Utility of native emission quenching of erythrosine B for the determination of diltiazem in different dosage forms.

This study introduces a practical and cost-effective method for tracking diltiazem (DLZ) analytically. It utilizes a fluorimetric approach that relies on the modulation of fluorescence intensity of a dye called erythrosine B. Through a one-pot experiment performed in an acidic environment, a complex is rapidly formed between DLZ and erythrosine B. By observing the decrease in erythrosine B emission, a linear calibration plot is established, enabling the detection and quantification of DLZ concentrations ranging from 40 to 850 ng/ml. The estimated limits of detection and quantitation were 10.5 and 32.1 ng/ml, respectively. The variables affecting the DLZ-dye complex system were carefully adjusted. The validity of the approach was confirmed through a thorough evaluation based on the criteria set by ICH guidelines. The accuracy and precision of the methodology were evaluated, and the standard deviation and relative standard deviation were below 2. The strategy was successfully employed to analyze DLZ in tablets and capsules, and no significant variation between the proposed and reported methods as the values of the estimated t-test and F-test at five determinations were below 2.306 and 6.338, respectively. Notably, the method adheres to the principle of green chemistry by utilizing distilled water as the dispersing medium.

The potential of three-dimensional printing for pediatric oral solid dosage forms.

Pediatric patients often require individualized dosing of medicine due to their unique pharmacokinetic and developmental characteristics. Current methods for tailoring the dose of pediatric medications, such as tablet splitting or compounding liquid formulations, have limitations in terms of dosing accuracy and palatability. This paper explores the potential of 3D printing as a solution to address the challenges and provide tailored doses of medication for each pediatric patient. The technological overview of 3D printing is discussed, highlighting various 3D printing technologies and their suitability for pharmaceutical applications. Several individualization options with the potential to improve adherence are discussed, such as individualized dosage, custom release kinetics, tablet shape, and palatability. To integrate the preparation of 3D printed medication at the point of care, a decentralized manufacturing model is proposed. In this setup, pharmaceutical companies would routinely provide materials and instructions for 3D printing, while specialized compounding centers or hospital pharmacies perform the printing of medication. In addition, clinical opportunities of 3D printing for dose-finding trials are emphasized. On the other hand, current challenges in adequate dosing, regulatory compliance, adherence to quality standards, and maintenance of intellectual property need to be addressed for 3D printing to close the gap in personalized oral medication.

Taste-masking methods in multiparticulate dosage forms with a focus on poorly soluble drugs.

In the past, the administration of medicines for children mainly involved changes to adult dosage forms, such as crushing tablets or opening capsules. However, these methods often led to inconsistent dosing, resulting in under- or overdosing. To address this problem and promote adherence, numerous initiatives, and regulatory frameworks have been developed to develop more child-friendly dosage forms. In recent years, multiparticulate dosage forms such as mini-tablets, pellets, and granules have gained popularity. However, a major challenge that persists is effectively masking the bitter taste of drugs in such formulations. This review therefore provides a brief overview of the current state of the art in taste masking techniques, with a particular focus on taste masking by film coating. Methods for evaluating the effectiveness of taste masking are also discussed and commented on. Another important issue that arises frequently in this area is achieving sufficient dissolution of poorly water-soluble drugs. Since the simultaneous combination of sufficient dissolution and taste masking is particularly challenging, the second objective of this review is to provide a critical summary of studies dealing with multiparticulate formulations that are tackling both of these issues.

Fluorescence based methodology with greenness consideration for concurrent estimation of anti-allergic medication; application to dosage form.

A green, sensitive and rapid spectrofluorimetric method for quantitative assay of an anti-allergic medication composed of montelukast and fexofenadine mixture in raw materials and dosage form was developed. The method was based on measuring the synchronous fluorimetric peak without interference, pre-separation or pre-extraction procedures. Montelukast was analyzed at 360 nm while fexofenadine was measured at 263 nm using Δλ = 20 nm for both drugs using ethanol as diluting solvent and acetate buffer of pH 4. The assay was rectilinear over the concentration range of 1.0-10.0 µg/mL for fexofenadine and 0.1-0.6 µg/mL for montelukast. The method was full validated according to ICH guidelines. The applicability of the method enables the assay of both drugs in raw materials, synthetic mixture as well as combined tablets. Moreover, the greenness of the method was assessed using different methods including; analytical eco-scale, GAPI and AGREE. All of these methods confirm that the proposed method is an eco-friendly method.

