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Journal of Medical Case Reports Nov 2021Excipients are widely used in pharmaceuticals, detergents, food, and drink because of their properties of low toxicity and hypoallergenicity. The excipient...
BACKGROUND
Excipients are widely used in pharmaceuticals, detergents, food, and drink because of their properties of low toxicity and hypoallergenicity. The excipient carboxymethylcellulose is used extensively as a thickener in foods such as baked goods, ice cream, gluten free, and reduced fat products, where it may be labeled as e-number E466. However, excipients can rarely cause type 1 hypersensitivity reactions. Several publications have described systemic allergy following carboxymethylcellulose exposure in pharmaceuticals, particularly systemic corticosteroids. Furthermore, there is one reported case in the literature of anaphylaxis following food containing carboxymethylcellulose.
CASE PRESENTATION
We identify a case of anaphylaxis in a 45-year-old atopic Caucasian woman on receiving an injectable suspension of the corticosteroid triamcinolone acetonide containing carboxymethylcellulose, and subsequent allergic symptoms on reexposure to carboxymethylcellulose in a commercial drink. Diagnosis of carboxymethylcellulose excipient allergy was confirmed through skin prick testing using Celluvisc carmellose 0.5% eye drops, which contain carboxymethylcellulose as the active ingredient.
CONCLUSION
This case highlights the importance of identifying excipients such as carboxymethylcellulose as causes of allergy, to reduce burden of further hypersensitivity reactions, not just to drugs but to other consumables.
Topics: Anaphylaxis; Carboxymethylcellulose Sodium; Drug Hypersensitivity; Excipients; Female; Humans; Middle Aged; Skin Tests
PubMed: 34819140
DOI: 10.1186/s13256-021-03180-y -
Biomedicine & Pharmacotherapy =... May 2023Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are... (Review)
Review
Nanodrug delivery systems have been widely used in disease treatment. However, weak drug targeting, easy to be cleared by the immune system, and low biocompatibility are great obstacles for drug delivery. As an important part of cell information transmission and behavior regulation, cell membrane can be used as drug coating material which represents a promising strategy and can overcome these limitations. Mesenchymal stem cell (MSC) membrane, as a new carrier, has the characteristics of active targeting and immune escape of MSC, and has broad application potential in tumor treatment, inflammatory disease, tissue regeneration and other fields. Here, we review recent progress on the use of MSC membrane-coated nanoparticles for therapy and drug delivery, aiming to provide guidance for the design and clinical application of membrane carrier in the future.
Topics: Membranes; Drug Delivery Systems; Cell Membrane; Nanoparticles; Mesenchymal Stem Cells; Excipients
PubMed: 36870279
DOI: 10.1016/j.biopha.2023.114451 -
PloS One 2022The use of starch, a natural polymeric material, and derivatives thereof is based on its adhesive, thickening, gelling, swelling, and film-forming properties, as well as...
The use of starch, a natural polymeric material, and derivatives thereof is based on its adhesive, thickening, gelling, swelling, and film-forming properties, as well as its ready availability. The objective of this research work is to develop an effective propylated Dioscorea abyssinica starch (PDAS) as a hydrophobic excipient for pharmaceutical applications with a reasonable price. This paper reports on the synthesis, characterization, and in vivo safety evaluation of PDAS. Native Dioscorea abyssinica starch (NDAS) was modified to its propylated form with propionic anhydride and characterized. Crystallinity, morphological structure, thermal behavior, solubility, and safety of PDAS were evaluated using x-ray diffraction, SEM, thermogravimetric, gravimetric, and toxicity studies, respectively. Propionyl content and degree of substitution (DS) of starch increased significantly (p < 0.05) with an increase in reaction time and temperature. Propionyl content and DS of starch increased significantly (p < 0.05) with a decrease in the ratio of starch to pyridine and starch to propionic anhydride in the reaction medium. FTIR spectra of PDAS indicated that hydroxyl groups participated in the propylation reaction. X-ray diffraction results showed that the chemical modification destroyed the crystalline structure of the NDAS. SEM of NDAS showed a rounded shape which became irregular after propylation. Thermogravimetric curves revealed that all the PDAS samples decomposed at higher temperatures than their native counterparts. At higher DS, swelling power and solubility in an aqueous environment significantly (p < 0.05) decreased below that of the native starch. PDAS with high DS, were soluble in organic solvents at room temperature. But PDAS with lower DS didn't dissolve in all types of organic solvents used. PDAS (DS = 2.842) in distilled water did not produce adverse effects in rats. Based on the results obtained, it can be concluded that PDAS can be considered as a generally safe excipient and fulfills the physicochemical properties of a hydrophobic excipient.
