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International Journal of Biological... Apr 2023Biopolysaccharides extracted from plants are mainly photosynthetic byproducts found in leaves, pods, stems, fruits, grains, seeds, corms, rhizomes, roots, bark exudates,... (Review)
Review
Biopolysaccharides extracted from plants are mainly photosynthetic byproducts found in leaves, pods, stems, fruits, grains, seeds, corms, rhizomes, roots, bark exudates, and other plant parts. Recently, these plant-derived biopolysaccharides have received a great deal of attention as pharmaceutical excipients in a range of different dosage forms because of several key advantages, such as widespread accessibility from nature as plant-based sources are readily available, sustainable production, availability of easy and cost-effective extraction methodologies, aqueous solubility, swelling capability in the aqueous medium, non-toxicity, biodegradability, etc. The current review presents a comprehensive overview of the uses of plant-derived biopolysaccharides as effective pharmaceutical excipients in the formulations of different kinds of dosage forms, for example gels, pastes, films, emulsions, suspensions, capsules, tablets, nanoparticles, microparticles, beads, buccal formulations, transdermal formulations, ocular formulations, nasal formulations, etc.
Topics: Excipients; Tablets; Drug Compounding; Capsules; Seeds; Solubility
PubMed: 36709807
DOI: 10.1016/j.ijbiomac.2023.123454 -
Pharmaceutical Research Dec 2021
Topics: Chemistry, Pharmaceutical; Excipients
PubMed: 34931284
DOI: 10.1007/s11095-021-03157-y -
Expert Opinion on Drug Delivery Apr 2017For almost two decades there has been intense debate about whether the amorphous solid state form could resolve the solubility problems and subsequent bioavailability... (Review)
Review
For almost two decades there has been intense debate about whether the amorphous solid state form could resolve the solubility problems and subsequent bioavailability issues of many small molecule drugs. Since the amorphous form is a high energy and unstable state of solid matter, any material in that form requires stabilization. Areas covered: This review examines the technologies being exploited to stabilize the amorphous state in co-amorphous formulations. The review emphasizes the importance of the appropriate selection criteria of stabilizing excipient and focuses on the mechanisms of stabilization. Expert opinion: An extensive literature review has revealed that the current research seeking to achieve stabilization of an amorphous form tends to be conducted on a case-by-case basis. This kind of approach is very inefficient since it can rarely be transferred to other cases. The greatest weakness in the selection of stabilizing excipient for co-amorphous formulations is that modern computational tools have rarely been utilized as a predictive tool in the selection of the excipient. It is evident that more research needs to be done to study larger datasets with modern in silico tools, chemometrics and advanced statistical tools to achieve a more predictive, and systematic approach for the screening of stabilizing excipients to be incorporated into co-amorphous formulations.
Topics: Biological Availability; Chemistry, Pharmaceutical; Drug Stability; Excipients; Solubility
PubMed: 27267873
DOI: 10.1080/17425247.2016.1198770 -
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 -
International Journal of Pharmaceutics Nov 2017Kaolinite AlSiO(OH) is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among... (Review)
Review
Kaolinite AlSiO(OH) is an abundant and inexpensive geomaterial regarded as one of the most common clay minerals in the earth's crust and the most widespread phase among the other kaolin polymorphs (halloysite, dickite and nacrite). Structurally, it is a hydrous aluminum phyllosilicate member belonging to the dioctahedral 1:1 kaolin mineral group. The particle size of the pseudohexagonal kaolinite platelets is normally <2μm (if compared to a human red blood cell of a typical diameter 6.2-8.2μm or to a virus particle of about 50nm diameter). The kaolinite platelets, either stacked together with a common booklet-like shape in a highly ordered structure (well crystallized) or disordered structure (poorly crystallized), consist of layers considered as a strong dipole of hydrophobic siloxane surface dominated by negative charges, and the other hydrophilic aluminol surface carries positive charges. Kaolinite has been used in many pharmaceutical applications as excipient or active ingredient, because it exhibits excellent physical, chemical and surface physicochemical properties. In addition to their classical pharmaceutical uses, kaolinite and its derivatives have been recently considered as a promising material in many biomedical innovation areas such as drug, protein and gene delivery based on the high interaction capacities with organic and biochemical molecules, bioadhesion and cellular uptake. Pharmaceutical kaolin grades are considerably demanded for usage as excipient in formulations of solid and semi-solid dosage forms. The most important functionalities of kaolin used as excipient are reported as diluent, binder, disintegrant, pelletizing and granulating, amorphizing, particle film coating, emulsifying and suspending agent. Because of its uninjured bioactivity, kaolinite has been also used as active agent for treatment of some common diseases. It can be topically administered as hemostatic agent, dermatological protector, anti-inflammatory agent and in pelotherapy, or orally as gastrointestinal protector, and antibacterial, antiviral, detoxification or antidiarrheal agent. With these premises, the future of kaolinite in health-care uses is strongly interesting, especially in the development of pharmaceutical and cosmetic industries. In biomedicinal investigations, it can be considered as a promising natural geomaterial for designing new derivatives that can contribute in the trials of discovering new therapeutic systems and treatment pathways of global challenge diseases such as cancer, viruses, antibiotic resistant bacteria, alzheimer, chronic skeletomuscular and geriatric diseases.
