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Sample records for pharmaceutical drug carriers

  1. Potential Use of Cyclodextrins as Drug Carriers and Active Pharmaceutical Ingredients.

    PubMed

    Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi

    2017-01-01

    Cyclodextrins (CyDs) are extensively used in various fields, and especially have been widely utilized as pharmaceutical excipients and drug carriers in the pharmaceutical field. Owing to the multi-functional and biocompatible characteristics, CyDs can improve the undesirable properties of drug molecules. This review outlines the current application of CyDs in pharmaceutical formulations, focusing on their use as CyD-based drug carriers for several kinds of drugs. Additionally, CyDs have great potential as active pharmaceutical ingredients against various diseases with few side effects.

  2. Applicability, Commercial Utility and Recent Patents on Starch and Starch Derivative as Pharmaceutical Drug Delivery Carrier.

    PubMed

    Pandey, Shreya; Malviya, Rishabha; Sharma, Pramod K

    2015-01-01

    Natural polymers are widely utilized in pharmaceutical and food industries. Starch, a major carbohydrate is a staple food in human and animal diets which is simply extractable from various sources, like potato, maize, corn, wheat, etc. It is widely used as a raw material in various food and non food industries as well as in paper, textile and other industries. This article summarizes the starch and modification of starch and to produce a novel molecule with various applications in industries including number of advances in pharmaceutical industry. The unique characteristics of starch and their modified form can be successfully used as drug delivery carriers in various pharmaceutical preparations. It is widely used as controlled and sustained release polymer, tablet disintegrant, drug delivery carrier, plasma volume expander and also finds its applicability in bone tissue engineering and in artificial red cells. It also includes the patents related to starch and modified starch based products and their commercial utility.

  3. Lipid-Based Nanoparticles as Pharmaceutical Drug Carriers: From Concepts to Clinic

    PubMed Central

    Puri, Anu; Loomis, Kristin; Smith, Brandon; Lee, Jae-Ho; Yavlovich, Amichai; Heldman, Eli; Blumenthal, Robert

    2010-01-01

    In recent years, various nanotechnology platforms in the area of medical biology, including both diagnostics and therapy, have gained remarkable attention. Moreover, research and development of engineered multifunctional nanoparticles as pharmaceutical drug carriers have spurred exponential growth in applications to medicine in the last decade. Design principles of these nanoparticles, including nano-emulsions, dendrimers, nano-gold, liposomes, drug-carrier conjugates, antibody-drug complexes, and magnetic nanoparticles, are primarily based on unique assemblies of synthetic, natural, or biological components, including but not limited to synthetic polymers, metal ions, oils, and lipids as their building blocks. However, the potential success of these particles in the clinic relies on consideration of important parameters such as nanoparticle fabrication strategies, their physical properties, drug loading efficiencies, drug release potential, and, most importantly, minimum toxicity of the carrier itself. Among these, lipid-based nanoparticles bear the advantage of being the least toxic for in vivo applications, and significant progress has been made in the area of DNA/RNA and drug delivery using lipid-based nanoassemblies. In this review, we will primarily focus on the recent advances and updates on lipid-based nanoparticles for their projected applications in drug delivery. We begin with a review of current activities in the field of liposomes (the so-called honorary nanoparticles), and challenging issues of targeting and triggering will be discussed in detail. We will further describe nanoparticles derived from a novel class of amphipathic lipids called bolaamphiphiles with unique lipid assembly features that have been recently examined as drug/DNA delivery vehicles. Finally, an overview of an emerging novel class of particles (based on lipid components other than phospholipids), solid lipid nanoparticles and nanostructured lipid carriers will be presented. We

  4. Carrier-mediated cellular uptake of pharmaceutical drugs: an exception or the rule?

    PubMed

    Dobson, Paul D; Kell, Douglas B

    2008-03-01

    It is generally thought that many drug molecules are transported across biological membranes via passive diffusion at a rate related to their lipophilicity. However, the types of biophysical forces involved in the interaction of drugs with lipid membranes are no different from those involved in their interaction with proteins, and so arguments based on lipophilicity could also be applied to drug uptake by membrane transporters or carriers. In this article, we discuss the evidence supporting the idea that rather than being an exception, carrier-mediated and active uptake of drugs may be more common than is usually assumed - including a summary of specific cases in which drugs are known to be taken up into cells via defined carriers - and consider the implications for drug discovery and development.

  5. Lyophilized silica lipid hybrid (SLH) carriers for poorly water-soluble drugs: physicochemical and in vitro pharmaceutical investigations.

    PubMed

    Yasmin, Rokhsana; Tan, Angel; Bremmell, Kristen E; Prestidge, Clive A

    2014-09-01

    Lyophilization was investigated to produce a powdery silica-lipid hybrid (SLH) carrier for oral delivery of poorly water-soluble drugs. The silica to lipid ratio, incorporation of cryoprotectant, and lipid loading level were investigated as performance indicators for lyophilized SLH carriers. Celecoxib, a nonsteroidal anti-inflammatory drug, was used as the model poorly soluble moiety to attain desirable physicochemical and in vitro drug solubilization properties. Scanning electron microscopy and confocal fluorescence imaging verified a nanoporous, homogenous internal matrix structures of the lyophilized SLH particles, prepared from submicron triglyceride emulsions and stabilized by porous silica nanoparticles (Aerosil 380), similar to spray-dried SLH. 20-50 wt % of silica in the formulation have shown to produce nonoily SLH agglomerates with complete lipid encapsulation. The incorporation of a cryoprotectant prevented irreversible aggregation of the silica-stabilized droplets during lyophilization, thereby readily redispersing in water to form micrometre-sized particles (<5 μm). The lyophilized SLH produced approximately 1.5-fold and fivefold increased drug solubilization than the pure drug under nondigesting and digesting conditions, respectively. The feasibility of lyophilization for producing nanostructured SLH formulations with desirable lipid loading and drug solubilization properties for enhanced oral delivery of poorly water-soluble therapeutics is confirmed. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association.

  6. Bile salts-containing vesicles: promising pharmaceutical carriers for oral delivery of poorly water-soluble drugs and peptide/protein-based therapeutics or vaccines.

    PubMed

    Aburahma, Mona Hassan

    2016-07-01

    Most of the new drugs, biological therapeutics (proteins/peptides) and vaccines have poor performance after oral administration due to poor solubility or degradation in the gastrointestinal tract (GIT). Though, vesicular carriers exemplified by liposomes or niosomes can protect the entrapped agent to a certain extent from degradation. Nevertheless, the harsh GIT environment exemplified by low pH, presence of bile salts and enzymes limits their capabilities by destabilizing them. In response to that, more resistant bile salts-containing vesicles (BS-vesicles) were developed by inclusion of bile salts into lipid bilayers constructs. The effectiveness of orally administrated BS-vesicles in improving the performance of vesicles has been demonstrated in researches. Yet, these attempts did not gain considerable attention. This is the first review that provides a comprehensive overview of utilizing BS-vesicles as a promising pharmaceutical carrier with a special focus on their successful applications in oral delivery of therapeutic macromolecules and vaccines. Insights on the possible mechanisms by which BS-vesicles improve the oral bioavailability of the encapsulated drug or immunological response of entrapped vaccine are explained. In addition, methods adopted to prepare and characterize BS-vesicles are described. Finally, the gap in the scientific researches tackling BS-vesicles that needs to be addressed is highlighted.

  7. Suspended biofilm carrier and activated sludge removal of acidic pharmaceuticals.

    PubMed

    Falås, P; Baillon-Dhumez, A; Andersen, H R; Ledin, A; la Cour Jansen, J

    2012-03-15

    Removal of seven active pharmaceutical substances (ibuprofen, ketoprofen, naproxen, diclofenac, clofibric acid, mefenamic acid, and gemfibrozil) was assessed by batch experiments, with suspended biofilm carriers and activated sludge from several full-scale wastewater treatment plants. A distinct difference between nitrifying activated sludge and suspended biofilm carrier removal of several pharmaceuticals was demonstrated. Biofilm carriers from full-scale nitrifying wastewater treatment plants, demonstrated considerably higher removal rates per unit biomass (i.e. suspended solids for the sludges and attached solids for the carriers) of diclofenac, ketoprofen, gemfibrozil, clofibric acid and mefenamic acid compared to the sludges. Among the target pharmaceuticals, only ibuprofen and naproxen showed similar removal rates per unit biomass for the sludges and biofilm carriers. In contrast to the pharmaceutical removal, the nitrification capacity per unit biomass was lower for the carriers than the sludges, which suggests that neither the nitrite nor the ammonia oxidizing bacteria are primarily responsible for the observed differences in pharmaceutical removal. The low ability of ammonia oxidizing bacteria to degrade or transform the target pharmaceuticals was further demonstrated by the limited pharmaceutical removal in an experiment with continuous nitritation and biofilm carriers from a partial nitritation/anammox sludge liquor treatment process. Copyright © 2011 Elsevier Ltd. All rights reserved.

  8. Engineering antiphagocytic biomimetic drug carriers

    PubMed Central

    Sawdon, Alicia; Peng, Ching-An

    2014-01-01

    Drug-delivery carriers have the potential to not only treat but also diagnose many diseases; however, they still lack the complexity of natural-particulate systems. Cell-based therapies using tumor-targeting T cells and tumor-homing mesenchymal stem cells have given researchers a means to exploit the characteristics exhibited by innate-biological entities. Similarly, immune evasion by pathogens has inspired the development of natural polymers to cloak drug carriers. The ‘marker-of-self’ CD47 protein, which is found ubiquitously on mammalian cell surfaces, has been used for evading phagocyte clearance of drug carriers. This review will focus on the recent progress of drug carriers co-opting the tricks that cells in nature use to hide safely under the radar of the body’s innate immune system. PMID:23883126

  9. Nanoparticulate carriers (NPC) for oral pharmaceutics and nutraceutics.

    PubMed

    Lopes, C M; Martins-Lopes, P; Souto, E B

    2010-02-01

    The introduction of nanoparticulate carriers (NPC) in the pharmaceutic and nutraceutic fields has changed the definitions of disease management and treatment, diagnosis, as well as the supply food chain in the agri-food sector. NPC composed of synthetic polymers, proteins or polysaccharides gather interesting properties to be used for oral administration of pharmaceutics and nutraceutics. Oral administration remains the most convenient way of delivering drugs (e.g. peptides, proteins and nucleic acids) since these suffer similar metabolic pathways as food supply. Recent advances in biotechnology have produced highly potent new molecules however with low oral bioavailability. A suitable and promising approach to overcome their sensitivity to chemical and enzymatic hydrolysis as well as the poor cellular uptake, would be their entrapment within suitable gastrointestinal (GI) resistant NPC. Increasing attention has been paid to the potential use of NPC for peptides, proteins, antioxidants (carotenoids, omega fatty acids, coenzyme Q10), vitamins, probiotics, for oral administration. This review focuses on the most important materials to produce NPC for oral administration, and the most recent achievements in the production techniques and bioactives successfully delivered by these means.

