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Polimery W Medycynie 2018Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their... (Review)
Review
Polymorphism of pharmaceutical substances has a significant impact on their physicochemical properties, durability, bioavailability and consequently on their pharmacological activity. Solid dosage forms may exist in both crystalline and amorphous forms. Amorphous varieties are characterized by higher solubility and dissolution rates, while crystalline forms show greater purity and storage stability. The choice between the crystalline or amorphous form of a drug is extremely important to ensure effective and safe pharmacotherapy. Statins - the most commonly used group of drugs in the treatment of lipid disorders - are an example of drugs that occur in many crystalline and amorphous forms. Statins belong to class II in the biopharmaceutical classification system (BCS), which means that they are poorly soluble, but permeate biological membranes well. The bioavailability of statins shows considerable variation, which is associated with the first-pass effect in the liver and the accumulation of the drug in the hepatocytes. The improvement of bioavailability after oral administration of poorly soluble medicinal substances remains one of the most challenging aspects of the drug development process. A specific polymorphic form is obtained by applying appropriate conditions during the process of its preparation under industrial conditions, including the use of a suitable solvent, a specific temperature or rate of crystallization. The article provides a comprehensive update on the current knowledge of the influence of polymorphic form on statin solubility and bioavailability. Research is still being carried out to obtain new polymorphic varieties of statins that are characterized by better physicochemical and pharmacokinetic parameters.
Topics: Biological Availability; Chemistry, Pharmaceutical; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Pharmaceutical Preparations; Solubility
PubMed: 30916495
DOI: 10.17219/pim/102978 -
BMC Pharmacology & Toxicology Aug 2023Gut dwelling microbes provide profound biochemical advantages to the host, including nutrient and drug absorption, metabolism, and excretion. It is an emerging...
Gut dwelling microbes provide profound biochemical advantages to the host, including nutrient and drug absorption, metabolism, and excretion. It is an emerging understanding that drug-response bias (particularly for orally intake medicine) is related to variation in the microbial composition in the gut. This Editorial at BMC Pharmacology and Toxicology introduces our collection which is discussing the role of gut microbes in modulating drugs' efficacy and bioavailability.
Topics: Gastrointestinal Microbiome; Biological Availability
PubMed: 37649091
DOI: 10.1186/s40360-023-00684-9 -
European Journal of Pharmaceutical... Sep 2022The infinite time of oral drug absorption was conceived from the first day of the birth of pharmacokinetics when H. Dost introduced the term pharmacokinetics in his book... (Review)
Review
The infinite time of oral drug absorption was conceived from the first day of the birth of pharmacokinetics when H. Dost introduced the term pharmacokinetics in his book published in 1953. He adopted the function developed by H. Bateman back in 1908 for the decay of the nuclei isotopes to describe oral drug absorption as a first-order process. We unveiled this false hypothesis relying on common wisdom i.e. drugs are absorbed in finite time. This false assumption had dramatic effects on the evolution of oral pharmacokinetics but most importantly on the bioavailability and bioequivalence concepts and metrics. This work focuses on the finite absorption time (FAT) concept, the relevant Physiologically Based Finite Time (PBFTPK) models developed and their applications in oral pharmacokinetics, bioavailability and bioequivalence. The crux of the matter is that drug absorption from the gastrointestinal tract takes place under sink conditions because of the high blood flow rate in the vena cava. The termination of oral, pulmonary and intranasal drug absorption at a specific time point, calls for regulatory changes in bioavailability and bioequivalence studies in terms of the study design and metrics used for the bioequivalence assessment.
Topics: Administration, Oral; Biological Availability; Gastrointestinal Tract; Humans; Male; Pharmacokinetics; Therapeutic Equivalency
PubMed: 35863551
DOI: 10.1016/j.ejps.2022.106265 -
Molecules (Basel, Switzerland) Nov 2022Cantharidin (CTD) is the main active ingredient isolated from Mylabris, and norcantharidin (NCTD) is a demethylated derivative of CTD, which has similar antitumor... (Review)
Review
Cantharidin (CTD) is the main active ingredient isolated from Mylabris, and norcantharidin (NCTD) is a demethylated derivative of CTD, which has similar antitumor activity to CTD and lower toxicity than CTD. However, the clinical use of NCTD is limited due to its poor solubility, low bioavailability, and toxic effects on normal cells. To overcome these shortcomings, researchers have explored a number of strategies, such as chemical structural modifications, microsphere dispersion systems, and nanodrug delivery systems. This review summarizes the structure-activity relationship of NCTD and novel strategies to improve the solubility and bioavailability of NCTD as well as reduce the toxicity. This review can provide evidence for further research of NCTD.