Topics: Animals; Biopharmaceutics; Excipients; Humans; Industry; Kaolin; Mud Therapy; Pharmacopoeias as Topic
PubMed: 28943206
DOI: 10.1016/j.ijpharm.2017.09.056 -
International Journal of Pharmaceutics Mar 2015Novel pharmaceutical excipients, and new derivatives of currently used excipients, are new chemical entities and as such have to go through extensive pharmacokinetic and...
Novel pharmaceutical excipients, and new derivatives of currently used excipients, are new chemical entities and as such have to go through extensive pharmacokinetic and toxicologic evaluations before they can be approved for use in pharmaceutical products. The high cost of these safety studies, long development timelines and risks of failure have hampered development of new excipients and drug delivery systems. Various, relatively simple, methods are used for prediction of pharmacokinetic properties of new drug candidates based on their physicochemical properties. Similar methods can be applied to predict pharmacokinetic and ADME properties of new excipients. Simple methods, like the Rule-of-Five and the Biopharmaceutics Classification System, can be applied for early prediction of pharmacokinetic and ADME properties of new excipients and drug delivery systems although the aims can be different. While the objectives in new drug development are to maximize drug bioavailability and pharmacologic response the objectives in new excipient development can be reduced excipient bioavailability and enhanced rate of elimination. Here pharmacokinetic properties of some currently used excipients are reviewed and shown how some of the simple methods used to predict drug-like properties can be applied to predict desired properties of novel excipients and drug delivery systems.
Topics: Animals; Biological Availability; Chemistry, Pharmaceutical; Drug Delivery Systems; Drug Design; Excipients; Humans; Pharmaceutical Preparations
PubMed: 25596414
DOI: 10.1016/j.ijpharm.2015.01.022 -
Journal of Pharmaceutical Sciences Dec 2015Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to...
Control of elemental impurities in pharmaceutical materials is currently undergoing a transition from control based on concentrations in components of drug products to control based on permitted daily exposures in drug products. Within the pharmaceutical community, there is uncertainty regarding the impact of these changes on manufactures of drug products. This uncertainty is fueled in part by a lack of publically available information on elemental impurity levels in common pharmaceutical excipients. This paper summarizes a recent survey of elemental impurity levels in common pharmaceutical excipients as well as some drug substances. A widely applicable analytical procedure was developed and was shown to be suitable for analysis of elements that are subject to United States Pharmacopoeia Chapter <232> and International Conference on Harmonization's Q3D Guideline on Elemental Impurities. The procedure utilizes microwave-assisted digestion of pharmaceutical materials and inductively coupled plasma mass spectrometry for quantitative analysis of these elements. The procedure was applied to 190 samples from 31 different excipients and 15 samples from eight drug substances provided through the International Pharmaceutical Excipient Council of the Americas. The results of the survey indicate that, for the materials included in the study, relatively low levels of elemental impurities are present.
