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1.
Appl Radiat Isot ; 214: 111531, 2024 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-39357257

RESUMO

99mTc is regarded as the most important medical isotope, and its supply issues have garnered significant attention. A simple and efficient separation method was performed for the production of 99mTc from 100Mo target in this study. The entire process involves accelerator irradiation, 99mTc/100Mo separation, and target material recovery. The key aspect is separation process, which including the high-temperature conversion of metal molybdenum targets and the selective solution of 99mTc with normal saline. This method can separate highly pure 99mTc within 1.5 h, with a separation efficiency exceeding 80%. The reagents used in the separation process are minimal, resulting in less radioactive waste. Additionally, the target material is easy to reclaim, with a recovery rate of over 95%.

2.
Environ Pollut ; : 125049, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39357554

RESUMO

The photo-dissolution of lead chromate pigments poses specific environmental hazards. In this study, we report that doping molybdenum in lead chromate pigments, resulting in commonly known molybdate red pigment, increases the risk of heavy metal leaching when exposed to light. Commercial molybdate red pigments undergo photo-dissolution when exposed to simulated sunlight and exhibit lower photostability compared to lead chromate pigments such as chrome yellow. After 24 hours of irradiation, the leaching rates of toxic lead and chromium from molybdate red pigments were 2.98 and 3.70 times higher, respectively, than those from chrome yellow pigments. The primary factor leading to decreased pigment photostability is the activation of pigment semiconductors facilitated by molybdenum doping. Molybdate red pigments exhibit a broader light absorption spectrum and more efficient separation and transfer of photogenerated charge carriers than chrome yellow pigments, boosting the photochemical activity. To the best of our knowledge, this is the first study to illustrate the doping effect on the photostability of commercial inorganic pigments and the consequent heavy metal leaching. Our results suggest that Mo doping reduces the photostability of lead chromate pigments, highlighting the potential elevated environmental risks associated with complex inorganic pigments.

3.
J Pharm Sci ; 2024 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-39389537

RESUMO

Atomic layer coating (ALC) is an emerging, solvent-free technique to coat amorphous solid dispersion (ASD) particles with a nanolayer ceramic coating that has been shown to improve powder characteristics and limit drug crystallization. Herein, we evaluate the impact of aluminum oxide coatings with varying thickness and conformality on the dissolution of ritonavir/copovidone ASDs. Release performance of powders, neat tablets, and formulated tablets was studied. Confocal fluorescence microscopy (CFM) was used to visualize particle hydration and phase separation during immersion of the ASD in aqueous media. CFM revealed particle hydration requires defects for solvent penetration, but coatings, regardless of thickness, had minor impacts on powder dissolution provided defects were present. In tablets where less surface area is exposed to the dissolution media due to gel formation, slowed hydration kinetics resulted in phase separation of the drug from the polymer in coated samples, limiting release. Formulation with two superdisintegrants, crospovidone and croscarmellose sodium, as well as lactose achieved ∼90% release in less than 10 minutes, matching the uncoated ASD particles of the same formulation. This study highlights the importance of hydration rate, as well as the utility of confocal fluorescence microscopy to provide insight into release and phase behavior of ASDs.

4.
Int J Pharm ; 666: 124789, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366529

RESUMO

Berberine hydrochloride (BER), a promising candidate in treating tumors, diabetes and pain management, has relatively low oral absorption and bioavailability due to its low intestinal permeability. To address these challenges, we developed a BER and lornoxicam cocrystal (BLCC) by a solvent evaporation method and characterized it using X-ray diffraction, differential scanning calorimetry and thermogravimetric analysis. Compared with BER, BLCC exhibited an instant release in pH 1.0 HCl and a sustained release up to 24 h in pH 6.8 buffer solutions and water. The Caco-2 permeability of BLCC has shown a remarkable increase compared to that of BER (i.e., Papp(a→b): 50.30 × 10-7vs 8.82 × 10-7 cm/s), which is attributed to the improved lipophilicity of BER (i.e., log P: 1.29 vs -1.83) and the reduced efflux amount of BER (i.e., ER: 1.71 vs 12.11). Furthermore, BLCC demonstrated a relative bioavailability of 410 % in comparison to the original BER, due to notably enhanced intestinal permeability of BLCC and its continuous dissolution in simulated intestinal fluid. BLCC has the potential to tailor the dissolution behavior, improve intestinal permeability, and boost the bioavailability of BER. This indicates that the cocrystal strategy holds promise as an effective approach to improving the oral absorption and bioavailability of active pharmaceutical molecules with low permeability during drug development.