A comprehensive assessment of machine learning algorithms for enhanced characterization and prediction in orodispersible film development.

Orodispersible films (ODFs) have emerged as innovative pharmaceutical dosage forms, offering patient-specific treatment through adjustable dosing and the combination of diverse active ingredients. This expanding field generates vast datasets, requiring advanced analytical techniques for deeper understanding of data itself. Machine learning is becoming an important tool in the rapidly changing field of pharmaceutical research, particularly in drug preformulation studies. This work aims to explore into the application of machine learning methods for the analysis of experimental data obtained by ODF characterization in order to obtain an insight into the factors governing ODF performance and use it as guidance in pharmaceutical development. Using a dataset derived from extensive experimental studies, various machine learning algorithms were employed to cluster and predict critical properties of ODFs. Our results demonstrate that machine learning models, including Support vector machine, Random forest and Deep learning, exhibit high accuracy in predicting the mechanical properties of ODFs, such as flexibility and rigidity. The predictive models offered insights into the complex interaction of formulation variables. This research is a pilot study that highlights the potential of machine learning as a transformative approach in the pharmaceutical field, paving the way for more efficient and informed drug development processes.

Is it advantageous to use quality by design (QbD) to develop nanoparticle-based dosage forms for parenteral drug administration?

Parenteral administration is one of the most commonly used drug delivery routes for nanoparticle-based dosage forms, such as lipid-based and polymeric nanoparticles. For the treatment of various diseases, parenteral administration include intravenous, subcutaneous, and intramuscular route. In drug development phase, multiparameter strategy with a focus on drug physicochemical properties and the specificity of the administration route is required. Nanoparticle properties in terms of size and targeted delivery, among others, are able to surpass many drawbacks of conventional dosage forms, but these unique properties can be a bottleneck for approval by regulatory authorities. Quality by Design (QbD) approach has been widely utilized in development of parenteral nanoparticle-based dosage forms. It fosters knowledge of product and process quality by involving sound scientific data and risk assessment strategies. A full and comprehensive investigation into the state of implementation and applications of the QbD approach in these complex drug products can highlight the gaps and challenges. In this review, the analysis of critical attributes and Design of Experiment (DoE) approach in different nanoparticulate systems, together with the proper utilization of Process Analytical Technology (PAT) applications are described. The essential of QbD approach for the design and development of nanoparticle-based dosage forms for delivery via parenteral routes is discussed thoroughly.

Ajuste de dosis según función renal en una paciente polimedicada incluida en el servicio de reacondicionamiento de medicamentos utilizando sistemas personalizados de dosificación (SPD) / Dose adjustment according to renal function in a polymedicated patient included in the medication reconditioning service using personalized dosing systems (SPD)

Paciente de 78 años, polimedicada e incluida en el servicio de Sistema Personalizado de Dosificación de Medicamentos (SPD). Al acudir a retirar su medicación nos informa que desde hace unos meses sufre cansancio, debilidad, mareos y confusión. Se realiza una revisión de la medicación, centrada en la dosificación de los medicamentos de metabolismo o eliminación renal, en función del valor de Filtrado Glomerular estimado de la paciente (FGe). Se realiza derivación al Médico de Atención Primaria (MAP) mediante un informe, en el que se recomienda la reducción de dosis de losartán y manidipino según el valor de FGe de la paciente. El MAP redujo la dosis de los antihipertensivos. Se efectuó seguimiento del caso, que permitió observar que la paciente dejó de presentar los síntomas descritos inicialmente.(AU)

Use of Magnetic Resonance Imaging for Visualization of Oral Dosage Forms in the Human Stomach: A Scoping Review.

