nurturing novel concepts and implementing innovative solutions. Additionally, it aims to address the issue of low female participation in economic activities within this sector. Utilising a structured questionnaire designed for data collection, this research employs both descriptive and inferential statistics to analyze the entrepreneurial traits exhibited by street vendors. The investigation centers on six key independent variables: proactive personality, competitive aggressiveness, risk-taking propensity, perceived capability, perceived opportunity, and innovation. The study’s findings revealed that, among the factors studied, perceived opportunity and innovation were statistically significant contributors to the entrepreneurial potential of street vendors in East London. Moreover, the research identifies that despite demonstrating similar entrepreneurial potential factors as their male counterparts, females exhibit notably lower participation rates within the informal trading sphere. This research holds significant implications for policy formulation and intervention strategies. By highlighting perceived opportunity and innovation as critical factors influencing entrepreneurial potential, the study provides actionable insights for policymakers aiming to enhance the entrepreneurial landscape among street vendors. Furthermore, the identification of gender-specific participation gaps emphasises the need for targeted policies and programs to increase female engagement in informal trading.

Influence of protein and leucine on in vitro accessibility and apparent permeability of phenolic compounds in blackberry-dairy blends

There is increasing consumer interest in performance nutrition beverages that improve muscle recovery, endurance and strength, and a desired product type would be dairy-blackberry beverages. However, the effect of phenolic compounds on the digestion of milk proteins, and the effect of milk proteins on the bioaccessibility and permeability of phenolic compounds through the intestinal wall is poorly understood. In this study, dairy-blackberry beverages were made by adding milk protein concentrate and/or leucine and freeze-dried blackberry puree to skimmed milk, to formulate beverages with different protein contents and two different leucine contents. These beverages were subjected to in vitro digestion, and their protein breakdown was analysed with electrophoresis. The accessibility of flavonoids, anthocyanins and individual phenolic compounds was determined and the apparent permeability (Papp) of individual phenolic compounds through Caco-2 cells was analysed. It was found that β-lactoglobulin in samples with a higher protein content was more resistant to digestion. An increase in protein had no influence on the bioaccessibility of flavonoids as a whole but increased the bioaccessibility of the subgroup anthocyanins from 13% in water to 64% in high protein milk. The Papp of cyanidin-3-O-glucoside, gallic acid, protocatechuic acid and rutin was determined. Milk proteins improved the Papp of gallic acid and cyanidin-3-O-glucoside, to a maximum value of 4.26 and 0.36 × 10⁻⁶ cm/s but had no clear influence on protocatechuic acid and rutin. In conclusion, higher milk protein levels were associated with increased bioavailability of anthocyanins and their metabolites, which could inform formulation strategies for performance nutrition.

“We need to talk about PICO”: Approaching the move from question formulation to search strategy

This paper begins with PICO and its place in health librarianship, before moving to discuss a model of teaching knowledge that may offer some new ways of thinking about PICO (or, perhaps, leaving PICO behind). My two main points of contention with the ubiquity of PICO in health librarianship are: 
 
 That it is only one among many approaches to question formulation; and
 That question formulation strategies are treated ‘as’ search formulation strategies.
 
 I am particularly interested in PICO’s ubiquity as a teaching tool for advanced information-seeking within health libraries, and the possible division between what health librarians are teaching and what they do when moving from question formulation to designing search strategies.

A dataset of formulation compositions for self-emulsifying drug delivery systems

Self-emulsifying drug delivery systems (SEDDS) are a well-established formulation strategy for improving the oral bioavailability of poorly water-soluble drugs. Traditional development of these formulations relies heavily on empirical observation to assess drug and excipient compatibility, as well as to select and optimize the formulation compositions. The aim of this work was to leverage previously developed SEDDS in the literature to construct a comprehensive SEDDS dataset that can be used to gain insights and advance data-driven approaches to formulation development. A dataset comprised of 668 unique SEDDS formulations encompassing 20 poorly water-soluble drugs was curated. While there are still opportunities to enhance the quality and quantity of data on SEDDS, this research lays the groundwork to potentially simplify the SEDDS formulation development process.