5.
Artigo em Inglês | MEDLINE | ID: mdl-39377384

RESUMO

Most of the newly discovered drug candidates are lipophilic and poorly water-soluble, making it a significant challenge for the pharmaceutical industry to formulate suitable drug delivery systems. This review gives insight into an overview of the liquisolid technique (LST) and summarizes the progress of its various applications in drug delivery. This novel technique involves converting liquid drugs or drugs in a liquid state (such as solutions, suspensions, or emulsions) into dry, nonadherent, free-flowing, and readily compressible powder mixtures by blending or spraying a liquid dispersion onto specific powder carriers and coating materials. In Liquisolid systems, the liquid medication is absorbed into the interior framework of carriers. Once the carrier's interior is saturated with liquid medication, a liquid layer forms on the surface of the carrier particles, which is instantly adsorbed by the fine coating material. As a result, a dry, free-flowing, and compressible powder mixture is formed. Compared to other solubility enhancement techniques, s.a. micronization, inclusion complexation, microencapsulation, nanosuspension, and self-nano emulsions, LST is relatively simple to prepare and may offer a cost-effective solution to enhance the solubility of poorly water-soluble drugs enhancing its bioavailability in drug formulation and delivery.

6.
Int J Pharm ; 666: 124808, 2024 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-39378956

RESUMO

In-line monitoring of critical quality attributes (CQAs) during a tableting process is an essential step toward a real-time release strategy. Such CQAs can be the tablet mass, the API content, dissolution, hardness and tensile strength. Since dissolution testing is laborious and time-consuming and cannot be performed in-line, it is desirable to replace dissolution testing with predictive models based on other CQAs that affect the dissolution characteristics, such as the tablet porosity and hardness. Traditionally, porosity is determined offline via gas adsorption methods or other techniques, such as Terahertz spectroscopy or gas in scattering media absorption spectroscopy. Tablet hardness is typically established using a hardness tester. While these destructive tests can readily be performed at-line, they have limited applicability in in-line settings for a high-percentage inspection. Optical coherence tomography (OCT) has recently been proposed as a possible tool for determining quality attributes. This work describes the first application of OCT for the prediction of tablet porosity and hardness. OCT measurements of tablets produced in a ConsiGma 25™ tableting line and a Stylcam 200R compaction simulator in several compaction force settings were performed and correlated with the porosity and hardness. It was demonstrated that OCT can easily be installed in-line and provide real-time information about critical material attributes. These insights confirm the applicability of OCT as a real-time quality control tool and its potential to replace time-consuming and destructive offline measurements.

