scholarly journals Co-Administration of Drugs and Parenteral Nutrition: In Vitro Compatibility Studies of Loop Diuretics for Safer Clinical Practice

Pharmaceutics ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 1092
Author(s):  
Szymon Tomczak ◽  
Maciej Stawny ◽  
Anna Jelińska

Parenteral nutrition (PN) admixtures are prone to interacting with drugs administered intravenously via a common catheter. This may cause a threat to a patient’s health and life. The literature that has been reported on the compatibility of loop diuretics with PN presents conflicting results. This work aimed to study the compatibility of furosemide and torsemide with PN used in clinical practice. Undiluted solutions of drugs were mixed with PN at various ratios determined by flow rates. In order to assess compatibility, visual control was followed by pH measurement, osmolality, mean emulsion droplet diameter (MDD), and zeta potential upon mixing and at 4 h of storage. No macroscopic changes that indicated lipid emulsion degradation were observed. After the addition of the drugs, the value of pH ranged from 6.37 ± 0.01 to 7.38 ± 0.01. The zeta potential was in reverse proportion to the drug concentration. The addition of the drugs did not affect the MDD. It may be suggested that the co-administration of furosemide or torsemide and PN caused no interaction. The absence of such signs of unwanted interactions allowed for the co-administration of the mentioned loop diuretics and PN at each of the studied ratios.

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 559 ◽  
Author(s):  
Maciej Stawny ◽  
Aleksandra Gostyńska ◽  
Katarzyna Dettlaff ◽  
Anna Jelińska ◽  
Eliza Główka ◽  
...  

Background: Ampicillin (AMP) is frequently administered parenterally in critically ill patients with meningitis or endocarditis. Many of them require parallel infusion of total parenteral nutrition (TPN) admixtures. The aim of the study was to determine the physicochemical stability of AMP in TPN admixtures. Methods: AMP was added to two formulations of TPN admixtures differing in the lipid emulsion (Lipofundin® MCT/LCT 20% or LIPIDem®). Samples were stored at 4 ± 1 °C with light protection, and at 25 ± 1 °C with and without light protection to assess the impact of temperature and light on formulation stability. Every 24 h the pH, zeta potential, mean droplet diameter (MDD) of a lipid emulsion, and AMP concentration using HPLC method were determined. The assessment of stability and compatibility of TPN admixtures with vitamins and trace elements was carried out immediately after preparation and after 24 h of storage. Results: The addition of AMP as well as vitamins and trace elements to the TPN admixtures did not affect their physical stability. An increase in the pH value of approx. 0.6 and reduction of zeta potential were observed. The MDD of the lipid emulsions was below the limit of 500 nm (dynamic light scattering (DLS) method) and no fat droplets greater than 525 nm were observed (light diffraction (LD) method). The content of AMP after the first 24 h was within the acceptable limit of 90% for TPN admixtures stored at 4 ± 1 °C and 25 ± 1 °C with light protection. Conclusions: The results showed that co-administration of AMP in the same bag with TPN admixture at the tested dose is possible when used ex tempore and with light protection.


Antibiotics ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 217
Author(s):  
Aleksandra Gostyńska ◽  
Ludwika Piwowarczyk ◽  
Malwina Nadolna ◽  
Anna Jelińska ◽  
Katarzyna Dettlaff ◽  
...  

Simultaneous administration of parenteral nutrition (PN) admixtures with intravenous antibiotics is a common clinical problem. Coadministration of drugs incompatible with PN admixture may affect its stability, especially in the context of lipid droplet size, which is a crucial parameter for patient safety. In the present study, we investigate the in vitro compatibility of meropenem (Meropenem 1000, MPM) with five commercial PN admixtures used worldwide: Kabiven, Olimel N9E, Nutriflex Lipid Special, Nutriflex Omega Special, and SmofKabiven. The appropriate volumetric ratios, reflecting their clinical practice ratios, were used to prepare the MPM–PN admixture samples. Physicochemical properties of MPM–PN admixtures samples were determined upon preparation and after four hours of storage. The pH changes for all MPM–PN admixtures samples did not exceed the assumed level of acceptability and ranged from 6.41 to 7.42. After four hours of storage, the osmolarity changes were ±3%, except MPM–Olimel N9E samples, for which differences from 7% to 11% were observed. The adopted level of acceptability of changes in zeta potential after four hours of storage (±3 mV) was met for MPM–Kabiven, MPM–Nutriflex Lipid Special, and MPM–Nutriflex Omega Special. The mean droplet diameter for all samples was below 500 nm. However, only in the case of Nutriflex Lipid Special and Nutriflex Omega Special, the addition of MPM did not cause the formation of the second fraction of lipid droplets. The coadministration of MPM via Y-site with Kabiven, Olimel N9E, and Smofkabiven should be avoided due to osmolarity fluctuations (MPM–Olimel), significant differences in zeta potential (MPM–Olimel, MPM–Smofkabiven), and the presence of the second fraction of lipid droplets >1000 nm (MPM–Kabiven, MPM–Olimel, and MPM–Smofkabiven). The assumed acceptance criteria for MPM compatibility of MPM with PN admixtures were met only for Nutriflex Lipid Special and Nutriflex Omega Special in 1:1, 2:1, and 4:1 volume ratios.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1017
Author(s):  
Aleksandra Gostyńska ◽  
Joanna Starkowska ◽  
Paulina Sobierajska ◽  
Anna Jelińska ◽  
Maciej Stawny

