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Journal of Ocular Pharmacology and... 2018Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With... (Review)
Review
Even though the very thought of an injection into the eye may be frightening, an estimated 6 million intravitreal (IVT) injections were made in the USA during 2016. With the introduction of new therapeutic agents, this number is expected to increase. In addition, drug products that are injectable in ocular compartments other than the vitreous humor are expected to enter the back of the eye market in the not so distant future. Besides the IVT route, some of the most actively investigated routes of invasive administration to the eye include periocular, subretinal, and suprachoroidal (SC) routes. While clinical efficacy is the driving force behind new injectable drug product development for the eye, safety is also being improved with time. In the case of IVT injections, the procedural guidelines have evolved over the years to improve patient comfort and reduce injection-related injury and infection. Similar advances are anticipated for other routes of administration of injectable products to the eye. In addition to procedural improvements, the design of needles, particularly those with smaller diameters, length, and controlled bevel angles are expected to improve overall safety and acceptance of injected ophthalmic drug products. A key development in this area is the introduction of microneedles of a length less than a millimeter that can target the SC space. In the future, needles with smaller diameters and lengths, potentially approaching nanodimensions, are expected to revolutionize ophthalmic disease management.
Topics: Administration, Ophthalmic; Animals; Drug Delivery Systems; Humans; Injections, Intraocular; Intravitreal Injections; Needles; Ophthalmic Solutions; Vitreous Body
PubMed: 29206556
DOI: 10.1089/jop.2017.0121 -
Drug Development and Industrial Pharmacy 2015Resveratrol, a natural compound found in grapes, has potential chemotherapy effects but very low oral bioavailability in humans.
CONTEXT
Resveratrol, a natural compound found in grapes, has potential chemotherapy effects but very low oral bioavailability in humans.
OBJECTIVE
To evaluate the solubility, pH stability profile, plasma protein binding (PPB) and stability in plasma for resveratrol.
METHODS
Solubility of resveratrol was measured in 10 common solvents at 25 °C using HPLC. The solution state pH stability of resveratrol was assessed in various United States Pharmacopeia buffers ranging from pH 2 to 10 for 24 h at 37 °C. Samples were analyzed up to 24 h. Human PPB was determined using ultracentrifugation technique. Standard solutions of drug were spiked to blank human plasma to yield final concentrations of 5, 12.5 or 25 μg/mL for determination. Finally, stability of resveratrol in human and rat plasma was also assessed at 37 °C. Aliquots of blank plasma were spiked with a standard drug concentration to yield final plasma concentration of 50 μg/mL. Samples were analyzed for resveratrol concentration up to 96 h.
RESULTS
Resveratrol has wide solubility ranging from 0.05 mg/mL in water to 374 mg/mL in polyethylene glycol 400 (PEG-400). Resveratrol is relatively stable above pH 6 and has maximum degradation at pH 9. The mean PPB of resveratrol is 98.3%. Resveratrol degrades in human and rat plasma in a first-order process with mean half lives of 54 and 25 h, respectively.
CONCLUSION
Resveratrol is more soluble in alcohol and PEG-400 and stable in acidic pH. It binds highly to plasma proteins and degrades slower in human then rat plasma.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biological Availability; Blood Proteins; Chemistry, Pharmaceutical; Chromatography, High Pressure Liquid; Drug Stability; Half-Life; Humans; Hydrogen-Ion Concentration; Male; Pharmaceutical Solutions; Protein Binding; Rats; Rats, Sprague-Dawley; Resveratrol; Solubility; Solvents; Species Specificity; Stilbenes
PubMed: 25224342
DOI: 10.3109/03639045.2014.958753 -
Current Medicinal Chemistry 2019Developing suitable medicines for genetic diseases requires a detailed understanding of not only the pathways that cause the disease, but also the identification of the... (Review)
Review
Developing suitable medicines for genetic diseases requires a detailed understanding of not only the pathways that cause the disease, but also the identification of the genetic components involved in disease manifestation. This article focuses on the complexities associated with ocular ciliopathies - a class of debilitating disorders of the eye caused by ciliary dysfunction. Ciliated cell types have been identified in both the anterior and posterior segments of the eye. Photoreceptors (rods and cones) are the most studied ciliated neurons in the retina, which is located in the posterior eye. The photoreceptors contain a specialized lightsensing outer segment, or cilium. Any defects in the development or maintenance of the outer segment can result in severe retinal ciliopathies, such as retinitis pigmentosa and Leber congenital amaurosis. A role of cilia in the cell types involved in regulating aqueous fluid outflow in the anterior segment of the eye has also been recognized. Defects in these cell types are frequently associated with some forms of glaucoma. Here, we will discuss the significance of understanding the genetic heterogeneity and the pathogenesis of ocular ciliopathies to develop suitable treatment strategies for these blinding disorders.
