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International Journal of Pharmaceutics May 2021Hyaluronic acid has become an interesting and important polymer as an excipient for pharmaceutical products due to its beneficial properties, like solubility,... (Review)
Review
Hyaluronic acid has become an interesting and important polymer as an excipient for pharmaceutical products due to its beneficial properties, like solubility, biocompatibility and biodegradation. To improve the properties of hyaluronic acid, different possibilities for chemical modifications are presented, and the opportunities as novel systems for drug delivery are discussed. This review gives an overview over the production of hyaluronic acid, the possibilities of its chemical modification and the current state of in vitro and in vivo research. Furthermore, market approved and commercially available products are reviewed and derivatives undergoing clinical trials and applying for market approval are shown. In particular, hyaluronic acid has been studied for different administrations in rheumatology, ophthalmology, local anesthetics, cancer treatment and bioengineering of tissues. The present work concludes with perspectives for future administration of pharmaceuticals based on hyaluronic acid.
Topics: Drug Delivery Systems; Excipients; Hyaluronic Acid; Pharmaceutical Preparations; Polymers
PubMed: 33845151
DOI: 10.1016/j.ijpharm.2021.120589 -
International Journal of Molecular... Nov 2020Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug... (Review)
Review
Conclusions from previously reported articles have revealed that many commonly used pharmaceutical excipients, known to be pharmacologically inert, show effects on drug transporters and/or metabolic enzymes. Thus, the pharmacokinetics (absorption, distribution, metabolism and elimination) of active pharmaceutical ingredients are possibly altered because of their transport and metabolism modulation from the incorporated excipients. The aim of this review is to present studies on the interaction of various commonly-used excipients on pre-systemic metabolism by CYP450 enzymes. Excipients such as surfactants, polymers, fatty acids and solvents are discussed. Based on all the reported outcomes, the most potent inhibitors were found to be surfactants and the least effective were organic solvents. However, there are many factors that can influence the inhibition of CYP450, for instance type of excipient, concentration of excipient, type of CYP450 isoenzyme, incubation condition, etc. Such evidence will be very useful in dosage form design, so that the right formulation can be designed to maximize drug bioavailability, especially for poorly bioavailable drugs.
Topics: ATP-Binding Cassette Transporters; Animals; Cytochrome P-450 Enzyme System; Excipients; Humans; Inactivation, Metabolic; Metabolic Clearance Rate; Pharmaceutical Preparations
PubMed: 33153099
DOI: 10.3390/ijms21218224 -
Journal of Pharmaceutical Sciences May 2022Alginates are naturally occurring polymers revealing low toxicity, good biocompatibility and biodegradability, excellent gelling and thickening properties, as well as... (Review)
Review
Alginates are naturally occurring polymers revealing low toxicity, good biocompatibility and biodegradability, excellent gelling and thickening properties, as well as low production cost and good availability. One of the most important features typical for alginates is the ability to undergo ionotropic gelation which is gel formation process occurring upon the contact with cations. Because of their advantageous properties, alginates have been extensively utilized in food and pharmaceutical industries. In this review the current knowledge regarding the most recent studies involving both popularly applied dosage forms, like tablets or hydrogels, and novel advanced drug delivery systems applied in targeted therapies are summarized and discussed. The presented studies indicate that although sodium alginate is a well-established polymer, it is still widely applied as pharmaceutical excipient and the presented research studies indicate that there are still research areas that can be explored and provide innovation in drug delivery systems.