7.
Artigo em Inglês | MEDLINE | ID: mdl-39366002

RESUMO

Nickel-rich layered oxides stand as ideal cathode candidates for high specific capacity and energy density next-generation lithium-ion batteries. However, increasing the Ni content significantly exacerbates structural degradation under high operating voltage, which greatly restricts large-scale commercialization. While strategies are being developed to improve cathode material stability, little is known about the effects of electrolyte-electrode interaction on the structural changes of cathode materials. Here, using LiNiO2 in contact with electrolytes with different proton-generating levels as model systems, we present a holistic picture of proton-induced structural degradation of LiNiO2. Through ab initio molecular dynamics calculations based on density functional theory, we investigated the mechanisms of electrolyte deprotonation, protonation-induced Ni dissolution, and cathode degradation and the impacts of dissolved Ni on the Li metal anode surfaces. We show that the proton-transfer reaction from electrolytes to cathode surfaces leads to dissolution of Ni cations in the form of NiOOHx, which stimulates cation mixing and oxygen loss in the lattice accelerating its layered-spinel-rock-salt phase transition. Migration of dissolved Ni2+ ions to the anode side causes their reduction into the metallic state and surface deposition. This work reveals that interactions between the electrolyte and cathode that result in protonation can be a dominant factor for the structural stability of Ni-rich cathodes. Considering this factor in electrolyte design should be of benefit for the development of future batteries.

8.
Int J Biol Macromol ; 281(Pt 1): 136265, 2024 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-39366627

RESUMO

The poor water solubility of nitrendipine (NT) results in low oral bioavailability, which hinders its practical application. Hydroxypropyl methylcellulose (HPMC) is a prominent drug carrier that has been applied in the biomedical field due to its significant characteristics, such as large surface area, biocompatibility and biodegradability. In this study, an efficient drug delivery system based on the preparation of NT/HPMC solid dispersion using supercritical antisolvent (SAS) technology was proposed. The effect of different operating parameters such as solvent, host guest ratio, concentration, temperature, and pressure on NT/HPMC was optimized to obtain dispersed particles with maximum solubility. The formed solid dispersion presents non-static spherical particles with a high surface area and small particle size. Importantly, in vitro drug release studies have demonstrated that the dissolution and solubility of NT in solid dispersion are significantly enhanced compared to pure drug. In vitro bioactivity experiments showed that the NT/HPMC solid dispersion has good biocompatibility and antibacterial performance. Thus, this study indicates that solid dispersion prepared using SAS technology are considered a promising drug delivery system.

9.
Nanomaterials (Basel) ; 14(19)2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39404296

RESUMO

Lopinavir (LPV) and ritonavir (RTV) are two of the essential antiretroviral active pharmaceutical ingredients (APIs) characterized by poor solubility. Hence, attempts have been made to improve both their solubility and dissolution rate. One of the most effective approaches used for this purpose is to prepare amorphous solid dispersions (ASDs). To our best knowledge, this is the first attempt aimed at developing ASDs via the electrospinning technique in the form of fibers containing LPV and RTV. In particular, the impact of the various polymeric carriers, i.e., Kollidon K30 (PVP), Kollidon VA64 (KVA), and Eudragit® E100 (E100), as well as the drug content as a result of the LPV and RTV amorphization were investigated. The characterization of the electrospun fibers included microscopic, DSC, and XRD analyses, the assessment of their wettability, and equilibrium solubility and dissolution studies. The application of the electrospinning process led to the full amorphization of both the APIs, regardless of the drug content and the type of polymer matrix used. The utilization of E100 as a polymeric carrier for LPV and KVA for RTV, despite the beads-on-string morphology, had a favorable impact on the equilibrium solubility and dissolution rate. The results showed that the electrospinning method can be successfully used to manufacture ASDs with poorly soluble APIs.

10.
Int J Pharm ; : 124831, 2024 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-39406304

RESUMO

Older adults are an inherently heterogeneous population with various underlying pathologies, medication use, and habits. In this study, the variability of this population was studied for the gastric and duodenal fluid volumes, as the amount of gastrointestinal volumes could play an essential role in the dissolution of drugs. The fluid volumes were retrospectively quantified by using magnetic resonance imaging (MRI). In 265 included fasted older individuals, the gastric fluid volume was 28.9 ±â€¯21.1 mL (arithmetic mean ±â€¯standard deviation). No significant covariate-effect on stomach fluid volume was observed for various medication use, pathologies, and habits (e.g. hypertension, smoking, proton-pump inhibitors (PPIs), and aspirin). The gastric fluid volume remained constant with increasing age and had a high variability. The volumes and the variability were, however, not higher than the gastric values reported in healthy younger adults. The duodenal fluid volume was 16.6 ±â€¯10.0 mL and a slight but statistically significant decrease with age was seen. In addition, cystic pancreas, obesity, diuretics, and PPI use demonstrated a moderate but significant correlation with the duodenal fluid volume. The findings of this study could be considered when developing and testing new drug candidates for the older adult population. For example, the volumes including their variability could be used as an input in physiologically based pharmacokinetic modelling approaches to predict drug exposure in this population.