Oral dosage forms are the most widely and frequently used formulations to deliver active pharmaceutical ingredients (APIs), due to their ease of administration and noninvasiveness. Knowledge of intragastric release rates and gastric mixing is crucial for predicting the API release profile, especially for immediate release formulations. However, knowledge of the intragastric fate of oral dosage forms in vivo to date is limited, particularly for dosage forms administered when the stomach is in the fed state. An improved understanding of gastric food processing, dosage form location, disintegration times, and food effects is essential for greater understanding for effective API formulation design. In vitro standard and controlled modeling has played a significant role in predicting the behavior of dosage forms in vivo. However, discrepancies are reported between in vitro and in vivo disintegration times, with these discrepancies being greatest in the fed state. Studying the fate of a dosage form in vivo is a challenging process, usually requiring the use of invasive methods, such as intubation. Noninvasive, whole body imaging techniques can however provide unique insights into this process. A scoping review was performed systematically to identify and critically appraise published studies using MRI to visualize oral solid dosage forms in vivo in healthy human subjects. The review identifies that so far, an all-purpose robust contrast agent or dosage form type has not been established for dosage form visualization and disintegration studies in the gastrointestinal system. Opportunities have been identified for future studies, with particular focus on characterizing dosage form disintegration for development after the consumption food, as exemplified by the standard Food and Drug Administration (FDA) high fat meal.

Systematic screening of photopolymer resins for stereolithography (SLA) 3D printing of solid oral dosage forms: Investigation of formulation factors on printability outcomes.

Pharmaceutical three-dimensional printing (3DP) is now in its golden age. Recent years have seen a dramatic increase in the research in 3D printed pharmaceuticals due to their potential to deliver highly personalised medicines, thus revolutionising the way medicines are designed, manufactured, and dispensed. A particularly attractive 3DP technology used to manufacture medicines is stereolithography (SLA), which features key advantages in terms of printing resolution and compatibility with thermolabile drugs. Nevertheless, the enthusiasm for pharmaceutical SLA has not been followed by the introduction of novel excipients specifically designed for the fabrication of medicines; hence, the choice of biocompatible polymers and photoinitiators available is limited. This work provides an insight on how to maximise the usefulness of the limited materials available by evaluating how different formulation factors affect printability outcomes of SLA 3D printed medicines. 156 photopolymer formulations were systematically screened to evaluate the influence of factors including photoinitiator amount, photopolymer molecular size, and type and amount of liquid filler on the printability outcomes. Collectively, these factors were found highly influential in modulating the print quality of the final dosage forms. Findings provide enhanced understanding of formulation parameters informing the future of SLA 3D printed medicines and the personalised medicines revolution.

Application of 3D printing in early phase development of pharmaceutical solid dosage forms.

Three-dimensional printing (3DP) is an emerging technology, offering the possibility for the development of dose-customized, effective, and safe solid oral dosage forms (SODFs). Although 3DP has great potential, it does come with certain limitations, and the traditional drug manufacturing platforms remain the industry standard. The consensus appears to be that 3DP technology is expected to benefit personalized medicine the most, but that it is unlikely to replace conventional manufacturing for mass production. The 3DP method, on the other hand, could prove well-suited for producing small batches as an adaptive manufacturing technique for enabling adaptive clinical trial design for early clinical studies. The purpose of this review is to discuss recent advancements in 3DP technologies for SODFs and to focus on the applications for SODFs in the early clinical development stages, including a discussion of current regulatory challenges and quality controls.

Charge transfer complex-based spectrophotometric analysis of famotidine in pure and pharmaceutical dosage forms.

A straightforward and efficient spectrum technique was created using Ortho-chloranil as the electron acceptor (-acceptor) in a charge transfer (CT) complex formation reaction to determine the concentration of famotidine (FMD) in solutions. Compared to the double-distilled blank solution, the reaction result detected a definite violet colour at a maximum absorption wavelength of 546 nm, For concentrations range 2-28 µg/ml, the technique demonstrated excellent compliance with Beer-Law and Lambert's, as evidenced by its molar absorptivity of 2159.648 L mol-1 cm-1. Lower detection limits of 0.3024 µg/ml and 1.471 µg/ml, respectively, were discovered. The complexes of famotidine and Ortho-chloranil were found to have a 2:1 stoichiometry. Additionally, the suggested approach effectively estimated famotidine concentrations in pharmaceutical formulations, particularly in tablet form.

In-lab synthesized turn-off fluorescence sensor for estimation of Gemigliptin and Rosuvastatin polypill appraised by Spider diagram, AGREE and whiteness metrics.