Topics: Drug Contamination; Elements; Excipients; Mass Spectrometry; Microwaves; Pharmaceutical Preparations
PubMed: 26398581
DOI: 10.1002/jps.24650 -
Drug Discovery Today Oct 2021Leucine is a promising excipient with several applications in the development of inhalable spray-dried powder of high- and low-dose drugs. The addition of leucine has... (Review)
Review
Leucine is a promising excipient with several applications in the development of inhalable spray-dried powder of high- and low-dose drugs. The addition of leucine has exhibited significant enhancing effects on the aerosolization and physical stability of the produced particles. Here, we focus not only on the applications of leucine in inhalable spray-drying powders, but also on the underlying mechanisms by which the formulation and processing parameters dictate the behavior of leucine during the drying process and, therefore, its functionalities within the dried powder. Additionally, we highlight the current regulatory status of leucine. Such insights are important for more efficient utilization of leucine in the future, both for dry powder inhaler formulations and other pharmaceutical applications.
Topics: Administration, Inhalation; Aerosols; Drug Development; Drug Stability; Dry Powder Inhalers; Excipients; Humans; Leucine; Pharmaceutical Preparations; Powders
PubMed: 33872799
DOI: 10.1016/j.drudis.2021.04.009 -
The Journal of Maternal-fetal &... 2015Because of the restraints on conducting studies on pharmaceutical use in sick newborns, many drugs are used off-label in this population. Moreover, industrially...
OBJECTIVE
Because of the restraints on conducting studies on pharmaceutical use in sick newborns, many drugs are used off-label in this population. Moreover, industrially manufactured pharmaceuticals may contain different excipients, which may be either untested or not licensed for use in neonates. The aim of our study was to determine the prevalence and pattern of pharmaceutical and excipient exposure in newborns hospitalized at the Department of Neonatology, Ljubljana, Slovenia.
METHODS
A longitudinal prospective cross-sectional study was performed during a one-month period and included all hospitalized neonates. Route of administration, site of action, type of manufacture, licensing status, type and concentrations of excipients for all pharmaceuticals given to the neonates were determined.
RESULTS
Twenty seven different pharmaceutical preparations were prescribed to a total of 48 hospitalized newborns. In most cases, newborns were prescribed various pharmaceuticals that were not approved for use in this population. Newborns were exposed to 60 different excipients in industrially manufactured pharmaceutical preparations. More than half of the received pharmaceuticals contained potentially harmful and harmful excipients.
CONCLUSIONS
Two-thirds of pharmaceutical preparations for neonates were used off-label. Newborns receive more auxiliary substances, which may be unsuitable for this age group and may even be toxic to them, via industrially manufactured pharmaceuticals.
Topics: Cross-Sectional Studies; Drug-Related Side Effects and Adverse Reactions; Excipients; Female; Hospitalization; Humans; Infant, Newborn; Infant, Newborn, Diseases; Longitudinal Studies; Male; Neonatology; Off-Label Use; Pharmaceutical Preparations; Pilot Projects; Practice Patterns, Physicians'; Prospective Studies; Slovenia
PubMed: 25316561
DOI: 10.3109/14767058.2014.976549 -
Pharmaceutical Development and... Feb 2020The powders used in the production of solid dosage forms must have ability to flow that allows their industrial processing. Although this property has been studied for...
The powders used in the production of solid dosage forms must have ability to flow that allows their industrial processing. Although this property has been studied for most of the powders, in this study non-expected flow behaviors were observed for the model excipient used, Microcrystalline Cellulose (MCC). Several fractions with different sizes were fractioned by sieving of the model excipient and its flow behaviors were analyzed by different methods. The shear cell results showed an increase of the flowability index () with the increase of the particle size and consolidation stress. Some related information has been referenced in the literature, however, in this work it was shown for different size fractions that the decreased above a certain consolidation stress value (2000-4000 N/m). The explanation of this phenomenon is based on the increase of cohesion. Furthermore, it was also observed that the fractions with sizes between 125-180 µm present a higher than bulk powder (F) with similar percentile (D50) indicating that this index is dependent on the size of the particles and also on its size distribution range. Thus, it can be affirmed that more homogeneous samples in size and with a narrower distribution present a better .
Topics: Cellulose; Excipients; Particle Size; Powders; Rheology; Technology, Pharmaceutical
PubMed: 31718375
DOI: 10.1080/10837450.2019.1688348