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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 -
Lung Oct 2020Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine... (Review)
Review
Most medicines are white bitter powders that are formulated as tablets and capsules but cough medicines are an exception where the taste and appearance of the medicine are more important to the patient than the pharmacology of the active ingredient. Excipients are generally defined as any ingredient in a medicine other than the active ingredient. In most medicines excipients play a supportive role in delivering the medicine, but in the case of cough medicines, excipients have more important and complex roles and they can also be the main active ingredient of the cough medicine as menthol, glycerol, and sugars, which are declared as active ingredients. This review searched the United Kingdom electronic medicines compendium (emc) and found over 100 excipients in 60 different liquid formulations of over the counter cough medicines. The excipients were divided into functional groups: sweeteners, thickeners, flavors, colors, antimicrobials, and buffers, and the incidence and function of the different excipients is discussed. When considering the efficacy of a cough medicine, clinicians and pharmacists tend to think of the pharmacology of antitussives such as dextromethorphan or expectorants such as guaifenesin, and they rarely consider the role of excipients in the efficacy of the medicine. This review discusses the functions and importance of excipients in cough medicines and provides some new information for clinicians, pharmacists, and all interested in the treatment of cough when considering the composition and efficacy of a cough medicine.
Topics: Humans; Antitussive Agents; Cough; Drug Compounding; Excipients; Nonprescription Drugs; Pharmaceutical Solutions; Treatment Outcome
PubMed: 32889596
DOI: 10.1007/s00408-020-00390-x -
Journal of Ocular Pharmacology and... Nov 2017Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At... (Review)
Review
Components of the ocular surface synergistically contribute to maintaining and protecting a smooth refractive layer to facilitate the optimal transmission of light. At the air-water interface, the tear film lipid layer (TFLL), a mixture of lipids and proteins, plays a key role in tear surface tension and is important for the physiological hydration of the ocular surface and for ocular homeostasis. Alterations in tear fluid rheology, differences in lipid composition, or downregulation of specific tear proteins are found in most types of ocular surface disease, including dry eye disease (DED). Artificial tears have long been a first line of treatment in DED and aim to replace or supplement tears. More recently, lipid-containing eye drops have been developed to more closely mimic the combination of aqueous and lipid layers of the TFLL. Over the last 2 decades, our understanding of the nature and importance of lipids in the tear film in health and disease has increased substantially. The aim of this article is to provide a brief overview of our current understanding of tear film properties and review the effectiveness of lipid-based products in the treatment of DED. Liposome lid sprays, emulsion eye drops, and other lipid-containing formulations are discussed.
Topics: Animals; Dry Eye Syndromes; Emulsions; Humans; Lipids; Lubricant Eye Drops; Meibomian Glands; Ophthalmic Solutions; Pharmaceutical Preparations; Tears
PubMed: 28956698
DOI: 10.1089/jop.2017.0052 -
Recent Patents on Drug Delivery &... 2014Nanoformulations (NF) are widely explored as potential alternatives for traditional ophthalmic formulation approaches. The effective treatment of ocular diseases using... (Review)
Review
Nanoformulations (NF) are widely explored as potential alternatives for traditional ophthalmic formulation approaches. The effective treatment of ocular diseases using conventional eye drops is often hampered by factors such as: physiological barriers, rapid elimination, protein binding, and enzymatic drug degradation. Combined, these factors are known to contribute to reduced ocular residence time and poor bioavailability. Recent research studies demonstrated that NF can significantly enhance the therapeutic efficacy and bioavailability of ocular drugs, compared to the established ophthalmic drug delivery strategies. The research studies resulted in a number of patent inventions, reporting a significant increase in therapeutic efficacy for various chronic ocular disease states of both the anterior and posterior ocular segments. This article reviews these patent disclosures in detail and emphasizes the therapeutic advantages conferred by the following nanoformulation approaches: Calcium Phosphate (CaP) nanoparticles, Liposomes, Nanoemulsions, Nanomicelles, and Hydrogels. The nanoformulation approaches were shown to enhance the ocular bioavailability by reducing the drugprotein binding, increasing the corneal resident time, enhancing the drug permeability and providing a sustained drug release. Further, the article discusses United States Food and Drug Administration (USFDA) approved ocular drugs employing nanotechnology and future developments. It should be noted that, despite the potential therapeutic promise demonstrated by nanotechnology for ocular drug delivery, the bench to bed transition from patent inventions to marketed drug products has been insignificant. Majority of the discussed technologies are still in development and testing phase for commercial viability. Further, studies are in progress to assess ocular tolerance and nanotoxicity for prolonged use of NF.
