-
Drug Discovery Today Aug 2019Delivering therapeutics to the eye is challenging on multiple levels: rapid clearance of eyedrops from the ocular surface requires frequent instillation, which is... (Review)
Review
Delivering therapeutics to the eye is challenging on multiple levels: rapid clearance of eyedrops from the ocular surface requires frequent instillation, which is difficult for patients; transport of drugs across the blood-retinal barrier when drugs are administered systemically, and the cornea when drugs are administered topically, is difficult to achieve; limited drug penetration to the back of the eye owing to the cornea, conjunctiva, sclera and vitreous barriers. Nanomedicine offers many advantages over conventional ophthalmic medications for effective ocular drug delivery because nanomedicine can increase the therapeutic index by overcoming ocular barriers, improving drug-release profiles and reducing potential drug toxicity. In this review, we highlight the therapeutic implications of nanomedicine for ocular drug delivery.
Topics: Animals; Drug Carriers; Drug Delivery Systems; Eye; Humans; Nanomedicine; Ophthalmic Solutions
PubMed: 31102733
DOI: 10.1016/j.drudis.2019.05.006 -
British Journal of Anaesthesia Jan 2006Fluid absorption is an unpredictable complication of endoscopic surgery. Absorption of small amounts of fluid (1-2 litre) occurs in 5-10% of patients undergoing... (Review)
Review
Fluid absorption is an unpredictable complication of endoscopic surgery. Absorption of small amounts of fluid (1-2 litre) occurs in 5-10% of patients undergoing transurethral prostatic resection and results in an easily overlooked mild transurethral resection (TUR) syndrome. Large-scale fluid absorption is rare but leads to symptoms severe enough to require intensive care. Pathophysiological mechanisms consist of pharmacological effects of the irrigant solutes, the volume effect of the irrigant water, dilutional hyponatraemia and brain oedema. Other less widely known factors include absolute losses of sodium by urinary excretion and morphological changes in the heart muscle, both of which promote a hypokinetic circulation. Studies in animals, volunteers and patients show that irrigation with glycine solution should be avoided. Preventive measures, such as low-pressure irrigation, might reduce the extent of fluid absorption but does not eliminate this complication. Monitoring the extent of absorption during surgery allows control of the fluid balance in the individual patient, but such monitoring is not used widely. However, the anaesthetist must be aware of the symptoms and be able to diagnose this complication. Treatment should be based on administration of hypertonic saline rather than on diuretics. New techniques, such as bipolar resectoscopes and vaporizing instead of resecting tissue, result in a continuous change of the prerequisites for fluid absorption and its consequences.
Topics: Absorption; Animals; Contraindications; Endoscopy; Extravasation of Diagnostic and Therapeutic Materials; Glycine; Humans; Hyponatremia; Male; Mannitol; Pharmaceutical Solutions; Therapeutic Irrigation; Transurethral Resection of Prostate
PubMed: 16317031
DOI: 10.1093/bja/aei279 -
Archives of Disease in Childhood Apr 2020To investigate the physical and chemical compatibility of pentoxifylline (PTX) with a range of parenteral medications used in neonatal intensive care.
OBJECTIVE
To investigate the physical and chemical compatibility of pentoxifylline (PTX) with a range of parenteral medications used in neonatal intensive care.
DESIGN
PTX and drug solutions were combined in glass vials, inspected for physical incompatibility and evaluated on the basis of PTX concentrations for chemical compatibility.
RESULTS
No precipitation, colour change or turbidity was observed in any of the test mixtures. The PTX concentration was approximately 5.5% lower when combined with undiluted calcium gluconate injection (100 mg/mL). The PTX concentration ratios for all other combinations, including diluted calcium gluconate injection (50 mg/mL), were in the range of 99.5%-102%.
CONCLUSION
In simulated Y-site conditions, PTX was found to be compatible with 15 parenteral medications and six total parenteral nutrition solutions. Based on PTX concentration tests, it would be prudent to avoid mixing PTX with undiluted calcium gluconate injection.
