Two in One: Size Characterization and Accelerated Short-Term Physical Stability of Dual-Drug Suspensions with Two Acidic Compounds (Indomethacin and Naproxen).

Co-delivering dual-drug systems have proven to be effective in, for example, anticancer therapy or HIV prophylaxis due to a higher target selectivity and therapeutic efficacy from compound synergism. However, various challenges regarding physical stability can arise during the formulation definition when multiple drug compounds are included in the same formulation. In this work, the focus was on aqueous suspensions, which could be applied as long-acting injectable formulations to release the drug compounds over weeks to months after administration.

Advantages of the refined Developability Classification System (rDCS) in early discovery.

Rat pharmacokinetic studies are commonly utilized in early discovery to support absorption, distribution, metabolism, and excretion optimization of active pharmaceutical ingredients (APIs). The aim of this work was to compare exposures from fit-for-purpose oral suspension and solution formulations in rats to guidance provided by the refined Developability Classification System (rDCS) with respect to identifying potential limits to oral absorption, formulation strategy selection, and to optimize oral bioavailability (BA). This investigation utilized six diverse APIs covering a large range of biorelevant solubility, metabolic stability, and oral BA in rats.

Hydrophobic ion pairing: lipophilicity improvement of anionic macromolecules by divalent cation mediated complex formation.

The aim of this study was to develop an alternative strategy to sufficiently increase the lipophilicity of anionic model macromolecules (MM) without the use of cationic counterions. Enoxaparin (ENO), insulin (INS) and poly-L-glutamic acid (PLG) were ion paired with anionic surfactants (sodium decanoate (DEC), sodium dodecyl sulfate (SDS), sodium stearate (SS) and sodium octadecyl sulfate (SOS)), mediated by divalent cations such as magnesium, calcium and zinc. Complexes were evaluated regarding their precipitation efficiency and logD.

Machine learning strengthened formulation design of pharmaceutical suspensions.

Many different formulation strategies have been investigated to oppose suboptimal treatment of long-term or chronic conditions, one of which are the nano- and microsuspensions prepared as long-acting injectables to prolong the release of an active pharmaceutical compound for a defined period of time by regulating the size of particles by milling. Typically, surfactant and/or polymers are added in the dispersion medium of the suspension during processing for stabilization purposes. However, current formulation investigations with milling are heavily based on prior expertise and trial-and-error approaches.

Biowaiver monographs for immediate-release solid oral dosage forms: Voriconazole.

According to the ICH M9 Guideline, the triazole antifungal voriconazole is a Biopharmaceutics Classification System (BCS) class II drug, being highly soluble at the highest dose strength but not at the highest single dose. Although the ICH M9 allows for consideration of BCS-based biowaivers in such cases, voriconazole does not meet the additional requirement of dose proportional pharmacokinetics (PK) over the therapeutic dose range. By contrast, if the classification were based on the FDA solubility criteria that were in place prior to ICH M9 (based on the highest dose strength), voriconazole would belong to BCS class I and thus qualify for the BCS-based biowaiver.

Biowaiver monographs for immediate-release solid oral dosage forms: Lemborexant.

Lemborexant is a dual orexin receptor antagonist assigned to class II of the Biopharmaceutics Classification System (BCS). Thus, the ICH M9 Guideline excludes immediate-release (IR) solid oral dosage forms containing lemborexant from BCS-based biowaivers, irrespective of their in vitro dissolution behavior. By contrast, classification of lemborexant according to the refined Developability Classification System (rDCS) falls into class I, indicating few biopharmaceutics risks.

Using the refined Developability Classification System (rDCS) to guide the design of oral formulations.

The refined Developability Classification System (rDCS) provides a comprehensive animal-free approach for assessing biopharmaceutical risks associated with developing oral formulations. This work demonstrates practical application of a recently advanced rDCS framework guiding formulation design for six diverse active pharmaceutical ingredients (APIs) and compares rDCS classifications with those of the Biopharmaceutics Classification System (BCS). While the BCS assigns five of the APIs to class II/IV, indicating potentially unfavorable biopharmaceutical attributes, the rDCS provides a more nuanced risk assessment.

Can We Simplify Liposome Manufacturing Using a Complex DoE Approach?

Microfluidic liposome production presents a streamlined pathway for expediting the translation of liposomal formulations from the laboratory setting to clinical applications. Using this production method, resultant liposome characteristics can be tuned through the control of both the formulation parameters (including the lipids and solvents used) and production parameters (including the production speed and mixing ratio). Therefore, the aim of this study was to investigate the relationship between not only total flow rate (TFR), the fraction of the aqueous flow rate over the organic flow rate (flow rate ratio (FRR)), and the lipid concentration, but also the solvent selection, aqueous buffer, and production temperature.

Temperature mapping of milling by dual centrifugation: A systematic investigation.

Using low quantities of drug compounds is often favorable in the early stages of drug development, especially for what require a large screening investigation to define the final formulation composition, such as nano- and microsuspensions. For that reason, the dual centrifugation approach has in the recent years been used due to its reproducible and fast-milling capacity with 40 samples in 2 mL vials simultaneously without the addition of cooling breaks due to a built-in cooling system. Nonetheless, heat can be dissipated into the samples during high-intensity milling, resulting in increased sample temperatures that potentially can affect thermolabile compounds and potential influence the obtained suspensions in the screening experiments if the used stabilizer has temperature dependent variations in the performance.