Topics: Animals; Ciliopathies; Eye Diseases; Glaucoma; Humans; Ophthalmic Solutions; Small Molecule Libraries
PubMed: 30221600
DOI: 10.2174/0929867325666180917102557 -
Journal of Ocular Pharmacology and... 2018Hydrogen sulfide (HS) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in... (Review)
Review
Hydrogen sulfide (HS) is a gaseous transmitter with well-known biological actions in a wide variety of tissues and organs. The potential involvement of this gas in physiological and pathological processes in the eye has led to several in vitro, ex vivo, and in vivo studies to understand its pharmacological role in some mammalian species. Evidence from literature demonstrates that 4 enzymes responsible for the biosynthesis of this gas (cystathionine β-synthase, CBS; cystathionine γ-lyase, CSE; 3-mercaptopyruvate sulfurtransferase, 3MST; and d-amino acid oxidase) are present in the cornea, iris, ciliary body, lens, and retina. Studies of the pharmacological actions of HS (using several compounds as fast- and slow-releasing gas donors) on anterior uveal tissues reveal an effect on sympathetic neurotransmission and the ability of the gas to relax precontracted iris and ocular vascular smooth muscles, responses that were blocked by inhibitors of CSE, CBS, and K channels. In the retina, there is evidence that HS can inhibit excitatory amino acid neurotransmission and can also protect this tissue from a wide variety of insults. Furthermore, exogenous application of HS-releasing compounds was reported to increase aqueous humor outflow facility in an ex vivo model of the porcine ocular anterior segment and lowered intraocular pressure (IOP) in both normotensive and glaucomatous rabbits. Taken together, the finding that HS-releasing compounds can lower IOP and can serve a neuroprotective role in the retina suggests that HS prodrugs could be used as tools or therapeutic agents in diseases such as glaucoma.
Topics: Animals; Aqueous Humor; Glaucoma; Humans; Hydrogen Sulfide; Ophthalmic Solutions
PubMed: 29215951
DOI: 10.1089/jop.2017.0077 -
AAPS PharmSciTech Dec 2015Myricetin (MYR) is a natural compound that has been investigated as a chemopreventative agent. MYR has been shown to suppresses ultraviolet B (UVB)-induced...
Myricetin (MYR) is a natural compound that has been investigated as a chemopreventative agent. MYR has been shown to suppresses ultraviolet B (UVB)-induced cyclooxygenase-2 (COX-2) protein expression and reduce the incidence of UVB-induced skin tumors in mice. Despite MYR's promise as a therapeutic agent, minimal information is available to guide the progression of formulations designed for future drug development. Here, data is presented describing the solid-state and solution characterization of MYR. Investigation into the solid-state properties of MYR identified four different crystal forms, two hydrates (MYR I and MYR II) and two metastable forms (MYR IA and MYR IIA). From solubility studies, it was evident that all forms are very insoluble (<5 μg/ml) in pure water. MYR I was found to be the most stable form at 23, 35, and 56°C. Stability determination indicated that MYR undergoes rapid apparent first-order degradation under basic pH conditions, and that degradation was influenced by buffer species. Apparent first-order degradation was also seen when MYR was introduced to an oxidizing solution. Improved stability was achieved after introducing 0.1% antioxidants to the solution. MYR was found to have good stability following exposure to ultraviolet radiation (UVR), which is a consideration for topical applications. Finally, a partitioning study indicated that MYR possess a log P of 2.94 which, along with its solid-state properties, contributes to its poor aqueous solubility. Both the solid-state properties and solution stability of MYR are important to consider when developing future formulations.
Topics: Chemistry, Pharmaceutical; Drug Stability; Flavonoids; Hydrogen-Ion Concentration; Pharmaceutical Solutions; Solubility; Ultraviolet Rays; Water
PubMed: 25986594
DOI: 10.1208/s12249-015-0329-6 -
Nutrition in Clinical Practice :... Jun 2015Parenteral nutrition (PN) is a life-sustaining therapy designed to deliver essential nutrients to patients unable to meet nutrition needs via the enteral route. PN may... (Review)
Review
Parenteral nutrition (PN) is a life-sustaining therapy designed to deliver essential nutrients to patients unable to meet nutrition needs via the enteral route. PN may be delivered via a 2-in-1 system (one solution containing amino acids, dextrose, electrolytes, vitamins, minerals, and fluids and one solution containing intravenous fat emulsions [IVFEs]) or via a 3-in-1 system (all nutrients mixed in one container). Although the use of 3-in-1 PN solutions is not necessarily therapeutically advantageous, certain benefits may exist such as the potential to reduce the risk of contamination due to decreased manipulations; ease of administration, particularly in the home care setting; possible cost savings; and reduced IVFE wastage. However, the incorporation of IVFE in 3-in-1 solutions also presents unique risks for the neonatal and pediatric population such as decreased stability, increased lipid globule size, decreased sterility and the potential for increased microbial growth/infectious complications, the need to use a larger filter size, precipitation and compatibility risks, and an increased chance of catheter occlusion. This review outlines the unique issues and challenges to be considered when formulating neonatal and pediatric 3-in-1 PN admixtures. While 3-in-1 PN solutions may be advantageous for certain pediatric populations, specifically those dependent on home PN, the risks do not outweigh the benefits in neonatal patients, and use should be avoided in this population.