Buccal delivery system of active pharmaceutical ingredients-ionic liquid (API-IL): Effects of API-IL loading and gelatin film concentration

Ionic liquid (IL) salt of active pharmaceutical ingredient (API) represents a promising formulation strategy to address low drug solubility and polymorphism prevalent in API solid crystals. The present work developed for the first time a buccal delivery system of API-IL via fast-dissolving API-IL-loaded gelatin films. Imidazolium-based ibuprofen salt was used as the model API-IL. The effects of API-IL loading and gelatin concentration on the film’s (i) mechanical strength, (ii) inter-batch uniformity in the films’ API payload, weight, and thickness, (iii) thermal stability, (iv) API dissolution and solubility enhancement were investigated. The plasticizer role of API-IL was evident, where minimum 30 wt% API-IL loading was needed to produce flexible yet mechanically-strong films. Lower API-IL loading produced brittle films due to insufficient plasticization facilitated by hydrogen bond interactions between API-IL and gelatin. Gelatin concentration influenced films’ mechanical strength, weight/thickness, and API dissolution rate. Depending on the API-IL loading and gelatin concentration, films with API payload (7–30 mg/cm2), thickness (300–900 µm), and weight (20–110 mg/cm2) were produced at nearly 100% efficiency and high inter-batch uniformity. API-IL existed as amorphous liquid in the film exhibiting fast API dissolution (100% in 15 min) and high kinetic solubility (8 times thermodynamic solubility) in simulated saliva fluid.

Advancement in Opioid Abuse-deterrent Formulation Technologies and Regulatory Expectation.

Chronic pain is a byproduct of many diseases and conditions. Along with long-term opioid medication use in chronic pain management, misuse of this vital medication has been a topic of much debate over the last two decades. Abuse-deterrent formulations play a critical role in comprehensive opioid risk management strategies, limiting the attractiveness and drug-liking qualities of an opioid drug by limiting their bioavailability, making abuse of the tampered opioid medication less appealing or rewarding, or impeding the extraction of the opioid drug and thus impeding the administration of the opioid formulation via alternative routes. The present article covers various regulatory actions, expectations in abuse-deterrent formulation approval, and emerging opioid abuse-deterrent formulation strategies, such as incorporating physical barriers, chemical barriers, aversion agents, pH modulating release properties, novel delivery systems, agonist/antagonist combinations, and prodrugs, as potential approaches to encountering the crisis of the opioid abuse epidemic. Looking at the severity of the opioid crisis across the globe now is the right time for various regulatory agencies to come under one roof to save society from the opioid epidemic, define the policy on how and when to prescribe opioid formulations to patients, perform abuse risk assessments, and make more efforts to approve only abusedeterrent opioid medication.

Design Rules for the Sequestration of Viruses into Polypeptide Complex Coacervates.

Encapsulation is a strategy that has been used to facilitate the delivery and increase the stability of proteins and viruses. Here, we investigate the encapsulation of viruses via complex coacervation, which is a liquid-liquid phase separation resulting from the complexation of oppositely charged polymers. In particular, we utilized polypeptide-based coacervates and explored the effects of peptide chemistry, chain length, charge patterning, and hydrophobicity to better understand the effects of the coacervating polypeptides on virus incorporation. Our study utilized two nonenveloped viruses, porcine parvovirus (PPV) and human rhinovirus (HRV). PPV has a higher charge density than HRV, and they both appear to be relatively hydrophobic. These viruses were compared to characterize how the charge, hydrophobicity, and patterning of chemistry on the surface of the virus capsid affects encapsulation. Consistent with the electrostatic nature of complex coacervation, our results suggest that electrostatic effects associated with the net charge of both the virus and polypeptide dominated the potential for incorporating the virus into a coacervate, with clustering of charges also playing a significant role. Additionally, the hydrophobicity of a virus appears to determine the degree to which increasing the hydrophobicity of the coacervating peptides can enhance virus uptake. Nonintuitive trends in uptake were observed with regard to both charge patterning and polypeptide chain length, with these parameters having a significant effect on the range of coacervate compositions over which virus incorporation was observed. These results provide insights into biophysical mechanisms, where sequence effects can control the uptake of proteins or viruses into biological condensates and provide insights for use in formulation strategies.