  10. Nanostructured lipid carriers system: recent advances in drug delivery.

    PubMed

    Iqbal, Md Asif; Md, Shadab; Sahni, Jasjeet Kaur; Baboota, Sanjula; Dang, Shweta; Ali, Javed

    2012-12-01

    Nanostructured lipid carrier (NLC) is second generation smarter drug carrier system having solid matrix at room temperature. This carrier system is made up of physiological, biodegradable and biocompatible lipid materials and surfactants and is accepted by regulatory authorities for application in different drug delivery systems. The availability of many products in the market in short span of time reveals the success story of this delivery system. Since the introduction of the first product, around 30 NLC preparations are commercially available. NLC exhibit superior advantages over other colloidal carriers viz., nanoemulsions, polymeric nanoparticles, liposomes, SLN etc. and thus, have been explored to more extent in pharmaceutical technology. The whole set of unique advantages such as enhanced drug loading capacity, prevention of drug expulsion, leads to more flexibility for modulation of drug release and makes NLC versatile delivery system for various routes of administration. The present review gives insights on the definitions and characterization of NLC as colloidal carriers including the production techniques and suitable formulations. This review paper also highlights the importance of NLC in pharmaceutical applications for the various routes of drug delivery viz., topical, oral, pulmonary, ocular and parenteral administration and its future perspective as a pharmaceutical carrier.

  11. Does Your Drug Expertise Include Clinical Pharmaceutics?

    PubMed

    Newton, David W

    2016-01-01

    Whose job is it to protect patients from harm from drug instabilities and incompatibilities and other aspects of clinical pharmaceutics? Pharmacists are better educated via multiple required general and organic chemistry prerequisite and professional curricula medicinal chemistry and pharmaceutics courses. Therefore, no healthcare professional other than pharmacists are nicknamed drug experts or are better formally educated to master drug chemistry in the bottle (i.e., injection stability and compatibility/incompatibility clinical pharmaceutics) as a prerequisite for drug administration to cause safe and effective drug chemistry in the body (i.e., clinical pharmacokinetics and pharmacology). To be a patient's last chance for safe and effective drug therapy requires terminal control by pharmacists over identification, retrieval, preparation, labeling, and counseling or instruction of drug therapy. Copyright© by International Journal of Pharmaceutical Compounding, Inc.

  12. Porous Carriers for Controlled/Modulated Drug Delivery

    PubMed Central

    Ahuja, G.; Pathak, K.

    2009-01-01

    Considerable research efforts have been directed in recent years towards the development of porous carriers as controlled drug delivery matrices because of possessing several features such as stable uniform porous structure, high surface area, tunable pore size and well-defined surface properties. Owing to wide range of useful properties porous carriers have been used in pharmaceuticals for many purposes including development of floating drug delivery systems, sustained drug delivery systems. Various types of pores like open, closed, transport and blind pores in the porous solid allow them to adsorb drugs and release them in a more reproducible and predictable manner. Pharmaceutically exploited porous adsorbents includes, silica (mesoporous), ethylene vinyl acetate (macroporous), polypropylene foam powder (microporous), titanium dioxide (nanoporous). When porous polymeric drug delivery system is placed in contact with appropriate dissolution medium, release of drug to medium must be preceded by the drug dissolution in the water filled pores or from surface and by diffusion through the water filled channels. The porous carriers are used to improve the oral bioavailability of poorly water soluble drugs, to increase the dissolution of relatively insoluble powders and conversion of crystalline state to amorphous state. PMID:20376211

  13. Bioremediation of industrial pharmaceutical drugs.

    PubMed

    Mansour, Hedi Ben; Mosrati, Ridha; Barillier, Daniel; Ghedira, Kamel; Chekir-Ghedira, Leila

    2012-07-01

    Recently, attention has been drawn toward the occurrence of pharmaceuticals in the environment. In recent years, many reports have been made on the occurrence of the large, differentiated group of pharmaceuticals in wastewater (PW), surface water, ground water, and in soil. The pharmaceutical sector is currently expanding in Tunisia, with more than 34 industries. The aim of this work was to evaluate the ability of Pseudomonas putida mt-2 to treat PW. P. putida was very efficient in reducing chemical oxygen demand (COD), total dissolved solids (TDS), and turbidity of solution (85.5, 89.1, and 81.5%, respectively). Genotoxicity of effluent, before and after biodegradation, was evaluated in vivo in mouse bone marrow by assessing the percentage of cells bearing different chromosome aberrations. Results indicated that PW showed a significant ability to induce DNA damage. In addition, PW induced a remarkable lipid peroxidation (LPO) effect, however, activities of both acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) were unchanged when treated with PW, compared to nontreated PW. This toxicity was imputed to the presence of pharmaceutical compounds in wastewater. However, chromosome aberration, as well as LPO of PW, were significantly reduced after bioremediation. Thus, the use of this strain for testing on the industrial scale seems possible and advantageous.

  14. Drug Information Residency Rotation with Pharmaceutical Industry.

    ERIC Educational Resources Information Center

    Cramer, Richard L.

    1986-01-01

    Program objectives of a drug information rotation at the Upjohn Company include improving communication between the pharmaceutical industry and hospital pharmacy/academia, exposing the resident to the challenges the industry encounters, improving proficiency in drug information practice, and providing insight into the working relationships of…

  15. Drug Information Residency Rotation with Pharmaceutical Industry.

    ERIC Educational Resources Information Center

    Cramer, Richard L.

    1986-01-01

    Program objectives of a drug information rotation at the Upjohn Company include improving communication between the pharmaceutical industry and hospital pharmacy/academia, exposing the resident to the challenges the industry encounters, improving proficiency in drug information practice, and providing insight into the working relationships of…

  16. IVAN: Intelligent Van for the Distribution of Pharmaceutical Drugs

    PubMed Central

    Moreno, Asier; Angulo, Ignacio; Perallos, Asier; Landaluce, Hugo; Zuazola, Ignacio Julio García; Azpilicueta, Leire; Astrain, José Javier; Falcone, Francisco; Villadangos, Jesús

    2012-01-01

    This paper describes a telematic system based on an intelligent van which is capable of tracing pharmaceutical drugs over delivery routes from a warehouse to pharmacies, without altering carriers' daily conventional tasks. The intelligent van understands its environment, taking into account its location, the assets and the predefined delivery route; with the capability of reporting incidences to carriers in case of failure according to the established distribution plan. It is a non-intrusive solution which represents a successful experience of using smart environments and an optimized Radio Frequency Identification (RFID) embedded system in a viable way to resolve a real industrial need in the pharmaceutical industry. The combination of deterministic modeling of the indoor vehicle, the implementation of an ad-hoc radiating element and an agile software platform within an overall system architecture leads to a competitive, flexible and scalable solution. PMID:22778659

  17. IVAN: intelligent van for the distribution of pharmaceutical drugs.

    PubMed

    Moreno, Asier; Angulo, Ignacio; Perallos, Asier; Landaluce, Hugo; García Zuazola, Ignacio Julio; Azpilicueta, Leire; Astrain, José Javier; Falcone, Francisco; Villadangos, Jesús

    2012-01-01

    This paper describes a telematic system based on an intelligent van which is capable of tracing pharmaceutical drugs over delivery routes from a warehouse to pharmacies, without altering carriers' daily conventional tasks. The intelligent van understands its environment, taking into account its location, the assets and the predefined delivery route; with the capability of reporting incidences to carriers in case of failure according to the established distribution plan. It is a non-intrusive solution which represents a successful experience of using smart environments and an optimized Radio Frequency Identification (RFID) embedded system in a viable way to resolve a real industrial need in the pharmaceutical industry. The combination of deterministic modeling of the indoor vehicle, the implementation of an ad-hoc radiating element and an agile software platform within an overall system architecture leads to a competitive, flexible and scalable solution.

  18. Electrosprayed nanoparticles for drug delivery and pharmaceutical applications

    PubMed Central

    Sridhar, Radhakrishnan; Ramakrishna, Seeram

    2013-01-01

    Nanotechnology based Pharma has emerged significantly and has influenced the Pharma industry up to a considerable extent. Nanoparticles technology holds a good share of the nanotech Pharma and is significant in comparison with the other domains. Electrospraying technology answers the potential needs of nanoparticle production such as scalability, reproducibility, effective encapsulation etc. Many drugs have been electrosprayed with and without polymer carriers. Drug release characteristics are improved with the incorporation of biodegradable polymer carriers which sustain the release of encapsulated drug. Electrospraying is acknowledged as an important technique for the preparation of nanoparticles with respect to pharmaceutical applications. Herein we attempted to consolidate the reports pertaining to electrospraying and their corresponding therapeutic application area. PMID:23512013

  19. Elastic liposomes as novel carriers: recent advances in drug delivery

    PubMed Central

    Hussain, Afzal; Singh, Sima; Sharma, Dinesh; Webster, Thomas J; Shafaat, Kausar; Faruk, Abdul

    2017-01-01

    Elastic liposomes (EL) are some of the most versatile deformable vesicular carriers that comprise physiologically biocompatible lipids and surfactants for the delivery of numerous challenging molecules and have marked advantages over other colloidal systems. They have been investigated for a wide range of applications in pharmaceutical technology through topical, transdermal, nasal, and oral routes for efficient and effective drug delivery. Increased drug encapsulation efficiency, enhanced drug permeation and penetration into or across the skin, and ultradeformability have led to widespread interest in ELs to modulate drug release, permeation, and drug action more efficiently than conventional drug-release vehicles. This review provides insights into the versatile role that ELs play in the delivery of numerous drugs and biomolecules by improving drug release, permeation, and penetration across the skin as well as stability. Furthermore, it provides future directions that should ensure the widespread use of ELs across all medical fields. PMID:28761343

  20. Biodegradable Polymeric Nanoparticles as the Delivery Carrier for Drug.

    PubMed

    Zhao, Kai; Li, Dan; Shi, Ci; Ma, Xueling; Rong, Guangu; Kang, Hong; Wang, Xiaohua; Sun, Bin

    2016-01-01

    Drug research and development has entered into the new epoch of innovation formulation, and the drug delivery system has been in the forefront of pharmaceutical innovation. Nanotechnology is widely used in fiber and textiles, electronics, space, agriculture, forensic science and medical therapeutics. It increasingly plays a significant role in drug delivery system. Compared with traditional delivery system, the nanoparticle drug delivery system has lots of merits, such as the high drug loading ability, the excellent biocompatibility, low toxicity, controlled and targeted drug release. We undertook a structured research of biodegradable polymeric nanoparticles used as delivery carrier for drug using a focused review question and inclusion/exclusion criteria. We have searched the bibliographic databases for peerreviewed research literature. The outstanding characteristics of the screened papers were described respectively, and a systematic content analysis methodology was used to analysis the findings. Seventy-three papers were included in the review, the majority defined leadership and governance approaches that had impacted upon the polymeric nanoparticles as the delivery carrier for drug in therapeutic applications and developments. Seven papers outlined the superiority characteristics of polymeric nanoparticles that applied in the field of vaccine. Forty-seven papers overviewed the application prospects of polymeric nanoparticles used as drug delivery carrier for cancer. These included current advances in research and clinical applications of polymeric nanoparticles. The review identified the drug delivery carrier of biodegradable polymeric nanoparticles, and we described the synthesis methods, applications and challenges of polymeric nanoparticles. The findings of this review identified that the biodegradable polymeric nanoparticles were used as delivery carrier for drug currently. It also indicates that the biodegradable polymeric nanoparticles play an

  1. Controlled Drug Release from Pharmaceutical Nanocarriers

    PubMed Central

    Lee, Jinhyun Hannah; Yeo, Yoon

    2014-01-01

    Nanocarriers providing spatiotemporal control of drug release contribute to reducing toxicity and improving therapeutic efficacy of a drug. On the other hand, nanocarriers face unique challenges in controlling drug release kinetics, due to the large surface area per volume ratio and the short diffusion distance. To develop nanocarriers with desirable release kinetics for target applications, it is important to understand the mechanisms by which a carrier retains and releases a drug, the effects of composition and morphology of the carrier on the drug release kinetics, and current techniques for preparation and modification of nanocarriers. This review provides an overview of drug release mechanisms and various nanocarriers with a specific emphasis on approaches to control the drug release kinetics. PMID:25684779

  2. [Pharmaceutical chemistry of drug-initiated photosensitivity].

