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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 -
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 -
Journal of Pharmacy & Pharmaceutical... 2010N-Methyl-2-pyrrolidone (NMP) or Pharmasolve is very strong solubilizing agent and it has important applications in different fields of industry. This review presents NMP... (Comparative Study)
Comparative Study Review
N-Methyl-2-pyrrolidone (NMP) or Pharmasolve is very strong solubilizing agent and it has important applications in different fields of industry. This review presents NMP physicochemical characteristics, application especially in pharmaceutical sciences, pharmacokinetic and toxicity. Characteristics of NMP such as physicochemical properties, solubilization efficacy, toxicity and adverse effects were compared with other common solvents used in the pharmaceutical industries. This review reveals that NMP is an acceptable pharmaceutical solvent and its efficacy, toxicity, and side effects are comparable with other common solvent.
Topics: Animals; Excipients; Humans; Pharmaceutical Preparations; Pyrrolidinones; Solubility; Solvents
PubMed: 21486529
DOI: 10.18433/j3p306 -
Immunology and Allergy Clinics of North... May 2022Excipients are the inactive ingredients in a drug or product that help to stabilize, preserve, or enhance the pharmacokinetics and bioavailability of the active... (Review)
Review
Excipients are the inactive ingredients in a drug or product that help to stabilize, preserve, or enhance the pharmacokinetics and bioavailability of the active ingredients. Excipient allergy is rare and hence often missed or misdiagnosed due to lack of awareness of the need to carefully review all drug ingredients. For the patient, excipient allergy can be frightening and potentially disruptive to health care delivery. This narrative review provides a clinically oriented, international, collaborative perspective on excipient allergy testing, management of future health care safety, limitations in our testing modalities, and barriers to optimal care.
Topics: Anaphylaxis; Excipients; Humans; Pharmaceutical Preparations
PubMed: 35469617
DOI: 10.1016/j.iac.2021.12.008 -
Acta Pharmaceutica (Zagreb, Croatia) Mar 2012Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such... (Review)
Review
Spherical crystallization of drugs is the process of obtaining larger particles by agglomeration during crystallization. The most common techniques used to obtain such particles are spherical agglomeration and quasi-emulsion solvent diffusion. Ammonia diffusion systems and crystallo-co-agglomeration are extensions of these techniques. By controlling process parameters during crystallization, such as temperature, stirring rate, type and amount of solvents, or excipient selection, it is possible to control the formation of agglomerates and obtain spherical particles of the desired size, porosity, or hardness. Researchers have reported that the particles produced have improved micromeritic, physical, and mechanical properties, which make them suitable for direct compression. In some cases, when additional excipients are incorporated during spherical crystallization, biopharmaceutical parameters including the bioavailability of drugs can also be tailored.
Topics: Ammonia; Chemistry, Pharmaceutical; Crystallization; Diffusion; Excipients; Particle Size; Pharmaceutical Preparations; Solubility; Solvents; Technology, Pharmaceutical
PubMed: 22472445
DOI: 10.2478/v10007-012-0010-5 -
Science Translational Medicine Mar 2019Oral forms of medications contain "inactive" ingredients to enhance their physical properties. Using data analytics, we characterized the abundance and complexity of... (Review)
Review
Oral forms of medications contain "inactive" ingredients to enhance their physical properties. Using data analytics, we characterized the abundance and complexity of inactive ingredients in approved medications. A majority of medications contain ingredients that could cause adverse reactions, underscoring the need to maximize the tolerability and safety of medications and their inactive ingredients.
Topics: Administration, Oral; Animals; Drug Compounding; Excipients; Humans; Pharmaceutical Preparations
PubMed: 30867323
DOI: 10.1126/scitranslmed.aau6753 -
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 -
Nutrients Mar 2019Despite being the most essential nutrient, water is commonly forgotten in the fields of pharmacy and nutrition. Hydration status is determined by water balance (the... (Review)
Review
Despite being the most essential nutrient, water is commonly forgotten in the fields of pharmacy and nutrition. Hydration status is determined by water balance (the difference between water input and output). Hypohydration or negative water balance is affected by numerous factors, either internal (i.e., a lack of thirst sensation) or external (e.g., polypharmacy or chronic consumption of certain drugs). However, to date, research on the interaction between hydration status and drugs/excipients has been scarce. Drugs may trigger the appearance of hypohydration by means of the increase of water elimination through either diarrhea, urine or sweat; a decrease in thirst sensation or appetite; or the alteration of central thermoregulation. On the other hand, pharmaceutical excipients induce alterations in hydration status by decreasing the gastrointestinal transit time or increasing the gastrointestinal tract rate or intestinal permeability. In the present review, we evaluate studies that focus on the effects of drugs/excipients on hydration status. These studies support the aim of monitoring the hydration status in patients, mainly in those population segments with a higher risk, to avoid complications and associated pathologies, which are key axes in both pharmaceutical care and the field of nutrition.
Topics: Body Water; Dehydration; Drug-Related Side Effects and Adverse Reactions; Excipients; Humans; Pharmaceutical Preparations
PubMed: 30897748
DOI: 10.3390/nu11030669 -
Pharmaceutical Research Nov 2022While excipients are often overlooked as the "inactive" ingredients in pharmaceutical formulations, they often play a critical role in protein stability and...
While excipients are often overlooked as the "inactive" ingredients in pharmaceutical formulations, they often play a critical role in protein stability and absorption kinetics. Recent work has identified an ultrafast absorbing insulin formulation that is the result of excipient modifications. Specifically, the insulin monomer can be isolated by replacing zinc and the phenolic preservative metacresol with phenoxyethanol as an antimicrobial agent and an amphiphilic acrylamide copolymer excipient for stability. A greater understanding is needed of the interplay between excipients, insulin association state, and stability in order to optimize this formulation. Here, we formulated insulin with different preservatives and stabilizing excipient concentrations using both insulin lispro and regular human insulin and assessed the insulin association states using analytical ultracentrifugation as well as formulation stability. We determined that phenoxyethanol is required to eliminate hexamers and promote a high monomer content even in a zinc-free lispro formulation. There is also a concentration dependent relationship between the concentration of polyacrylamide-based copolymer excipient and insulin stability, where a concentration greater than 0.1 g/mL copolymer is required for a mostly monomeric zinc-free lispro formulation to achieve stability exceeding that of Humalog in a stressed aging assay. Further, we determined that under the formulation conditions tested zinc-free regular human insulin remains primarily hexameric and is not at this time a promising candidate for rapid-acting formulations.
Topics: Humans; Insulin; Excipients; Insulin Lispro; Insulin, Regular, Human; Zinc; Drug Stability
PubMed: 35978148
DOI: 10.1007/s11095-022-03367-y