Topics: Alginates; Drug Carriers; Drug Delivery Systems; Excipients; Glucuronic Acid; Hexuronic Acids; Polymers
PubMed: 34986359
DOI: 10.1016/j.xphs.2021.12.024 -
Journal of Controlled Release :... Aug 2020Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix... (Review)
Review
Hydroxypropylmethylcellulose (HPMC), also known as Hypromellose, is a traditional pharmaceutical excipient widely exploited in oral sustained drug release matrix systems. The choice of numerous viscosity grades and molecular weights available from different manufacturers provides a great variability in its physical-chemical properties and is a basis for its broad successful application in pharmaceutical research, development, and manufacturing. The excellent mucoadhesive properties of HPMC predetermine its use in oromucosal delivery systems including mucoadhesive tablets and films. HPMC also possesses desirable properties for formulating amorphous solid dispersions increasing the oral bioavailability of poorly soluble drugs. Printability and electrospinnability of HPMC are promising features for its application in 3D printed drug products and nanofiber-based drug delivery systems. Nanoparticle-based formulations are extensively explored as antigen and protein carriers for the formulation of oral vaccines, and oral delivery of biologicals including insulin, respectively. HPMC, being a traditional pharmaceutical excipient, has an irreplaceable role in the development of new pharmaceutical technologies, and new drug products leading to continuous manufacturing processes, and personalized medicine. This review firstly provides information on the physical-chemical properties of HPMC and a comprehensive overview of its application in traditional oral drug formulations. Secondly, this review focuses on the application of HPMC in modern pharmaceutical technologies including spray drying, hot-melt extrusion, 3D printing, nanoprecipitation and electrospinning leading to the formulation of printlets, nanoparticle-, microparticle-, and nanofiber-based delivery systems for oral and oromucosal application. Hypromellose is an excellent excipient for formulation of classical dosage forms and advanced drug delivery systems. New methods of hypromellose processing include spray draying, hot-melt extrusion, 3D printing, and electrospinning.
Topics: Drug Compounding; Drug Liberation; Excipients; Hypromellose Derivatives; Solubility; Tablets; Technology, Pharmaceutical; Viscosity
PubMed: 32479845
DOI: 10.1016/j.jconrel.2020.05.045 -
PDA Journal of Pharmaceutical Science... 2020It is important to identify, assess, and address current barriers to implementation of post-approval changes that are intended to ensure continued (uninterrupted)... (Review)
Review
It is important to identify, assess, and address current barriers to implementation of post-approval changes that are intended to ensure continued (uninterrupted) operations and drive innovation and continual improvement in a maximally efficient, agile, and flexible pharmaceutical manufacturing sector. Leveraging the International Conference for Harmonisation Quality Guideline Q10 provides regulatory relief when it comes to addressing changes related to excipients, specifically excipient supplier's name and address changes, which will ensure a sustainable, reliable global supply and the availability of high quality product to patients through the entire commercial lifecycle of a product without extensive regulatory oversight.
Topics: Chemistry, Pharmaceutical; Drug Industry; Equipment and Supplies Utilization; Excipients; Humans; Quality Control
PubMed: 32179712
DOI: 10.5731/pdajpst.2019.011239 -
Journal of Pharmaceutical Sciences Jan 2018Drug solubility could affect the therapeutic use of a drug because the biological activity of a drug is only possible if some fraction of a dissolved drug can permeate... (Review)
Review
Drug solubility could affect the therapeutic use of a drug because the biological activity of a drug is only possible if some fraction of a dissolved drug can permeate and overcome biological membranes to reach its site of action. The solubility-permeation interplay is therefore, probably the most important factor in determining a successful therapeutic outcome of any drug because more than 40% of marketed drugs and more than 70% of pipeline drugs show poor water solubility. Several solubilization techniques are used and include, balancing of pH-pK properties, employment of cosolvents, and the solubilization by host-guest carriers. A relatively new addition to the polymer plethora of solubilizers are the poly(amidoamine) dendrimers. These highly branched, "tree-like" nanocarriers have a significant solubilization capacity for drugs in their cavities and also potentially via their terminals. Despite their successful solubilization capability, they are still plagued by some undesired properties such as cytotoxicity. Poly(amidoamine) however, seems to be a very lucrative target to develop into a pharmaceutical excipient, which will ultimately be confirmed by an official pharmacopeial monograph.