    PubMed

    Rácz, Ákos; Tóth, Lívia

    2015-01-01

    The photosensitivity originated from drugs is a common problem in medical and pharmaceutical practice. It is of prominent importance in drug development and in regulatory issues. The photosensitizer effect of drug substances is determined by their chemical structures, and it mainly originates from aromatic chromophore systems and photo-dissociable bonds forming free radicals. The photodegradation may happen in many different types of chemical reaction pathways. Our aim is to demonstrate in this review the interrelations between structure and photodegradation. We show examples for the different reaction types, with drugs from different pharmacologic therapeutic classes. The in vivo chemical reactivity of photodegradates of pharmaceutical substances, the in vitro methods of investigation for testing photoreactivity and phototoxicity, and briefly the clinical tests for photosensitivity disorders are also discussed.

  3. Pharmaceutical drugs chatter on Online Social Networks.

    PubMed

    Wiley, Matthew T; Jin, Canghong; Hristidis, Vagelis; Esterling, Kevin M

    2014-06-01

    The ubiquity of Online Social Networks (OSNs) is creating new sources for healthcare information, particularly in the context of pharmaceutical drugs. We aimed to examine the impact of a given OSN's characteristics on the content of pharmaceutical drug discussions from that OSN. We compared the effect of four distinguishing characteristics from ten different OSNs on the content of their pharmaceutical drug discussions: (1) General versus Health OSN; (2) OSN moderation; (3) OSN registration requirements; and (4) OSNs with a question and answer format. The effects of these characteristics were measured both quantitatively and qualitatively. Our results show that an OSN's characteristics indeed affect the content of its discussions. Based on their information needs, healthcare providers may use our findings to pick the right OSNs or to advise patients regarding their needs. Our results may also guide the creation of new and more effective domain-specific health OSNs. Further, future researchers of online healthcare content in OSNs may find our results informative while choosing OSNs as data sources. We reported several findings about the impact of OSN characteristics on the content of pharmaceutical drug discussion, and synthesized these findings into actionable items for both healthcare providers and future researchers of healthcare discussions on OSNs. Future research on the impact of OSN characteristics could include user demographics, quality and safety of information, and efficacy of OSN usage.

  4. Synthetic Lipoproteins as Carriers for Drug Delivery.

    PubMed

    Huang, Gangliang; Liu, Yang; Huang, Hualiang

    2016-01-01

    Synthetic lipoprotein is an effective carrier of targeted delivery for drugs. It has the very small size, good biocompatibility, suitable half-life, and specific lipoprotein receptorbinding capacity. Compared with the traditional natural lipoprotein, synthetic lipoprotein not only retains the original biological characteristics and functions, but also exhibits the excellent characteristics in drug delivery. Herein, the advantages, development, applications, and prospect of synthetic lipoproteins as drug carriers were summarized.

  5. Pharmaceutical financial assistance programs for HIV drugs.

    PubMed

    Bowers, M

    1998-04-01

    Access to new anti-HIV drugs and drugs for opportunistic infections is a problem for many Americans without good insurance plans. AIDS Drug Assistance Programs (ADAP) exist in all States, but their funding levels and drug formularies vary widely. Most major pharmaceutical companies have established programs to help individuals receive the drugs they need. This extensive list is intended to help identify programs, most of which require physician participation, and eliminate wasted time and duplicate efforts. The drugs are listed by brand name and company, specifying the financial criteria needed to obtain the drugs. The comprehensive list includes eligibility requirements, paperwork needed to enter the programs, and the amount of drug that is provided.

  6. Inorganic Nanomaterials as Carriers for Drug Delivery.

    PubMed

    Chen, Shizhu; Hao, Xiaohong; Liang, Xingjie; Zhang, Qun; Zhang, Cuimiao; Zhou, Guoqiang; Shen, Shigang; Jia, Guang; Zhang, Jinchao

    2016-01-01

    For safe and effective therapy, drugs must be delivered efficiently and with minimal systemic side effects. Nanostructured drug carriers enable the delivery of small-molecule drugs as well as nucleic acids and proteins. Inorganic nanomaterials are ideal for drug delivery platforms due to their unique physicochemical properties, such as facile preparation, good storage stability and biocompatibility. Many inorganic nanostructure-based drug delivery platforms have been prepared. Although there are still many obstacles to overcome, significant advances have been made in recent years. This review focuses on the status and development of inorganic nanostructures, including silica, quantum dots, gold, carbon-based and magnetic iron oxide-based nanostructures, as carriers for chemical and biological drugs. We specifically highlight the extensive use of these inorganic drug carriers for cancer therapy. Finally, we discuss the most important areas in the field that urgently require further study.

  7. Defining Patient Centric Pharmaceutical Drug Product Design.

    PubMed

    Stegemann, Sven; Ternik, Robert L; Onder, Graziano; Khan, Mansoor A; van Riet-Nales, Diana A

    2016-09-01

    The term "patient centered," "patient centric," or "patient centricity" is increasingly used in the scientific literature in a wide variety of contexts. Generally, patient centric medicines are recognized as an essential contributor to healthy aging and the overall patient's quality of life and life expectancy. Besides the selection of the appropriate type of drug substance and strength for a particular indication in a particular patient, due attention must be paid that the pharmaceutical drug product design is also adequately addressing the particular patient's needs, i.e., assuring adequate patient adherence and the anticipate drug safety and effectiveness. Relevant pharmaceutical design aspects may e.g., involve the selection of the route of administration, the tablet size and shape, the ease of opening the package, the ability to read the user instruction, or the ability to follow the recommended (in-use) storage conditions. Currently, a harmonized definition on patient centric drug development/design has not yet been established. To stimulate scientific research and discussions and the consistent interpretation of test results, it is essential that such a definition is established. We have developed a first draft definition through various rounds of discussions within an interdisciplinary AAPS focus group of experts. This publication summarizes the outcomes and is intended to stimulate further discussions with all stakeholders towards a common definition of patient centric pharmaceutical drug product design that is useable across all disciplines involved.

  8. Nanogel Carrier Design for Targeted Drug Delivery

    PubMed Central

    Eckmann, D. M.; Composto, R. J.; Tsourkas, A.; Muzykantov, V. R.

    2014-01-01

    Polymer-based nanogel formulations offer features attractive for drug delivery, including ease of synthesis, controllable swelling and viscoelasticity as well as drug loading and release characteristics, passive and active targeting, and the ability to formulate nanogel carriers that can respond to biological stimuli. These unique features and low toxicity make the nanogels a favorable option for vascular drug targeting. In this review, we address key chemical and biological aspects of nanogel drug carrier design. In particular, we highlight published studies of nanogel design, descriptions of nanogel functional characteristics and their behavior in biological models. These studies form a compendium of information that supports the scientific and clinical rationale for development of this carrier for targeted therapeutic interventions. PMID:25485112

  9. Halloysite - interesting nanotubular carrier for drugs.

    PubMed

    Rabišková, Miloslava

    2012-12-01

    Halloysite is a naturally occurring mineral similar to kaolin, possessing a special particle shape in the form of ultramicroscopic multi-layered hollow cylinders. It is utilizable in many industrial branches and due to its advantages, e.g. biocompatibility, drug entrapment, high mechanical strength and easy natural availability also on the pharmaceutical field and in medicine. It can bind drugs on the surface or inside of tubules and increase drug stability or change its release. Surface of the tubules can be readily modified for the application in drug delivery systems. Halloysite was reported as promising material for bone implants and controlled delivery of biomacromolecules. This review is dealing with pharmaceutical and biomedical usage of this interesting material and is including original experimental work published recently.

  10. Organized polysaccharide fibers as stable drug carriers

    PubMed Central

    Janaswamy, Srinivas; Gill, Kristin L.; Campanella, Osvaldo H.; Pinal, Rodolfo

    2013-01-01

    Many challenges arise during the development of new drug carrier systems, and paramount among them are safety, solubility and controlled release requirements. Although synthetic polymers are effective, the possibility of side effects imposes restrictions on their acceptable use and dose limits. Thus, a new drug carrier system that is safe to handle and free from side effects is very much in need and food grade polysaccharides stand tall as worthy alternatives. Herein, we demonstrate for the first time the feasibility of sodium iota-carrageenan fibers and their distinctive water pockets to embed and release a wide variety of drug molecules. Structural analysis has revealed the existence of crystalline network in the fibers even after encapsulating the drug molecules, and iota-carrageenan maintains its characteristic and reproducible double helical structure suggesting that the composites thus produced are reminiscent of cocrystals. The melting properties of iota-carrageenan:drug complexes are distinctly different from those of either drug or iota-carrageenan fiber. The encapsulated drugs are released in a sustained manner from the fiber matrix. Overall, our research provides an elegant opportunity for developing effective drug carriers with stable network toward enhancing and/or controlling bioavailability and extending shelf-life of drug molecules using GRAS excipients, food polysaccharides, that are inexpensive and non–toxic. PMID:23544530

  11. Deoxycholate-hydrogels: novel drug carrier systems for topical use.

    PubMed

    Valenta, C; Nowack, E; Bernkop-Schnürch, A

    1999-08-05

    Na-deoxycholate (Na-DOC) forms a viscous thixotropic gel when in contact with excess buffer systems. The resulting gels have been tested as novel drug carrier systems for topical use. The influence of differing amounts of mannitol, glycerol and xylitol on the viscous modulus (G"/Pa) was evaluated by oscillatory measurements. Na-DOC (0.5%) in phosphate buffered saline (PBS) with 5% mannitol was chosen as an optimised formulation, taking into account viscosity, distribution and appearance. The release rate of the model drug rutin through an artificial membrane was higher than those from hydroxyethylcellulose- (HEC) and sodium polyacrylate (NaC934)-gels; permeation through excised rat skin was also highest for the Na-DOC systems. The results indicate that Na-DOC significantly increases the membrane permeability. The microbial stability was in the same range as HEC- and NaC934-gels, making a preservation necessary. Na-DOC-gels are novel low molecular weight, multifunctional drug carriers, which also act as penetration enhancers. Their thixotropy is an additional advantage for better application to large skin areas, nasal, vaginal and buccal membranes. Therefore, Na-DOC-gels can be considered promising, alternative drug carrier systems for topical pharmaceutical as well as cosmetic use.