Prevalence of co-morbidities and referral patterns in routine preoperative evaluation: A retrospective observational analysis in a tertiary care government hospital

The initial interaction between patients and anaesthesiologists during pre-anaesthesia check-ups (PAC) is a crucial opportunity to diagnose and pre-optimize co-morbidities that might go unnoticed. This proactive approach contributes to safe anaesthesia administration, uneventful intra-operative experiences, and smooth post-operative recovery. Our study assesses the prevalence of diverse co-morbidities within a tertiary care centre's PAC. After analysing data from 3 months involving 905 patients, 624 individuals exhibited co-morbidities, with 217 cases being newly identified within the PAC clinic. Among female patients, anaemia emerged as the most prevalent anomaly (219 cases), while hypertension dominated among male patients (171 cases). Overall, anaemia constituted the most common co-morbidity (362 cases). A comprehensive clinical assessment during the Pre-Anaesthetic Clinic empowers formulation strategies for pre-optimization and treatment of co-morbidities. Timely intervention is pivotal, not only to prevent surgery delays but also to avert potentially catastrophic outcomes arising from untreated conditions. This approach translates into expedited patient recovery, minimizing anaesthesia-related complications. The Pre-Anaesthetic Clinic plays a pivotal role in diagnosing and intervening in patient co-morbidities. Beyond diagnosis, it is a crucial early intervention and treatment platform, significantly enhancing the overall surgical recovery process.

Exploring the Chemical Composition of Female Zucchini Flowers for Their Possible Use as Nutraceutical Ingredient.

The zucchini (Cucurbita pepo L.) plant is well known for its fruits; however, its edible flowers appear to contain several active molecules, including polyphenols, which display poor bioaccessibility after gastrointestinal digestion (GiD). This study explores the bioaccessibility of polyphenols and antioxidant capacity within zucchini flower extracts during simulated GiD. Two nutraceutical formulations, non-acid-resistant (NAcR) and acid-resistant (AcR) capsules containing an aqueous extract of zucchini flowers, were employed in this investigation. Additionally, high-resolution mass spectrometry (Q-Orbitrap HRMS) was utilized for a comprehensive analysis of their polyphenolic constituents. Predominantly, rutin and isorhamnetin-3-rutinoside were the most prevalent compounds detected in the samples (514.62 and 318.59 mg/kg, respectively). Following in vitro GiD, the extract encapsulated in AcR capsules exhibited enhanced bioaccessibility during both the duodenal (189.2 and 162.5 mg GAE/100 g, respectively) and colonic stages (477.4 and 344.7 mg GAE/100 g, respectively) when compared with the extract encapsulated in NAcR capsules. This suggests that gastric acidity adversely impacted the release of polyphenols from NAcR capsules. In conclusion, the aqueous zucchini flower extract emerges as a promising and readily accessible source of dietary polyphenols. Moreover, the utilization of AcR capsules presents a potential nutraceutical formulation strategy to improve polyphenol bioaccessibility, enhancing its applicability in promoting health and well-being.

Long-acting dolutegravir formulations prevent neurodevelopmental impairments in a mouse model.

