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Acta Poloniae Pharmaceutica 2011Interest in use of the polysaccharide chitosan as a pharmaceutical excipient by different dose routes and for a number of applications is not new but it still does not... (Review)
Review
Interest in use of the polysaccharide chitosan as a pharmaceutical excipient by different dose routes and for a number of applications is not new but it still does not appear to be present in any marketed drugs. Also a novel excipient in a new formulation requires a lot of safety consideration. Published literature showed that chitosan has low oral toxicity and prior human exposure has occurred through use in dietary supplements and food additive, medical device and cosmetic applications. Although systemic exposure to chitosan may be limited, this needs a more careful assessment of its safety as a parenteral excipient. Chitosan has local biological activity in the form of hemostatic action, facilitates platelet adhesion, cholesterol lowering and weight management. Chitosan has become an upcoming research area as a novel excipient in controlled drug delivery, which necessitates us to get an overall information about it.
Topics: Animals; Chemistry, Pharmaceutical; Chitosan; Delayed-Action Preparations; Drug Carriers; Drug Delivery Systems; Excipients; Humans
PubMed: 21928704
DOI: No ID Found -
Drug Development and Industrial Pharmacy Sep 2019Sorbitol is a popular sugar alcohol which has been used as an excipient in formulations of various drugs. Although from a safety perspective the presence of sorbitol in... (Review)
Review
Sorbitol is a popular sugar alcohol which has been used as an excipient in formulations of various drugs. Although from a safety perspective the presence of sorbitol in drug formulations does not raise a concern, reports have emerged and these suggest that sorbitol in drug formulations may alter oral absorption and bioavailability of certain drugs. The focus of this article was to review the published literature of various drugs where pharmacokinetic data has been reported for the drug alone drug administered with sorbitol and provide perspectives on the pharmacokinetic findings. Interestingly, for BCS class I drugs such as theophylline, metoprolol, the oral absorption, and bioavailability were generally not affected by sorbitol. However, theophylline oral absorption and bioavailability were decreased when sustained release formulation was used in place of immediate release formulation. For drugs such as risperidone (BCS class II) and lamivudine and ranitidine (BCS class III), the solution formulations showed diminished oral bioavailability in presence of sorbitol, whereas cimetidine and acyclovir (BCS class III), did not show any changes in pharmacokinetic profiles due to sorbitol. Finally, the presence of activated charcoal with sorbitol showed different pharmacokinetic outcome for BCS class I and II drugs.
Topics: Administration, Oral; Biological Availability; Charcoal; Delayed-Action Preparations; Drug Compounding; Excipients; Gastrointestinal Absorption; Humans; Sorbitol
PubMed: 31271324
DOI: 10.1080/03639045.2019.1640722 -
Indian Pediatrics Sep 2020To study the excipients exposure among neonates in a neonatal intensive care unit. (Observational Study)
Observational Study
OBJECTIVE
To study the excipients exposure among neonates in a neonatal intensive care unit.
METHOD
Prospective observational study was conducted from January, 2017 to June, 2019. Details of administered drugs were collected from the hospital case files. List of excipients of formulations and their quantities were collected from package insert leaflets or by contacting the manufacturers. Excipients were grouped into four categories based on available safety data. Calculated daily exposures to the excipients (mg/kg/day) were compared with adult acceptable daily intake.
RESULTS
More than half of the included 746 neonates were exposed to harmful excipients. 12.3% and 12.7% of neonates received higher than acceptable daily intake of sodium metabisulphite and sunset yellow FCF, respectively.
CONCLUSION
There is a high risk of exposure of neonates to harmful excipients, and clinicians need to be aware of this during neonatal care.
Topics: Adult; Drug Compounding; Excipients; Humans; Infant, Newborn; Intensive Care Units, Neonatal; Prospective Studies
PubMed: 32999107
DOI: No ID Found -
Pharmaceutical Development and... May 2014Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol,... (Review)
Review
Various fillers/binders which are applied for the formulation of solid oral dosage forms are assessed for their benefits and drawbacks, including lactose, sorbitol, mannitol, microcrystalline cellulose and calcium hydrogen phosphate dihydrate. A focus of this work was to evaluate the application of mannitol in comparison to other common fillers/binders as it was observed that this excipient is gaining more and more attention in pharmaceutical formulation development and production. While one of the main advantages of conventional fillers/binders such as lactose, microcrystalline cellulose and calcium hydrogen phosphate dihydrate is their low price level, mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the API and the patient's body, its good compactibility and the ability to produce extremely robust tablets. Additionally, the suitability of mannitol for the emerging formulation technology of orally disintegrating tablets is pointed out. In summary, it is emphasized that the selection of the filler/binder is highly individual, depending, for example, on the preferred characteristics of the final solid dosage form, the applied API and the available budget. However, mannitol exhibits many strong advantages which can be expected to result in a more widespread application in the near future.