  12. Essential drugs and registration of pharmaceuticals: the Sri Lankan experience.

    PubMed Central

    Weerasuriya, K.

    1993-01-01

    Many factors influence the regulation of pharmaceuticals in a country. The essential drugs concept, formulated by the World Health Organization to assist developing countries in selecting appropriate drugs, also provides a basis for regulation. Sri Lanka has long regulated pharmaceuticals as part of its health policy. Over 70% of 3436 pharmaceutical product registrations were found to be drugs (or alternatives) named in the country's essential drugs list. This is despite the fact that product registrations are mainly for the private health care sector, and the list is for the state sector. The essential drugs concept therefore appears to have influenced the pharmaceuticals registered in Sri Lanka. PMID:8490987

  13. Synthetic biology for pharmaceutical drug discovery.

    PubMed

    Trosset, Jean-Yves; Carbonell, Pablo

    2015-01-01

    Synthetic biology (SB) is an emerging discipline, which is slowly reorienting the field of drug discovery. For thousands of years, living organisms such as plants were the major source of human medicines. The difficulty in resynthesizing natural products, however, often turned pharmaceutical industries away from this rich source for human medicine. More recently, progress on transformation through genetic manipulation of biosynthetic units in microorganisms has opened the possibility of in-depth exploration of the large chemical space of natural products derivatives. Success of SB in drug synthesis culminated with the bioproduction of artemisinin by microorganisms, a tour de force in protein and metabolic engineering. Today, synthetic cells are not only used as biofactories but also used as cell-based screening platforms for both target-based and phenotypic-based approaches. Engineered genetic circuits in synthetic cells are also used to decipher disease mechanisms or drug mechanism of actions and to study cell-cell communication within bacteria consortia. This review presents latest developments of SB in the field of drug discovery, including some challenging issues such as drug resistance and drug toxicity.

  14. New Preparative Approaches for Micro and Nano Drug Delivery Carriers.

    PubMed

    Bochicchio, Sabrina; Dalmoro, Annalisa; Barba, Anna Angela; d'Amore, Matteo; Lamberti, Gaetano

    2017-01-01

    The full success of pharmacological therapies is strongly depending on the use of suitable, efficient and smart drug delivery systems (DDSs). Thus DDSs development is one of the main challenges in pharmaceutical industry both to achieve tailored carrier systems based on drug features and to promote manufacturing innovations to reduce energetic resources, emissions, wastes and risks. Main functions of an ideal DDS are: to protect loaded active molecules from degradation in physiological environments; to deliver them in a controlled manner and towards specific organs or tissues, to allow the maintenance of drug concentration within therapeutic window. Smart features, such as those able to induce active molecule release upon the occurrence of specific physiological stimuli, are also desirable. Under the manufacturing point of view, the current industrial scenery is obliged to respond to the increasing market requirements and to the mandatory rules in sustainable productions such as raw material and energy savings. In this work a general framework on drug delivery systems preparation techniques is presented. In particular two sections on innovation in preparative approaches carried out are detailed. These latter involve the use of microwave and ultrasonic energy applied in the production of polymeric and lipidic delivery systems on micro- and nanometric scale. The novelties of these preparative approaches are emphasized and examples of developed drug delivery carriers, loaded with vitamins and drug mimicking siRNA, are shown.

  15. Advancing drug discovery: a pharmaceutics perspective.

    PubMed

    Kwong, Elizabeth

    2015-03-01

    Current industry perspective of how discovery is conducted seems to be fragmented and does not have a unified overall outlook of how discovery challenges are being addressed. Consequently, well-defined processes and drug-likeness criteria are being viewed as "broken" and will not maintain future R&D productivity. In this commentary, an analysis of existing practices for defining successful development candidates resulted in a 5 "must do" list to help advance Drug Discovery as presented from a Pharmaceutics perspective. The 5 "must do" list includes: what an ideal discovery team model should look like, what criteria should be considered for the desired development candidate profile, what the building blocks of the development candidate should look like, and how to assess the development risks of the candidate.

  16. Hollow mesoporous silica as a high drug loading carrier for regulation insoluble drug release.

    PubMed

    Geng, Hongjian; Zhao, Yating; Liu, Jia; Cui, Yu; Wang, Ying; Zhao, Qinfu; Wang, Siling

    2016-08-20

    The purpose of this study was to develop a high drug loading hollow mesoporous silica nanoparticles (HMS) and apply for regulation insoluble drug release. HMS was synthesized using hard template phenolic resin nanoparticles with the aid of cetyltrimethyl ammonium bromide (CTAB), which was simple and inexpensive. To compare the difference between normal mesoporous silica (NMS) and hollow mesoporous silica in drug loading efficiency, drug release behavior and solid state, NMS was also prepared by soft template method. Transmission electron microscopy (TEM), specific surface area analysis, FT-IR and zeta potential were employed to characterize the morphology structure and physicochemical property of these carriers. The insoluble drugs, carvedilol and fenofibrate(Car and Fen), were chosen as the model drug to be loaded into HMS and NMS. We also chose methylene blue (MB) as a basic dye to estimate the adsorption ability of these carriers from macroscopic and microscopic view, and the drug-loaded carriers were systematically studied by differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV-vis spectrophotometry. What' more, the in vivo process of HMS was also study by confocal microscopy and in vivo fluorescence imaging. In order to confirm the gastrointestinal safety of HMS, the pathological examination of stomach and intestine also be evaluated. HMS allowed a higher drug loading than NMS and exhibited a relative sustained release curve, while NMS was immediate-release. And the effect of preventing drugs crystallization was weaker than NMS. As for in vivo process, HMS was cleared relatively rapidly from the mouse gastrointestinal and barely uptake by intestinal epithelial cell in this study due to its large particle size. And the damage of HMS to gastrointestinal could be ignored. This study provided a simple method to obtain high drug loading and regulation insoluble drug release, expanded the application of inorganic carriers in drug delivery system

  17. Nanostructured lipid carriers (NLCs) for drug delivery and targeting.

    PubMed

    Fang, Chia-Lang; Al-Suwayeh, Saleh A; Fang, Jia-You

    2013-01-01

    Nanostructured lipid carriers (NLCs) are drug-delivery systems composed of both solid and liquid lipids as a core matrix. It was shown that NLCs reveal some advantages for drug therapy over conventional carriers, including increased solubility, the ability to enhance storage stability, improved permeability and bioavailability, reduced adverse effect, prolonged half-life, and tissue-targeted delivery. NLCs have attracted increasing attention in recent years. This review describes recent developments in drug delivery using NLCs strategies. The structures, preparation techniques, and physicochemical characterization of NLCs are systematically elucidated in this review. The potential of NLCs to be used for different administration routes is highlighted. Special attention is paid to parenteral injection and topical delivery since these are the most common routes for investigating NLCs. Relevant issues for the introduction of NLCs to market, including pharmaceutical and cosmetic applications, are discussed. The related patents of NLCs for drug delivery are also reviewed. Finally, the future development and current obstacles needing to be resolved are elucidated.

  18. Vesicular carriers for dermal drug delivery.

    PubMed

    Sinico, Chiara; Fadda, Anna Maria

    2009-08-01

    The skin can offer several advantages as a route of drug administration although its barrier nature makes it difficult for most drugs to penetrate into and permeate through it. During the past decades there has been a lot of interest in lipid vesicles as a tool to improve drug topical delivery. Vesicular systems such as liposomes, niosomes, ethosomes and elastic, deformable vesicles provide an alternative for improved skin drug delivery. The function of vesicles as topical delivery systems is controversial with variable effects being reported in relation to the type of vesicles and their composition. In fact, vesicles can act as drug carriers controlling active release; they can provide a localized depot in the skin for dermally active compounds and enhance transdermal drug delivery. A wide variety of lipids and surfactants can be used to prepare vesicles, which are commonly composed of phospholipids (liposomes) or non-ionic surfactants (niosomes). Vesicle composition and preparation method influence their physicochemical properties (size, charge, lamellarity, thermodynamic state, deformability) and therefore their efficacy as drug delivery systems. A review of vesicle value in localizing drugs within the skin at the site of action will be provided with emphasis on their potential mechanism of action.

  19. China: current trends in pharmaceutical drug discovery.

    PubMed

    Luo, Ying

    2008-04-01

    Pharmaceutical discovery and development is expensive and highly risky, even for multinational corporations. As a developing country with limited financial resources, China has been seeking the most cost-effective means to reach the same level of innovation and productivity as Western countries in the pharmaceutical industry sector. After more than 50 years of building up talent and experience, the time for China to become a powerhouse in pharmaceutical innovation is finally approaching. Returnee scientists to China are one of the reasons for the wave of new discovery and commercialization occurring within the country. The consolidation of local Chinese pharmaceutical companies and foreign investment is also providing an agreeable environment for the evolution of a new generation of biotechnology. The opportunity for pharmaceutical innovation is also being expedited by the entry of multinational companies into the Chinese pharmaceutical market, and by the outsourcing of research from these companies to China.

  20. Uptake Carriers and Oncology Drug Safety

    PubMed Central

    Sprowl, Jason A.

    2014-01-01

    Members of the solute carrier (SLC) family of transporters are responsible for the cellular influx of a broad range of endogenous compounds and xenobiotics in multiple tissues. Many of these transporters are highly expressed in the gastrointestinal tract, liver, and kidney and are considered to be of particular importance in governing drug absorption, elimination, and cellular sensitivity of specific organs to a wide variety of oncology drugs. Although the majority of studies on the interaction of oncology drugs with SLC have been restricted to the use of exploratory in vitro model systems, emerging evidence suggests that several SLCs, including OCT2 and OATP1B1, contribute to clinically important phenotypes associated with those agents. Recent literature has indicated that modulation of SLC activity may result in drug-drug interactions, and genetic polymorphisms in SLC genes have been described that can affect the handling of substrates. Alteration of SLC function by either of these mechanisms has been demonstrated to contribute to interindividual variability in the pharmacokinetics and toxicity associated with several oncology drugs. In this report, we provide an update on this rapidly emerging field. PMID:24378324

  1. Target Nanoparticles for Therapy - SANS and DLS of Drug Carrier Liposomes and Polymer Nanoparticles

    NASA Astrophysics Data System (ADS)

    Nawroth, T.; Johnson, R.; Krebs, L.; Khoshakhlagh, P.; Langguth, P.; Hellmann, N.; Goerigk, G.; Boesecke, P.; Bravin, A.; Le Duc, G.; Szekely, N.; Schweins, R.