Topics: Administration, Ophthalmic; Animals; Chemistry, Pharmaceutical; Delayed-Action Preparations; Drug Delivery Systems; Humans; Nanoparticles; Ophthalmic Solutions; Patents as Topic
PubMed: 25262835
DOI: 10.2174/1872211308666140926112000 -
Wiley Interdisciplinary Reviews.... 2014Many vision threatening ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in... (Review)
Review
Many vision threatening ocular diseases such as age-related macular degeneration (AMD), diabetic retinopathy, glaucoma, and proliferative vitreoretinopathy may result in blindness. Ocular drug delivery specifically to the intraocular tissues remains a challenging task due to the presence of various physiological barriers. Nonetheless, recent advancements in the field of nanomicelle-based novel drug delivery system could fulfil these unmet needs. Nanomicelles consists of amphiphilic molecules that self-assemble in aqueous media to form organized supramolecular structures. Micelles can be prepared in various sizes (10-1000 nm) and shapes depending on the molecular weights of the core and corona forming blocks. Nanomicelles have been an attractive carrier for their potential to solubilize hydrophobic molecules in aqueous solution. In addition, small size in nanometer range and highly modifiable surface properties have been reported to be advantageous in ocular drug delivery. In this review, various factors influencing rationale design of nanomicelles formulation and disposition are discussed along with case studies. Despite the progress in the field, influence of various properties of nanomicelles such as size, shape, surface charge, rigidity of structure on ocular disposition need to be studied in further details to develop an efficient nanocarrier system.
Topics: Animals; Drug Carriers; Humans; Hydrophobic and Hydrophilic Interactions; Micelles; Nanostructures; Ophthalmic Solutions; Rabbits
PubMed: 24888969
DOI: 10.1002/wnan.1272 -
Journal of Pharmaceutical and... Feb 2018Infliximab is a monoclonal antibody widely used for the treatment of inflammatory diseases. Over the past few years, many studies have assessed that monoclonal... (Comparative Study)
Comparative Study
Infliximab is a monoclonal antibody widely used for the treatment of inflammatory diseases. Over the past few years, many studies have assessed that monoclonal antibodies are prone to aggregation under stress conditions. The aim of this study was to investigate the stability of solutions of an infliximab biosimilar (Inflectra) at different concentrations (0.4, 2 and 10 mg/mL). These solutions were separately submitted to three temperature conditions that are likely to happen during the drug dispensing system: -20 °C, 5 °C and 25 °C. To perform a complete characterization of infliximab physicochemical and structural stability, a wide range of analytical techniques was employed including: visual inspection, subvisible particles counting (HIAC), dynamic light scattering (DLS), size exclusion chromatography (SEC), cation exchange chromatography (CEX), and analysis of primary, secondary and tertiary structure. When stored at 25 °C, chemical instability was the main limiting factor (highlighted by CEX), while SEC showed only some acceptable variations. After a single freeze-thawing cycle, the amount of subvisible particles was significantly increased. Some variations were also visible in CEX and the hydrodynamic diameter was increased after thawing 10 mg/mL samples. In regard of these results, infliximab (Inflectra) solutions should not be used after a single freeze-thawing cycle between reconstitution and administration to the patient. The results showed stability at 5 °C of up to 14 days for 10 mg/mL solutions and 90 days for 0.4 and 2 mg/mL solutions, whilst samples stored at 25 °C were stable only 7 days at 10 mg/mL and 30 days when diluted.
Topics: Antirheumatic Agents; Biosimilar Pharmaceuticals; Chromatography, Gel; Chromatography, Ion Exchange; Drug Compounding; Drug Stability; Infliximab; Nanoparticles; Nephelometry and Turbidimetry; Osmolar Concentration; Peptide Mapping; Pharmaceutical Solutions; Protein Aggregates; Protein Stability; Spectrophotometry, Ultraviolet; Spectroscopy, Fourier Transform Infrared; Technology, Pharmaceutical; Temperature; Time Factors
PubMed: 29287266
DOI: 10.1016/j.jpba.2017.12.012 -
TheScientificWorldJournal 2013Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug... (Review)
Review
Ophthalmic drug delivery is one of the most attractive and challenging research area for pharmaceutical scientists and ophthalmologists. Absorption of an ophthalmic drug in conventional dosage forms is seriously limited by physiological conditions. The use of nonionic or ionic biodegradable polymers in aqueous solutions and colloidal dosage forms such as liposomes, nanoparticles, nanocapsules, microspheres, microcapsules, microemulsions, and dendrimers has been studied to overcome the problems mentioned above. Dendrimers are a new class of polymeric materials. The unique nanostructured architecture of dendrimers has been studied to examine their role in delivery of therapeutics and imaging agents. Dendrimers can enhance drug's water solubility, bioavailability, and biocompatibility and can be applied for different routes of drug administration successfully. Permeability enhancer properties of dendrimers were also reported. The use of dendrimers can also reduce toxicity versus activity and following an appropriate application route they allow the delivery of the drug to the targeted site and provide desired pharmacokinetic parameters. Therefore, dendrimeric drug delivery systems are of interest in ocular drug delivery. In this review, the limitations related to eye's unique structure, the advantages of dendrimers, and the potential applications of dendrimeric systems to ophthalmology including imaging, drug, peptide, and gene delivery will be discussed.