11.
Int J Pharm ; : 124809, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39384028

RESUMO

Development of novel active pharmaceutical ingredients (API) for oral use often face challenges due to low bioavailability. Nanoparticle-based drug delivery systems and cyclodextrin (CD) encapsulation offer promising solutions by enhancing API solubility or dissolution rates. Porous silicon nanoparticles have shown potential to encapsulate APIs in their amorphous form within pores, improving dissolution rates compared to crystalline counterparts. A novel synthesis approach, circumventing the expensive and tedious Si wafer material synthesis, has been developed using centrifugal Chemical Vapor Deposition (cCVD). Herein, various cCVD Si particles were evaluated for their ability to enhance the dissolution rate of the model drugs celecoxib (CEL), phenytoin (PHT), griseofulvin (GRI), diclofenac (DCF), and naproxen (NAP). Our findings demonstrate increased dissolution rates of all tested APIs when formulated with cCVD Si particles, compared to free API in pH 7.4 or pH 2.0. Particle characteristics were largely retained after loading, and the solid state of the loaded APIs were evaluated using Differential Scanning Calorimetry (DSC). Dissolution kinetics were influenced by the particle properties, mass loading and API characteristics. Loading of CD-CEL, -GRI and -DCF complexes into the cCVD Si particles showed a potential for further enhanced dissolution rates, representing the first reported investigation of this combination. In conclusion, the cCVD Si particles are promising for improving the dissolution rate of poorly soluble drugs, potentially due to precipitation of amorphous or metastable forms. Further enhancements were observed upon loading CD-drug complexes, thereby offering promising strategies for optimizing drug bioavailability.

12.
Eur J Popul ; 40(1): 29, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39388039

RESUMO

Union dissolution has severe consequences for women's economic well-being. Theoretical work links these consequences to ethnic inequality. Ethnic groups vary in terms of separation rates, female employment, repartnering trajectories, kin support, and reliance on welfare benefits. The current study examines whether ethnicity moderates the dissolution penalty. To do so, the authors draw on register data, covering women from five major ethnic groups in the Netherlands: Dutch, Antillean, Surinamese, Moroccan, and Turkish. The authors describe women's income trajectories from 1 year before to 5 years after union dissolution. Using decomposition techniques, changes in household income are decomposed into changes in six underlying income sources (i.e., earnings, benefits, alimony, partner income, and coresident family income). The results show that ethnicity moderates the dissolution penalty and, especially, the contribution of the various income sources when recovering from dissolution.

13.
Xenobiotica ; : 1-15, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39361244

RESUMO

Drug products meeting the dissolution specifications is crucial in order to ensure consistent clinical performance. However, in certain cases, wider dissolution specifications may be required based on product behaviour. While the justification of such wider specifications may be challenging from a regulatory context, approaches such as physiological-based biopharmaceutics modeling (PBBM) can be utilised for this purpose.Product DRL is a fixed-dose combination product consisting of immediate release (IR) and extended-release (ER) portions. For the ER portion, the dissolution specifications consisted of four time points, and a proposal was made to relax the specification at the 2h time point (from 50-70% to 45-67%) to reduce the batch failures at the commercial scale.To support the wider specification, a PBBM was developed and extensively validated with literature & in-house studies. Virtual bioequivalence was performed using the pivotal clinical study data.Virtual dissolution profiles for proposed wider specifications were generated using three different approaches. The incorporation of lower and upper dissolution profiles into the model indicated the absence of impact on in vivo performance thereby justifying the specifications.Regulatory acceptance of proposed specifications with PBBM indicated the significance of using modeling approaches to reduce repeated testing thereby facilitating faster approvals.