Topics: Animals; Dendrimers; Drug Carriers; Drug Liberation; Excipients; Humans; Polyamines; Solubility
PubMed: 29045886
DOI: 10.1016/j.xphs.2017.10.011 -
Regulatory Toxicology and Pharmacology... Oct 2000Pharmaceutical excipients have a vital role in drug formulations, a role that has tended to be neglected as evidenced by the lack of mechanisms to assess excipient... (Review)
Review
Pharmaceutical excipients have a vital role in drug formulations, a role that has tended to be neglected as evidenced by the lack of mechanisms to assess excipient safety outside a new drug application process. Currently, it is assumed that an excipient is "approved" when the new drug formulation, of which it is a constituent, receives regulatory acceptance. Existing regulations and guidelines indicate that new (novel) excipients should be treated as new chemical entities with full toxicological evaluation. No guidance is available for potentially useful materials (essentially new excipients) available from other industries, e.g., food additives or for established excipients with a new application, e.g., dose route change. However, despite this situation, drug companies are actively evaluating new materials or applying new uses to established excipients. Recently developed excipients (e.g., materials giving "sugar-free" status to medical preparations, the cyclodextrins, and the hydrofluoroalkane inhalation propellants) and excipients undergoing development (e.g., chitosan, various enteric coating substances, liposomes, polymers derived from glycolic and lactic acids, and vaccine adjuvants) are all discussed. In light of many other areas of drug development having recently benefited from new or updated regulatory guidance, specific guidance to assist companies in the development of their excipients is urgently needed. Also, an excipient testing strategy would be an excellent topic for inclusion for International Conference on Harmonisation (ICH) consideration. Such guidance/discussion would complement the current advances in pharmacopoeial standardization of excipient quality. As a consequence, it may be possible to have excipients reviewed by a committee of an international pharmacopoeia with the safety data assessed by elected experts and published.
Topics: Chemistry, Pharmaceutical; Drug Approval; Drug Evaluation, Preclinical; Excipients; Humans; International Cooperation; Legislation, Drug; Toxicity Tests
PubMed: 11067777
DOI: 10.1006/rtph.2000.1421 -
Pharmaceutical Research Sep 1998Chitosan has been investigated as an excipient in the pharmaceutical industry, to be used in direct tablet compression, as a tablet disintegrant, for the production of... (Review)
Review
Chitosan has been investigated as an excipient in the pharmaceutical industry, to be used in direct tablet compression, as a tablet disintegrant, for the production of controlled release solid dosage forms or for the improvement of drug dissolution. Chitosan has, compared to traditional excipients, been shown to have superior characteristics and especially flexibility in its use. Furthermore, chitosan has been used for production of controlled release implant systems for delivery of hormones over extended periods of time. Lately, the transmucosal absorption promoting characteristics of chitosan has been exploited especially for nasal and oral delivery of polar drugs to include peptides and proteins and for vaccine delivery. These properties, together with the very safe toxicity profile, makes chitosan an exciting and promising excipient for the pharmaceutical industry for present and future applications.
Topics: Absorption; Chitin; Chitosan; Delayed-Action Preparations; Drug Compounding; Excipients; Humans; Industry; Solubility
PubMed: 9755881
DOI: 10.1023/a:1011929016601 -
Regulatory Toxicology and Pharmacology... Apr 2010Interest 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. Including a novel excipient in a new drug formulation requires a number of safety considerations. Review of the published literature showed that chitosan has low oral toxicity and local tolerance potential supporting use in non-parenteral formulations. Prior human oral exposure has occurred through use of chitosan dietary supplements and food additive, medical device and cosmetic applications. Although systemic exposure to parent chitosan may be limited (due to digestion in the gastrointestinal tract), any that is absorbed will likely undergo enzyme degradation to naturally occurring glucosamine, and N-acetylglucosamine, its copolymers, which are excreted or used in the amino sugar pool. Chitosan has local biological activity in the form of haemostatic action and, together with its ability to activate macrophages and cause cytokine stimulation (which has resulted in interest in medical device and wound healing applications), may result in a more careful assessment of its safety as a parenteral excipient.
Topics: Chemistry, Pharmaceutical; Chitosan; Excipients; Humans; Product Surveillance, Postmarketing
PubMed: 19788905
DOI: 10.1016/j.yrtph.2009.09.015 -
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