Topics: Administration, Oral; Chemistry, Pharmaceutical; Excipients; Humans; Mannitol; Tablets
PubMed: 23528124
DOI: 10.3109/10837450.2013.775154 -
AAPS PharmSciTech Jul 2018Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical... (Review)
Review
Zein is the main storage protein of corn and it has several industrial applications. Mainly in the last 10-15 years, zein has emerged as a potential pharmaceutical excipient with unique features. Zein is a natural, biocompatible and biodegradable material produced from renewable sources. It is insoluble, yet due to its amphiphilic nature, it has self-assembling properties, which have been exploited for the formation of micromicroparticle and nanoparticle and films. Moreover, zein can hydrate so it has been used in swellable matrices for controlled drug release. Other pharmaceutical applications of zein in oral drug delivery include its incorporation in solid dispersions of poorly soluble drugs and in colonic drug delivery systems. This review describes the features of zein significant for its use as a pharmaceutical excipient for oral drug delivery, and it summaries the literature relevant to macroscopic zein-based oral dosage forms, i.e. tablets, capsules, beads and powders. Particular attention is paid to the most novel formulations and applications of zein. Moreover, gaps of knowledge as well as possible venues for future investigations on zein are highlighted.
Topics: Administration, Oral; Drug Delivery Systems; Excipients; Tablets; Zein
PubMed: 29736888
DOI: 10.1208/s12249-018-1035-y -
Therapeutic Innovation & Regulatory... Mar 2024Since the awareness of adverse effects associated with pharmaceutical excipients in drug formulations, these excipients are no longer considered inert substances.... (Review)
Review
Since the awareness of adverse effects associated with pharmaceutical excipients in drug formulations, these excipients are no longer considered inert substances. Numerous countries have recognized the potential risks that they pose to patients and have implemented diverse regulations to evaluate their safety, compatibility, toxicity, and quality. Regulatory authorities have proactively implemented measures to evaluate excipients and have formulated comprehensive guidelines that manufacturers are obligated to follow. This review primarily highlights the different provisions governing the utilization of excipients in drug formulation by regulatory authorities worldwide. Nonetheless, it is worth noting that there are still many countries that do not perceive excipients as posing a potential threat.
Topics: Humans; Excipients; Drug-Related Side Effects and Adverse Reactions
PubMed: 38055157
DOI: 10.1007/s43441-023-00597-z -
Expert Opinion on Drug Delivery Jan 2018Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin... (Review)
Review
INTRODUCTION
Natural pharmaceutical excipients have been applied extensively in the past decades owing to their safety and biocompatibility. Zein, a natural protein of plant origin offers great benefit over other synthetic polymers used in controlled drug and biomedical delivery systems. It was used in a variety of medical fields including pharmaceutical and biomedical drug targeting, vaccine, tissue engineering, and gene delivery. Being biodegradable and biocompatible, the current review focuses on the history and the medical application of zein as an attractive still promising biopolymer.
AREAS COVERED
The current review gives a broadscope on zein as a still promising protein excipient in different fields. Zein- based drug and biomedical delivery systems are discussed with special focus on current and potential application in controlled drug delivery systems, and tissue engineering.
EXPERT OPINION
Zein as a protein of natural origin can still be considered a promising polymer in the field of drug delivery systems as well as in tissue engineering. Although different researchers spotted light on zein application in different industrial fields extensively, the feasibility of its use in the field of drug delivery replenished by investigators in recent years has not yet been fully approached.
Topics: Animals; Drug Delivery Systems; Excipients; Gene Transfer Techniques; Humans; Pharmaceutical Preparations; Tissue Engineering; Zein
PubMed: 28662354
DOI: 10.1080/17425247.2017.1349752 -
AAPS PharmSciTech Jun 2019Excipients have always been a key input into pharmaceutical products, profoundly affecting product quality. Currently, most of our knowledge of excipient critical...
Excipients have always been a key input into pharmaceutical products, profoundly affecting product quality. Currently, most of our knowledge of excipient critical quality attributes is empirical, gained through experience, and shared through publications and other sources. The behavior of excipients is complicated, with many different failure modes that depend on the type of dosage form. Even within the same dosage form, there can be multiple failure modes depending on the manufacturing method. This complex behavior creates many possible combinations to assess when designing a formulation or evaluating regulatory submissions. Formulation science could be improved if data from different sources could be made widely available through an interactive system using a consistent, structured format to help formulators and regulators assess the risk of excipient usage for a particular dosage form with a particular manufacturing method. This paper describes a decision support system that was created for assessing excipient risk in different types of formulations and considering different types of manufacturing methods, dosage forms, and excipient functionality. The Excipient Risk Assessment System consists of a database that stores knowledge about factors that affect formulation design and a decision support processor that manages selections for creating formulation scenarios and assigning risk. Formulation and risk assessment data are provided by formulation science experts. This enables the system to assess compatibility among excipients, functionality, dosage forms, and manufacturing methods selected for formulations. The interface guides users through the creation of formulation scenarios and displays customized, interactive risk assessment reports for users to search and explore.
