The VitraCell: A new in vitro test setup for intravitreal dosage forms.

International compendia specify setting the flow for testing dry powder inhalers (DPIs) with the pressure ratio across the flow control valve ≤0.5. This guidance derives from thermodynamic theory, but there is no requirement that the flow control equipment demonstrates adherence to this theory. There is therefore a need to define and test for acceptable flow control valve performance, enabling DPI manufacturers to determine whether their test equipment is achieving the expected flow control. Herein, we present flow control data for two valves common in the inhaler testing community and describe the need for qualification specifications for flow control equipment with such valves. We devised a simple laboratory apparatus and method for determining the mass flow rate through two common flow control valves in their commercial configuration. In the test method, the pressure ratio across the valve is lowered from ∼0.7 to 0.3. This range of pressure ratio covers the standard test requirement that the pressure ratio must be 0.5 or less and maps the transition of compressible flow through the valve to the point where the air flow theoretically remains constant. A common industrial valve, mentioned specifically in Pharm. Eur. 2.9.18 and in earlier editions of United States Pharmacopeia 601, exhibits nearly constant flow when the pressure ratio is <0.5. Another valve in widespread use exhibits a continued slight increase in mass flow rate even as the pressure ratio is decreased below 0.5. Inhaler testing laboratories should test whether their equipment exhibits the constant flow condition that is often assumed when the pressure ratio across the flow control valve is 0.5 or smaller. Quantitative specifications, yet to be developed, for qualifying commercial flow control equipment must account for both the transient start-up and the steady-state flow in DPI testing.

ABSTRACT Background Targeted laryngeal drug delivery is clinically valuable for procedures requiring rapid topical anesthesia. This study evaluated how the mist from a soft-mist inhaler (Softbreezer) interacts with realistic upper-airway anatomy to influence lidocaine deposition. Research design and methods An in vitro experimental setup was used to assess deposition from the soft mist inhaler across four upper-airway geometries: two simplified models and two subject-specific models. Each model was tested at inhalation flow rates of 15 and 30 L min−1. Deposition was quantified across five anatomical regions. High-speed imaging (6100 fps, 20 μs exposure) characterized plume velocity and cone angle. Results Droplet size distributions were consistent across flow rates (Dv 50 ≈ 16 μm). The subject-specific realistic oral inhalation model achieved the highest laryngeal deposition at 5.3% of the delivered dose at 30 L min−1, compared with 2.1% in the simplified Virginia Commonwealth University model and 1.6% in the subject-specific artificially opened mouth model. The United States Pharmacopoeia model underestimated upper-airway deposition. High-speed imaging confirmed a slow, coherent plume with minimal turbulence. Conclusions Physiologically realistic airway geometry captured during oral inhalation should more accurately represent the flow transitions governing laryngeal deposition.

A review of the State-of-the-Art: progress in ultrasonic and acoustic techniques for quality assessment in the development and manufacturing of oral solid dosage forms - Part II: Applications and emerging directions.

Intravitreal drug delivery requires reliable in vitro models that replicate the structural, mechanical and diffusional properties of the native vitreous body. With the increasing number of patients affected by age-related eye diseases, the need for developing novel therapies is rising. In this study, the diffusion of triamcinolone acetonide was investigated in various hydrogel-based vitreous substitutes using a modified pharmacopeial dissolution test method (United States Pharmacopeia apparatus 7) equipped with 3d-printed gel baskets and dialysis membranes in order to find the most promising in vitro vitreous substitute. Diffusion kinetics and rheological stability were evaluated in comparison to porcine vitreous as the biological reference. One-component gels like those consisting of a single gelling agent (hyaluronic acid gels, hypromellose gels and polyacrylamide gels) failed to achieve both rheological similarity and physiologically relevant diffusion behavior. In contrast, two-component non-covalent hydrogels, particularly hyaluronic acid-agar formulations, exhibited markedly improved performance. The already rheologically optimized formulation consisting of 0.22 % hyaluronic acid and 0.09 % agar most closely matched the diffusion profile of triamcinolone acetonide in porcine vitreous, while supplementation of the acceptor medium with additional 0.22 % hyaluronic acid further enhanced rheological stability over the experimental period. These findings highlight this hydrogel as a promising in vitro vitreous substitute for preclinical diffusion studies, offering a reproducible and potentially physiologically more relevant platform for in vitro intravitreal drug testing.