Topics: Solubility; Biological Availability; Bridged Bicyclo Compounds, Heterocyclic; Cantharidin
PubMed: 36431851
DOI: 10.3390/molecules27227740 -
Wiley Interdisciplinary Reviews.... Nov 2021Nano drug delivery systems (NDDS) offer promising solution for the translation of future nanomedicines. As bioavailability and therapeutic outcomes can be improved by... (Review)
Review
Nano drug delivery systems (NDDS) offer promising solution for the translation of future nanomedicines. As bioavailability and therapeutic outcomes can be improved by altering the drug release from these NDDS, it becomes essential to thoroughly understand their drug release kinetics. Moreover, U.S. Food and Drug Administration requires critical evaluation of potential safety, efficacy, and public health impacts of nanomaterials. Spiraling up market share of NDDS has also stimulated the pharmaceutical industry to develop their cost-effective generic versions after the expiry of patent and associated exclusivity. However, unlike the conventional dosage forms, the in vivo disposition of NDDS is highly intricate and different from their in vitro behavior. Significant challenges exist in the establishment of in vitro-in vivo correlation (IVIVC) due to incomplete understanding of nanoparticles' in vivo biofate and its impact on in vitro experimental protocols. A rational design of dissolution may serve as quality and quantity control tool and help develop a meaningful IVIVC for favorable economic implications. Clinically relevant drug product specifications (critical quality attributes) can be identified by establishing a link between in vitro performance and in vivo exposure. In vitro dissolution may also play a pivotal role to understand the dissolution-mediated clearance and safety of NDDS. Prevalent in vitro dissolution methods for NDDS and their limitations are discussed in this review, among which USP 4 is gaining more interest recently. Researchers are working diligently to develop biorelevant in vitro release assays to ensure optimal therapeutic performance of generic versions of these NDDS. This article focuses on these studies and presents important considerations for the future development of clinically relevant in vitro release methods. This article is categorized under: Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine.
Topics: Biological Availability; Drug Delivery Systems; Drug Liberation; Nanomedicine; Nanoparticle Drug Delivery System; Solubility
PubMed: 34132050
DOI: 10.1002/wnan.1732 -
Postepy Higieny I Medycyny... Dec 2014Many proteins of food reveal biological activity. In the sequence of these proteins also numerous biologically active peptides are encrypted. These peptides are released... (Review)
Review
Many proteins of food reveal biological activity. In the sequence of these proteins also numerous biologically active peptides are encrypted. These peptides are released during proteolysis naturally occurring in the gastrointestinal tract, food fermentation or during designed enzymatic hydrolysis in vitro. Biopeptides may exert multiple activities, affecting the cardiovascular, endocrine, nervous and immune systems. An especially rich source of bioactive proteins and biopeptides is egg. Bioactive peptides released from egg white proteins have been well described, whereas egg yolk proteins as precursors of biopeptides are less well characterized. This manuscript describes biologically active proteins and peptides originating from egg yolk and presents their potential therapeutic role.
Topics: Biological Availability; Egg Proteins; Food; Humans; Peptides; Protein Biosynthesis
PubMed: 25834095
DOI: 10.5604/17322693.1133600 -
International Journal of Molecular... Nov 2022Quercetin and its glycosides, such as isoquercitrin or rutin, are among the most ubiquitous flavonoids present in plants. They possess numerous health-promoting... (Review)
Review
Quercetin and its glycosides, such as isoquercitrin or rutin, are among the most ubiquitous flavonoids present in plants. They possess numerous health-promoting properties, whose applicability is, however, limited by poor water solubility and absorption issues. Enzymatically modified isoquercitrin (EMIQ) is an isoquercitrin derivative obtained from rutin via enzymatic transformations that greatly enhance its bioavailability. Due to advantageous reports on its safety and bioactivity, EMIQ is currently gaining importance as a food additive and a constituent of dietary supplements. This review summarizes the thus-far-conducted investigations into the metabolism, toxicity, biological properties, and molecular mechanisms of EMIQ and presents a comprehensive characterization of this valuable substance, which might represent the future of flavonoid supplementation.