Topics: Chemistry, Pharmaceutical; Decision Support Techniques; Excipients; Humans; Pharmaceutical Preparations; Risk Assessment
PubMed: 31214878
DOI: 10.1208/s12249-019-1440-x -
Pharmaceutical Nanotechnology 2020Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion... (Review)
Review
Self-emulsifying drug delivery system (SEDDS) is a kind of solid or liquid formulation composed of drugs, oil, surfactant and cosurfactant. It could form a fine emulsion (micro/nano) in the gastrointestinal tract after oral administration. Later on, the formed emulsion is absorbed through the lymphatic pathway. The oral bioavailability of drugs in SEDDS would be improved for bypassing the first-pass effect of the liver. Therefore, SEDDS has become a vital strategy to increase the oral bioavailability of poor watersoluble drugs. In addition, there is no aqueous phase in SEDDS, thus SEDDS is a homogeneous system, consequently being suitable for large-scale production and more stable than conventional emulsion. However, the role of formulation aspects in the biological property of SEDDS is not fully clear. In order to prepare the satisfying SEDDS to improve oral drug bioavailability, we need to fully understand the various factors that affect the in vivo behavior of SEDDS. In this review, we would explore the role of ingredient (drugs, oils, surfactant and cosurfactant) of SEDDS in increasing oral drug bioavailability. We would also discuss the effect of physicochemical property (particle size and zeta potential) of SEDDS on the oral drug bioavailability enhancement. This review would provide an approach to develop a rational SEDDS to improving oral drug bioavailability. Lay Summary: Self-emulsifying drug-delivery system (SEDDS) has been proven to be promising in ameliorating the oral bioavailability of poor water-soluble drugs. This review highlighted the influence of excipients and physicochemical property of SEDDS on the formation of emulsion and the oral absorption of drugs in the body.
Topics: Administration, Oral; Animals; Biological Availability; Drug Carriers; Drug Compounding; Emulsions; Excipients; Humans; Particle Size; Pharmaceutical Preparations; Technology, Pharmaceutical
PubMed: 32781978
DOI: 10.2174/2211738508666200811104240 -
European Journal of Pharmaceutics and... Aug 2023Pharmaceutical excipients are an important part of biological products. However, few attempts have been made to distinguish between the risk of inflammation associated...
BACKGROUND
Pharmaceutical excipients are an important part of biological products. However, few attempts have been made to distinguish between the risk of inflammation associated with the biological products themselves and that associated with excipients. The analysis of early immune response risk associated with excipients added to biological products is an important step in exploring the complex mechanism of side effects in susceptible patients.
METHODS AND RESULTS
In this study, nanoparticle impurities (NPIs) were extracted from trehalose and characterized. A mouse popliteal lymph node cell (PLNA) model, a mouse spleen lymphocyte model, a human peripheral blood mononuclear cell cytokine release model, and a macrophage complement activation model were established to comprehensively evaluate the early immune risk related to impurities in the trehalose excipient. Although popliteal lymph node cell counts in mice did not show significant differences, all other models indicated possible immune risk. In the PLNA model, NPIs caused significant toe thickening in mice, whereby the content of IgE and MCP-1 increased significantly. NPIs significantly increased the proliferation and differentiation of spleen lymphocytes according to the CCK-8 assay and flow cytometry. After treatment with NPIs, the release of IgE and a variety of cytokines (MIP-1α, IFN-γ, IL-2, IL-8, TNF-α, IL-6, IL-1α) in human peripheral blood cells was significantly increased according to ELISA, while a concomitant increase of C3a/C5a as well as C4a/Bb proved that NPIs activated the complement system.
CONCLUSION
NPIs from trehalose elicited an immune response in vitro, and the immune response to trehalose may be related to NPIs and not the excipient itself. Different batches of trehalose showed different immune response effects. The currents research suggests that when trehalose is applied in high-risk administration routes, NPIs should be assessed and reasonably controlled.
Topics: Humans; Mice; Animals; Excipients; Trehalose; Leukocytes, Mononuclear; Cytokines; Immunity; Immunoglobulin E; Biological Products
PubMed: 37354998
DOI: 10.1016/j.ejpb.2023.06.011