Introduction Strengthening the local pharmaceutical industry in the Democratic Republic of the Congo to produce affordable, effective, and high-quality medicines contributes to improved health outcomes and economic development. The government grants a monopoly to local manufacturers for the production of certain generic medicines, such as amoxicillin. These products are required to meet established quality, safety, and efficacy standards to adequately address population health needs. Purpose The objective of this study was to evaluate the interchangeability of different brands of amoxicillin produced by local manufacturers in the Democratic Republic of the Congo with a reference (innovator) product through comparative in vitro dissolution testing. Methods Two generic products manufactured by local pharmaceutical companies and one innovator product were evaluated. For each product, one batch was randomly purchased from authorised wholesalers. Analyses were conducted using high-performance liquid chromatography in accordance with the United States Pharmacopeia–National Formulary (USP–NF, 2024). Twelve dosage units were analysed to establish dissolution profiles. Comparative dissolution testing was performed at different pH conditions (1.2, 4.5, and 6.8) using a paddle-type dissolution apparatus. Quantification was carried out by UV spectrophotometry, and dissolution profiles were compared using the difference factor (f₁) and similarity factor (f₂). Acceptable ranges were 0–15 for f₁ and 50–100 for f₂. Results All samples complied with the USP–NF 2024 specifications. However, dissolution recovery rates differed across sampling points. The fit factor analysis demonstrated interchangeability with the reference product only at pH 1.2, while no similarity was observed at pH 4.5 and 6.8. Conclusion The findings indicate potential concerns regarding the efficacy and interchangeability of locally manufactured generic amoxicillin products compared with the innovator product. Manufacturers should re-evaluate their formulations, considering all factors influencing dissolution performance. In addition, regulatory authorities should strengthen post-marketing surveillance to ensure the quality of pharmaceutical products.

Background/Objectives: Biorelevant in vitro dissolution testing is used increasingly to predict complex mechanisms in the gastrointestinal (GI) tract that determine oral bioavailability. However, the limited use of non-compendial systems is driven by the lack of widely accepted, standardized validation frameworks. This ongoing gap continues to restrict their adoption relative to United States Pharmacopeia (USP) apparatus. While the physiological relevance and biopredictive capabilities of the tiny-TIM and TIM-1 in vitro GI models have been demonstrated in previous studies, their inter-laboratory reproducibility has not been systematically established. Therefore, this international ring study evaluates the reproducibility of in vitro simulations of GI transit and absorption of paracetamol in fasted- and fed-state conditions in tiny-TIM and TIM-1. Methods: Three laboratories used TIM-1 and five used tiny-TIM to simulate oral administration of a 500 mg paracetamol solution to a healthy adult. Paracetamol solution was selected as a well-characterized and widely available BCS I compound to minimize formulation and solubility effects and focus on system performance, enabling the generation of a generic validation dataset for the reproducibility of TIM experiments. Results: Paracetamol bioaccessibility profiles were repeatable and reproducible (all pairwise f2 > 50). Maximum differences in total bioaccessible paracetamol were 0.9% (TIM-1) and 2.8% (tiny-TIM) within laboratories and 3.4 and 5.9% between laboratories. Inter-lab variability at individual time points remained <4.0% (fasted) and 5.2% (fed). Both TIM models produced biopredictive metrics, correctly predicting no food effect on total paracetamol bioaccessibility and capturing delayed tmax. Gastric and intestinal environments showed repeatable pH, temperature, and GI transit characteristics, with fluctuations across transit stages that mirrored reported in vivo patterns. Conclusions: These results demonstrate that TIM systems can reproducibly simulate gastrointestinal conditions across laboratories and generate consistent measurements of drug product performance, despite the complexity of the dynamic processes involved. While this evaluation involving a single BCS I drug solution should not be directly extrapolated to experiments with poorly soluble compounds or different formulations, it supports the use of TIM systems as robust in vitro models in drug product development. This study provides a standardized, inter-laboratory, baseline performance dataset to support regulatory submissions incorporating TIM data and enable more confident interpretation of TIM experiments.

