Solid Form Research Articles

Phase-separated polymer blends for controlled drug delivery by tuning morphology

Controlling drug release rate and providing physical and chemical stability to the active pharmaceutical ingredient are key properties of oral solid dosage forms. Here, we demonstrate a formulation strategy using phase-separated polymer blends where the morphology provides a route for tuning the drug release profile. By utilising phase separation of a hydrophobic and a hydrophilic polymer, the hydrophilic component will act as a channelling agent, creating a porous network upon dissolution that will dictate the release characteristics. With ptychographic X-ray tomography and scanning transmission X-ray microscopy we reveal how the morphology depends on both polymer fraction and presence of drug, and how the drug is distributed over the polymer domains. Combining X-ray imaging results with dissolution studies reveal how the morphologies are correlated with the drug release and showcase how tuning the morphology of a polymer matrix in oral formulations can be utilised as a method for controlled drug release.

Therapeutic potential of phytocompounds of Bacopa monnieri (L.) Wettst (literature review)

The aim of the work was to evaluate the pharmacological effects and therapeutic potential of individual compounds and extracts of B. monnieri based on the analysis of data from scientific periodicals regarding chemical composition and biological action. Theoretically significant were the studies of the materials of the scientific-metric database PubMed and Google Scholar over the last five years regarding the chemical composition and biological action of extracts based on B. monnieri and their individual components. The search query was carried out by the Latin name of the plant, with the exception of publications related to botanical research. In separate PubChem searches, names of individual phytocompounds were used to establish structure and distribution in plants. The SuperPred web server was used to predict therapeutic potential. The authors analyzed the chemical composition of the extracts, presented the structural and pharmacological characteristics of bacosides and their aglycones: bacosin and juubogenin, cucurbitacin E, loliolide, betulinic and asiatic acids and the flavonoid oroxindin. The mechanism of action of bacoside on β-amyloid is characterized and illustrated. Using machine learning, the prospects for using the main compounds of bacopa to create drugs were calculated taking into account the ATC classification, their biological effects and alternative plant sources were given. Experimental animal studies of whole aqueous or ethanolic extracts of B. monnieri have been found to support a cognitive enhancement effect. The extract was not toxic to humans. Numerous clinical trials show the effectiveness of the use of extracts in the treatment of anhedonia, depression, Alzheimer's disease, Parkinson's disease, dementia and hyperactivity. An analysis of clinical studies in Ukraine shows that drugs based on B. monnieri can be used in the complex treatment of cognitive impairment associated with dyscirculatory encephalopathy in adults and perinatal CNS damage in children. Considering the amphiphilicity of bacosides and the non-toxicity of extracts, they can be involved in the development of various dosage forms with a wide range of therapeutic applications. Further study of the pharmacological action of B. monnieri and the development of drug technology for solid and liquid dosage forms based on it are promising.

Review article on self emulsifying system

The solubility challenges faced by the pharmaceutical industry, particularly with orally administered drugs, are indeed significant. Low aqueous solubility often leads to poor dissolution and subsequently, low bioavailability, which can result in inconsistent drug effects among patients. Various methods have been explored to address this issue, including salt formation, solid dispersion, and complex formation.Among these approaches, Self-Emulsifying Drug Delivery Systems (SEDDS) have emerged as a promising solution for enhancing the solubility of lipophilic drugs. SEDDS consist of isotropic mixtures of hydrophilic solvents, co-solvents, and surfactants. They possess the unique ability to form fine oil-in-water micro emulsions upon mild agitation and dilution in aqueous media, such as gastrointestinal fluids.The advancement in SEDDS technology encompasses improvements in composition, evaluation methods, development of different dosage forms, and techniques for converting liquid SEDDS into solid forms. These advancements not only enhance solubility but also offer versatility in administration routes and dosage forms, thereby expanding the potential applications of SEDDS in pharmaceutical formulations.This comprehensive review provides valuable insights into the latest developments in SEDDS, offering a detailed account of its composition, evaluation parameters, diverse dosage forms, and innovative techniques for solidification. Moreover, it highlights the diverse applications of SEDDS across various therapeutic areas, underscoring its growing significance in modern pharmaceutical research and development.