The World Health Organization has recommended dolutegravir (DTG) as a preferred first-line treatment for treatment naive and experienced people living with human immunodeficiency virus type one (PLWHIV). Based on these recommendations 15 million PLWHIV worldwide are expected to be treated with DTG regimens on or before 2025. This includes pregnant women. Current widespread use of DTG is linked to the drug's high potency, barrier to resistance, and cost-effectiveness. Despite such benefits, potential risks of DTG-linked fetal neurodevelopmental toxicity remain a concern. To this end, novel formulation strategies are urgently needed in order to maximize DTG's therapeutic potentials while limiting adverse events. In regard to potential maternal fetal toxicities, we hypothesized that injectable long-acting nanoformulated DTG (NDTG) could provide improved safety by reducing drug fetal exposures compared to orally administered native drug. To test this notion, we treated pregnant C3H/HeJ mice with daily oral native DTG at a human equivalent dosage (5mg/kg; n = 6) or vehicle (control; n = 8). These were compared against pregnant mice injected with intramuscular (IM) NDTG formulations given at 45 (n = 3) or 25 (n = 4) mg/kg at one or two doses, respectively. Treatment began at gestation day (GD) 0.5. Magnetic resonance imaging scanning of live dams at GD 17.5 was performed to obtain T1 maps of the embryo brain to assess T1 relaxation times of drug-induced oxidative stress. Significantly lower T1 values were noted in daily oral native DTG-treated mice, whereas comparative T1 values were noted between control and NDTG-treated mice. This data reflected prevention of DTG-induced oxidative stress when delivered as NDTG. Proteomic profiling of embryo brain tissues harvested at GD 17.5 demonstrated reductions in oxidative stress, mitochondrial impairments, and amelioration of impaired neurogenesis and synaptogenesis in NDTG-treated mice. Pharmacokinetic (PK) tests determined that both daily oral native DTG and parenteral NDTG achieved clinically equivalent therapeutic plasma DTG levels in dams (4,000-6,500ng/mL). Importantly, NDTG led to five-fold lower DTG concentrations in embryo brain tissues compared to daily oral administration. Altogether, our preliminary work suggests that long-acting drug delivery can limit DTG-linked neurodevelopmental deficits.

Model predictive control–based robust-control strategy of distribution control for a grid-connected AC microgrid

The challenge of ensuring the reliable running of power systems has gotten more difficult in recent years due to the rising complexity of power system networks. The decreasing accessibility of fossil fuels has necessitated a greater dependence on renewable energy sources, such as solar systems, wind power, and hydroelectric power, by the international community. As a result, there is an increasing demand for AC microgrids to offer an effective approach for distributing power. The power system networks that consist of microgrids frequently have a significant number of failures, surpassing 80%. These failures occur because microgrids are susceptible to unexpected changes in different distributed generating sources. The variations greatly impair the operating efficiency of the microgrid and have negative consequences for the distribution system. The microgrid consists of numerous dispersed generation units and local loads. The load in a microgrid exhibits parametric uncertainty, which adds to the fluctuation observed in its performance. The formulated control strategy is Model Predictive Control, which aims to achieve robust performance even in the presence of unaccounted-for loads, dynamic loads, harmonic loads, and both balanced and unbalanced loads. The authors of this paper have developed a control approach that utilizes model predictive control (MPC) and is characterized by its robustness and optimality. MPC has the ability to predict the future behavior of a certain system. The controller successfully mitigates and reduces any disruptions that may occur within the power distribution system by taking into account its healthy characteristics. The model is implemented in the MATLAB Simulink environment, where it produces an accurate and appropriate total harmonic distortion value. The model was compared to previous efforts and significantly improved by increasing some crucial parameters by up to 90%. The value functions as a measure of the controller's performance quality and the improved efficiency of the microgrid system.