“Through expert panels, committees, and direct outreach, we rely on the community to tell us where resources and harmonization are needed most.”Analytical variability and limited harmonization of critical quality attributes continue to constrain the scalable, reproducible development of cell and gene therapies. Divergent methods for parameters such as AAV empty-to-full capsid ratios, genome titers, and potency increase development burden and complicate regulatory alignment across highly customized platforms. The United States Pharmacopeia (USP) is advancing modality-focused reference standards, raw material controls, and fit-for-purpose analytical guidance to improve comparability and reduce uncertainty. Establishing shared, science-based benchmarks will be central to strengthening quality frameworks and sustaining confidence as these advanced therapies mature.

The bacterial endotoxin method uses amoebocyte lysate reagents from the horseshoe crab (Limulus polyphemus or Tachypleus tridentatus) to detect and quantify bacterial endotoxin in injectable medications and medical devices. Two types of recombinant reagents have been introduced by various manufacturers, and the equivalency of these results to natural Limulus Amoebocyte Lysate (LAL) reagents has been recently assessed by the United States, European, and Japanese Pharmacopoeia. Recombinant reagents and amoebocyte lysate reagents appear to be highly comparable, according to several investigations.Limulus Amoebocyte Lysate assays are currently the gold standard. LAL is used in vitro for the precise detection of endotoxins and is based on the endotoxin-activated Factor C-mediated clotting cascade. In our quality control laboratory, we tested several categories of drug samples using different compendial methods for detection of bacterial endotoxin method that provides reliable and consistent results. Since 2024, a bacterial endotoxin test based on recombinant cascade reagent (rCR), the endotoxin sensor recombinant factor C, factor B, and pro-clotting enzyme inside of LAL, has been used as an animal-free alternative to LAL. The non-animal derived reagents rCR, which uses cloned genes from the genome of the Limulus polyphemus horseshoe crab to detect and measure bacterial endotoxins.In addition to providing ethical and environmental benefits over traditional LAL assays, rCR eliminates interfering Horseshoe Crab blood components, allowing for extremely specific endotoxin detection. For rCR test performance in routine setting, a comparative study was conducted of compendial bacterial endotoxin testing by LAL with alternates animal-free reagents rCR and summarize the evidence presented by using analysis of different categories of pharmaceutical products. According to the compendial endotoxin testing requirements, all results were acceptable. When the rCR assay was applied rather of the LAL test, no interference was seen in certain samples. In this study, that rCR and LAL are equivalent and comparable.

Administration of poor-quality medications can result in various effects that jeopardize the drugs’ safety and effectiveness. Due to a lack of adequate post-market surveillance studies, making decisions regarding the quality of medicines, including metformin hydrochloride tablets, available in Mekelle City is challenging. Thus, the aim of the study was to evaluate the quality of different brands of metformin hydrochloride tablets sold in Mekelle City, Tigray Regional State, Ethiopia. A total of eight brands of 500 mg metformin hydrochloride tablets were collected from drug retail outlets in Mekelle City. In vitro quality control tests were conducted based on the WHO visual inspection tool and United States Pharmacopeia (USP) specifications. These included visual inspection, weight variation, thickness, hardness, friability, disintegration time, dissolution, and an assay of active ingredient. One-way ANOVA was used to compare all parameters of quality control. A difference was deemed statistically significant when P < 0.05. One-way ANOVA, model-independent approaches, and model-dependent approaches were used to compare the dissolution profiles and to determine the nature of active pharmaceutical ingredient release. This study showed that all metformin hydrochloride brands marketed in Mekelle City complied with the WHO visual inspection and USP specifications for visual inspection, weight variation, friability, disintegration time, and assay of the active ingredient. Of the samples tested, brand E and brand F exhibited the highest and lowest hardness values, respectively, at 313.88 N and 10.06 N. Moreover, all eight brands evaluated released more than 80% of their drug contents within 30 min as outlined in the USP. However, the difference factor (f1) and similarity factor (f2) have indicated that only brands A, E, and H were similar (can be used interchangeably) with the comparator product. Weibull release model suits the drug release data, which had the highest correlation coefficient. All brands met pharmacopoeial specifications, but significant variations in hardness and dissolution profiles were observed, with only three brands showing profile similarity to the comparator. Hence, the finding serves as an alert to examine the dossier evaluations and legal approval processes of the Ethiopian Food and Drug Authority.