Moisture‐Driven Actuators

AbstractWater constitutes a huge circulation network in solid, liquid and gaseous forms that contains inestimable recyclable energy. Obtaining energy from gaseous moisture is challenging but of great significance to promote the energy upgrading. The emergence of moisture‐driven actuator (MDA) provides an effective way in converting moisture energy to mechanical energy. The MDA can combine with water molecules through hygroscopicity and swell to produce macroscopic deformation. Due to the wide distribution of humidity and the wireless driving mode, MDA shows great application potential in the fields of environmental monitoring, remote control and energy harvesting. This paper comprehensively reviews the research progress of MDA from aspects of hydrophilic materials, structures, preparing methods, multi‐response integration and applications, aiming at providing guidance for the design, preparation and application of MDA. Besides, the challenges faced by MDA are analyzed and corresponding solutions are proposed, which points out the next stage developing direction of MDA.

Sublethal Damage Caused by Cold Plasma on Bacillus cereus Cells: Impact on Cell Viability and Biofilm-Forming Capacity.

The Bacillus cereus group represents a serious risk in powdered and amylaceous foodstuffs. Cold plasma (the fourth state of matter) is emerging as an alternative effective nonthermal technology for pasteurizing a wide range of matrices in solid, liquid, and powder form. The present study aims to evaluate the mechanisms involved in Bacillus cereus inactivation via cold plasma, focusing on (i) the technology's ability to generate damage in cells (at the morphological and molecular levels) and (ii) studying the effectiveness of cold plasma in biofilm mitigation through the direct effect and inhibition of the biofilm-forming capacity of sublethally damaged cells post-treatment. Dielectric barrier discharge cold plasma (DBD-CP) technology was used to inactivate B. cereus, B. thuringiensis, and B. mycoides under plasma power settings of 100, 200, and 300 W and treatment times ranging from 1 to 10 min. Inactivation levels were achieved in 2-7 log10 cycles under the studied conditions. Percentages of sublethally damaged cells were observed in a range of 45-98%, specifically at treatment times below 7 min. The sublethally damaged cells showed poration, erosion, and loss of integrity at the superficial level. At the molecular level, proteins and DNA leakage were also observed for B. cereus but were minimal for B. mycoides. Biofilms formed by B. cereus were progressively disintegrated under the DBD-CP treatment. The greater the CP treatment intensity, the greater the tearing of the bacteria's biofilm network. Additionally, cells sublethally damaged by DBD-CP were evaluated in terms of their biofilm-forming capacity. Significant losses in the damaged cells' biofilm network density and aggregation capacity were observed when B. cereus was recovered after inactivation at 300 W for 7.5 min, compared with the untreated cells. These results provide new insights into the future of tailored DBD-CP design conditions for both the inactivation and biofilm reduction capacity of B. cereus sensu lato species, demonstrating the effectiveness of cold plasma and the risks associated with sublethal damage generation.

Water-in-oil emulsions as micro-reactors for achieving extremely rapid and high hydrogen uptakes into clathrate hydrates

As humanity transitions to a low-carbon future, hydrogen, with its high energy density and zero carbon emissions, is gaining prominence, and efficient hydrogen storage is thus a critical area of research. Storing hydrogen in a solid form by forming hydrates, ensuring straightforward formation and dissociation, environmental friendliness, and stability, is emerging as a new technology. In particular, the use of thermodynamic promoters such as tetrahydrofuran (THF) to form binary hydrogen hydrates enables hydrogen storage under much milder conditions compared to traditional compression and liquefaction processes. However, slow hydrate formation kinetics currently hinder commercialization, necessitating breakthroughs in this area. This study reports extremely rapid and high hydrogen uptake in binary hydrogen + THF hydrates by utilizing a water-in-oil emulsion. A hydrogen storage capacity of approximately 51.23 mmol H2/mol H2O and the hydrogen uptake rate of 91.71 mol min−1 m−3 water were achieved, significantly outperforming existing studies conducted at pressures below 15 MPa. This remarkable kinetics was achieved by controlling the distribution of THF within a ternary emulsion system composed of water, isooctane, and THF. Phase equilibrium measurements and a series of kinetic tests validated that using an excess of THF over stoichiometric amounts can lead to such high and rapid hydrogen uptake. Consequently, a hydrate formation mechanism in the emulsified system was suggested based on the results of a Raman analysis, water droplet size measurements, and 1H NMR analysis. These results will pave the way for further advances in practical hydrate-based hydrogen storage technology.