Topics: Animals; Rats; Dioscorea; Starch; Excipients; Solvents
PubMed: 36441719
DOI: 10.1371/journal.pone.0276965 -
Scientific Reports Oct 2022Silver nanoparticles (AgNPs) exhibit unusual biocidal properties thanks to which they find a wide range of applications in diverse fields of science and industry....
Silver nanoparticles (AgNPs) exhibit unusual biocidal properties thanks to which they find a wide range of applications in diverse fields of science and industry. Numerous research studies have been devoted to the bactericidal properties of AgNPs while less attention has been focused on their fungicidal activity. Our studies were therefore oriented toward determining the impact of AgNPs characterized by different physicochemical properties on Fusarium avenaceum and Fusarium equiseti. The main hypothesis assumed that the fungicidal properties of AgNPs characterized by comparable morphology can be shaped by stabilizing agent molecules adsorbed on nanoparticle surfaces. Two types of AgNPs were prepared by the reduction of silver ions with sodium borohydride (SB) in the presence of trisodium citrate (TC) or cysteamine hydrochloride (CH). Both types of AgNPs exhibited a quasi-spherical shape. Citrate-stabilized AgNPs (TCSB-AgNPs) of an average size of 15 ± 4 nm were negatively charged. Smaller (12 ± 4 nm), cysteamine-capped AgNPs (CHSB-AgNPs) were characterized by a positive surface charge and higher silver ion release profile. The phytopathogens were exposed to the AgNPs in three doses equal to 2.5, 5 and 10 mg L over 24 and 240 h. Additionally, the impact of silver ions delivered in the form of silver nitrate and the stabilizing agents of AgNPs on the fungi was also investigated. The response of phytopathogens to these treatments was evaluated by determining mycelial growth, sporulation and changes in the cell morphology. The results of our studies showed that CHSB-AgNPs, especially at a concentration of 10 mg L, strongly limited the vegetative mycelium growth of both species for short and long treatment times. The cell imaging revealed that CHSB-AgNPs damaged the conidia membranes and penetrated into the cells, while TCSB-AgNPs were deposited on their surface. The fungistatic (lethal) effect was demonstrated only for silver ions at the highest concentration for the F. equiseti species in the 240 h treatment. The number of spores of both Fusarium species was significantly reduced independently of the type of silver compounds used. Generally, it was found that the positively charged CHSB-AgNPs were more fungicidal than negatively charged TCSB-AgNPs. Thereby, it was established that the stabilizing agents of AgNPs and surface charge play a crucial role in the shaping of their fungicidal properties.
