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PloS One 2020Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product... (Review)
Review
Due to the complexity and fragility of biological drug products, several challenges exist in their formulation development. Excipients are added to increase product stability, maintain tonicity, and facilitate drug delivery. The potential implications of these additive substances merit clinical consideration. We assessed the safety risk of excipients on the basis of their type and variability through an assessment framework, which quantifies excipient complexity in 230 biological formulations, and identifies excipient-related adverse events through published case reports. A biologic on average contained 4.45 excipients, half of that found in oral medications. The frequency distribution was heavily skewed towards the most commonly occurring excipients: water (40.4%), sodium chloride (38.3%), polysorbate 80 (28.7%), sucrose (24.4%), and mannitol (20.9%), with 44.4% of formulations not listing the concentration of the most commonly occurring inactive ingredients. A literature search revealed only 17 case reports of excipient-related adverse events, suggesting the need for more clarity for clinicians on the safety of chemical additives. These cases included injection site reactions, anaphylaxis, hyperglycemia, and acute renal failure. With the expansion of the biopharmaceutical market, it is important to consider the safety data of biologic excipients, so that therapy can be tailored appropriately for a specific patient.
Topics: Acute Kidney Injury; Anaphylaxis; Chemistry, Pharmaceutical; Excipients; Humans; Hyperglycemia; Mannitol; Polysorbates; Sodium Chloride; Sucrose; Water
PubMed: 32584876
DOI: 10.1371/journal.pone.0235076 -
Molecules (Basel, Switzerland) Feb 2023Pharmaceutical analysis refers to an area of analytical chemistry that deals with active compounds either by themselves (drug substance) or when formulated with... (Review)
Review
Pharmaceutical analysis refers to an area of analytical chemistry that deals with active compounds either by themselves (drug substance) or when formulated with excipients (drug product). In a less simplistic way, it can be defined as a complex science involving various disciplines, e.g., drug development, pharmacokinetics, drug metabolism, tissue distribution studies, and environmental contamination analyses. As such, the pharmaceutical analysis covers drug development to its impact on health and the environment. Moreover, due to the need for safe and effective medications, the pharmaceutical industry is one of the most heavily regulated sectors of the global economy. For this reason, powerful analytical instrumentation and efficient methods are required. In the last decades, mass spectrometry has been increasingly used in pharmaceutical analysis both for research aims and routine quality controls. Among different instrumental setups, ultra-high-resolution mass spectrometry with Fourier transform instruments, i.e., Fourier transform ion cyclotron resonance (FTICR) and Orbitrap, gives access to valuable molecular information for pharmaceutical analysis. In fact, thanks to their high resolving power, mass accuracy, and dynamic range, reliable molecular formula assignments or trace analysis in complex mixtures can be obtained. This review summarizes the principles of the two main types of Fourier transform mass spectrometers, and it highlights applications, developments, and future perspectives in pharmaceutical analysis.
Topics: Mass Spectrometry; Excipients; Fourier Analysis; Drug Development
PubMed: 36903305
DOI: 10.3390/molecules28052061 -
Journal of Investigational Allergology... 2020The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions... (Review)
Review
The European Medicines Agency (EMA) defines excipients as the constituents of a pharmaceutical form apart from the active substance. Delayed hypersensitivity reactions (DHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of DHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to perform a literature review on allergy to pharmaceutical excipients and to record the DHRs described with various types of medications, specifically due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient, in order to obtain a list of the excipients most frequently involved for each type of medication.
Topics: Disease Management; Disease Susceptibility; Drug Compounding; Drug Hypersensitivity; Drug-Related Side Effects and Adverse Reactions; Excipients; Humans; Hypersensitivity, Delayed; Pharmaceutical Preparations
PubMed: 32376520
DOI: 10.18176/jiaci.0562 -
Journal of Investigational Allergology... Apr 2020The European Medicines Agency defines excipients as the constituents of a pharmaceutical form apart from the active substance. Immediate hypersensitivity reactions... (Review)
Review
The European Medicines Agency defines excipients as the constituents of a pharmaceutical form apart from the active substance. Immediate hypersensitivity reactions (IHRs) caused by excipients contained in the formulation of medications have been described. However, there are no data on the prevalence of IHRs due to drug excipients. Clinical manifestations of allergy to excipients can range from skin disorders to life-threatening systemic reactions. The aim of this study was to review the literature on allergy to pharmaceutical excipients and to record the IHRs described with various types of medications, specifically reactions due to the excipients contained in their formulations. The cases reported were sorted alphabetically by type of medication and excipient in order to obtain a list of the excipients most frequently involved for each type of medication.