Gemigliptin-Rosuvastatin single-pill combination is a promising therapeutic tool in the effective control of hyperglycemia and hypercholesterolemia. Organic sensors with high quantum yields have profoundly significant applications in the pharmaceutical industry, such as routine quality control of marketed formulations. Herein, the fluorescence sensor, 2-Morpholino-4,6-dimethyl nicotinonitrile 3, (λex; 226 nm, λem; 406 nm), was synthesized with a fluorescence quantum yield of 56.86% and fully characterized in our laboratory. This sensor showed high efficiency for the determination of Gemigliptin (GEM) and Rosuvastatin (RSV) traces through their stoichiometric interactions and simultaneously fractionated by selective solvation. The interaction between the stated analytes and sensor 3 was a quenching effect. Various experimental parameters and the turn-off mechanism were addressed. The adopted approach fulfilled the ICH validation criteria and showed linear satisfactory ranges, 0.2-2 and 0.1-1 µg/mL for GEM and RSV, respectively with nano-limits of detection less than 30 ng/mL for both analytes. The synthesized sensor has been successfully applied for GEM and RSV co-assessment in their synthetic polypill with excellent % recoveries of 98.83 ± 0.86 and 100.19 ± 0.64, respectively. No statistically significant difference between the results of the proposed and reported spectrophotometric methods in terms of the F- and t-tests. Ecological and whiteness appraisals of the proposed study were conducted via three novel approaches: the Greenness Index via Spider Diagram, the Analytical Greenness Metric, and the Red-Green-Blue 12 model. The aforementioned metrics proved the superiority of the adopted approach over the previously published one regarding eco-friendliness and sustainability. Our devised fluorimetric turn-off sensing method showed high sensitivity, selectivity, feasibility, and rapidity with minimal cost and environmental burden over other sophisticated techniques, making it reliable in quality control labs.

Microfluidic nanoparticle synthesis for oral solid dosage forms: A step toward clinical transition processes.

Nanomedicine provides various opportunities for addressing medical challenges associated with drug bioavailability, stability, and efficacy. In particular, oral nanoparticles (NPs) represent an alternative strategy to enhance the solubility and stability of active ingredients through the gastrointestinal tract. The nanocarriers could be used for both local and systemic targeting, enabling controlled release of encapsulated drugs. This approach allows more efficient therapies. In this work, we aim to develop reliable oral solid dosage forms incorporating NPs produced by either one pot synthesis or continuous production, following protocols that yield highly consistent outcomes, promoting their technology transfer and clinical use. Microfluidics technology was selected to allow an automated and highly productive synthetic approach suitable for the highly throughput production. In particular, innovative systems, which combine advantage of NPs and solid dosage formulation, were designed, developed, and characterized demonstrating the possibility to obtaining oral administration. The resulting NPs were thus carried on oral dosage forms, i.e., pellets and minitablets. NPs resulted stable after dosage forms manufacturing, leading to confidence also on protection of encapsulated drugs. Indomethacin was used as a tracer to test biopharmaceutical behaviour. Anti-inflammatories or cytotoxic chemotherapeutics could be vehiculated leading to a breakthrough in the treatment of severe diseases allowing the oral administration of these drugs. We believe that the advancement achieved with the results of our work paves the way for the progression of nanoproducts into clinical transition processes.

Adherencia al tratamiento en paciente polimedicado con sistemas personalizados de dosificación (SPD) y su impacto en salud / Adherence to treatment in polymedicated patients using Monitored Dosage Systems (MDS) and their impact on health

Los Sistemas Personalizados de Dosificación (SPD) son una herramienta eficaz, segura y homologada para el reacondicionamiento de fármacos en farmacia comunitaria. Estos implican la revisión del uso del medicamento (RUM) y la colaboración con el médico de atención primaria (MAP). En el presente artículo se describe el caso de una paciente de 57 años intervenida de lumbociatalgia en 2021 y 2022, con dolor crónico mal controlado y aturdimiento derivado del olvido y/o duplicidad de las tomas. Durante la dispensación habitual se detectan estos problemas relacionados con el medicamento (PRM) y se deriva a la paciente al servicio SPD. Tras la implantación del mismo, la paciente mejora a nivel cognitivo, eliminando el aturdimiento y controlando el dolor, lo que supuso un aumento en su calidad de vida. En conclusión, se destaca la importancia de los diferentes servicios disponibles en la farmacia para mejorar la calidad de vida del paciente, la adherencia al tratamiento y la detección de PRM. (AU)