14.
Eur J Pharm Biopharm ; : 114532, 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39395653

RESUMO

For pediatric radiological procedures (RP), pentobarbital sodium (PNa) can be used orally or rectally to replace intravenous anesthesia. Since no commercial PNa suppositories exist, they must be prepared by compounding pharmacies. This study aims to develop fast-dissolving PNa suppositories for fast pharmacological activity during RP. We prepared gelatin (G), gelatin/polyethylene glycol 4000 (GP), and polyethylene glycol 4000 (P) suppositories, with and without pH adjustment, and assessed their dosage uniformity (DU), softening time, rupture resistance, and in-vitro dissolution. An optimal formulation was selected, and PNa release was compared to that of fat-based suppositories using dissolution tests. Additionally, the quality control process (analytical performance, safety/eco-friendliness and productivity/practical effectiveness) of these formulas were compared using a RGB method. All hydrophilic formulas (HF) met the DU requirement (AV < 8 %) except for P (AV 15.62 ±â€¯4 %). pH adjustment enhanced G and GP suppositories resistance to 2.2 ±â€¯0.2 kg and 2.0 ±â€¯0.3 kg, respectively, and allowed 100 % release of PNa in under 10 min. In contrast, lipophilic formulas released less than 80 % of PNa at best after 120 min. These results show the biopharmaceutical suitability of HF for RP compared to lipophilic ones, but a pharmacokinetic study is needed to confirm data.

15.
Funct Compos Mater ; 5(1): 14, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39391170

RESUMO

In the production of polymeric drug delivery devices, dissolution profile and mechanical properties of the drug loaded polymeric matrix are considered important Critical Quality Attributes (CQA) for quality assurance. However, currently the industry relies on offline testing methods which are destructive, slow, labour intensive, and costly. In this work, a real-time method for predicting these CQAs in a Hot Melt Extrusion (HME) process is explored using in-line NIR and temperature sensors together with Machine Learning (ML) algorithms. The mechanical and drug dissolution properties were found to vary significantly with changes in processing conditions, highlighting that real-time methods to accurately predict product properties are highly desirable for process monitoring and optimisation. Nonlinear ML methods including Random Forest (RF), K-Nearest Neighbours (KNN) and Recursive Feature Elimination with RF (RFE-RF) outperformed commonly used linear machine learning methods. For the prediction of tensile strength RFE-RF and KNN achieved R 2 values 98% and 99%, respectively. For the prediction of drug dissolution, two time points were considered with drug release at t = 6 h as a measure of the extent of burst release, and t = 96 h as a measure of sustained release. KNN and RFE-RF achieved R 2 values of 97% and 96%, respectively in predicting the drug release at t = 96 h. This work for the first time reports the prediction of drug dissolution and mechanical properties of drug loaded polymer product from in-line data collected during the HME process. Supplementary Information: The online version contains supplementary material available at 10.1186/s42252-024-00063-5.

