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European Journal of Dermatology : EJD Sep 2022Generic drugs may differ from brand-name drugs in nature and quantity of excipients. Hypersensitivity to generic drugs is a subject of growing importance given their key... (Review)
Review
Generic drugs may differ from brand-name drugs in nature and quantity of excipients. Hypersensitivity to generic drugs is a subject of growing importance given their key role in healthcare spending policies, however, a review of published data highlighted that relevant data is sparse. No scientific rationale has emerged for labelling patients allergic to all generic drugs, and hypersensitivity to generic drugs may rather be explored on a case-by-case basis. In the case of hypersensitivity without any change in medication, it is advisable to check for a switch from a brand-name to a generic drug, and if hypersensitivity to a generic drug is suspected, its composition must be checked.
Topics: Humans; Drugs, Generic; Hypersensitivity; Excipients; Product Labeling
PubMed: 36468717
DOI: 10.1684/ejd.2022.4291 -
Journal of Pharmaceutical and... Sep 2016Mixed-mode chromatography (MMC) is a fast growing area in recent years, thanks to the new generation of mixed-mode stationary phases and better understanding of... (Review)
Review
Mixed-mode chromatography (MMC) is a fast growing area in recent years, thanks to the new generation of mixed-mode stationary phases and better understanding of multimode interactions. MMC has superior applications in the separation of compounds that are not retained or not well resolved by typical reversed-phase LC methods, especially for polar and charged molecules. Due to the multiple retention modes that a single MMC column can offer, often MMC provides additional dimension to a separation method by adjusting the mobile phase conditions. Mixed-mode media is also an effective way to clean up complex sample matrices for purification purposes or for sensitive detection of trace amounts of analytes. In this article, we discuss mixed-mode stationary phases and separation mechanisms and review recent advances in pharmaceutical and biopharmaceutical applications including the analysis and/or purification of counterions, small molecule drugs, impurities, formulation excipients, peptides and proteins.
Topics: Chemistry, Pharmaceutical; Chromatography, Reverse-Phase; Excipients; Peptides; Pharmaceutical Preparations; Proteins
PubMed: 27236100
DOI: 10.1016/j.jpba.2016.05.007 -
The AAPS Journal Jan 2022The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the... (Review)
Review
The objective of this review article is to summarize literature data pertinent to potential excipient effects on intestinal drug permeability and transit. Despite the use of excipients in drug products for decades, considerable research efforts have been directed towards evaluating their potential effects on drug bioavailability. Potential excipient concerns stem from drug formulation changes (e.g., scale-up and post-approval changes, development of a new generic product). Regulatory agencies have established in vivo bioequivalence standards and, as a result, may waive the in vivo requirement, known as a biowaiver, for some oral products. Biowaiver acceptance criteria are based on the in vitro characterization of the drug substance and drug product using the Biopharmaceutics Classification System (BCS). Various regulatory guidance documents have been issued regarding BCS-based biowaivers, such that the current FDA guidance is more restrictive than prior guidance, specifically about excipient risk. In particular, sugar alcohols have been identified as potential absorption-modifying excipients. These biowaivers and excipient risks are discussed here. Graphical Abstract.
Topics: Animals; Biological Availability; Biopharmaceutics; Drug Compounding; Drug Development; Drug and Narcotic Control; Excipients; Humans; Permeability; Pharmaceutical Preparations; Therapeutic Equivalency
PubMed: 34988701
DOI: 10.1208/s12248-021-00670-1 -
Journal of Food and Drug Analysis Jun 2021Quality control (QC) is the most important key issue in the pharmaceutical industry to ensure the quality of drug products. Many analytical instruments and techniques in... (Review)
Review
Quality control (QC) is the most important key issue in the pharmaceutical industry to ensure the quality of drug products. Many analytical instruments and techniques in pharmaceutical analysis are applied to assess the quality and quantity of the drugs. In the current and future trends, a combination of digitization, automation and hyphenation with high throughput on-line performance will be the topics for the future of pharmaceutical QC. The hyphenated analytical techniques have recently received great attention as unique means to solve complex analytical problems in a short period of time. This review article is an update on the recent potential applications of hyphenated technique developed from the coupling of a rapid separation or induction technique (differential scanning calorimetry; DSC) and an on-line spectroscopic (Fourier transform infrared; FTIR) detection technology to carry out an one-step solid-state analysis in pharmaceutical formulation developments, including (1) intramolecular condensation of pharmaceutical polymers, (2) intramolecular cyclization of drugs and sweetener, (3) polymorphic transformation of drugs and excipients, (4) drug-polymer (excipient) interaction, (5) fast cocrystal screening and formation. This simultaneous DSC-FTIR microspectroscopy can also provide an easy and direct method for one-step screening and qualitative detection of drug stability in real time.