    2016-09-01

    T arget Nano-Pharmaceutics shall improve therapy and diagnosis of severe diseases, e.g. cancer, by individual targeting of drug-loaded nano-pharmaceuticals towards cancer cells, and drug uptake receptors in other diseases. Specific ligands, proteins or cofactors, which are recognized by the diseased cells or cells of food and drug uptake, are bound to the nanoparticle surface, and thus capable of directing the drug carriers. The strategy has two branches: a) for parenteral cancer medicine a ligand set (2-5 different, surface-linked) are selected according to the biopsy analysis of the patient tissue e.g. from tumor.; b) in the oral drug delivery part the drug transport is enforced by excipients/ detergents in combination with targeting materials for cellular receptors resulting in an induced drug uptake. Both targeting nanomaterials are characterized by a combination of SANS + DLS and SAXS or ASAXS in a feedback process during development by synthesis, nanoparticle assembly and formulation.

  2. Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast

    PubMed Central

    2011-01-01

    Background The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. Results To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. Conclusions As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs. PMID:22023736

  3. Genome-wide assessment of the carriers involved in the cellular uptake of drugs: a model system in yeast.

    PubMed

    Lanthaler, Karin; Bilsland, Elizabeth; Dobson, Paul D; Moss, Harry J; Pir, Pınar; Kell, Douglas B; Oliver, Stephen G

    2011-10-24

    The uptake of drugs into cells has traditionally been considered to be predominantly via passive diffusion through the bilayer portion of the cell membrane. The recent recognition that drug uptake is mostly carrier-mediated raises the question of which drugs use which carriers. To answer this, we have constructed a chemical genomics platform built upon the yeast gene deletion collection, using competition experiments in batch fermenters and robotic automation of cytotoxicity screens, including protection by 'natural' substrates. Using these, we tested 26 different drugs and identified the carriers required for 18 of the drugs to gain entry into yeast cells. As well as providing a useful platform technology, these results further substantiate the notion that the cellular uptake of pharmaceutical drugs normally occurs via carrier-mediated transport and indicates that establishing the identity and tissue distribution of such carriers should be a major consideration in the design of safe and effective drugs.

  4. Lipid formulation as a drug carrier for drug delivery.

    PubMed

    Tomii, Yoshifumi

    2002-01-01

    In recent years, a Drug Delivery System (DDS), a preparative approach attracts the attention in the development of new drugs. DDS focuses on the regulation of the in vivo dynamics, such as absorption, distribution, metabolism, and elimination, thereby improving the effectiveness and the safety of the drugs by an applicable use of drug preparation technologies. A conventional intravenous dosage form of Amphotericin B (AmB), Fungizone, is the most effective clinically available for treating fungal infections. However, the clinical efficacy of AmB is limited by its adverse effects. Several lipid formulations, such as Liposomal AmB (L-AmB), AmB lipid complex (ABLC), and AmB colloidal dispersion (ABCD), with reduced side effects have been developed. These formulations are reported to have excellent safety and efficacy. However, comparable efficacy can be achieved only when they are administered at high doses than AmB. One of the problems of using these formulations is that they are easily taken up by the reticuloendothelial system (RES). An artificial lipoprotein-like particles, a novel drug carrier Lipid Nano-Sphere (LNS), which is 25 - 50 nm in size and is composed of phospholipids and simple lipid. LNS show a higher plasma concentration of drugs and lower uptake by RES-tissue different forms other lipid base drug carriers. In vitro and in vivo, LNS incorporating AmB, NS-718, shows reduced toxicity, while maintaining activity against fungi. LNS have a unique characteristic as an effective carrier of AmB for treatment of fungal infection.

  5. The role of the carrier in the formulation of pharmaceutical solid dispersions. Part I: crystalline and semi-crystalline carriers.

    PubMed

    Van Duong, Tu; Van den Mooter, Guy

    2016-11-01

    As a consequence of the target and drug candidate identification process, drugs with higher hydrophobicity and/or lipophilicity are being selected for further development, leading to solubility and dissolution rate limited oral bioavailability, and hence potential failure of the intended therapeutic goal. Solid dispersions were introduced as a formulation strategy in the early 1960s to tackle this issue and are still an area of intensive research activity. Areas covered: There has been a shift in the type of carriers that were used in the formulation of solid dispersions as nowadays, amorphous carriers are most often used, whereas in early stages of solid dispersions development, crystalline and semi-crystalline carriers were most commonly applied. In this review, we will discuss several aspects related to the use of crystalline and semi-crystalline carriers such as their molecular and related physical structure, and their physical chemical properties related to formulation of poorly soluble drugs. Expert opinion: The inherent crystallinity of this type of carrier hinders the formation of high-load solid solutions as mainly the amorphous domains of a carrier are able to accommodate drug molecules. Hence these carriers are not currently first choice excipients to formulate solid dispersions.

  6. Microcap pharmaceutical firms: linking drug pipelines to market value.

    PubMed

    Beach, Robert

    2012-01-01

    This article examines predictors of the future market value of microcap pharmaceutical companies. This is problematic since the large majority of these firms seldom report positive net income. Their value comes from the potential of a liquidity event such as occurs when a key drug is approved by the FDA. The typical scenario is one in which the company is either acquired by a larger pharmaceutical firm or enters into a joint venture with another pharmaceutical firm. Binary logistic regression is used to determine the impact of the firm's drug treatment pipeline and its investment in research and development on the firm's market cap. Using annual financial data from 2007 through 2010, this study finds that the status of the firm's drug treatment pipeline and its research and development expenses are significant predictors of the firm's future stock value relative to other microcap pharmaceutical firms.

  7. Carrier-Based Drug Delivery System for Treatment of Acne

    PubMed Central

    Vyas, Amber; Kumar Sonker, Avinesh

    2014-01-01

    Approximately 95% of the population suffers at some point in their lifetime from acne vulgaris. Acne is a multifactorial disease of the pilosebaceous unit. This inflammatory skin disorder is most common in adolescents but also affects neonates, prepubescent children, and adults. Topical conventional systems are associated with various side effects. Novel drug delivery systems have been used to reduce the side effect of drugs commonly used in the topical treatment of acne. Topical treatment of acne with active pharmaceutical ingredients (API) makes direct contact with the target site before entering the systemic circulation which reduces the systemic side effect of the parenteral or oral administration of drug. The objective of the present review is to discuss the conventional delivery systems available for acne, their drawbacks, and limitations. The advantages, disadvantages, and outcome of using various carrier-based delivery systems like liposomes, niosomes, solid lipid nanoparticles, and so forth, are explained. This paper emphasizes approaches to overcome the drawbacks and limitations associated with the conventional system and the advances and application that are poised to further enhance the efficacy of topical acne formulations, offering the possibility of simplified dosing regimen that may improve treatment outcomes using novel delivery system. PMID:24688376

  8. Albumin-Based Nanodevices as Drug Carriers.

    PubMed

    Loureiro, Ana; Azoia, Nuno G; Gomes, Andreia C; Cavaco-Paulo, Artur

    2016-01-01

    Nanomedicine, the application of nanotechnology to medicine, is being increasingly used to improve and exploit the advantages of efficient drug delivery. Different nanodevices have been developed in recent years, among them protein-based nanoparticles which have gained considerable interest. Albumin is a versatile protein carrier with several characteristics that make it an ideal candidate for drug delivery, such as its availability, its biocompatibility, its biodegradability, and its lack of toxicity and immunogenicity. This review embodies an overview of different methods available for production of albumin-based nanoparticles, with focus on high-energy emulsification methods. A comparison between production by using sonication, which involves acoustic cavitation, and the high pressure homogenization method, where occurs hydrodynamic cavitation, is presented. Taking into account important properties of nanoparticles required for intravenous administration, the use of poloxamers, tri-block copolymer surfactants is discussed as it improves blood circulation time and bioavailability of nanoparticles. Thus, nanoparticles can be engineered to provide adequate features to therapeutic applications, in which can be included surface functionalization with targeting agents. Different albumin-based formulations and their therapeutic applications are presented in this review, with emphasis on applications in cancer therapy, where albumin-based strategies are promising for targeted drug delivery in innovative clinical strategies.

  9. The pharmaceutical biochemistry group: where pharmaceutical chemistry meets biology and drug delivery.

    PubMed

    Kalia, Yogeshvar N; Perozzo, Remo; Scapozza, Leonardo

    2012-01-01

    Successful drug discovery and development of new therapeutics is a long, expensive multidisciplinary process needing innovation and the integration of smart cutting edge science and technology to overcome the challenges in taking a drug from the bench to the bedside. The research activities of the Pharmaceutical Biochemistry group span the drug discovery and development process, providing an interface that brings together pharmaceutical chemistry, biochemistry, structural biology, computational chemistry and biopharmaceutics. Formulation and drug delivery are brought into play at an earlier stage when facing the perennial challenge of transforming a potent molecule in vitro into a therapeutic agent in vivo. Concomitantly, drug delivery results can be understood at a molecular level. This broad range of interdisciplinary research activities and competences enables us to address key challenges in modern drug discovery and development, provides a powerful collaborative platform for other universities and the pharmaceutical industry and an excellent training platform for pharmacists and pharmaceutical scientists who will later be involved in drug discovery and development.

  10. Predicting drug efficacy: knockouts model pipeline drugs of the pharmaceutical industry.

    PubMed

    Zambrowicz, Brian P; Turner, C Alexander; Sands, Arthur T

    2003-10-01

    One of the major challenges for the pharmaceutical industry is to develop innovative drugs to new targets from the human genome. A systematic approach for target selection could significantly increase the rate of successful new drug development, thereby enhancing industry productivity. It has previously been shown that mouse knockout phenotypes for the targets of the 100 best-selling pharmaceutical drugs correlate well with known drug efficacy. Furthermore, physiological validation of novel pipeline targets of the pharmaceutical industry has been provided using mouse knockout data. These data demonstrate an excellent correlation between knockout phenotype and anticipated drug efficacy, establishing an important marker for superior new drug targets from the genome.

  11. Drug discovery in pharmaceutical industry: productivity challenges and trends.

    PubMed

    Khanna, Ish

    2012-10-01

    Low productivity, rising R&D costs, dissipating proprietary products and dwindling pipelines are driving the pharmaceutical industry to unprecedented challenges and scrutiny. In this article I reflect on the current status of the pharmaceutical industry and reasons for continued low productivity. An emerging 'symbiotic model of innovation', that addresses underlying issues in drug failure and attempts to narrow gaps in current drug discovery processes, is discussed to boost productivity. The model emphasizes partnerships in innovation to deliver quality products in a cost-effective system. I also discuss diverse options to build a balanced research portfolio with higher potential for persistent delivery of drug molecules.