A Self-Healing, Flowable, Yet Solid Electrolyte Suppresses Li-Metal Morphological Instabilities.

Lithium metal (Li0) solid-state batteries encounter implementation challenges due to dendrite formation, side reactions, and movement of the electrode-electrolyte interface in cycling. Notably, voids and cracks formed during battery fabrication/operation are hot spots for failure. Here, a self-healing, flowable yet solid electrolyte composed of mobile ceramic crystals embedded in a reconfigurable polymer network is reported. This electrolyte can auto-repair voids and cracks through a two-step self-healing process that occurs at a fast rate of 5.6µm h-1. A dynamical phase diagram is generated, showing the material can switch between liquid and solid forms in response to external strain rates. The flowability of the electrolyte allows it to accommodate the electrode volume change during Li0 stripping. Simultaneously, the electrolyte maintains a solid form with high tensile strength (0.28MPa), facilitating the regulation of mossy Li0 deposition. The chemistries and kinetics are studied by operando synchrotron X-ray and in situ transmission electron microscopy (TEM). Solid-state NMR reveals a dual-phase ion conduction pathway and rapid Li+ diffusion through the stable polymer-ceramic interphase. This designed electrolyte exhibits extended cycling life in Li0-Li0 cells, reaching 12000 h at 0.2mA cm-2 and 5000 h at 0.5mA cm-2. Furthermore, owing to its high critical current density of 9mA cm-2, the Li0-LiNi0.8Mn0.1Co0.1O2 (NMC811) full cell demonstrates stable cycling at 5mA cm-2 for 1100 cycles, retaining 88% of its capacity, even under near-zero stack pressure conditions.

Recent developments in the physical structure of solid formulations: a comprehensive review

Recent developments in the physical structure of solid formulations: a comprehensive review

Esophageal transit of solid oral dosage forms – impact of different surface materials characterized in vitro and in vivo by MRI in healthy volunteers

Acceptable swallowability and complete esophageal transit are decisive for the safe and effective administration of solid oral dosage forms. This applies in particular to the main user group of medicines, older adults, who often suffer from swallowing difficulties. It is well known that surface properties play an important role in this respect. In the past, this has led to the development of numerous coating formulations for tablets with improved swallowability. However, in vitro and especially in vivo data investigating a positive effect of different coating materials is limited. Therefore, we investigated coating materials being based on polyvinyl alcohol, hydroxypropyl methylcellulose, and a copolymer of methacrylate in respect to their influence on swallowability and esophageal transit of a tablet formulation. They were compared to uncoated tablets as well as to hard gelatin capsules. Three in vitro assays suitable for routine use in pharmaceutical development were performed: i.) Wettability test in artificial saliva; ii.) Swelling measurement in artificial saliva; iii.) Measurement of the adhesion between surface materials and a simulated mucosa surface. All three assays resulted in a differentiation of the surface materials. The coated tablets showed favorable behavior compared to uncoated tablets and hard gelatin capsules. To test the effect of the different materials in vivo, an intervention study was conducted. 36 adults were included and the likeliness of prolonged esophageal transit of (un-)coated tablets as well as a hard gelatin capsule of the same weight was objectively evaluated by means of magnetic resonance imaging. While hard gelatin capsules showed highest rates for prolonged esophageal transit, the tendency for adhesion was reduced for uncoated tablets, and least for coated tablets, i.e., prolonged esophageal transit in 22.2 %, 11.1 %, and ≤5.6 % of the cases, respectively. Further differentiation of the coating materials was not possible. Subjective evaluations of each participant with respect to subjective swallowability and esophageal transit did not correlate well with the objective measurements by means of magnetic resonance imaging. The use of coatings in general has a positive influence on esophageal transit. However, the selection of coating type seems to be of greater importance in respect to patients' oral perception of the dosage forms compared to their influence on the probability for prolonged esophageal transit.