Topics: Drug Hypersensitivity; Excipients; Humans; Hypersensitivity, Immediate
PubMed: 32327401
DOI: 10.18176/jiaci.0476 -
Pharmaceutical Research May 2015Lipid excipients are applied for numerous purposes such as taste masking, controlled release, improvement of swallowability and moisture protection. Several melting... (Review)
Review
Lipid excipients are applied for numerous purposes such as taste masking, controlled release, improvement of swallowability and moisture protection. Several melting techniques have evolved in the last decades. Common examples are melt coating, melt granulation and melt extrusion. The required equipment ranges from ordinary glass beakers for lab scale up to large machines such as fluid bed coaters, spray dryers or extruders. This allows for upscaling to pilot or production scale. Solvent free melt processing provides a cost-effective, time-saving and eco-friendly method for the food and pharmaceutical industries. This review intends to give a critical overview of the published literature on experiences, formulations and challenges and to show possibilities for future developments in this promising field. Moreover, it should serve as a guide for selecting the best excipients and manufacturing techniques for the development of a product with specific properties using solvent free melt processing.
Topics: Crystallization; Drug Compounding; Excipients; Freezing; Lipids
PubMed: 25788447
DOI: 10.1007/s11095-015-1661-y -
Advanced Drug Delivery Reviews Oct 2021Materials and manufacturing processes share a common purpose of enabling the pharmaceutical product to perform as intended. This review on the role of polymeric... (Review)
Review
Materials and manufacturing processes share a common purpose of enabling the pharmaceutical product to perform as intended. This review on the role of polymeric materials in additive manufacturing of oral dosage forms, focuses on the interface between the polymer and key stages of the additive manufacturing process, which determine printability. By systematically clarifying and comparing polymer functional roles and properties for a variety of AM technologies, together with current and emerging techniques to characterize these properties, suggestions are provided to stimulate the use of readily available and sometimes underutilized pharmaceutical polymers in additive manufacturing. We point to emerging characterization techniques and digital tools, which can be harnessed to manage existing trade-offs between the role of polymers in printer compatibility versus product performance. In a rapidly evolving technological space, this serves to trigger the continued development of 3D printers to suit a broader variety of polymers for widespread applications of pharmaceutical additive manufacturing.
Topics: Excipients; Polymers; Printing, Three-Dimensional; Technology, Pharmaceutical
PubMed: 34390775
DOI: 10.1016/j.addr.2021.113923 -
Polimery W Medycynie 2014This review deals with the targeting of drugs to the lower gastrointestinal tract i.e. colon. Colonic drug delivery becomes important for localized action as well as for... (Review)
Review
This review deals with the targeting of drugs to the lower gastrointestinal tract i.e. colon. Colonic drug delivery becomes important for localized action as well as for improved systemic availability of peptide and proteins. Drugs which have absorption window in the colonic region have been targeted using different novel technologies. pH sensitive polymers and prodrug based formulation have been used for the delivery of drugs into the colon. Different natural polymers have been used successfully for the delivery of drugs into the colon. Natural polymers are less toxic, biodegradable and easily available with a wide range of molecular weight and varying chemical compositions. One of the supporting properties associated with these polymers is that natural polymers can be used as approved pharmaceutical excipient.
Topics: Absorbable Implants; Administration, Oral; Biological Availability; Chemistry, Pharmaceutical; Coated Materials, Biocompatible; Colon; Drug Carriers; Drug Delivery Systems; Excipients; Hydrogen-Ion Concentration; Molecular Weight; Pharmaceutical Preparations; Polysaccharides; Prodrugs; Pulse Therapy, Drug
PubMed: 24967782
DOI: No ID Found -
Biomolecules Aug 2019Extensive efforts are being made to find alternative uses for lignin (LIG). In the present work the use of this biopolymer as excipient to prepare tablets was studied....