  12. Causes of drug shortages in the legal pharmaceutical framework.

    PubMed

    De Weerdt, Elfi; Simoens, Steven; Hombroeckx, Luc; Casteels, Minne; Huys, Isabelle

    2015-03-01

    Different causes of drug shortages can be linked to the pharmaceutical legal framework, such as: parallel trade, quality requirements, economic decisions to suspend or cease production, etc. However until now no in-depth study of the different regulations affecting drug shortages is available. The aim of this paper is to provide an analysis of relevant legal and regulatory measures in the European pharmaceutical framework which influence drug shortages. Different European and national legislations governing human medicinal products were analyzed (e.g. Directive 2001/83/EC and Directive 2011/62/EU), supplemented with literature studies. For patented drugs, external price referencing may encompass the largest impact on drug shortages. For generic medicines, internal or external reference pricing, tendering as well as price capping may affect drug shortages. Manufacturing/quality requirements also contribute to drug shortages, since non-compliance leads to recalls. The influence of parallel trade on drug shortages is still rather disputable. Price and quality regulations are both important causes of drug shortages or drug unavailability. It can be concluded that there is room for improvement in the pharmaceutical legal framework within the lines drawn by the EU to mitigate drug shortages. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Pharmaceutical cocrystals: the coming wave of new drug substances.

    PubMed

    Brittain, Harry G

    2013-02-01

    Solid crystalline phases containing two cocrystallized components offer a new development pathway whereby one can potentially improve the physical characteristics (i.e., equilibrium solubility, dissolution rate, solid-state stability, etc.) of a drug substance that exhibits a profile that is less than desirable. In this commentary, the topic of pharmaceutical cocrystals will be briefly explored, and a short exposition of the solubility and dissolution rate advantages that have been realized in various systems will be provided. The Guidance for Industry document recently proposed by United States Food and Drug Administration will be outlined, and its requirements explained. Finally, the subset of pharmaceutical cocrystals that consist of a drug substance and a salt of that substance (termed a salt cocrystal) will be examined to illustrate this additional class of pharmaceutical cocrystals that may offer significant scientific and regulatory advantages.

  14. Polymeric carriers: role of geometry in drug delivery

    PubMed Central

    Simone, Eric A; Dziubla, Thomas D; Muzykantov, Vladimir R

    2009-01-01

    The unique properties of synthetic nanostructures promise a diverse set of applications as carriers for drug delivery, which are advantageous in terms of biocompatibility, pharmacokinetics, targeting and controlled drug release. Historically, more traditional drug delivery systems have focused on spherical carriers. However, there is a growing interest in pursuing non-spherical carriers, such as elongated or filamentous morphologies, now available due to novel formulation strategies. Unique physiochemical properties of these supramolecular structures offer distinct advantages as drug delivery systems. In particular, results of recent studies in cell cultures and lab animals indicate that rational design of carriers of a given geometry (size and shape) offers an unprecedented control of their longevity in circulation and targeting to selected cellular and subcellular locations. This article reviews drug delivery aspects of non-spherical drug delivery systems, including material selection and formulation, drug loading and release, biocompatibility, circulation behavior, targeting and subcellular addressing. PMID:19040392

  15. Cyclodextrin-based nanosponges as drug carriers

    PubMed Central

    Zanetti, Marco; Cavalli, Roberta

    2012-01-01

    Summary Cyclodextrin-based nanosponges, which are proposed as a new nanosized delivery system, are innovative cross-linked cyclodextrin polymers nanostructured within a three-dimensional network. This type of cyclodextrin polymer can form porous insoluble nanoparticles with a crystalline or amorphous structure and spherical shape or swelling properties. The polarity and dimension of the polymer mesh can be easily tuned by varying the type of cross-linker and degree of cross-linking. Nanosponge functionalisation for site-specific targeting can be achieved by conjugating various ligands on their surface. They are a safe and biodegradable material with negligible toxicity on cell cultures and are well-tolerated after injection in mice. Cyclodextrin-based nanosponges can form complexes with different types of lipophilic or hydrophilic molecules. The release of the entrapped molecules can be varied by modifying the structure to achieve prolonged release kinetics or a faster release. The nanosponges could be used to improve the aqueous solubility of poorly water-soluble molecules, protect degradable substances, obtain sustained delivery systems or design innovative drug carriers for nanomedicine. PMID:23243470

  16. Homochiral drugs: a demanding tendency of the pharmaceutical industry.

    PubMed

    Núñez, María C; García-Rubiño, M Eugenia; Conejo-García, Ana; Cruz-López, Olga; Kimatrai, María; Gallo, Miguel A; Espinosa, Antonio; Campos, Joaquín M

    2009-01-01

    The issue of drug chirality is now a major theme in the design and development of new drugs, underpinned by a new understanding of the role of molecular recognition in many pharmacologically relevant events. In general, three methods are utilized for the production of a chiral drug: the chiral pool, separation of racemates, and asymmetric synthesis. Although the use of chiral drugs predates modern medicine, only since the 1980's has there been a significant increase in the development of chiral pharmaceutical drugs. An important commercial reason is that as patents on racemic drugs expire, pharmaceutical companies have the opportunity to extend patent coverage through development of the chiral switch enantiomers with desired bioactivity. Stimulated by the new policy statements issued by the regulatory agencies, the pharmaceutical industry has systematically begun to develop chiral drugs in enantiometrically enriched pure forms. This new trend has caused a tremendous change in the industrial small- and large-scale production to enantiomerically pure drugs, leading to the revisiting and updating of old technologies, and to the development of new methodologies of their large-scale preparation (as the use of stereoselective syntheses and biocatalyzed reactions). The final decision whether a given chiral drug will be marketed in an enantiomerically pure form, or as a racemic mixture of both enantiomers, will be made weighing all the medical, financial and social proficiencies of one or other form. The kinetic, pharmacological and toxicological properties of individual enantiomers need to be characterized, independently of a final decision.

  17. Marketing pharmaceutical drugs to women in magazines: a content analysis.

    PubMed

    Sokol, Jennifer; Wackowski, Olivia; Lewis, M J

    2010-01-01

    To examine the prevalence and content of pharmaceutical ads in demographically different women's magazines. A content analysis was conducted using one year's worth of 5 different women's magazines of varying age demographics. Magazines differed in the proportion of drug ads for different health conditions (eg, cardiovascular) and target audience by age demographic. Use of persuasive elements (types of appeals, evidence) varied by condition promoted (eg, mental-health drug ads more frequently used emotional appeals). Ads placed greater emphasis on direction to industry information resources than on physician discussions. Prevalence of pharmaceutical advertising in women's magazines is high; continued surveillance is recommended.

  18. Including carrier-mediated transport in oral uptake prediction of nutrients and pharmaceuticals in humans.

    PubMed

    O'Connor, Isabel A; Veltman, Karin; Huijbregts, Mark A J; Ragas, Ad M J; Russel, Frans G M; Hendriks, A Jan

    2014-11-01

    Most toxicokinetic models consider passive diffusion as the only mechanism when modeling the oral uptake of chemicals. However, the overall uptake of nutrients and xenobiotics, such as pharmaceuticals and environmental pollutants, can be increased by influx transport proteins. We incorporated carrier-mediated transport into a one-compartment toxicokinetic model originally developed for passive diffusion only. The predictions were compared with measured oral uptake efficiencies of nutrients and pharmaceuticals, i.e. the fraction of the chemical reaching systemic circulation. Including carrier-mediated uptake improved model predictions for hydrophilic nutrients (RMSE=10% vs. 56%, Coefficient of Efficiency CoE=0.5 vs. -9.6) and for pharmaceuticals (RMSE=21% vs. 28% and CoE=-0.4 vs. -1.1). However, the negative CoE for pharmaceuticals indicates that further improvements are needed. Most important in this respect is a more accurate estimation of vMAX and KM as well as the determination of the amount of expressed and functional transport proteins both in vivo and in vitro. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. Augmenting drug-carrier compatibility improves tumour nanotherapy efficacy

    NASA Astrophysics Data System (ADS)

    Zhao, Yiming; Fay, François; Hak, Sjoerd; Manuel Perez-Aguilar, Jose; Sanchez-Gaytan, Brenda L.; Goode, Brandon; Duivenvoorden, Raphaël; de Lange Davies, Catharina; Bjørkøy, Astrid; Weinstein, Harel; Fayad, Zahi A.; Pérez-Medina, Carlos; Mulder, Willem J. M.

    2016-04-01

    A major goal of cancer nanotherapy is to use nanoparticles as carriers for targeted delivery of anti-tumour agents. The drug-carrier association after intravenous administration is essential for efficient drug delivery to the tumour. However, a large number of currently available nanocarriers are self-assembled nanoparticles whose drug-loading stability is critically affected by the in vivo environment. Here we used in vivo FRET imaging to systematically investigate how drug-carrier compatibility affects drug release in a tumour mouse model. We found the drug's hydrophobicity and miscibility with the nanoparticles are two independent key parameters that determine its accumulation in the tumour. Next, we applied these findings to improve chemotherapeutic delivery by augmenting the parent drug's compatibility; as a result, we achieved better antitumour efficacy. Our results help elucidate nanomedicines' in vivo fate and provide guidelines for efficient drug delivery.

  20. Sex, gender, and pharmaceutical politics: From drug development to marketing.

    PubMed

    Fisher, Jill A; Ronald, Lorna M

    2010-08-01

    Biological sex differences and sociocultural gender norms affect the provision of health care products and services, but there has been little explicit analysis of the impact of sex differences and gender norms on the regulation of pharmaceutical development and marketing. This article provides an overview of the regulation of pharmaceuticals and examines the ways that regulatory agencies account for sex and gender in their review of scientific data and marketing materials. The primary focus is on the US context, but information is also included about regulatory models in Europe, Canada, and Japan for comparative purposes. Specific examples show how sex differences and gender norms influence scientific and policy decisions about pharmaceuticals. The United States and Canada were found to be the only countries that have explicit requirements to include women in clinical trials and to perform sex-based subgroup analysis on study results. The potential influence of politics on regulatory decisions may have led to an uneven application of standards, as seen through the examples of mifepristone (for abortion) and sildenafil citrate (for erectile dysfunction). Three detailed case studies illustrate the importance of considering sex and gender in pharmaceutical development and marketing: Phase I clinical trials; human papillomavirus quadrivalent vaccine; and tegaserod, a drug for irritable bowel syndrome. Sex and gender play important roles in pharmaceutical regulation, from the design of clinical trials and the approval of new drugs to advertising and postmarketing surveillance. However, regulatory agencies pay insufficient attention to both biological sex differences and sociocultural gender norms. This disregard perpetuates inequalities by ignoring drug safety problems that predominate in women and by allowing misleading drug marketing that reinforces gender stereotypes. Recommendations have been made to improve the regulation of pharmaceuticals in regard to sex and

  1. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    ERIC Educational Resources Information Center

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  2. Drug Design, Development, and Delivery: An Interdisciplinary Course on Pharmaceuticals

    ERIC Educational Resources Information Center

    Prausnitz, Mark R.; Bommarius, Andreas S.