Innovative Techniques for Pharmaceutical Waste Management: Enhancing Drug Recovery and Environmental Sustainability

The pharmaceutical sector is a major component of current healthcare, manufacturing and distributing drugs, biological substances, and medical equipment. Despite its advantages, the sector creates enormous waste, including materials for packaging, production by-products, expired or unused drugs, and other residues, creating health and environmental issues. Appropriate pharmaceutical waste handling and medication recovery strategies are vital for limiting these problems. This article aims to investigate and evaluate multiple techniques for recovering pharmaceuticals from pharmaceutical waste, highlighting the significance of sustainable waste management in the pharmaceutical sector. The paper emphasizes the need to use modern methods such as liquid-liquid extraction, membrane crystallization, solid-liquid extraction, and adsorption to recover drugs from pharmaceutical waste. Liquid-liquid extraction exhibits excellent adaptability and efficiency for varied Active Pharmaceutical Ingredients (APIs), whereas membrane crystallization provides low-energy solutions for thermally sensitive compounds. Solid-liquid extraction is useful for recovering APIs from solid dosage forms, while adsorption approaches exploit substances like activated carbon for organic component recovery. Each process has particular benefits and disadvantages, with the selection of methodology based on waste properties and recovery objectives. It emphasizes the promise of these technologies for high extraction yields, purity, and environmental sustainability, supporting effective pharmaceutical waste management procedures. Additionally, difficulties such as cost-effectiveness, scalability, and regulatory compliance are addressed, pointing to opportunities for future research and development to improve the efficacy of drug recovery procedures. In conclusion, using advanced techniques to recover pharmaceuticals from pharmaceutical waste offers a viable way to implement sustainable waste recovery procedures and lessen the pharmaceutical industry's negative environmental effects.

Supramolecular cyclodextrin complexes of biologically active nitrogen heterocycles

The review is devoted to the rapidly developing field of modern supramolecular chemistry - cyclodextrin complexes of biologically active nitrogen heterocycles, such as piperidines, piperazines, morpholines and pyridines. Interest in cyclodextrin complexes is growing due to the search and construction of supramolecular assemblies for targeted drug delivery. The latter is achieved as a result of supramolecular self-assembly, based on the principles of molecular recognition, and is one of the areas of modern chemistry, leading to the creation of new materials with new properties. This review fully demonstrates the ongoing scientific and practical interest in the problem of encapsulation with cyclodextrins, including nanoencapsulation. Encapsulation with cyclodextrins provides a wide range of advantages: obtaining solid dosage forms from liquid ones, stabilizing and protecting active substances from the adverse effects of external factors, increasing solubility, increasing bioavailability, reducing toxicity, prolonging action, etc. The presented review includes recent advances in the field of supramolecular complexes of biologically active nitrogen heterocycles with cyclodextrins and concludes with a discussion and identification of future promising directions for research. The review presents the results of supramolecular self-assembly of biologically active azaheterocycles with cyclodextrins.

Prediction Model for Coformer Screening of Energetic Eutectics Based on Flory‐Huggins Interaction Parameter

AbstractBased on intermolecular interactions, Flory‐Huggins interaction parameter χAB>0 was presented as a prediction model to screen the coformer of energetic eutectics. To evaluate the predictive accuracy of this model, 80 energetic eutectics were collected from literatures. The molecular structures were optimized by computationally cheap molecular mechanics and high precision dispersion‐corrected density functional, respectively. Then the weighted Monte Carlo method was used to calculate the mixing energy ΔEmix of the binary system and thus derive the dimensionless χAB. The results show that the prediction accuracy is up to 85% based on M06‐2X‐D3/6‐311+G (d, p) optimization geometry and RESP charge, much greater than 45% of molecular mechanics method. Furthermore, size/shape mismatch between eutectic molecules was considered by shape index and molecular volume to enrich the prediction model. Based on this prediction model, a new energetic eutectic MTNP‐TNT was discovered, whose χAB value is 3.376 obtained by M06‐2X‐D3/6‐311+G (d, p) method. Experimentally, the classical “V” phase diagram drawn from the differential scanning calorimetry (DSC) data also suggests the MTNP‐TNT eutectic with eutectic temperature of 54.41°C at the molar ratio of 51.50: 48.50. Theoretical and experimental results successfully validate the χAB>0 prediction model for screening the coformers of energetic eutectics. This work opens a way for the crystal engineering of energetic eutectic solid forms with attractive physicochemical properties using a computational approach.