Determination of trace elements in ibuprofen drug products using microwave-assisted acid digestion and inductively coupled plasma-mass spectrometry

Trace elements are found in most drugs as a result of the drug formulation and drug production methods. An inductively coupled plasma-mass spectrometry method for the determination of 24 trace elements (Mg, Ti, V, Cr, Mn, Cu, Fe, Co, Ni, Zn, As, Se, Mo, Ru, Rh, Pd, Ag, Cd, Sb, Ba, Ir, Pt, Au, and Pb) in solid ibuprofen tablets was established in relation to the ICH Q3D(R1) guideline, to evaluate the possibility of linking trace elemental profiles to drug formulation strategies, and to differentiate between drug products based on the trace elemental profiles. Ten European ibuprofen drug products were evaluated (n=3). The sample preparation was performed by microwave-assisted acid digestion using only 10 mg of homogenized sample and 900 μL of a mix of 65% HNO3, 37% HCl, and 30% H2O2. Solid residuals primarily composed of insoluble SiO2 excipients were removed by centrifugation. Only concentrations of Mg, Fe, Ti, Mn, Cr, and Ni were detected above the limits of detection and did not exceed the ICH Q3D(R1) guideline permitted daily exposure limits. The trace elemental profiles were evaluated through principal component analysis. Three principal components describing 96% of the variance were useful in grouping the ibuprofen drug products, and the detected trace elemental remnants could be related to drug formulation and drug production strategies. An in-house quality control material was used in lack of certified reference materials and was in combination with spike recoveries used for method validation. Good spike recoveries (94–119%) were obtained for all measured trace elements except Mg. Mg showed acceptable spike recoveries (75–155%) for mid and high-spike concentrations, but poor recoveries (30–223%) were detected with low spike concentrations in spike matrices containing high amounts of Mg. Overall, the method is suggested applicable for solid drugs containing insoluble SiO2 excipients and drugs comparable to ibuprofen.

Enhancing transmucosal delivery of CBD through nanoemulsion: in vitro and in vivo studies.

Cannabidiol (CBD) has gained significant attention as a complementary and alternative medicine due to its promising therapeutic properties. However, CBD faces obstacles when administered orally due to its poor solubility in water, leading to limited absorption into the bloodstream and low and variable bioavailability. Therefore, the development of innovative delivery approaches that can enhance CBD's bioavailability, facilitate administration, and promote patient adherence is crucial. We propose a new approach for buccal delivery of CBD based on a self-assembling nanoemulsion (NE) made of a mixture of surfactants (Tween 80 and Labrasol) and medium chain triglycerides (MCTs). The NE formulation showed properties suitable for buccal administration, including appropriate size, CBD content, and surface properties, and, if compared to a CBD-MCT solution, it exhibited better control of administered doses, faster dissolution in buccal medium, and enhanced stability. The CBD-NE effectively released its active load within 5h, remained stable even when diluted in simulated buccal fluids, and could be easily administered through a commercially available spray, providing consistent and reproducible doses of NE with optimized properties. In vitro permeation studies demonstrated that the CBD-NE facilitated swift and consistent permeation through the buccal mucosa, resulting in a higher concentration in the acceptor compartment compared to CBD-MCT. Furthermore, the in vivo study in mice showed that a single buccal administration of CBD-NE led to a quicker onset of action than a CBD solution in MCT, while maintaining the same plasma levels over time and leading to typically higher plasma concentrations compared to those usually achieved through oral administration. In conclusion, our CBD-NE represents a promising alternative formulation strategy for buccal CBD administration, overcoming the challenges associated with conventional formulations such as variable bioavailability and low control of administered doses.

Design and elucidation of an insecticide from natural compounds targeting mitochondrial proteins of Aedes aegypti