Objective: Altered gastrointestinal physiology in Crohn’s disease and cholestasis may affect the intraluminal environment and impact the dissolution of orally administered drugs. Rifampicin exhibits pH and bile salt–dependent solubility, making it susceptible to variations in gastrointestinal conditions. The present research investigates in vitro dissolution behaviour of rifampicin in biorelevant media that simulate both healthy and disease-specific gastrointestinal environments. Methods: Biorelevant dissolution medium that mimic the fasted-state intestinal conditions for healthy people, Crohn’s disease, and cholestasis were created by modifying pH, bile salt concentration, and the levels of mucin and inflammatory cytokines based on reported physiological values. Rifampicin fast-dissolving tablets (100 mg) were tested using United States Pharmacopeia (USP) Apparatus II (900 mL, 37 °C ± 0.5 °C) and spectrophotometric analysis. Dissolution profiles were analyzed descriptively. Results: Rifampicin demonstrated slower drug release in Crohn’s disease–simulated medium (FaSSIF-CD) compared with FaSSIF-NA ( healthy condition). Drug release at 60 minutes exceeded 90% in FaSSIF control, whereas in FaSSIF-CD, it was limited to approximately 58–62% (p &lt; 0.05). Conversely, dissolution in the cholestasis medium exhibited no significant divergence from the FaSSIF-NA under the evaluated conditions. The data demonstrate significant diversity in dissolution behaviour among media that simulate both healthy and disease-altered gastrointestinal environments. Conclusion: These findings support the idea that physiological characteristics of the gastrointestinal environment may affect how rifampicin dissolves, as well as highlight the importance of media composition in predicting oral bioavailability in pathological states. Additional research with adequate clinical data is needed to go deeper into these findings and examine the molecular impacts on specific components.

E-liquids can be unintentionally contaminated with various harmful substances, and the nicotine and glycols they contain can undergo oxidation, leading to the formation of degradation products and by-products. A sample of 150 e-liquid products produced by 56 companies, 77% of which were manufactured in the Republic of Korea, was selected and analyzed qualitatively and quantitatively for 123 hazardous chemicals using six analytical methods. This paper reports on a total of 91 compounds, which are considered unintended contaminants among the hundreds of chemicals identified in e-liquids. Of these, 41 compounds were identified and quantified for the first time in e-liquids in this study, 18 were classified as carcinogens (Groups 1, 2A, and 2B) by the International Agency for Research on Cancer (IARC), and 8 were classified as carcinogens, mutagens, and reproductive toxicants (CMR) by the European Union. The 25 organic solvents detected are regulated by the United States Pharmacopeia. Ethylene glycol exceeded the residual solvent limit by up to 368-fold in 71 brands, ethanol by up to 26-fold in 3 brands, and isobutyl acetate by up to 1.9-fold in 4 brands. Compared with previous studies, our findings indicate a positive trend towards reduced levels of well-known hazardous substances in e-liquids. However, many carcinogenic and toxic substances were still detected at high concentrations, and numerous additional hazardous substances were newly identified and quantified. These results raise serious questions about the quality of e-cigarettes and their suitability as nicotine replacements. The detected substances and their concentrations should be incorporated in regulatory policies for e-cigarettes.