Topics: Administration, Ophthalmic; Animals; Dendrimers; Diffusion; Drug Carriers; Humans; Ophthalmic Solutions
PubMed: 24396306
DOI: 10.1155/2013/732340 -
American Family Physician May 2004Cryosurgery is a highly effective treatment for a broad range of benign skin problems. With appropriate instruction and supervised experience, family physicians can... (Review)
Review
Cryosurgery is a highly effective treatment for a broad range of benign skin problems. With appropriate instruction and supervised experience, family physicians can master the technique quickly. Cryosurgery is best suited for use in patients with light skin and for treatment of lesions in most non-hair-bearing areas of the body. Spray methods include the timed spot freeze technique, the rotary or spiral pattern, and the paintbrush method. Benign skin lesions that are suitable for freezing include actinic keratosis, solar lentigo, seborrheic keratosis, viral wart, molluscum contagiosum, and dermatofibroma. Cryosurgery requires little time and fits easily into the physician's office schedule. Advantages of this treatment include a short preparation time, low risk of infection, and minimal wound care. In addition, cryosurgery requires no expensive supplies or injectable anesthesia, and the patient does not have to return for suture removal. Potential side effects include bleeding, blister formation, headache, hair loss, and hypopigmentation, but rarely scarring. Skin lesions often can be treated in a single session, although some require several treatments.
Topics: Cryosurgery; Forms and Records Control; Humans; Nitrogen; Pharmaceutical Solutions; Skin Diseases
PubMed: 15168956
DOI: No ID Found -
Indian Journal of Ophthalmology Jul 2014The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been... (Review)
Review
The topically applied drugs as drops are washed off from the eye in very short period, resulting in low ocular bioavailability of drugs. Number of approaches have been attempted to increase the bioavailability and the duration of action of ocular drugs. This review provides an insight into various novel approaches; hydrophilic nanogels, solid lipid nanoparticles, and nanosponges applied very recently in the delivery of insoluble drugs, prolonging the ocular residence time, minimize pre-corneal drug loss and, therefore, bioavailability and therapeutic efficacy of the drugs. Despite various scientific approaches, efficient ocular drug delivery remains a challenge for pharmaceutical scientists.
Topics: Drug Delivery Systems; Humans; Nanoparticles; Ophthalmic Solutions; Retinal Diseases
PubMed: 25116766
DOI: 10.4103/0301-4738.138301 -
American Journal of Health-system... Dec 2015The results of a study to determine the stability of solutions of furosemide and chlorothiazide over 96 hours are reported.
PURPOSE
The results of a study to determine the stability of solutions of furosemide and chlorothiazide over 96 hours are reported.
METHODS
Chlorothiazide and furosemide were diluted in 5% dextrose USP to final concentrations of 10 and 1 mg/mL, respectively, and combined. In addition, sample solutions of chlorothiazide in dextrose, furosemide in dextrose, and dextrose alone were prepared for control purposes. The resulting solutions were analyzed immediately after preparation and 24, 48, 72, and 96 hours later using a liquid chromatography-tandem mass spectroscopy (LC-MS/MS) system with an electrospray ionization source. Mixtures and samples were diluted 10,000-fold prior to LC-MS/MS analysis so that concentrations of both drugs would be within the assay's linear range of detection.
RESULTS
LC-MS/MS analysis showed that chlorothiazide typically eluted at 2.6 minutes and furosemide at 4.8 minutes. Each compound was degraded by exposure to strong ultraviolet light in a time-dependent manner. Both unmixed and mixed solutions retained over 90% of the original concentrations of chlorothiazide and furosemide for up to 96 hours. Furosemide and chlorothiazide are commonly used concomitantly to maximize diuresis in pediatric patients; the study findings suggest that solutions of furosemide and chlorothiazide can be combined in the same syringe without loss of stability for up to 96 hours.
CONCLUSION
Solutions of chlorothiazide (10 mg/mL) and furosemide (1 mg/mL) stored either separately or together in polypropylene syringes remained stable for up to 96 hours at room temperature and protected from light.
Topics: Chlorothiazide; Chromatography, Liquid; Diuretics; Drug Stability; Drug Storage; Furosemide; Humans; Pharmaceutical Solutions; Syringes; Tandem Mass Spectrometry
PubMed: 26637518
DOI: 10.2146/ajhp150023