    2011-01-01

    We developed a new interdisciplinary course on pharmaceuticals to address needs of undergraduate and graduate students in chemical engineering and other departments. This course introduces drug design, development, and delivery in an integrated fashion that provides scientific depth in context with broader impacts in business, policy, and ethics.…

  3. Natural collagenic skeleton of marine sponges in pharmaceutics: Innovative biomaterial for topical drug delivery.

    PubMed

    Langasco, Rita; Cadeddu, Barbara; Formato, Marilena; Lepedda, Antonio Junior; Cossu, Massimo; Giunchedi, Paolo; Pronzato, Roberto; Rassu, Giovanna; Manconi, Renata; Gavini, Elisabetta

    2017-01-01

    The growing interest in the use of recyclable and biodegradable natural materials has become a relevant topic in pharmaceutics. In this work, we suggest the use and valorization of natural horny skeleton of marine sponges (Porifera, Dictyoceratida) as bio-based dressing for topical drug delivery. Biomaterial characterization focusing on morpho-functional traits, swelling behavior, fluid uptake performances, glycosaminoglycans content and composition and microbiological quality assessment was carried out to investigate the collagenic skeleton properties. After grinding and sieving processes, l-cysteine hydrochloride-loaded formulations were designed in form of powder or polymeric film by testing various drug concentrations and different drying parameters. Drug content, SEM analyses and in vitro permeation studies were performed to test the suitability of skeleton-based formulations. To this respect, drying time and temperature are key parameters for skeleton-mediated drug crystallization. Consequently, this behavior seems to influence drug loading and permeation profiles of formulations. The high percentages of drug are found after absorption into sponge powder and in vitro permeation studies demonstrate that cysteine is released more slowly than the pure drug within 1h. Such a system is attractive because it combines the known healing properties of cysteine with the advantageous potentials of the collagen/proteoglycan network, which can act as biocompatible carrier able to absorb the excess of the wound exudate while releasing the drug. Furthermore, due to its glycosaminoglycans content, natural sponge skeletal scaffold might act as bioactive-biomimetic carrier regulating the wound healing processes.

  4. Recent advances of chitosan nanoparticles as drug carriers

    PubMed Central

    Wang, Jun Jie; Zeng, Zhao Wu; Xiao, Ren Zhong; Xie, Tian; Zhou, Guang Lin; Zhan, Xiao Ri; Wang, Shu Ling

    2011-01-01

    Chitosan nanoparticles are good drug carriers because of their good biocompatibility and biodegradability, and can be readily modified. As a new drug delivery system, they have attracted increasing attention for their wide applications in, for example, loading protein drugs, gene drugs, and anticancer chemical drugs, and via various routes of administration including oral, nasal, intravenous, and ocular. This paper reviews published research on chitosan nanoparticles, including its preparation methods, characteristics, modification, in vivo metabolic processes, and applications. PMID:21589644

  5. Sodium montmorillonite/amine-containing drugs complexes: new insights on intercalated drugs arrangement into layered carrier material.

    PubMed

    Bello, Murilo L; Junior, Aridio M; Vieira, Bárbara A; Dias, Luiza R S; de Sousa, Valéria P; Castro, Helena C; Rodrigues, Carlos R; Cabral, Lucio M

    2015-01-01

    Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems.

  6. Core competencies for pharmaceutical physicians and drug development scientists.

    PubMed

    Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

    2013-01-01

    Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide.

  7. Core competencies for pharmaceutical physicians and drug development scientists

    PubMed Central

    Silva, Honorio; Stonier, Peter; Buhler, Fritz; Deslypere, Jean-Paul; Criscuolo, Domenico; Nell, Gerfried; Massud, Joao; Geary, Stewart; Schenk, Johanna; Kerpel-Fronius, Sandor; Koski, Greg; Clemens, Norbert; Klingmann, Ingrid; Kesselring, Gustavo; van Olden, Rudolf; Dubois, Dominique

    2013-01-01

    Professional groups, such as IFAPP (International Federation of Pharmaceutical Physicians and Pharmaceutical Medicine), are expected to produce the defined core competencies to orient the discipline and the academic programs for the development of future competent professionals and to advance the profession. On the other hand, PharmaTrain, an Innovative Medicines Initiative project, has become the largest public-private partnership in biomedicine in the European Continent and aims to provide postgraduate courses that are designed to meet the needs of professionals working in medicines development. A working group was formed within IFAPP including representatives from PharmaTrain, academic institutions and national member associations, with special interest and experience on Quality Improvement through education. The objectives were: to define a set of core competencies for pharmaceutical physicians and drug development scientists, to be summarized in a Statement of Competence and to benchmark and align these identified core competencies with the Learning Outcomes (LO) of the PharmaTrain Base Course. The objectives were successfully achieved. Seven domains and 60 core competencies were identified and aligned accordingly. The effective implementation of training programs using the competencies or the PharmaTrain LO anywhere in the world may transform the drug development process to an efficient and integrated process for better and safer medicines. The PharmaTrain Base Course might provide the cognitive framework to achieve the desired Statement of Competence for Pharmaceutical Physicians and Drug Development Scientists worldwide. PMID:23986704

  8. Quality specifications for peptide drugs: a regulatory-pharmaceutical approach.

    PubMed

    Vergote, Valentijn; Burvenich, Christian; Van de Wiele, Christophe; De Spiegeleer, Bart

    2009-11-01

    Peptide drugs, as all types of pharmaceuticals, require adequate specifications (i.e. quality attributes, procedures and acceptance criteria) as part of their quality assurance to ensure the safety and efficacy of drug substances (i.e. active pharmaceutical ingredients) and drug products (i.e. finished pharmaceutical dosage forms). Compendial monographs are updated regularly to keep up with the most recent advances in peptide synthesis (e.g. reduced by-products) and analytical technology. Nevertheless, currently applied pharmacopoeial peptide specifications are barely harmonized yet (e.g. large differences between the European Pharmacopoeia and the United States Pharmacopeia), increasing the manufacturers' burden of performing analytical procedures in different ways, using different acceptance criteria. Additionally, the peptide monographs are not always consistent within a single pharmacopoeia. In this review, we highlight the main differences and similarities in compendial peptide specifications (including identification, purity and assay). Based on comparison, and together with additional information from peptide drug substance manufacturers and public evaluation reports on registration files of non-pharmacopoeial peptide drugs, a consistent monograph structure is proposed.

  9. Direct Analysis of Pharmaceutical Drugs Using Nano-DESI MS

    PubMed Central

    Cardoso-Palacios, Carlos

    2016-01-01

    Counterfeit pharmaceutical drugs imply an increasing threat to the global public health. It is necessary to have systems to control the products that reach the market and to detect falsified medicines. In this work, molecules in several pharmaceutical tablets were directly analyzed using nanospray desorption electrospray ionization mass spectrometry (nano-DESI MS). Nano-DESI is an ambient surface sampling technique which enables sampling of molecules directly from the surface of the tablets without any sample pretreatment. Both the active pharmaceutical ingredients (APIs) and some excipients were detected in all analyzed tablets. Principal component analysis was used to analyze mass spectral features from different tablets showing strong clustering between tablets with different APIs. The obtained results suggest nano-DESI MS as future tool for forensic analysis to discern APIs present in unknown tablet samples. PMID:27766177

  10. Effects of drug-carrier interactions on drug dissolution from binary and ternary matrices

    NASA Astrophysics Data System (ADS)

    Iqbal, Zafar

    For nearly five decades, pharmaceutical researchers have studied solid solutions of drugs in polymers as a potential means to enhance the dissolution of drugs with poor aqueous solubility. This has become of greater importance in recent years because most new potential drug compounds (new chemical entities) exhibit poor water solubility and present great challenges to scientists who must design dosage forms from which the drugs are bioavailable. During the formulation of a solid solution, the drug undergoes physical but not chemical alterations that increase its chemical potential in the formulation relative to that of the pure drug in its stable form. This increased chemical potential is responsible for enhanced dissolution as well as physical instabilities, such as amorphous to crystalline conversions and precipitation within the solid state. The chemical potential is derived from the Gibbs free energy, so it is reasonable to explain the behavior of solid solution systems in terms of thermodynamics. Solid solutions and dispersions have been extensively studied by pharmaceutical scientists, both with regard to manufacturing aspects and the proposal of various models in attempts to explain the physical bases for how these systems work. Recently, Dave and Bellantone proposed a model based on the thermodynamic changes resulting from the formulation of binary solid solutions of a drug in the polymer PVP. Their model introduced a modification of the F-H theory, which was used to quantify the drug-polymer interaction energies and calculate the entropy of mixing of the drug and polymer. In this work, the model of Dave and Bellantone was extended to include three-component systems, consisting of one drug mixed in a carrier matrix consisting of mixture of two polymers or a polymer and a surfactant. For this research, solid solutions were formed using various drug weight fractions in the formulations. The study focused on the following points: (1) Prepare solid solution

  11. The interaction of encapsulated pharmaceutical drugs with a silica matrix.

    PubMed

    Morais, Everton C; Correa, Gabriel G; Brambilla, Rodrigo; Radtke, Claudio; Baibich, Ione Maluf; dos Santos, João Henrique Z

    2013-03-01

    A series of seven drugs, namely, fluoxetine, gentamicin, lidocaine, morphine, nifedipine, paracetamol and tetracycline, were encapsulated. The encapsulated systems were characterized using a series of complementary techniques: Fourier-transform infrared spectroscopy (FT-IR), diffusive reflectance spectroscopy in the UV-vis region (DRS) and X-ray photoelectron spectroscopy (XPS). According to the DRS spectra, most of the encapsulated systems showed a band shift of the maximum absorption when compared with the corresponding bare pharmaceutical. Additionally, after encapsulation, the drugs exhibited infrared band shifts toward higher wavenumbers, which in turn provided insight into potential sites for interaction with the silica framework. The amine group showed a band shift in the spectra of almost all the drugs (except nifedipine and tetracycline). This finding indicates the possibility of a hydrogen bonding interaction between the drug and the silica via electron donation from the amine group to the silica framework. XPS confirmed this interaction between the pharmaceuticals and the silica through the amine group. A correlation was observed between the textural characteristics of the solids and the spectroscopic data, suggesting that the amine groups from the pharmaceuticals were more perturbed upon encapsulation.

  12. Partial nitrifying granule stimulated by struvite carrier in treating pharmaceutical wastewater.

    PubMed

    Wang, Guowen; Wang, Dong; Xu, Xiaochen; Yang, Fenglin

    2013-10-01

    Aerobic granule was successfully cultivated in SBR (sequencing batch reactor) by struvite carrier (magnesium ammonium phosphate, MgNH4PO4), which can increase polysaccharides to 42.2 mg/gMLVSS (mixed liquor volatile suspended solid) versus only 28.4 mg/gMLVSS of the sludge without it. Meanwhile, it was found that struvite play a positive role in initial granulation and bacterial group distribution in treating pharmaceutical wastewater, involving effect of solid surface and special contents of struvite. The results of fluorescence in situ hybridization technique indicate that ammonia-oxidizing bacteria can dominate over nitrite-oxidizing bacteria in mature granules. COD removal efficiency of 90 % and NO2 (-)-N:(NO2 (-)-N + NO3 (-)-N) accumulation efficiency of 89 % were achieved in stable state. Emphasis is placed on that struvite addition can be applied as a new-type carrier to promote formation of partial nitrification granular sludge.