Topics: Antifungal Agents; Metal Nanoparticles; Excipients; Silver; Surface Properties; Ions
PubMed: 36302952
DOI: 10.1038/s41598-022-22659-2 -
Advanced Drug Delivery Reviews Jul 2021Protein therapeutics carry inherent limitations of membrane impermeability and structural instability, despite their predominant role in the modern pharmaceutical... (Review)
Review
Protein therapeutics carry inherent limitations of membrane impermeability and structural instability, despite their predominant role in the modern pharmaceutical market. Effective formulations are needed to overcome physiological and physicochemical barriers, respectively, for improving bioavailability and stability. Knowledge of membrane affinity, cellular internalization, encapsulation, and release of drug-loaded carrier vehicles uncover the structural basis for designing and optimizing biopharmaceuticals with enhanced delivery efficiency and therapeutic efficacy. Understanding stabilizing and destabilizing interactions between protein drugs and formulation excipients provide fundamental mechanisms for ensuring the stability and quality of biological products. This article reviews the molecular studies of biologics using solution and solid-state NMR spectroscopy on structural attributes pivotal to drug delivery and stability. In-depth investigation of the structure-function relationship of drug delivery systems based on cell-penetrating peptides, lipid nanoparticles and polymeric colloidal, and biophysical and biochemical stability of peptide, protein, monoclonal antibody, and vaccine, as the integrative efforts on drug product design, will be elaborated.
Topics: Animals; Biological Availability; Biological Products; Drug Carriers; Drug Delivery Systems; Drug Design; Drug Stability; Excipients; Humans; Magnetic Resonance Spectroscopy; Proteins
PubMed: 33609600
DOI: 10.1016/j.addr.2021.02.007 -
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 -
BioMed Research International 2021Orally disintegrating tablets (ODTs) rapidly disintegrate or dissolve in the oral cavity without using water. Demand for ODTs has increased, and the field has overgrown... (Review)
Review
Orally disintegrating tablets (ODTs) rapidly disintegrate or dissolve in the oral cavity without using water. Demand for ODTs has increased, and the field has overgrown in the pharmaceutical industry and academia. It is reported that ODTs have several advantages over other conventional tablets. Since some of them are absorbed from the mouth, pharynx, and esophagus as the saliva passes down into the stomach, in such cases, the bioavailability of the drug improves meaningfully. Furthermore, the immediate release property of ODTs makes them a popular oral dosage form in patients with swallowing challenges, children, and for cases with a need for rapid onset of action. The current review article explains the features of active ingredients and excipients used in the formulation of ODTs, discusses multiple ODT formulation and preparation techniques with their merits and demerits, and also, offers remedies for problems associated with ODTs. Moreover, quality control steps and required considerations are presented.
Topics: Administration, Oral; Animals; Biological Availability; Chemistry, Pharmaceutical; Excipients; Humans; Quality Control; Stomach; Tablets
PubMed: 34977245
DOI: 10.1155/2021/6618934 -
Pharmacology Research & Perspectives Feb 2022The bioavailability of drugs is often related to intestinal metabolism and transport mechanisms. In previous studies, pharmaceutical excipients were recognized as inert...
The pharmaceutical excipient PEG400 affect the absorption of baicalein in Caco-2 monolayer model by interacting with UDP-glucuronosyltransferases and efflux transport proteins.
The bioavailability of drugs is often related to intestinal metabolism and transport mechanisms. In previous studies, pharmaceutical excipients were recognized as inert substances in clinical safety evaluations. However, a large number of studies have shown that pharmaceutical excipients regulate the metabolism and transport of drugs in the body and improve the bioavailability. The pharmaceutical excipient polyethylene glycol 400 (PEG400) as a good solubilizer and surfactant has the potential to improve the bioavailability of drugs. The combined action of UDP-glucuronosyltransferases (UGTs) and efflux transport proteins is responsible for the intestinal disposition and poor bioavailability of baicalein. Our aim is to study the effect of PEG400 on the absorption of baicalein on the Caco-2 monolayer, and confirm the interaction of PEG400 with UGTs (UGT1A8 and UGT1A9) and efflux transports. We initially found that baicalein in the Caco-2 monolayer would be metabolized into glucuronide conjugates BG and B6G under the action of UGT1A8 and UGT1A9 on the endoplasmic reticulum membrane, and then mainly excreted to different sides by acting of MRP and BCRP. The addition of PEG400 significantly accelerated the metabolism of B in Caco-2 cells and increased the penetration of BG and B6G. Furthermore, PEG400 also significantly decreased the efflux ratio of BG and B6G, which was the evidence of the interaction with the efflux transporters. In the in vitro intestinal microsome regeneration system, low concentration PEG400 decreased the K value of UGT1A8 and UGT1A9 (key enzymes that mediate the production of BG and B6G); high concentration PEG400 enhanced the V value of UGT1A8 and UGT1A9. In conclusion, our results determined that PEG400 interacted with some UGTs and efflux transporters, which were the main factors affecting the absorption of baicalein.