Topics: Quercetin; Biological Availability; Rutin; Glycosides; Solubility
PubMed: 36499113
DOI: 10.3390/ijms232314784 -
International Journal of Pharmaceutics Jul 2022Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis... (Review)
Review
Cocrystals have been extensively used to improve the physicochemical properties and bioavailability of active pharmaceutical ingredients. Cocrystals of anti-tuberculosis medications are among those commonly reported. This review provides a summary of the tuberculosis antibiotic cocrystals reported in the literature, providing the main results on current tuberculosis medications utilized in cocrystals. Moreover, anti-tuberculosis cocrystals limitations and advantages are described, including evidence for enhanced solubility, stability and effect. Opportunities to enhance anti-tuberculosis medications and fixed dose combinations using cocrystals are given. Several cocrystal pairs are suggested to enhance the effectiveness of anti-tuberculosis drugs.
Topics: Anti-Bacterial Agents; Biological Availability; Crystallization; Solubility
PubMed: 35738333
DOI: 10.1016/j.ijpharm.2022.121924 -
Ultrasonics Sonochemistry Oct 2021Quercetin (QUR) have got the attention of scientific society frequently due to their wide range of potential applications. QUR has been the focal point for research in... (Review)
Review
Quercetin (QUR) have got the attention of scientific society frequently due to their wide range of potential applications. QUR has been the focal point for research in various fields, especially in food development. But, the QUR is highly unstable and can be interrupted by using conventional assessment methods. Therefore, researchers are focusing on novel extraction and non-invasive tools for the non-destructive assessment of QUR. The current review elaborates the different novel extraction (ultrasound-assisted extraction, microwave-assisted extraction, supercritical fluid extraction, and enzyme-assisted extraction) and non-destructive assessment techniques (fluorescence spectroscopy, terahertz spectroscopy, near-infrared spectroscopy, hyperspectral imaging, Raman spectroscopy, and surface-enhanced Raman spectroscopy) for the extraction and identification of QUR in agricultural products. The novel extraction approaches facilitate shorter extraction time, involve less organic solvent, and are environmentally friendly. While the non-destructive techniques are non-interruptive, label-free, reliable, accurate, and environmental friendly. The non-invasive spectroscopic and imaging methods are suitable for the sensitive detection of bioactive compounds than conventional techniques. QUR has potential therapeutic properties such as anti-obesity, anti-diabetes, antiallergic, antineoplastic agent, neuroprotector, antimicrobial, and antioxidant activities. Besides, due to the low bioavailability of QUR innovative drug delivery strategies (QUR loaded gel, QUR polymeric micelle, QUR nanoparticles, glucan-QUR conjugate, and QUR loaded mucoadhesive nanoemulsions) have been proposed to improve its bioavailability and providing novel therapeutic approaches.
Topics: Antioxidants; Biological Availability; Drug Delivery Systems; Nanoparticles; Quercetin
PubMed: 34358980
DOI: 10.1016/j.ultsonch.2021.105686 -
International Journal of Molecular... Mar 2023The low bioaccessibility of hesperetin and piperine hampers their application as therapeutic agents. Piperine has the ability to improve the bioavailability of many...
The low bioaccessibility of hesperetin and piperine hampers their application as therapeutic agents. Piperine has the ability to improve the bioavailability of many compounds when co-administered. The aim of this paper was to prepare and characterize the amorphous dispersions of hesperetin and piperine, which could help to improve solubility and boost the bioavailability of both plant-origin active compounds. The amorphous systems were successfully obtained by means of ball milling, as confirmed by XRPD and DSC studies. What's more, the FT-IR-ATR study was used to investigate the presence of intermolecular interactions between the systems' components. Amorphization enhanced the dissolution rate as a supersaturation state was reached, as well as improving the apparent solubility of both compounds by 245-fold and 183-fold, respectively, for hesperetin and piperine. In the in vitro permeability studies simulating gastrointestinal tract and blood-brain barrier permeabilities, these increased by 775-fold and 257-fold for hesperetin, whereas they were 68-fold and 66-fold for piperine in the GIT and BBB PAMPA models, respectively. Enhanced solubility had an advantageous impact on antioxidant as well as anti-butyrylcholinesterase activities-the best system inhibited 90.62 ± 0.58% of DPPH radicals and 87.57 ± 1.02% butyrylcholinesterase activity. To sum up, amorphization considerably improved the dissolution rate, apparent solubility, permeability, and biological activities of hesperetin and piperine.
Topics: Solubility; Spectroscopy, Fourier Transform Infrared; Permeability; Biological Availability
PubMed: 36902286
DOI: 10.3390/ijms24054859