Topics: Calorimetry, Differential Scanning; Drug Stability; Excipients; Spectroscopy, Fourier Transform Infrared
PubMed: 35696204
DOI: 10.38212/2224-6614.3345 -
Biomolecules Nov 2019Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients. Nevertheless, developments in cyclodextrin research have shown that... (Review)
Review
Cyclodextrins, since their discovery in the late 19th century, were mainly regarded as excipients. Nevertheless, developments in cyclodextrin research have shown that some of these hosts can capture and include biomolecules, highlighting fatty acids and cholesterol, which implies that they are not inert and that their action may be used in specific medicinal purposes. The present review, centered on literature reports from the year 2000 until the present day, presents a comprehensive description of the known biological activities of cyclodextrins and their implications for medicinal applications. The paper is divided into two main sections, one devoted to the properties and applications of cyclodextrins as active pharmaceutical ingredients in a variety of pathologies, from infectious ailments to cardiovascular dysfunctions and metabolic diseases. The second section is dedicated to the use of cyclodextrins in a range of biomedical technologies.
Topics: Animals; Biomedical Technology; Cyclodextrins; Excipients; Humans
PubMed: 31795222
DOI: 10.3390/biom9120801 -
International Journal of Pharmaceutics Feb 2023The surface of particles is the hotspot of interaction with their environment and is therefore a major target for particle engineering. Particles with tailored coatings...
The surface of particles is the hotspot of interaction with their environment and is therefore a major target for particle engineering. Particles with tailored coatings are greatly desired for a range of different applications. Amorphous coatings applied via film coating or microencapsulation have frequently been described in the pharmaceutical context and usually result in homogeneous surfaces. In the present study we have been exploring the feasibility of coating core particles with crystalline substances, a matter that has rarely been investigated. The expansion of the range of possible coating materials to include small organic molecules enables completely new product properties to be achieved. We present an approach based on temperature cycles performed in a tubular crystallizer to result in engineered crystalline coatings on excipient core particles. By manipulating the process settings and by the choice of coating substance we are able to tailor surface roughness, topography as well as surface chemistry. Benefits of our approach are demonstrated by using resulting particles as carriers in dry-powder-inhaler formulations. Depending on the resulting surface chemistry and surface roughness, coated carrier particles show varying fitness for delivering the model API salbutamol sulphate to the lung.
Topics: Drug Carriers; Temperature; Particle Size; Powders; Administration, Inhalation; Albuterol; Dry Powder Inhalers; Excipients; Surface Properties
PubMed: 36596318
DOI: 10.1016/j.ijpharm.2022.122577 -
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 -
Molecules (Basel, Switzerland) Nov 2023Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but...
Polyethylene glycol 400 (PEG400) is a widely used pharmaceutical excipient in the field of medicine. It not only enhances the dispersion stability of the main drug but also facilitates the absorption of multiple drugs. Our previous study found that the long-term application of PEG400 as an adjuvant in traditional Chinese medicine preparations resulted in wasting and weight loss in animals, which aroused our concern. In this study, 16S rRNA high-throughput sequencing technology was used to analyze the diversity of gut microbiota, and LC-MS/MS Q-Exactive Orbtriap metabolomics technology was used to analyze the effect of PEG400 on the metabolome of healthy mice, combined with intestinal pathological analysis, aiming to investigate the effects of PEG400 on healthy mice. These results showed that PEG400 significantly altered the structure of gut microbiota, reduced the richness and diversity of intestinal flora, greatly increased the abundance of (), increased the proportion of Bacteroidetes to Firmicutes, and reduced the abundance of many beneficial bacteria. Moreover, PEG400 changed the characteristics of fecal metabolome in mice and induced disorders in lipid and energy metabolism, thus leading to diarrhea, weight loss, and intestinal inflammation in mice. Collectively, these findings provide new evidence for the potential effect of PEG400 ingestion on a healthy host.
Topics: Mice; Animals; Gastrointestinal Microbiome; Excipients; RNA, Ribosomal, 16S; Chromatography, Liquid; Tandem Mass Spectrometry; Metabolome; Weight Loss
PubMed: 38005284
DOI: 10.3390/molecules28227562 -
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 -
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