The Langmuir-Blodgett trough (Langmuir film balance) can be used to understand the stabilizer concentrations in aqueous nano- and microsuspensions.

Aqueous suspensions of poorly soluble, crystalline drug particles in the sub-micron range hold the ability to regulate the drug release for a defined period of time after e.g., intramuscular, or subcutaneous administration, working as an eminent formulation strategy for the preparation of long-acting injectables.

Towards the outbreak tail, what is the public opinion about wastewater surveillance in the United States?

National opinions on a wide variety of public health topics can change over time and have highly contextual nuances. This study is a follow-up to prior inquiries into the knowledge of wastewater-based epidemiology, privacy concerns surrounding sample collection, and the use of data acquired, along with privacy awareness from an online survey conducted in the metropolitan United States during the winter of 2023. Mentions of wastewater-surveillance-related terms in the media remained common.

Patient-Centric Long-Acting Injectable and Implantable Platforms─An Industrial Perspective.

The increasing focus on patient centricity in the pharmaceutical industry over the past decade and the changing healthcare landscape, driven by factors such as increased access to information, social media, and evolving patient demands, has necessitated a shift toward greater connectivity and understanding of patients' unique treatment needs. One pharmaceutical technology that has supported these efforts is long acting injectables (LAIs), which lower the administration frequency for the patient's provided convenience, better compliance, and hence better therapeutical treatment for the patients. Furthermore, patients with conditions like the human immunodeficiency virus and schizophrenia have positively expressed the desire for less frequent dosing, such as that obtained through LAI formulations.

A Systematic Investigation of Process Parameters for Small-Volume Aqueous Suspension Production by the Use of Focused Ultrasonication.

Aqueous suspensions containing crystalline drug in the sub-micron range is a favorable platform for long-acting injectables where particle size can be used to obtain a desired plasma-concentration profile. Stabilizers are added to the suspensions and screened extensively to define the optimal formulation composition. In the initial formulation screening the amount of drug compound can be limited, necessitating milling methods for small-volume screening predictable for scale-up.

Multiple sclerosis in Denmark (1950-2023): mean age, sex distribution, incidence and prevalence.

With rising life expectancy and advancements in disease management, we expect the multiple sclerosis population is getting older. However, evidence supporting this hypothesis remains sparse. Our study aimed to determine whether the mean age of the Danish multiple sclerosis population has increased and to analyse the developments in sex distribution, incidence, and prevalence, all of which affect age composition.

A Stratified Analysis of Supersaturation and Precipitation Effects Based on the Refined Developability Classification System (rDCS).

Supersaturation and precipitation within the gastrointestinal tract can influence oral absorption of active pharmaceutical ingredients (APIs). Supersaturation of weakly basic APIs upon transfer from the stomach into the small intestine may enhance their absorption, while salt forms of poorly soluble weak acids may generate supersaturated solutions in both stomach and intestine. Likewise, APIs with solubility-limited absorption may be developed as enabling formulations intended to produce supersaturated solutions of the API in the gut.

Wastewater threshold as an indicator of COVID-19 cases in correctional facilities for public health response: A modeling study.

Although prison facilities are not fully isolated from the communities in which they are located, most of the population is confined and requires high levels of health vigilance and protection. This study aimed to examine the dynamic relationship between facility-level wastewater viral concentrations and the probability of at least one positive COVID-19 case within the facility. The study period was from January 11, 2021 to May 8, 2023.

Predictions of biorelevant solubility change during dispersion and digestion of lipid-based formulations.

Computational approaches are increasingly explored in development of drug products, including the development of lipid-based formulations (LBFs), to assess their feasibility for achieving adequate oral absorption at an early stage. This study investigated the use of computational pharmaceutics approaches to predict solubility changes of poorly soluble drugs during dispersion and digestion in biorelevant media. Concentrations of 30 poorly water-soluble drugs were determined pre- and post-digestion with in-line UV probes using the MicroDISS Profiler™.

Environmental Levels of Volatile Organic Compounds, Race, and Socioeconomic Markers Correlate with Areas of High Colorectal Cancer Incidence.

Background: Ambient levels of volatile organic compounds (VOCs) released from nearby industrial plants have shown positive associations with increased colorectal cancer (CRC) rates. The objective of this study is to analyze the distribution of CRC in the context of socioeconomic status and its correlation with community environmental data.

Methods: A retrospective study analyzed CRC patients from 2021 to 2023.

Where Does Wastewater-Based Epidemiology Fall in Medical Student Education?

Doctors are well-trained in the collection, analysis, and interpretation of individual stool or urine sample data; however, wastewater-based epidemiology (WBE) combines the excretion of many community members into an anonymous health sample tied to a geographic location. We advocate for the inclusion of WBE in medical education. WBE offers physicians an opportunity to better care for patients with diseases seen at health clinics and doctors' offices, customize and inform treatment, and accept positive results as true positives, backed by the contextual information provided by wastewater findings.

A study of hydrophobic domain formation of polymeric drug precipitation inhibitors in aqueous solution.

Despite the widespread use of polymers as precipitation inhibitors in supersaturating drug formulations, the current understanding of their mechanisms of action is still incomplete. Specifically, the role of hydrophobic drug interactions with polymers by considering possible supramolecular conformations in aqueous dispersion is an interesting topic. Accordingly, this study investigated the tendency of polymers to create hydrophobic domains, where lipophilic compounds may nest to support drug solubilisation and supersaturation.