To describe the development and implementation of a standardized, pharmacy-led assessment of risk (AOR) process for investigational products (IPs) in compliance with United States Pharmacopeia (USP) chapter <800> across a large academic health network. USP <800> mandates institutions to maintain a hazardous drug list but offers limited guidance for investigational agents. The US National Institute for Occupational Safety and Health (NIOSH) has a published list of hazardous drugs that institutions should reference. However, the list only includes agents approved through December 2015, leaving a large gap in hazardous drug standardization for marketed products, providing less precedent for those working with investigational agents. In response, a multidisciplinary workgroup led by pharmacy services developed a system-wide IP AOR process. Two distinct tools incorporating toxicological and biosafety criteria were created to assess small-molecule and biopharmaceutical agents. A centralized database and oversight committee were established to ensure consistency, transparency, and regulatory compliance. As of July 2025, 255 IPs were assessed: 8 high-risk hazardous, 126 low-risk hazardous, and 121 nonhazardous agents. The process has enabled appropriate labeling, safe handling, and efficient review workflows across research pharmacies. The IP AOR process demonstrates the essential role of pharmacists in operationalizing USP <800> requirements for investigational drugs. This model supports occupational safety, regulatory compliance, and scalable implementation across health systems engaged in clinical research. The process outlined in this manuscript is applicable to both investigational agents and any newly marketed drugs being brought into an institution that haven't been reviewed by NIOSH for inclusion on their list.

ABSTRACT The stability of sorbic acid as a preservative in pharmaceutical semisolid dosage forms has not been adequately characterized. In this study, the degradation behavior of sorbic acid was systematically investigated in a model semisolid formulation containing progesterone, polymeric excipients, oils, glycerine, and water. A stability‐indicating liquid chromatographic method was developed and validated for the quantitative determination of sorbic acid. Chromatographic separation was achieved under isocratic conditions using 0.1% orthophosphoric acid and acetonitrile at a flow rate of 1.0 mL/min, with UV detection at 254 nm. The method demonstrated clear separation of sorbic acid from degradation products and formulation components and was validated for specificity, linearity, precision, accuracy, and robustness in accordance with ICH Q2(R2), Chinese Pharmacopoeia ⟨9101⟩, and United States Pharmacopoeia ⟨1225⟩ guidelines. Stability studies revealed a significant decline in sorbic acid content during storage, which was strongly influenced by the presence of the steroidal drug, polymeric excipients, and acidic pH of the semisolid matrix. These findings highlight the need for careful preservative stability evaluation during semisolid formulation development.

The bacterial endotoxin test in the Chinese pharmacopoeia: A journey of international harmonization and national consideration.

USP < 73> ATP Bioluminescence-Based Microbiological Methods for the Detection of Contamination in Short-Life Products is a new chapter in the USP and becomes effective August 2025. This new rapid method will allow even shorter sterility incubation times based on microbial detection, microorganism generation time(s), applying growth phase curves rationale and utilizing ATP bioluminescence testing.The application of microorganism time studies for medical device and pharmaceutical products will greatly benefit with urgent heath care needs by having data and results available sooner for sterility assurance and critical decision making based upon rapid microbiological methods (RMMs).This poster presentation will focus on experimental data based upon alternative microbiological methods and ATP-bioluminescence results related to microbial detection times, inoculation criteria, generation times and ATP-Bioluminescence technology on various types of microorganism types and testing conditions.

Following the legalization of recreational cannabis in Canada under the Cannabis Act (2018), regulatory frameworks were implemented to ensure product safety, quality, and consistency within the legal market. Previous studies revealed significantly greater pesticide contamination in illicit cannabis than in licensed products. In light of these findings, the present study expands contaminant surveillance to include the quantification of Δ⁹-tetrahydrocannabinol (THC) and a broader range of potential toxicants, including metals, pesticides, mycotoxins, and microbial agents. Fifty licensed cannabis products were purchased across Canadian provinces, and 50 illicit samples were obtained via law enforcement seizures. All the samples were tested via validated, accredited/attested methods. THC content was assessed using LC-UV-MS. Pesticides were analyzed via LC-MS/MS and GC-MS/MS; metals via ICP-MS/MS; mycotoxins via LC-MS/MS; and microbial contamination using MALDI-TOF. THC levels in 48% of licensed products deviated by more than 20% from their labeled concentrations. Microbiological testing revealed that 20% of legal products exceeded the European Pharmacopoeia microbial limits, prompting regulatory responses and voluntary recall. In contrast, 55% of the illicit products exceeded the aerobic plate count thresholds, and 73% surpassed the yeast and mold limits. Mycotoxins were undetected in licensed products but were present in 12% of illicit samples. Pesticide residues were found at trace levels (0.01 µg/g) for myclobutanil and dichlobenil in two licensed samples, whereas 94% of illicit samples contained pesticides, averaging 3.4 compounds per sample across 24 unique active ingredients. Metal analysis revealed higher levels of arsenic, cadmium, lead, and mercury in illicit products than in their licensed counterparts. However, licensed samples presented higher chromium concentrations, with peak values approximately threefold greater than those observed in illicit cannabis. The concentrations of arsenic, barium, chromium, copper, molybdenum, nickel, and vanadium exceeded the permissible daily exposure limits of the United States Pharmacopeia (USP) in one or both product categories. These findings demonstrate that licensed THC levels differ from their label claims as well as in contaminants between licensed and illicit cannabis products. The results provide evidence to inform regulatory oversight, enhance public health risk assessments, and support informed decision-making by consumers and policymakers in the context of a legal cannabis framework.