Topics: Chemical Phenomena; Fat Emulsions, Intravenous; Humans; Infusions, Intravenous; Intensive Care, Neonatal; Parenteral Nutrition; Pentoxifylline; Pharmaceutical Preparations; Pharmaceutical Solutions; Vasodilator Agents
PubMed: 31871042
DOI: 10.1136/archdischild-2019-317912 -
British Journal of Anaesthesia Feb 2018The consensus that i.v. resuscitation fluids should be considered as drugs with specific dose recommendations, contraindications, and side-effects has led to an... (Review)
Review
The consensus that i.v. resuscitation fluids should be considered as drugs with specific dose recommendations, contraindications, and side-effects has led to an increased attention for the choice of fluid during perioperative care. In particular, the debate concerning possible adverse effects of unbalanced fluids and hydroxyethyl starches resulted in a re-evaluation of the roles of different fluid types in the perioperative setting. This review provides a concise overview of the current knowledge regarding the efficacy and safety of distinct fluid types for perioperative use. First, basic physiological aspects and possible side-effects are explained. Second, we focus on considerations regarding fluid choice for specific perioperative indications based on an analysis of available randomized controlled trials.
Topics: Adult; Child; Colloids; Fluid Therapy; Humans; Hydroxyethyl Starch Derivatives; Infusions, Intravenous; Perioperative Care; Pharmaceutical Solutions; Postoperative Care
PubMed: 29406187
DOI: 10.1016/j.bja.2017.10.022 -
International Journal of Molecular... Nov 2020Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some... (Review)
Review
Solubility, bioavailability, permeation, polymorphism, and stability concerns associated to solid-state pharmaceuticals demand for effective solutions. To overcome some of these drawbacks, ionic liquids (ILs) have been investigated as solvents, reagents, and anti-solvents in the synthesis and crystallization of active pharmaceutical ingredients (APIs), as solvents, co-solvents and emulsifiers in drug formulations, as pharmaceuticals (API-ILs) aiming liquid therapeutics, and in the development and/or improvement of drug-delivery-based systems. The present review focuses on the use of ILs in the pharmaceutical field, covering their multiple applications from pharmaceutical synthesis to drug delivery. The most relevant research conducted up to date is presented and discussed, together with a critical analysis of the most significant IL-based strategies in order to improve the performance of therapeutics and drug delivery systems.
Topics: Biological Availability; Chemistry, Pharmaceutical; Crystallization; Drug Delivery Systems; Humans; Ionic Liquids; Pharmaceutical Preparations; Pharmaceutical Solutions; Solubility; Solvents
PubMed: 33167474
DOI: 10.3390/ijms21218298 -
Journal of Managed Care & Specialty... Jan 2023Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative...
Matching-adjusted indirect comparison of phase 3 clinical trial outcomes of OC-01 (varenicline solution) nasal spray and lifitegrast 5% ophthalmic solution for the treatment of dry eye disease.