Spontaneous formation of polymeric nanoribbons in water driven by π‐π interactions

A simple method was developed to produce polymeric nanoribbons and other nanostructures in water. This approach incorporates a perylene diimide (PDI) functionalized by hydrophilic triethylene glycol (TEG) as a hydrophobic supramolecular structure directing unit (SSDU) into the core of hydrophilic poly(N,N‐dimethylacrylamide) (PDMAc) chains using RAFT polymerization. All PDI‐functional polymers dissolved spontaneously in water, forming different nanostructures depending on the degree of polymerization (DPn): nanoribbons and nanocylinders for DPn = 14 and 22, and spheres for DPn > 50 as determined by cryo‐TEM and SAXS analyses. UV‐VIS absorption spectroscopy was used to monitor the evolution of the PDI absorption signal upon dissolution. In solid form, all polymers show a H‐aggregate absorption signature, but upon dissolution in water, the shortest DPn forming nanoribbons evolved to show HJ‐aggregate absorption signals. Over time, the J‐aggregate band increased in intensity, while cryo‐TEM monitoring evidenced an increase in the nanoribbon’s width. Heating the nanoribbons above 60 °C, triggered a morphological transition from nanoribbons to nanocylinders, due to the disappearance of J‐aggregates, while H‐aggregates were maintained. The study shows that the TEG‐PDI is a powerful SSDU to promote 2D or 1D self‐assembly of polymers depending on DPn through simple dissolution in water.

Spontaneous formation of polymeric nanoribbons in water driven by π-π interactions.

A simple method was developed to produce polymeric nanoribbons and other nanostructures in water. This approach incorporates a perylene diimide (PDI) functionalized by hydrophilic triethylene glycol (TEG) as a hydrophobic supramolecular structure directing unit (SSDU) into the core of hydrophilic poly(N,N-dimethylacrylamide) (PDMAc) chains using RAFT polymerization. All PDI-functional polymers dissolved spontaneously in water, forming different nanostructures depending on the degree of polymerization (DPn): nanoribbons and nanocylinders for DPn = 14 and 22, and spheres for DPn > 50 as determined by cryo-TEM and SAXS analyses. UV-VIS absorption spectroscopy was used to monitor the evolution of the PDI absorption signal upon dissolution. In solid form, all polymers show a H-aggregate absorption signature, but upon dissolution in water, the shortest DPn forming nanoribbons evolved to show HJ-aggregate absorption signals. Over time, the J-aggregate band increased in intensity, while cryo-TEM monitoring evidenced an increase in the nanoribbon's width. Heating the nanoribbons above 60 °C, triggered a morphological transition from nanoribbons to nanocylinders, due to the disappearance of J-aggregates, while H-aggregates were maintained. The study shows that the TEG-PDI is a powerful SSDU to promote 2D or 1D self-assembly of polymers depending on DPn through simple dissolution in water.

Graphene/chitosan nanoreactors for ultrafast and precise recovery and catalytic conversion of gold from electronic waste

The extraction of gold (Au) from electronic waste (e-waste) has both environmental impact and inherent value. Improper e-waste disposal poses environmental and health risks, entailing substantial remediation and healthcare costs. Large efforts are applied for the recovery of Au from e-waste using complex processes which include the dissolution of Au, its adsorption in an ionic state and succeeding reduction to metallic Au. These processes themselves being complex and utilizing harsh chemicals contribute to the environmental impact of e-waste. Here, we present an approach for the simultaneous recovery and reduction of Au3+ and Au+ ions from e-waste to produce solid Au0 forms, thus skipping several technological steps. We develop a nanoscale cross-dimensional composite material via self-assembly of two-dimensional graphene oxide and one-dimensional chitosan macromolecules, capable of acting simultaneously as a scavenger of gold ions and as a reducing agent. Such multidimensional architecture doesn't require to apply any voltage for Au adsorption and reduction and solely relies on the chemisorption kinetics of Au ions in the heterogeneous GO/CS nanoconfinements and their chemical reduction on multiple binding sites. The cooperative phenomena in ionic absorption are responsible for the extremely high efficiency of gold extraction. The extraction capacity reaches 16.8 g/g for Au3+ and 6.2 g/g for Au+, which is ten times larger than any existing gold adsorbents can propose. The efficiency is above 99.5 wt.% (current limit is 75 wt.%) and extraction ability is down to very low concentrations of 3 ppm.