Developing new pesticides poses a significant challenge in designing next-generation natural insecticides that selectively target specific pharmacological sites while ensuring environmental friendliness. In this study, we aimed to address this challenge by formulating novel natural pesticides derived from secondary plant metabolites, which exhibited potent insecticide activity. Additionally, we tested their effect on mitochondrial enzyme activity and the proteomic profile of Ae. aegypti, a mosquito species responsible for transmitting diseases. Initially, 110 key compounds from essential oils were selected that have been reported with insecticidal properties; then, to ensure safety for mammals were performed in silico analyses for toxicity properties, identifying non-toxic candidates for further investigation. Subsequently, in vivo tests were conducted using these non-toxic compounds, focusing on the mosquito's larval stage. Based on the lethal concentration (LC), the most promising compounds as insecticidal were identified as S-limonene (LC50 = 6.4 ppm, LC95 = 17.2 ppm), R-limonene (LC50 = 9.86 ppm, LC95 = 27.7 ppm), citronellal (LC50 = 40.5 ppm, LC95 = 68.6 ppm), R-carvone (LC50 = 61.4 ppm, LC95 = 121 ppm), and S-carvone (LC50 = 62.5 ppm, LC95 = 114 ppm). Furthermore, we formulated a mixture of R-limonene, S-carvone, and citronellal with equal proportions of each compound based on their LC50. This mixture specifically targeted mitochondrial proteins and demonstrated a higher effect that showed by each compound separately, enhancing the insecticidal activity of each compound. Besides, the proteomic profile revealed the alteration in proteins involved in proliferation processes and detoxification mechanisms in Ae. aegypti. In summary, our study presents a formulation strategy for developing next-generation natural insecticides using secondary plant metabolites with the potential for reducing the adverse effects on humans and the development of chemical resistance in insects. Our findings also highlight the proteomic alteration induced by the formulated insecticide, showing insight into the mechanisms of action and potential targets for further exploration in vector control strategies.

Composite polymeric microsponge‐based long‐acting gel formulation for topical delivery of mupirocin

AbstractTopical delivery of medicaments in a controlled manner is still a promising area of research. Drug‐containing dammar gum‐ethyl cellulose composite microsponge loaded gel formulation (D‐MSPG) was developed for controlled topical delivery of mupirocin. The drug‐loaded microsponges (D‐MSPs) were formulated by the quasi‐emulsion solvent diffusion method and were evaluated for morphology, particle size distribution, entrapment efficiency, thermal properties, and crystallinity. The optimized D‐MSPs (entrapment efficiency 91.5 ± 4.0% and particle size of 55.15 ± 2.9 μm) were dispersed in carbopol 934 gel (D‐MSPG). The final product was characterized for pH, viscosity, texture, spreadability, consistency, syneresis, in vitro drug release, and ex vivo skin penetration study. A comparative study with marketed formulation was performed. For optimized gel formulation (G4), drug content was 104.19 ± 1.68%, and drug release was 84.19% after 24 h. The pH of the optimized gel was observed to be 6.05 ± 0.04. Viscosity of the optimized gel formulation was found to be 1212.15 ± 434.85 mPa‐s at 50 s−1. The steady‐state flux (J) in ex vivo skin permeation was observed to be 53.96 μg cm−2 h−1 and the permeability coefficient was 2.69 cm/h for the optimized gel formulation. According to the findings, the D‐MSPG‐based formulation strategy can act well to prolong the topical delivery of mupirocin or similar drug molecules.

Old drug, new tricks: polymer-based nanoscale systems for effective cytarabine delivery.

Cytarabine, an antimetabolite antineoplastic agent, has been utilized to treat various cancers. However, because of its short half-life, low stability, and limited bioavailability, achieving an optimal plasma concentration requires continuous intravenous administration, which can lead to toxicity in normal cells and tissues. Addressing these limitations is crucial to optimize the therapeutic efficacy of cytarabine while minimizing its adverse effects. The use of novel drug delivery systems, such as polymer-based nanocarriers have emerged as promising vehicles for targeted drug delivery due to their unique properties, including high stability, biocompatibility, and tunable release kinetics. In this review, we examine the application of various polymer-based nanocarriers, including polymeric nanoparticles, polymeric micelles, dendrimers, polymer-drug conjugates, and nano-hydrogels, for the delivery of cytarabine. The article highlights the limitations of conventional cytarabine administration which often lead to suboptimal therapeutic outcomes and systemic toxicity. The rationale for using polymer-based nanocarriers is discussed, highlighting their ability to overcome challenges by providing controlled drug release, improved stability, and enhanced targeting capabilities. In summary, this review offers a valuable resource for drug delivery scientists by providing insights into the design principles, formulation strategies, and potential applications of polymer-based nanocarriers that can enhance the therapeutic efficacy of cytarabine.