The administration of three-in-one parenteral nutrition (PN) admixtures to pediatric patients requires special consideration, specifically concerning quality and physicochemical stability. The introduction of a new parenteral amino acid solution into the market prompted us to evaluate Aminoplasmal Paed-based PN admixtures’ stability. The study aimed to determine the physicochemical parameters of the chosen variations of PN admixtures and search for a correlation between its composition and those parameters. One hundred and sixty-eight variations of PN admixtures intended for patients weighing from 10 to 25 kg and aged from 1 to 12 years and differing in the quantitative composition of electrolytes were selected for the study. The samples were prepared using each of the four intravenous lipid emulsions dedicated to pediatric patients: Intralipid 20%, Clinoleic 20%, Lipidem 20%, and Smoflipid 20%. The stability of the PN admixtures was assessed by visual inspection and determination of pH, osmolality, zeta potential, and hydrodynamic mean droplet diameter (MDD) immediately upon preparation and after seven days of storage at the temperature of 5 ± 1 °C with light protection. Pearson’s correlation was used to quantify the relationships between selected ingredients of the PN admixtures and the physicochemical parameters. The PN admixtures were characterized by pH ranging from 5.91 to 7.04, osmolality ranging from 1238 to 1678 mOsm/kg, and zeta potential ranging from −41.3 to −2.16 mV. The changes in pH and osmolality after seven days of storage did not exceed 0.2 and 4.4%, respectively. The homogeneity of the PN admixtures was confirmed by determining the polydispersity index, which ranged from 0.06 to 0.2. The MDD of the studied formulas ranged from 235 to 395 nm and from 233 to 365 nm immediately upon preparation and after the storage period, respectively. Correlations between selected components of the PN admixtures and some physicochemical parameters were found. All Aminoplasmal Paed 10%-based PN admixtures were characterized by appropriate physicochemical quality to be administered via the central veins, both immediately upon preparation and after seven days of storage at the temperature of 5 ± 1 °C with light protection. The applied electrolyte concentrations ranges and types of lipid emulsions in the selected macronutrient quantitative compositions allowed the PN admixtures to remain stable for seven days within the specified limits.


2019 ◽  
Vol 49 (8) ◽  
Author(s):  
Suelen Santos da Silva ◽  
Maiara Taís Bazana ◽  
Cassandra de Deus ◽  
Marina Lopes Machado ◽  
Larissa Marafiga Cordeiro ◽  
...  

ABSTRACT: Oil-in-water (O/W) nanoemulsion containing goldenberry extract was elaborated using a high-energy ultrasonic bath method. Physicochemical characterization of the formulation was carried out by determining pH, mean droplet diameter, polydispersity index (PDI) and zeta potential. Nanoemulsion toxicity was assessed using in vitro assays with tumor and non-tumor cell lines, and in vivo using Caenorhabditis elegans. The pH of the nanoemulsion was 3.84, the mean droplet diameter was 268 ± 7 nm, PDI 0.113 and zeta potential -13.94 mV. Results of the cytotoxicity assays employing non-tumor cells indicated that the extract associated or not with nanoemulsion maintained cell viability at different concentrations tested. In the assays using tumor lineage, it is observed that the nanoemulsion containing the extract had higher antitumor activity than the free extract. As for the in vivo tests, there was no change in the survival rate of the worms.