Comprehensive analysis of respiratory pharmaceuticals in dietary supplements using advanced chromatographic techniques

Recently, the number of people suffering from respiratory symptoms has continued to increase because of COVID-19 and particulate contamination. Accordingly, the demand for respiratory-related dietary supplements is increasing. Over the past few years, dietary supplements adulterated with pharmaceutical drugs have continued to appear, increasing the risk of side effects; thus, preventive measures are needed. In this study, we developed a simultaneous analysis method for 11 respiratory-related pharmaceutical compounds using ultra-performance liquid chromatography with a photodiode array (UPLC-PDA). The sample preparation method was optimized by comparing filtration and two clean-up methods (QuEChERS), for solid and liquid formulations, and the optimal analytical conditions were established by comparing various analysis parameters. Concerning method validation, all parameters meet International Council for Harmonisation guidelines. Subsequently, 54 types of dietary supplements promoting relief of respiratory-related symptoms were purchased online and analyzed using UPLC-PDA. As a result, theobromine, azelastine, and dexamethasone were detected in three products. In addition, the detected compounds were confirmed by comparing fragmentation patterns using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). This study will contribute to preemptively blocking dietary supplements adulterated with respiratory-related drugs from entering the market and can be used as a reference for future research.

Formulation and Evaluation of Nano Suspension Based Oro Disoersible Film of Aripiprazole

The present study was aimed to enhance the solubility and dissolution of BCS class 4 drug aripiprazole, by nano formulation approach. Acid-base neutralization method had been used to produced nanosuspension. The nanosuspensions remained stable without any aggregations with particle size 209.6nm and PDI 0.247. Zeta potential was found to be 3.5mV. Drug content, Entrapment and solubility of nanosuspension formulations were determined. In vitro drug release of the selected formulation has shown a drug release of 95.63% by the end of 1 hr, whereas plain drug suspension has shown only 12.3% release. XRD and DSC studies revealed that the solid form of aripiprazole altered from the crystalline state to the amorphous state after incorporation into nanosuspensions. Hence, from the results, it can be concluded that Aripiprazole, when formulated by acid-base neutralization method as a nanosuspension, leads to enhanced solubility, dissolution, and stability