The primary objective of the current study is to establish and validate for the first time a method to determine and quantify praziquantel (PZQ) and its main degradation products loaded in poly(methyl methacrylate–co-2-(diethylamino)ethyl methacrylate) P(MMA-co-DEAEMA) microparticles. A high-performance liquid chromatography (HPLC) approach was developed and validated in accordance with the United States Pharmacopeia (USP) guidelines, addressing parameters such as accuracy, linearity, solution stability, precision, specificity, robustness, sensitivity, and system suitability. The method employed a gradient mobile phase consisting of ultrapure water and acetonitrile, flowing at a rate of 1 mL/minute over a Phenomenex Kinetex® C18 column (5 µm, 100 Å, 250 × 4.6 mm) maintained at 35 °C. Detection was performed at the wavelength of 210 nm using a DAD/UV detector. Samples of the active pharmaceutical ingredient (API) praziquantel, microencapsulated praziquantel, placebo, and a mixture of related substances (A, B, and C) were prepared with 0.5% formic acid in water/ethanol, 45:55 v/v as the diluent, and injected at 20 °C. The method demonstrated a limit of quantification (LOQ) of 0.20 µg/mL for praziquantel and related substances. The method exhibited an excellent linear response, with all correlation coefficients (R2) values exceeding 0.998, which is well above the recommended specified limit of R2 &gt; 0.995. Percent recoveries fell within the acceptable range of (95.0–105.0%), and all results indicated a percentage of relative standard deviation (%RSD) ≤ 2.0, indicating a robust methodology. Thus, the proposed HPLC technique proved to be selective, accurate, sensitive, and consistent in analyzing both the material content and its main degradation products.

Background: Succinylcholine chloride is essential for achieving neuromuscular blockade during emergency airway management. The manufacturer specifies a 14-day stability period for 20 mg/mL vials at room temperature, which limits implementation of prefilled-syringe protocols. Aim: This study aims to investigate the chemical stability of succinylcholine chloride after transfer from manufacturer vials to polypropylene syringes during extended room-temperature storage. Methods: A validated high-performance liquid chromatography with ultraviolet detection (HPLC-UV) method was developed to quantify percent recovery. Ten 20 mg/mL succinylcholine chloride vials were used: five samples were stored refrigerated (2&amp;ndash;8&amp;deg;C; controls; n = 5), and five were transferred to polypropylene syringes and stored at room temperature (20&amp;ndash;25&amp;deg;C; n = 5). Samples were analyzed over 90 days. The HPLC-UV method met United States Pharmacopeia criteria for accuracy, precision (&lt;5% error and % relative standard deviation), and linearity (R2 &gt; 0.99). Results: Succinylcholine chloride maintained &gt;90% of the initial concentration over 90 days in polypropylene syringes stored at room temperature (93.13% on day 90) and in refrigerated controls (93.97% on day 90). No significant differences were observed between storage conditions (p&gt;0.05). All samples remained physically stable, with no visible color change or precipitate. Conclusion: Despite its ester bonds, succinylcholine chloride remained chemically stable in polypropylene syringes for up to 90 days at room temperature. Relevance for Patients: These findings support the extended stability of prefilled succinylcholine syringes, which may improve emergency preparedness; however, sterility validation remains necessary before clinical implementation.

In-office compounding of buffered lidocaine and epinephrine - A stability and safety review.