16.
AAPS PharmSciTech ; 25(7): 241, 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39402222

RESUMO

The present study was aimed to ameliorate the issue of solubility and thereby, bioavailability of ketoprofen, a BCS Class II drug. The sustained release matrix tablets (MT) were prepared using surfactant-assisted wet granulation (SAWG) with 1-5% of different surfactants. The tablet characteristics were within the compendial limits. The selected sustained release-compliant matrix tablet formulation containing granules prepared using 3% Soluplus® (MT2) released the drug by swelling-erosion. In human volunteers, MT2 attained the maximum plasma concentration (Cmax) of 5.72µg /ml ± 0.30 h, time to Cmax (Tmax) of 5.56 ± 0.30 h and maintained the plasma concentration above its minimum effective concentration (MEC), 0.7 µg.ml-1 till 24h. A control formulation, prepared from granules without surfactant (MT16), promptly attained Cmax of 9.62 ± 0.76 µg/ml within 1h but rapidly declined to below MEC in 8h. Area under the curve from initial point to infinity (AUC0-∞) of MT2 (78.65 ± 7.64 µg.h.ml-1) was 2.29 folds higher than 34.39 ± 3.06 µg.h.ml-1 of MT16. With decreased Cmax, increased AUC0-∞, delayed Tmax and retained ketoprofen concentration above MEC for longer time, MT2 corresponded with the in-vitro sustained drug release characteristic. There is a likelihood of administration of once-a-day single dose of MT2 without plasma fluctuations, expected from two doses of MT16. SAWG helped developing a swellable-erodible sustained release matrix tablet formulation of ketoprofen with the desired biopharmaceutical and pharmacokinetics properties, merely by addition of Soluplus® in granules and without incorporation of any special ingredients or the major manipulation of the formulative ingredients in the formulation.


Assuntos
Disponibilidade Biológica , Preparações de Ação Retardada , Cetoprofeno , Solubilidade , Tensoativos , Comprimidos , Cetoprofeno/administração & dosagem , Cetoprofeno/farmacocinética , Cetoprofeno/química , Tensoativos/química , Humanos , Preparações de Ação Retardada/farmacocinética , Preparações de Ação Retardada/administração & dosagem , Masculino , Adulto , Anti-Inflamatórios não Esteroides/farmacocinética , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/química , Química Farmacêutica/métodos , Adulto Jovem , Polietilenoglicóis/química , Polivinil/química , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Área Sob a Curva , Excipientes/química
17.
Materials (Basel) ; 17(19)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39410475

RESUMO

Difficult-to-cut titanium matrix composites (TiB+TiC)/Ti6Al4V have extensive application prospects in the fields of biomedical and aerospace metal microcomponents due to their excellent mechanical properties. Jet electrochemical micromilling (JEMM) technology is an ideal method for machining microstructures that leverages the principle of electrochemical anodic dissolution. However, the matrix Ti6Al4V is susceptible to passivation during electrochemical milling, and the inclusion of high-strength TiB whiskers and TiC particles as reinforcing phases further increases the machining difficulty of (TiB+TiC)/Ti6Al4V. In this study, a novel approach using NaCl+NaNO3 mixed electrolyte for the JEMM of (TiB+TiC)/Ti6Al4V was adopted. Electrochemical behaviors were measured in NaCl and NaCl+NaNO3 electrolytes. In the mixed electrolyte, a higher transpassive potential was required to break down the passive film, which led to better corrosion resistance of (TiB+TiC)/Ti6Al4V, and the exposed reinforcing phases on the dissolved surface were significantly reduced. The results of the JEMM machining indicate that, compared to NaCl electrolyte, using mixed electrolyte effectively mitigates stray corrosion at the edges of micro-grooves and markedly improves the uniformity of both groove depth and width dimensions. Additionally, the surface quality was noticeably improved, with a reduction in Ra from 2.84 µm to 1.03 µm and in Rq from 3.41 µm to 1.40 µm.

18.
AAPS PharmSciTech ; 25(7): 230, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39354249

RESUMO

This study aimed to establish a feasible dissolution method for inhalation aerosols. A method of collecting fine particles was investigated to capture aerosol particles less than 4 µm in diameter for dissolution tests. This dose collection method enabled the aerosol particles to be uniformly distributed on the glass fiber filter, thus considerably reducing particle agglomeration. Budesonide was used as a model drug. The aerodynamic particle size distribution (APSD) of the meter-dose inhaler (MDI) was compared by replacing actuators with different orifice sizes. Dissolution tests were conducted on fine particle doses collected using various actuators, and the dissolution profiles were modeled. The fine particle dose decreased with an increasing orifice size of the actuator. Actuators with different orifice sizes would affect the dissolution behavior of inhaled drugs. This finding was supported by similarity factor f2 analysis, suggesting the dissolution method has a discriminative capacity. The results of various model fits showed that the dissolution profiles produced by the different actuators could be fitted well using the Weibull mathematical model. The method employed in this study could offer a potential avenue for exploring the relationship between the orifice size of the actuator and the dissolution behavior of inhaled corticosteroids. This dissolution method was simple, reproducible, and suitable for determining the dissolution of inhalation aerosols.