12210 Prognostic Determinants of Aggressive Histology Papillary Thyroid Carcinoma: A Pathway to Personalized Treatment

Abstract Disclosure: M. Almaghrabi: None. G. Sindi: None. H. Sasseville: None. S. Radi: None. M. Tamilia: None. Background: Papillary thyroid carcinoma (PTC), the most common form of thyroid malignancy, generally presents with a favorable prognosis. However, aggressive variants of Papillary Thyroid Carcinoma (AV-PTC), such as tall cell, hobnail, columnar, and solid forms, pose significant challenges in prognosis and treatment, due to their unique pathological behaviors and increased risks of recurrence and mortality. The management debate for AV-PTC without invasive characteristics is ongoing. It's argued that aggressive histology alone should not dictate the clinical management of PTC patients lacking aggressive features. Objectives: This study aims to investigate the prognostic impact of invasive features in AV-PTC and their implications on clinical outcomes. Methods: We conducted a retrospective cohort study of AV-PTC patients treated from 2008 to 2022, analyzing medical records to identify prognostic factors related to disease recurrence, persistence, and overall survival. This involved distinguishing between groups with invasive characteristics—identified as one of the following: extrathyroidal extension, lymphovascular invasion, the presence of positive lymph nodes, or the detection of distant metastases upon diagnosis, and non-invasive AV-PTC groups. Results: Key findings from our comparison between invasive and non-invasive groups of AV-PTC highlighted significant factors associated with poorer outcomes in the invasive group. These included multifocality (P=0.001), larger tumor size (P=0.047), extra thyroid extension (P=0.002), lymph vascular invasion (P<0.001), the presence of contralateral nodules (P=0.018), and positive surgical margins (P=0.003). Moreover, advanced tumor stage and increased lymph node involvement were more common in invasive cases (P=0.012, P=0.040). Despite no significant differences in genetic mutations between groups (P=0.396), the Ki-67 index was numerically higher in the invasive group. Hemithyroidectomy followed by completion thyroidectomy, performed in 12 patients (22.2%). Survival analysis further highlighted the significance of these invasive features, with Kaplan-Meier curves indicating a 5-year freedom from recurrence rate of 77.18% and a 10-year rate of 68.61%. Univariable Cox regression revealed that the tumor size, positive margins, and tumor stage predicted recurrence. Seven patients had distant metastasis, and all were in the invasion group (18.92%) p= 0.088. Conclusion: Our study emphasizes the critical role of certain invasive features in determining the prognosis of AV-PTC. The adoption of more extensive treatments for patients without invasive features highlights the complexity of treating AV-PTC and the importance of personalized treatment plans. This research advances our understanding of AV-PTC, advocating for individualized approaches to enhance patient outcomes. Presentation: 6/3/2024

Solvates and Polymorphs of Axitinib: Characterization and Phase Transformation.

Axitinib (AXTN) is an oral tyrosine kinase inhibitor for the treatment of early to advanced renal cell carcinoma. In this work, solvates of AXTN were prepared in five solvents and subjected to desolvation treatment. The crystal form A of AXTN can form solvates in acetonitrile, DMF, acetic acid, acetic acid + water, and methanol. Different ratios of AXTN and acetic acid will form different products (solvate or directly crystallized into another crystal form (form IV)). The characterization results of thermal analyses confirmed the types of the five solvates. The obtained solvates were desolvated using methods of solid-phase desolvation (heating, exposure to solvent steam, microwave) and solvent-mediated phase transformation (SMPT). The desolvated solids were characterized by PXRD, TGA, DSC, FT-IR, and SEM, and it was ultimately inferred that a new crystal form (form Z) of AXTN could be formed after desolvation. In addition, the solvates obtained in this work experienced mutual transformation via SMPT, which depends on the type of solvents or mixed solvents. The phase transformations of different solid forms were summarized. This study is instructive for exploring solvates and polymorphs of AXTN and understanding phase transitions under different environments.

Thermal Compatibility of New ACEI Derivatives with Popular Excipients Used to Produce Solid Pharmaceutical Formulations.

Background/Objectives: Increasing drugs' stability and adequately protecting them against degradation will ensure a decrease in their price and broader availability of pharmaceutical substances. This is of great importance, especially for drugs used to treat the most common diseases in the population, such as hypertension. The study examined two newly synthesized substances from the angiotensin I-converting enzyme inhibitor (ACEI) group as potential drugs. ACEIs are among the leading drugs used in the treatment of hypertension in the world. The chemical modifications of the tested substances applied concerned the places most susceptible to degradation. The presented work analyzed the compatibility of new derivatives with selected excipients used in pharmacy. Methods: Thermogravimetric (TGA) and differential thermal analyses (c-DTA) were used as the main methods. In addition, non-thermal methods such as colorimetry analysis, Fourier-transform infrared (FTIR) and UV spectroscopy were used. Results: Based on the conducted studies, it can be concluded that the incompatibility of IND-1 with glucose anhydrous and lactose monohydrate occurs only when the mixture is stored at higher temperatures. For the remaining IND-1 and IND-2 mixtures with excipients, compatibility was demonstrated. Conclusions: The obtained results confirmed the usefulness of the applied thermal analyses (TGA and c-DTA) for assessing the compatibility of the tested potential drugs with excipients. However, in the case of incompatibility reactions of substances occurring under the influence of elevated temperatures, such as the Maillard reaction, it is necessary to use non-thermal methods to obtain the right result.