Topics: Amino Acids; Child; Electrolytes; Fat Emulsions, Intravenous; Glucose; Humans; Infant, Newborn; Parenteral Nutrition; Pediatrics; Risk Assessment; Trace Elements; Vitamins
PubMed: 25857309
DOI: 10.1177/0884533615580596 -
Perfusion Oct 2022Cardioplegic solutions are used in cardiac surgery to achieve controlled cardiac arrest during operations, making surgery safer. Cardioplegia can either be blood or... (Review)
Review
Cardioplegic solutions are used in cardiac surgery to achieve controlled cardiac arrest during operations, making surgery safer. Cardioplegia can either be blood or crystalloid based, with perceived pros and cons of each type. Whilst it is known that cardioplegia causes cardiac arrest, there is debate over which cardioplegic solution provides the highest degree of myocardial protection during arrest. Myocardial damage is measured post-operatively by biomarkers such as serum TnT, TnI or CK-MB. It is known that the outcomes of minimally invasive valve surgery are comparable to full sternotomy valve operations. Despite there being a wide diversity in use of different cardioplegic solutions across the world, this comprehensive literature review found no superiority of one cardioplegic solution over the other for myocardial protection during minimally invasive valve procedures.
Topics: Biomarkers; Cardioplegic Solutions; Crystalloid Solutions; Heart Arrest; Heart Arrest, Induced; Humans
PubMed: 34080459
DOI: 10.1177/02676591211012554 -
Journal of Pharmacy & Pharmaceutical... 2019Dry eye disease (DED) is a common inflammatory disorder of the ocular surface. Millions of people are affected by DED worldwide. Lifitegrast is a novel drug designed to... (Review)
Review
Dry eye disease (DED) is a common inflammatory disorder of the ocular surface. Millions of people are affected by DED worldwide. Lifitegrast is a novel drug designed to inhibit DED-associated ocular inflammation. Four clinical trials have shown that lifitegrast is well tolerated and effective in improving symptoms and signs of DED over 12 weeks. A fifth trial showed long-term safety over 1 year. Lifitegrast has been in clinical use for more than one year in the United States and was recently approved in Canada (in December 2017). In this review, we discuss lifitegrast's novel mechanism of action and provide an overview of its clinical trial program.
Topics: Animals; Clinical Trials as Topic; Dry Eye Syndromes; Humans; Ophthalmic Solutions; Phenylalanine; Sulfones; Treatment Outcome
PubMed: 30636670
DOI: 10.18433/jpps29895 -
The Journal of Thoracic and... May 2020
Topics: Cardioplegic Solutions; Heart Arrest, Induced; Myocardium
PubMed: 31103203
DOI: 10.1016/j.jtcvs.2019.03.114 -
Blood Purification 2006Although hemodialysis is a mature therapy, a growing population of patients with more complex medical problems and limitations on resources will require technological... (Review)
Review
Although hemodialysis is a mature therapy, a growing population of patients with more complex medical problems and limitations on resources will require technological innovations to improve the safety, reliability and efficiency of the therapy. The past several years have seen design changes to dialyzers that have provided incremental improvements in small solute clearance and more substantial improvements in the clearance of large solutes. New functions have been added to dialysis machines that help ensure reliable delivery of the dialysis prescription and enable full advantage to be taken of improvements in dialyzer clearance of large molecules. In addition, feedback control systems have been developed that may help reduce the untoward side effects which many patients experience during hemodialysis. Whether or not a particular innovation enters routine clinical use will depend on demonstrating that it improves clinical outcomes, its cost, and, in some cases, on a more enlightened approach by regulatory authorities.
Topics: Dialysis Solutions; Health Care Costs; Humans; Membranes, Artificial; Renal Dialysis
PubMed: 16361833
DOI: 10.1159/000089429