Extensive efforts are being made to find alternative uses for lignin (LIG). In the present work the use of this biopolymer as excipient to prepare tablets was studied. For this purpose, LIG was combined with microcrystalline cellulose (MCC) and used as excipients to prepare directly compressed tablets containing a model drug, tetracycline (TC). The excipients contained different concentrations of LIG: 100%, 75%, 50%, 25% and 0% (/). Two different compression forces were used (two and five tonnes). When formulations were prepared using LIG as the only excipient, tablets were formed, but they showed lower densities and crushing strength than the ones obtained with only MCC or LIG/MCC blends. Moreover, tablets prepared using five tonnes of compression force showed TC releases ranging from 40% to 70% of the drug loading. On the other hand, the tablets prepared using two tonnes of compression force showed a faster and more efficient TC release, between 60% and 90%. The presence of LIG in the tablets modified significantly the release profile and the maximum amount of TC released. Finally, a DPPH (2,2-diphenyl-1-picrylhydrozyl) assay was performed to confirm that the presence of LIG provided antioxidant properties to the formulations. Accordingly, LIG has potential as a pharmaceutical excipient.
Topics: Cellulose; Chemistry, Pharmaceutical; Drug Compounding; Excipients; Lignin; Tablets; Tetracycline
PubMed: 31466387
DOI: 10.3390/biom9090423 -
Advanced Drug Delivery Reviews Nov 2023Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical... (Review)
Review
Surfactants are a diverse group of compounds that share the capacity to adsorb at the boundary between distinct phases of matter. They are used as pharmaceutical excipients, food additives, emulsifiers in cosmetics, and as household/industrial detergents. This review outlines the interaction of surfactant-type excipients present in oral pharmaceutical dosage forms with the intestinal epithelium of the gastrointestinal (GI) tract. Many surfactants permitted for human consumption in oral products reduce intestinal epithelial cell viability in vitro and alter barrier integrity in epithelial cell monolayers, isolated GI tissue mucosae, and in animal models. This suggests a degree of mis-match for predicting safety issues in humans from such models. Recent controversial preclinical research also infers that some widely used emulsifiers used in oral products may be linked to ulcerative colitis, some metabolic disorders, and cancers. We review a wide range of surfactant excipients in oral dosage forms regarding their interactions with the GI tract. Safety data is reviewed across in vitro, ex vivo, pre-clinical animal, and human studies. The factors that may mitigate against some of the potentially abrasive effects of surfactants on GI epithelia observed in pre-clinical studies are summarised. We conclude with a perspective on the overall safety of surfactants in oral pharmaceutical dosage forms, which has relevance for delivery system development.
Topics: Animals; Humans; Excipients; Drug Compounding; Pharmaceutical Preparations; Intestines; Surface-Active Agents
PubMed: 37739041
DOI: 10.1016/j.addr.2023.115086 -
Advanced Drug Delivery Reviews Oct 2011SiRNA is the trigger of RNA interference, a mechanism discovered in the late 1990s. To release the therapeutic potential of this versatile but large and fragile... (Review)
Review
SiRNA is the trigger of RNA interference, a mechanism discovered in the late 1990s. To release the therapeutic potential of this versatile but large and fragile molecule, excipients are used which either interact by electrostatic interaction, passively encapsulate siRNA or are covalently attached to enable specific and safe delivery of the drug substance. Controlling the delicate balance between protective complexation and release of siRNA at the right point and time is done by understanding excipients-siRNA interactions. These can be lipids, polymers such as PEI, PLGA, Chitosans, Cyclodextrins, as well as aptamers and peptides. This review describes the mechanisms of interaction of the most commonly used siRNA delivery vehicles, and looks at the results of their clinical and preclinical studies.
Topics: Animals; Clinical Trials as Topic; Drug Delivery Systems; Drug Evaluation, Preclinical; Excipients; Humans; RNA Interference; RNA, Small Interfering; Static Electricity; Time Factors
PubMed: 21945846
DOI: 10.1016/j.addr.2011.09.003