Accelerator production, radiochemical separation and nanoradiopharmaceutical formulation using 69Ge: A next generation PET probe

Positron emission tomography (PET) has revolutionized the field of molecular imaging of cancer. The driving forces in the latest resurgence of PET are the advances in nano-oncology and availability of newer radioisotopes with attractive nuclear decay characteristics. Germanium-69 (69Ge; T½ = 39 h, 21 % β+, Emax = 1205 keV) is one such radioisotope whose potential is yet to be fully explored for PET imaging. The adequately long half-life of 69Ge, makes it an ideal choice for PET imaging using radiolabeled nanoformulations, which are expected to circulate for a relatively longer time in the biological system. In this study, we report the production of 69Ge via 69Ga (p, n) 69Ge reaction using natural Ga2O3 target. A facile radiochemical separation method based on selective precipitation of Ga at pH ∼7 was developed for isolating no-carrier-added (NCA) 69Ge from the irradiated target in a form suitable for in vivo animal studies. A chelator-free approach was optimized for radiolabeling superparamagnetic arginine grafted iron oxide nanoparticles (AMNPs) with 69Ge for potential use in dual modality PET/magnetic resonance imaging (MRI) and magnetic hyperthermia therapy of cancer. The radiolabeling yield of 69Ge-AMNPs was >95 % and the radiolabeled nanoformulation was stable even after 72 h. As a proof of concept, the suitability of the radiolabeled nanoformulation for in vivo PET imaging was demonstrated in Wistar rats. Overall, this strategy of production, radiochemical separation and radiopharmaceutical formulation might aid towards development of potent agents for cancer theranostics.

Beyond origination charges: The pass-through of GSE upfront fee adjustments in 2022

In 2022, a policy increased mortgage guarantee fees for government-sponsored enterprises (GSE) purchases in high-cost areas. Given that the adjustment is specific to selected loan types, we employ a difference-in-differences approach to evaluate the shifts in origination charges for affected mortgages relative to unaffected ones. We find that the increases in origination charges only encapsulate a minor fraction of the escalated costs faced by lenders. Instead, lenders appear to adapt by elevating the interest rates. This research illuminates an unforeseen response from lenders and underscores the necessity for nuanced strategies in housing finance policy formulation.

Supercritical fluid technology as a strategy for nifedipine solid dispersions formulation: In vitro and in vivo evaluation

Supercritical fluid technology (SFT) is an insufficiently investigated approach for the production of solid dispersions, it is environmentally acceptable and has a high potential for application in the pharmaceutical industry. The aim of this work was to formulate and characterize nifedipine solid dispersions (SDs) produced by the SFT and compare the results with ones obtained by the classical solvent based kneading method. The following in vitro tests were conducted: assay and yield, solvent residues, solid state characterization (FTIR, DSC, XRD), flowability, hygroscopicity, solubility, dissolution and stability. Additionally, bioavailability was examined on an animal model (Wistar rats). The formulation selection for in vivo study was performed using the multilevel categoric experimental design and the health risk assessment. Solid state characterization revealed that formulation obtained by the SFT method and higher ratio of polymer (1:5) have had nifedipine in completely amorphous form. Polymer ratio and method of SDs preparation do influence the investigation characteristics. Dissolution rate was fastest in SDs prepared by the SFT and higher polymer ration (1:5). In vivo data of selected SDs prepared by the kneading (ratio 1:1) and the SFT (ratio 1:5) showed alteration in pharmacokinetic profile after i.v. and p.o. application.