GYNECOLOGY ◽  
2020 ◽  
Vol 21 (6) ◽  
pp. 36-40
Author(s):  
Anna G. Burduli ◽  
Natalia A. Kitsilovskaya ◽  
Yuliya V. Sukhova ◽  
Irina A. Vedikhina ◽  
Tatiana Y. Ivanets ◽  
...  

The review presents data on metabolites in the follicular fluid (FF) from the perspective of reproductive medicine and their use in order to predict outcomes of assisted reproductive technology (ART) programs. It considers various components of this biological medium (hormones, lipids, melatonin, etc.) with an assessment of their predictive value in prognosis of the effectiveness of in vitro fertilization (IVF) programs. The data on experimental directions in this field and the prospects for their use in clinical practice are presented. The article emphasizes that the growing clinical need and the unsolved problem of increasing the effectiveness of ART programs determine the need for further studies of the FF composition. Materials and methods. The review includes data related to this topic from foreign and Russian articles found in PubMed which were published in recent years. Results. Given the established fact of a direct effect of FF composition on growth and maturation of oocytes, and further, on the fertilization process, various FF metabolites are actively investigated as non-invasive markers of quality of oocytes/embryos. The article provides data on the experimental directions in this field and the prospects for their use in clinical practice. However, clinical studies of a relation between various FF metabolites levels and outcomes of IVF programs are contradictory. Conclusion. Owing large economic cost for treatment of infertility with IVF, there is need for expansion and intensification of studies to identify and use reliable predictors in prognosis of ART programs outcomes.


Author(s):  
Rupali L. Shid ◽  
Shashikant N. Dhole ◽  
Nilesh Kulkarni ◽  
Santosh L Shid

Poor water solubility and slow dissolution rate are issues for the majority of upcoming and existing biologically active compounds. Simvastatin is poorly water-soluble drug and its bioavailability is very low from its crystalline form. The purpose of this study wasto increase the solubility and dissolution rate of simvastatin by the  preparation of nanosuspension by emulsification solvent diffusion method at laboratory scale. Prepared nanosus-pension was evaluated for its particle size and in vitro dissolution study and characterized by zeta potential,differential scanning calorimetry (DSC) and X-Ray diffractometry (XRD), motic digital microscopy, entrapment efficiency, total drug content, saturated solubility study and in vivo study. A 23 factorial design was employed to study the effect of independent variables, amount of SLS (X1), amount of PVPK-30 (X2) and poloxamer-188 (X3) and dependent variables are total drug content and polydispersity Index. The obtained results showed that particle size (nm) and rate of dissolution has been improved when nanosuspension prepared with the higherconcentration of PVPK-30 with the higher concentration of PVP K-30 and Poloxamer-188 and lower concentration of SLS. The particle size and zeta potential of optimized formulation was found to be 258.3 nm and 23.43. The rate of dissolution of the optimized nanosuspension was enhanced (90% in 60min), relative to plain simvastatin  (21% in 60 min), mainly due to the formation of nanosized particles. These results indicate the suitability of 23 factorial  design for preparation of simvastatin loaded nano-suspension significantly improved in vitro dissolution rate and thus possibly enhance fast onset of therapeutic drug effect. In vivo study shows increase in bioavailability in nanosuspension formulation than the plain simvastatin drug.


2020 ◽  
Vol 26 (14) ◽  
pp. 1543-1555 ◽  
Author(s):  
Meltem E. Durgun ◽  
Emine Kahraman ◽  
Sevgi Güngör ◽  
Yıldız Özsoy

Background: Topical therapy is preferred for the management of ocular fungal infections due to its superiorities which include overcoming potential systemic side effects risk of drugs, and targeting of drugs to the site of disease. However, the optimization of effective ocular formulations has always been a major challenge due to restrictions of ocular barriers and physiological conditions. Posaconazole, an antifungal and highly lipophilic agent with broad-spectrum, has been used topically as off-label in the treatment of ocular fungal infections due to its highly lipophilic character. Micellar carriers have the potential to improve the solubility of lipophilic drugs and, overcome ocular barriers. Objective: In the current study, it was aimed optimization of posaconazole loaded micellar formulations to improve aqueous solubility of posaconazole and to characterize the formulations and to investigate the physical stability of these formulations at room temperature (25°C, 60% RH), and accelerated stability (40°C, 75% RH) conditions. Method: Micelles were prepared using a thin-film hydration method. Pre-formulation studies were firstly performed to optimize polymer/surfactant type and to determine their concentration in the formulations. Then, particle size, size distribution, and zeta potential of the micellar formulations were measured by ZetaSizer Nano-ZS. The drug encapsulation efficiency of the micelles was quantified by HPLC. The morphology of the micelles was depicted by AFM. The stability of optimized micelles was evaluated in terms of particle size, size distribution, zeta potential, drug amount and pH for 180 days. In vitro release studies were performed using Franz diffusion cells. Results: Pre-formulation studies indicated that single D-ɑ-tocopheryl polyethylene glycol succinate (TPGS), a combination of it and Pluronic F127/Pluronic F68 are capable of formation of posaconazole loaded micelles at specific concentrations. Optimized micelles with high encapsulation efficiency were less than 20 nm, approximately neutral, stable, and in aspherical shape. Additionally, in vitro release data showed that the release of posaconazole from the micelles was higher than that of suspension. Conclusion: The results revealed that the optimized micellar formulation of posaconazole offers a potential approach for topical ocular administration.