Matching-adjusted indirect comparison (MAIC) is a methodology for cross-study comparisons after adjusting for baseline characteristic imbalances. It is a comparative analytical approach used across therapeutic areas absent head-to-head trial outcomes. To compare the efficacy of OC-01 (varenicline solution) 0.03 mg nasal spray (OC-01 VNS) to lifitegrast 5% ophthalmic solution on tear production and patient-reported eye dryness in patients with dry eye disease (DED) using data from phase 3 clinical trials via MAIC analysis. Individual patient data (IPD) from the phase 3 registrational trial of OC-01 VNS and aggregate data from 2 phase 3 trials of lifitegrast in the publicly available XIIDRA New Drug Application were used. Using unanchored MAIC methods, IPD were weighted on clinically relevant baseline variables (age, race, sex, baseline Schirmer's test score [STS], and Eye Dryness Score [EDS]) to produce weighted OC-01 VNS datasets matched to the same lifitegrast datasets' variables. Least-squares (LS) mean change from baseline (CFB) in STS for OC-01 VNS was calculated using the identical analysis of covariance model and covariates used to calculate the same values for lifitegrast in the XIIDRA New Drug Application and was then compared. LS mean EDS (based on a 100- point Visual Analogue Scale) was compared via analysis of covariance in the weighted OC-01 VNS and lifitegrast datasets. OC-01 VNS at 2 and 4 weeks compared to lifitegrast data at 2 and 6 weeks. Data from 511 subjects (n = 260 treated; 251 vehicle control [VC]) in the OC-01 VNS phase 3 trial, 588 (n = 293 treated, 295 VC) in the lifitegrast phase 3 OPUS-1 trial, and 718 (n = 358 treated, 360 VC) in the lifitegrast phase 3 OPUS-2 trial were analyzed. The LS mean STS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 and OPUS-2 ( < 0.0001 for all comparisons). The LS mean EDS CFB for OC-01 VNS at 2 and 4 weeks was significantly greater than that for lifitegrast at 2 and 6 weeks in OPUS-1 ( < 0.0001 for both comparisons) and at 4 weeks vs lifitegrast at 6 weeks in OPUS-2 ( < 0.0001). This MAIC analysis demonstrates OC-01 VNS produced significantly greater improvement in mean STS and comparable or greater improvement in EDS compared with lifitegrast in phase 3 trials. These findings suggest a potentially greater magnitude of improvement achieved with OC-01 VNS compared with lifitegrast for the treatment of DED within the conditions of the analysis methodology. D White is a consultant for Oyster Point Pharma, Inc. L Hendrix, M Macsai, and A Gibson are employees and shareholders for Oyster Point Pharma, Inc. L Sun was an employee of COEUS, Clinical Research at the time of study conduct and received funding from Oyster Point Pharma, Inc. I Tam is an employee of COEUS, Clinical Research and received funding from Oyster Point Pharma, Inc. Oyster Point Pharma, Inc was involved in the study design, data collection, data analysis, and preparation of the manuscript and is the manufacturer/licensee of OC-01 (varenicline solution) nasal spray. Oyster Point Pharma, Inc., sponsored the phase 3 OC-01 (varenicline solution) clinical study from which analysis data were obtained.
Topics: Humans; Data Collection; Dry Eye Syndromes; Nasal Sprays; Ophthalmic Solutions; Treatment Outcome; Varenicline
PubMed: 36030415
DOI: 10.18553/jmcp.2022.22208 -
Molecules (Basel, Switzerland) Aug 2022A new, simple and sensitive ion chromatography (IC) method for the determination of sodium, potassium, magnesium, calcium and chloride in a parenteral nutrition (PN)...
A new, simple and sensitive ion chromatography (IC) method for the determination of sodium, potassium, magnesium, calcium and chloride in a parenteral nutrition (PN) solution was developed and validated. Before sample analysis, a sample pretreatment by calcination was applied which could totally remove interference from other constituents of the PN solution. Methanesulfonic acid (MSA) and sodium hydroxide were used as the mobile phase for the determination of cations and anions, respectively. The calibration curves showed good correlation between analyte peak area and concentration (r2 > 0.999). Detection limits ranged from 0.0001 to 0.02 mg/L and quantification limits from 0.0002 to 0.06 mg/L. Relative standard deviation (RSD) values for repeatability and inter-day precision did not exceed 1.0% and the recoveries for all analytes were between 99.1−101.1%. The robustness was verified by using an experimental design.
Topics: Anions; Cations; Chlorides; Chromatography, Ion Exchange; Parenteral Nutrition Solutions
PubMed: 36014505
DOI: 10.3390/molecules27165266 -
Peritoneal Dialysis International :... 2008Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components...
BACKGROUND
Conventional peritoneal dialysis (PD) solutions elicit vasodilation, which is implicated in the variable rate of solute transport during the dwell. The components causing such vasoactivity are still controversial. This study was conducted to define the vasoactive components of conventional and new PD solutions.
METHODS
Three visceral peritoneal microvascular levels were visualized by intravital video microscopy of the terminal ileum of anesthetized rats. Anesthesia-free decerebrate conscious rats served as control. Microvascular diameter and blood flow by Doppler measurements were conducted after topical peritoneal exposure to 4 clinical PD solutions and 6 prepared solutions designed to isolate potential vasoactive components of the PD solution.