Assuntos
Aerossóis , Budesonida , Tamanho da Partícula , Solubilidade , Aerossóis/química , Administração por Inalação , Budesonida/química , Budesonida/administração & dosagem , Inaladores Dosimetrados , Química Farmacêutica/métodos
19.
Pharm Res ; 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39375241

RESUMO

PURPOSE: For locally-acting dry powder inhalers (DPIs), developing novel analytical tools that are able to evaluate the state of aggregation may provide a better understanding of the impact of material properties and processing parameters on the in vivo performance. This study explored the utility of the Morphologically-Directed Raman Spectroscopy (MDRS) and dissolution as orthogonal techniques to assess microstructural equivalence of the aerosolized dose of DPIs collected with an aerosol collection device. METHODS: Commercial DPIs containing different strengths of Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX) as monotherapy and combination products were sourced from different regions. These inhalers were compared with aerodynamic particle size distribution (APSD), dissolution, and MDRS studies. RESULTS: APSD testing alone might not be able to explain differences reported elsewhere in in vivo studies of commercial FP/SX drug products with different Advair® strengths and/or batches. Dissolution studies demonstrated different dissolution rates between Seretide™ 100/50 and Advair® 100/50, whereas Flixotide™ 100 and Flovent® 100 had similar dissolution rates between each other. These differences in dissolution profiles were supported by MDRS results: the dissolution rate is increased if the fraction of FP associated with high soluble components is increased. Principle component analysis was used to identify the agglomerate classes that better discriminate different products. CONCLUSIONS: MDRS and dissolution studies of the aerosolized dose of DPIs were successfully used as orthogonal techniques. This study highlights the importance of further assessing in vitro tools that are able to provide a bridge between material attributes or process parameters and in vivo performance.

20.
J Pharm Bioallied Sci ; 16(Suppl 3): S2306-S2308, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39346473

RESUMO

Background: Both the mechanical cleansing effect and the irrigants' capacity to disintegrate tissue are necessary for irrigation to be successful. Strong antibacterial but not poisonous to the periapical tissues and increased pulp tissue dissolution irrigant are all desirable qualities in an irrigant. Aim: To assess and compare the antibacterial properties and pulp tissue dissolving activity of various irrigation solutions. Methods and Materials: A total of 240 human mandibular permanent premolar teeth that were extracted recently for periodontal or orthodontic reasons were used in this investigation. Following irrigation, blood agar plates were used to conduct colony-forming unit (CFU) counts of the microorganism breeding colonies. Next, log CFU was computed. Before evaluating the ability of the five distinct irrigants utilized in this investigation to dissolve the frozen pulp tissues, the tissues were first smashed into smaller pieces using a mallet. Results: The bacterial count after irrigation in category 1 (normal saline), category 2 (aqueous ozone), category 3 (ethylenediaminetetraacetic acid (EDTA)), category 4 (chlorhexidine gluconate (CHX)), category 5 (super-oxidized water), and category 6 (sodium hypochlorite (NaOCl)) was 6.08 ± 0.87 log CFU mL-1, 0.92 ± 0.89 log CFU mL-1, 4.15 ± 0.20 log CFU mL-1, 3.34 ± 0.46 log CFU mL-1, 0.21 ± 0.52 log CFU mL-1, and 0.00 ± 0.00 log CFU mL-1, respectively. Conclusion: NaOCl has maximum antimicrobial reduction and pulp tissue dissolution property.

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