Author(s):  
Gülsel Yurtdaş Kırımlıoğlu ◽  
Sinan Özer ◽  
Gülay Büyükköroğlu ◽  
Yasemin Yazan

Background: Considering the low ocular bioavailability of conventional formulations used for ocular bacterial infection treatment, there’s a need for designing efficient novel drug delivery systems that may enhance of precorneal retention time and corneal permeability. Aim and Objective: The current research focuses on developing nanosized and non-toxic Eudragit® RL 100 and Kollidon® SR nanoparticles loaded with moxifloxacin hydrochloride (MOX) for its prolonged release to be promising for effective ocular delivery. Methods: In this study, MOX was incorporation was carried out by spray drying method aiming ocular delivery. In vitro characteristics were evaluated in detail with different methods. Results: MOX was successfully incorporated into Eudragit® RL 100 and Kollidon® SR polymeric nanoparticles by spray-drying process. Particle size, zeta potential, entrapment efficiency, particle morphology, thermal, FTIR, XRD and NMR analyses and MOX quantification using HPLC method were carried out to evaluate the nanoparticles prepared. MOX loaded nanoparticles demonstrated nanosized and spherical shape while in vitro release studies demonstrated modified release pattern which followed Korsmeyer-Peppas kinetic model. Following successful incorporation of MOX into the nanoparticles, the formulation (MOX: Eudragit® RL 100, 1:5) (ERL-MOX 2) was selected for further studies by the reason of its better characteristics like cationic zeta potential, smaller particle size, narrow size distribution and more uniform prolonged release pattern. Moreover, ERL-MOX 2 formulation remained stable for 3 months and demonstrated higher cell viability values for MOX. Conclusion: In vitro characterization analyses showed that non-toxic, nano-sized and cationic ERLMOX 2 formulation has the potential of enhancing ocular bioavailability.


2019 ◽  
Vol 15 (1) ◽  
pp. 87-102 ◽  
Author(s):  
Surbhi Dhawan ◽  
Sanju Nanda

Background: Since ancient times, people have been using natural resources for photoprotection purposes. One such highly recognised natural agent is pomegranate seed oil, considered as wonder oil owing to the presence of several beneficial phytoconstituents. </P><P> Objective: The study aimed to establish the photoprotective potential of pomegranate seed oil through various in vitro and biochemical studies along with the formation of nanoemulsion, an efficient topical delivery system for the oil. </P><P> Method: Photo-protective potential of the oil was estimated by determining in vitro antioxidant and anti-inflammatory activity, total phenolic content, anti elastase, antihyaluronidase and anticollagenase activities of the oil. Ultrasonication method was used to formulate nanoemulsions. The optimisation was done following the central composite design. The characterisation was done by particle size analysis, zeta potential, polydispersity index, pH, viscosity, stability testing and transmission electron microscopy. The optimised nanoemulsion was loaded into a gel base for topical application and further release studies were carried out. </P><P> Results: The IC50 values of anti-elastase, anti-collagenase and anti-hyaluronidase were found to be 309 mg/ml, 4 mg/ml and 95 mg/ml respectively. The results of anti-oxidant and anti-inflammatory activity were also significant, which thereby established the photo-protective potential of the oil. The optimum batch 2 had particle size 83.90 nm, 0.237 PDI and -5.37 mV zeta potential. The morphology was confirmed by TEM. Batch 2 was incorporated into a gel base and release studies showed 74.12 % release within 7 hours. </P><P> Conclusion: Pomegranate seed oil possesses a potential photo-protective ability. Nanoemulsions proved to be a promising carrier for the topical delivery of the oil.


Sign in / Sign up

Export Citation Format

Share Document