Monitored Dosage Systems (MDS) are an efficient, reliable and approved device for drug reconditioning in pharmacy. These systems imply a review on proper drug use and the collaboration between primary health care and pharmacists. The case study describes a female patient with a surgical intervention due to lumbosciatica in 2021 and 2022. Patient describes uncontrolled chronic pain and confusion related to improper drug use. During regular dispensing of her medication, these medicine-related problems (MRP) were detected and the patient was referred to the MDS service. After its implementation, the patient’s confusion was eliminated and pain management was achieved, increasing her quality of life. As a conclusion, the different health services provided by the pharmacy can improve a patient’s quality of life, treatment adherence and MRP detection. (AU)

Biowaiver Monograph for Immediate-Release Solid Oral Dosage Forms: Isavuconazonium Sulfate.

A Biopharmaceutics Classification System (BCS)-based biowaiver monograph is presented for isavuconazonium sulfate. A BCS-based biowaiver is a regulatory option to substitute appropriate in vitro data for in vivo bioequivalence studies. Isavuconazonium sulfate is the prodrug of isavuconazole, a broad-spectrum azole antifungal indicated for invasive fungal infections. While the prodrug can be classified as a BCS Class III drug with high solubility but low permeability, the parent drug can be classified as a BCS Class II drug with low solubility but high permeability. Interestingly, the in vivo behavior of both is additive and leads isavuconazonium sulfate to act like a BCS class I drug substance after oral administration. In this work, experimental solubility and dissolution data were evaluated and compared with available literature data to investigate whether it is feasible to approve immediate release solid oral dosage forms containing isavuconazonium sulfate according to official guidance from the FDA, EMA and/or ICH. The risks associated with waiving a prodrug according to the BCS-based biowaiver guidelines are reviewed and discussed, noting that current regulations are quite restrictive on this point. Further, results show high solubility but instability of isavuconazonium sulfate in aqueous media. Although experiments on the dissolution of the capsule contents confirmed 'very rapid' dissolution of the active pharmaceutical ingredient (API) isavuconazonium sulfate, its release from the commercial marketed capsule formulation Cresemba is limited by the choice of capsule shell material, providing an additional impediment to approval of generic versions via the BCS-Biowaiver approach.

Quality of measuring devices enclosed with paediatric oral liquid dosage forms of medicines registered in Sri Lanka.

INTRODUCTION: Oral liquid dosage forms remain popular in several middle income countries. The accuracy of liquid dosage form dosing depends on the accuracy and availability of measuring devices. Lack of quality oral liquid measuring devices will lead to medication errors. Hence there is an urgent need to describe the quality of manufacturer supplied measuring devices enclosed with paediatric oral liquid dosage forms currently registered in Sri Lanka. METHODOLOGY: Standards for measuring devices were developed after a detailed literature search. Multidisciplinary panel rated each standard for the necessity criteria on a 9 point Likert scale. Standards with overall panel median score of ≥ 7 with agreement were selected. A cross-sectional study was done. All the measuring devices, labels and instructions enclosed with the registered products were assessed against the standards developed. Three volumes of liquid antibacterials were measured using the enclosed measuring device. Accuracy of the volumes was measured. RESULTS: Of the total products (n = 202) only 126 were packed with a dosing device. Around quarter of the oral liquid dosage forms (n = 36) did not have a measuring device. More than half of the measuring devices aligned with all the standards developed. Out of 44 oral liquid paediatric antimicrobials measuring cups (n = 25, 56.8%, 95% CI: 41%-72%) were enclosed more and less error was seen with measuring cups. CONCLUSION: The quality of oral liquid measuring devices were not satisfactory. Quality could be further improved if the regulatory body request the manufactures/importers to adhere to the standards developed. Correct volumes were not measured using the measuring devices provided with the liquid antimicrobial agents.