RESULTS
All clinically available PD solutions produced a rapid and generalized vasodilation at all intestinal microvascular levels, regardless of the osmotic solute. The pattern and magnitude of this dilation was not affected by anesthesia but was determined by arteriolar size, the osmotic solute, and the solution's buffer anion system. The greatest dilation occurred in the small precapillary arterioles and was elicited by conventional PD solution and heat re-sterilized solution containing low glucose degradation products (GDPs). Hypertonic mannitol solutions produced a dilation that was approximately 50% less than the dilation obtained with glucose solutions with identical osmolarity and buffer. Increasing a solution's osmolarity did not produce a parallel increase in the magnitude of dilation, suggesting a nonlinear relationship between the two variables. Lactate dissolved in an isotonic solution was completely non-vasoactive unless the solution's H(+) concentration was increased. At low pH, isotonic lactate produced a rapid but transient vasodilation. This vascular reactivity was similar in magnitude and pattern to that obtained with the isotonic 7.5% icodextrin solution (Extraneal; Baxter Healthcare, Deerfield, Illinois, USA).
CONCLUSIONS
(1) Hyperosmolarity is the major vasoactive component of PD solution. (2) Hyperosmolarity and active intracellular glucose uptake account together for approximately 75% of PD solution-induced dilation, whereas GDPs contribute to approximately 25%. (3) Lactate is vasoactive only at low pH (high [H(+)]). (4) The magnitude of PD solution-mediated vasodilation is partially dependent on the nature of the osmotic solute, the GDP contents, and the [H(+)], which determine the vasoactivity of the lactate-buffer anion system. Studies are required to define the molecular mechanisms of PD-induced vasodilation and to determine the vasoactive properties of these solutions after chronic infusion.
Topics: Animals; Biological Transport; Buffers; Dialysis Solutions; Glucans; Glucose; Icodextrin; Lactates; Male; Microcirculation; Osmolar Concentration; Peritoneal Cavity; Peritoneal Dialysis; Peritoneum; Random Allocation; Rats; Rats, Sprague-Dawley; Rats, Wistar; Regional Blood Flow; Vasodilation
PubMed: 18474922
DOI: No ID Found -
European Journal of Pharmaceutics and... Nov 2022Despite the advances in the field of pharmaceutical materials and technology, topical administration remains a method of choice for the treatment of eye diseases such as...
Despite the advances in the field of pharmaceutical materials and technology, topical administration remains a method of choice for the treatment of eye diseases such as glaucoma, with eye drops being a leading dosage form. Their main disadvantage is a very short drug residence time and thus poor drug bioavailability, leading to the necessity of continuous repeated dosing. Mucoadhesive electrospun nanofibers are promising candidates for overcoming these challenges, while still benefiting from topical ocular administration. As an alternative for eye drops, a nanofibrous drug delivery system (DDS) for the delivery of brinzolamide (BRZ), based on β-cyclodextrin (β-CD), hydroxypropyl cellulose (HPC) and polycaprolactone (PCL), was designed. The results showed β-CD/BRZ guest-host interactions, successful drug incorporation into the nanofibers, and the possibility of more accurate dosing in comparison with the control eye drops. Drug permeation through sheep corneas was almost linear in time, achieving therapeutic concentrations in the receptor medium, and mucoadhesion to sheep eye mucosa was relatively high in case of formulations with high HPC content. All formulations were biocompatible, their mechanical properties were sufficient to handle them without caution and UV irradiation was suitable to reduce bioburden of the fibers matrix, yet no antibacterial properties of BRZ were observed.
Topics: Sheep; Animals; Nanofibers; Thiazines; Drug Delivery Systems; Ophthalmic Solutions; Glaucoma
PubMed: 36167272
DOI: 10.1016/j.ejpb.2022.09.008 -
Clinical Journal of the American... Jun 2019
Topics: Dialysis Solutions; Humans; Peritoneal Dialysis
PubMed: 31123182
DOI: 10.2215/CJN.04660419