Topics: Antioxidants; Biological Availability; Biological Transport; Caco-2 Cells; Excipients; Flavanones; Glucuronosyltransferase; Humans; Intestinal Absorption; Membrane Transport Proteins; Microsomes; Polyethylene Glycols; UDP-Glucuronosyltransferase 1A9
PubMed: 35148019
DOI: 10.1002/prp2.928 -
European Journal of Pharmaceutics and... Sep 2022Parenteral formulations are indispensable in clinical practice and often are the only option to administer drugs that cannot be administrated through other routes, such... (Review)
Review
Parenteral formulations are indispensable in clinical practice and often are the only option to administer drugs that cannot be administrated through other routes, such as proteins and certain anticancer drugs - which are indispensable to treat some of the most prevailing chronic diseases worldwide (like diabetes and cancer). Additionally, parenteral formulations play a relevant role in emergency care since they are the only ones that provide an immediate action of the drug after its administration. However, the development of parenteral formulations is a complex task owing to the specific quality and safety requirements set for these preparations and the intrinsic properties of the drugs. Amongst all the strategies that can be useful in the development of parenteral formulations, the formation of water-soluble host-guest inclusion complexes with cyclodextrins (CDs) has proven to be one of the most advantageous. CDs are multifunctional pharmaceutical excipients able to form water-soluble host-guest inclusion complexes with a wide variety of molecules, particularly drugs, and thus improve their apparent water-solubility, chemical stability, and bioavailability, to make them suitable for parenteral administration. Besides, CDs can be employed as building blocks of more complex injectable drug delivery systems with enhanced characteristics, such as nanoparticles and supramolecular hydrogels, that has been found particularly beneficial for the delivery of anticancer drugs. However, only a few CDs are considered safe when parenterally administered, and some of these types are already approved to be used in parenteral dosage forms. Therefore, the application of CDs in the development of parenteral formulations has been a more common practice in the last few years, due to their significant worldwide acceptance by the health authorities, promoting the development of safer and more efficient injectable drug delivery systems.
Topics: Cyclodextrins; Drug Compounding; Drug Delivery Systems; Excipients; Hydrogels; Solubility; Water
PubMed: 35868490
DOI: 10.1016/j.ejpb.2022.07.007 -
Polimery W Medycynie 2023The introduction of tablet dosage forms has brought a revolution in the pharmaceutical drug delivery system. Different forms of tablets have been developed based on the... (Review)
Review
The introduction of tablet dosage forms has brought a revolution in the pharmaceutical drug delivery system. Different forms of tablets have been developed based on the target site, the onset of action, and therapeutic drug delivery methods. Fast-disintegrating tablets (FDTs) are the most promising pharmaceutical dosage form, especially for pediatric and geriatric patients having difficulty swallowing. The key feature of FDTs is quick drug release soon after their administration through the oral cavity. With innovations in the formulation of FDTs, the demand for excipients with better functionalities, particularly in terms of flow and compression characteristics, has increased. Co-processed excipients are a mixture of 2 or more conventional excipients that provides significant benefits over the individual excipients while minimizing their shortcomings. Such multifunctional co-processed excipients minimize the number of excipients that are to be incorporated into tablets during the manufacturing process. The present review discusses FTDs formulated from co-processed excipients, their manufacturing techniques, and the latest research, patents and commercially available co-processed FDTs.
Topics: Humans; Child; Aged; Excipients; Chemistry, Pharmaceutical; Drug Liberation; Tablets; Solubility; Drug Compounding
PubMed: 36929642
DOI: 10.17219/pim/158009