  13. Exploration of Macroporous Polymeric Sponges As Drug Carriers.

    PubMed

    Duan, Gaigai; Bagheri, Amir Reza; Jiang, Shaohua; Golenser, Jacob; Agarwal, Seema; Greiner, Andreas

    2017-08-31

    Achieving high drug loading capacity and controlling drug delivery are two main challenges related to drug carriers. In this study, polymeric macroporous sponges with very high pore volume and large porosity are introduced as a new-type of drug carrier. Due to the high pore volume (285 and 166 cm(3)/g for the sponges with densities of 3.5 and 6.0 mg/cm(3), respectively), the sponges exhibit very high drug loading capacities with average values of 1870 ± 114 and 2697 ± 73 mg/g in the present study, which is much higher than the meso and microporous drug carriers (<1500 mg/g). In order to control the release profiles, an additional poly(p-xylylene) (PPX) coating was deposited by chemical vapor deposition on the drug loaded sponge. Consequently, Artemisone (ART) release in the aqueous medium could be retarded, depending on the density of the sponge and the thickness of the coating. In future, the new 3D polymeric sponges would be highly beneficial as drug carriers for the programmed release of drugs for treatment of chronic diseases.

  14. Pharmaceutical nanotechnology for oral delivery of anticancer drugs.

    PubMed

    Mei, Lin; Zhang, Zhiping; Zhao, Lingyun; Huang, Laiqiang; Yang, Xiang-Liang; Tang, Jintian; Feng, Si-Shen

    2013-06-15

    Oral chemotherapy is an important topic in the 21st century medicine, which may radically change the current regimen of chemotherapy and greatly improve the quality of life of the patients. Unfortunately, most anticancer drugs, especially those of high therapeutic efficacy such as paclitaxel and docetaxel, are not orally bioavailable due to the gastrointestinal (GI) drug barrier. The molecular basis of the GI barrier has been found mainly due to the multidrug efflux proteins, i.e. P-type glycoproteins (P-gp), which are rich in the epithelial cell membranes in the GI tract. Medical solution for oral chemotherapy is to apply P-gp inhibitors such as cyclosporine A, which, however, suppress the body's immune system either, thus causing medical complication. Pharmaceutical nanotechnology, which is to apply and further develop nanotechnology to solve the problems in drug delivery, may provide a better solution and thus change the way we make drug and the way we take drug. This review is focused on the problems encountered in oral chemotherapy and the pharmaceutical nanotechnology solutions such as prodrugs, nanoemulsions, dendrimers, micelles, liposomes, solid lipid nanoparticles and nanoparticles of biodegradable polymers. Proof-of-concept in vitro and in vivo results for oral delivery of anticancer drugs by the various nanocarriers, which can be found so far from the literature, are provided.

  15. Linked open drug data for pharmaceutical research and development

    PubMed Central

    2011-01-01

    There is an abundance of information about drugs available on the Web. Data sources range from medicinal chemistry results, over the impact of drugs on gene expression, to the outcomes of drugs in clinical trials. These data are typically not connected together, which reduces the ease with which insights can be gained. Linking Open Drug Data (LODD) is a task force within the World Wide Web Consortium's (W3C) Health Care and Life Sciences Interest Group (HCLS IG). LODD has surveyed publicly available data about drugs, created Linked Data representations of the data sets, and identified interesting scientific and business questions that can be answered once the data sets are connected. The task force provides recommendations for the best practices of exposing data in a Linked Data representation. In this paper, we present past and ongoing work of LODD and discuss the growing importance of Linked Data as a foundation for pharmaceutical R&D data sharing. PMID:21575203

  16. [Essential drugs and pharmaceutical care: reflection on the access to drugs through lawsuits in Brazil].

    PubMed

    Sant'ana, João Maurício Brambati; Pepe, Vera Lúcia Edais; Osorio-de-Castro, Claudia Garcia Serpa; Ventura, Miriam

    2011-02-01

    The guarantee of pharmaceutical care as a legal right established by the Brazilian federal constitution of 1988 led to an increase in lawsuits to put that right into practice. This phenomenon has been dubbed the judicialization of pharmaceutical care. Studies on this topic have revealed, on the one hand, deficiencies in the access of Unified Health Care (SUS) users to drugs included in Ministry of Health pharmaceutical care lists, and, on the other hand, limitations of the legal system to deal with the situation. The present article addresses these issues in the context of the conceptual framework that supports the Brazilian drug policy and pharmaceutical care policy, especially the notions of essential drugs and allocation of scarce resources.

  17. Microfluidics-assisted in vitro drug screening and carrier production

    PubMed Central

    Tsui, Jonathan H.; Lee, Woohyuk; Pun, Suzie H.; Kim, Jungkyu; Kim, Deok-Ho

    2013-01-01

    Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. PMID:23856409

  18. Microfluidics-assisted in vitro drug screening and carrier production.

    PubMed

    Tsui, Jonathan H; Lee, Woohyuk; Pun, Suzie H; Kim, Jungkyu; Kim, Deok-Ho

    2013-11-01

    Microfluidic platforms provide several unique advantages for drug development. In the production of drug carriers, physical properties such as size and shape, and chemical properties such as drug composition and pharmacokinetic parameters, can be modified simply and effectively by tuning the flow rate and geometries. Large numbers of carriers can then be fabricated with minimal effort and with little to no batch-to-batch variation. Additionally, cell or tissue culture models in microfluidic systems can be used as in vitro drug screening tools. Compared to in vivo animal models, microfluidic drug screening platforms allow for high-throughput and reproducible screening at a significantly lower cost, and when combined with current advances in tissue engineering, are also capable of mimicking native tissues. In this review, various microfluidic platforms for drug and gene carrier fabrication are reviewed to provide guidelines for designing appropriate carriers. In vitro microfluidic drug screening platforms designed for high-throughput analysis and replication of in vivo conditions are also reviewed to highlight future directions for drug research and development. © 2013.

  19. SLN for topical application in skin diseases--characterization of drug-carrier and carrier-target interactions.

    PubMed

    Küchler, Sarah; Herrmann, Werner; Panek-Minkin, Grazyna; Blaschke, Tobias; Zoschke, Christian; Kramer, Klaus D; Bittl, Robert; Schäfer-Korting, Monika

    2010-05-10

    The modes of drug-particle interactions considerably influence drug delivery by nanoparticulate carrier systems and drug penetration into the skin. The exact mechanism of the drug loading and its release are still ambiguous. Therefore, the loading process, the interaction of the agent and the lipid matrix of solid lipid nanoparticles (SLNs) as well as the uptake of the loaded agent by skin lipids were analysed by electron spin resonance (ESR) and parelectric spectroscopy (PS) using spin probes (TEMPO, TEMPOL, and CAT-1) as model drugs differing in their lipophilicity. The spin probes were closely attached to the particles lipid surface (TEMPO) or located in the layers of the surfactant (CAT-1), respectively. Furthermore, two distinct sub-compartments on the SLN were found. To simulate the processes at the phase boundary SLN dispersion/skin, skin lipid mixtures were prepared and the transfer process of the spin labels was followed by ESR tomography. Transfer rates were related to the lipophilicity of the spin probe, the lipid mixture and the applied pharmaceutical formulation, SLN dispersion and aqueous solution, respectively. In particular, SLN accelerated in particular the distribution of the lipophilic agents. Copyright 2010 Elsevier B.V. All rights reserved.

  20. Recent advancements in the cardiovascular drug carriers.

    PubMed

    Singh, Baljeet; Garg, Tarun; Goyal, Amit K; Rath, Goutam

    2016-01-01

    Cardiovascular disease is the disease that affects the cardiovascular system, vascular diseases of the brain and kidney, and peripheral arterial disease. Despite of all advances in pharmacological and clinical treatment, heart failure is a leading cause of morbidness and mortality worldwide. Many new therapeutic advance strategies, including cell transplantation, gene delivery or therapy, and cytokines or other small molecules, have been research to treat heart failure. The main aim of this review article is to focus on nano carriers advancement and addressing the problems associated with old and modern therapeutics such as nonspecific effects and poor stability.

  1. Role of solid carriers in pharmaceutical performance of solid supersaturable SEDDS of celecoxib.

    PubMed

    Chavan, Rahul B; Modi, Sameer R; Bansal, Arvind K

    2015-11-10

    Self emulsifying drug delivery system (SEDDS) has been increasingly used for improving the oral bioavailability of poorly water soluble drugs. SEDDS can be solidified by adsorbing them on different solid carriers. In the present study, the impact of properties of solid carrier on drug release profile from solid SEDDS was investigated. Celecoxib (CEL) loaded supersaturable SEDDS (S-SEDDS) was prepared and optimized by using optimal response surface design. Optimum composition of S-SEDDS corresponded to 10:45:45% v/v ratio of oil (Capryol 90), surfactant (Tween 20) and cosurfactant (Transcutol HP) with Soluplus (40 mg) as precipitation inhibitor. Different grades of silicon dioxide were selected based on their properties like surface area, porosity and hydrophobicity-hydrophilicity, and used for preparation of solid S-SEDDS (SS-SEDDS) by adsorption method. All SS-SEDDS formulations in release studies, gave droplet size, PDI and zeta potential similar to S-SEDDS. The percent drug release after 120min from CEL powder, S-SEDDS and SS-SEDDS with Sylysia 350 fcp, Aerosil 300 Pharma, Aerosil 200 Pharma and Aerosil R 972 Pharma was found to be 0.58%, 100%, 38.44%, 9.63%, 2.53% and 5.99%, respectively. Drug release profiles were compared by using model independent methods. The differential drug release behavior of SS-SEDDS was attributed to the different physico-chemical properties of solid carriers. SS-SEDDS with Sylysia 350 fcp showed higher drug release and greater dissolution efficiency. Oral bioavailability study also demonstrated 2.34 fold increase in Cmax and 4.82 fold increase in AUC (0-24h) when compared with CEL powder. This study highlights the rational for selection of solid carriers in the formulation development of solid SEDDS.

  2. Diisocyanate mediated polyether modified gelatin drug carrier for controlled release

    PubMed Central

    Vijayakumar, Vediappan; Subramanian, Kaliappagounder

    2013-01-01

    Gelatin is an extensively studied biopolymer hydrogel drug carrier due to its biocompatibility, biodegradability and non-toxicity of its biodegraded products formed in vivo. But with the pristine gelatin it is difficult to achieve a controlled and desirable drug release characteristics due to its structural and thermal lability and high solubility in aqueous biofluids. Hence it is necessary to modify its solubility and structural stability in biofluids to achieve controlled release features with improved drug efficacy and broader carrier applications. In the present explorations an effort is made in this direction by cross linking gelatin to different extents using hitherto not studied isocyanate terminated poly(ether) as a macrocrosslinker prepared from poly(ethylene glycol) and isophorone diisocyanate in dimethyl sulfoxide. The crosslinked samples were analyzed for structure by Fourier transform-infrared spectroscopy, thermal behavior through thermogravimetric analysis and differential scanning calorimetry. The cross linked gelatins were biodegradable, insoluble and swellable in biofluids. They were evaluated as a carrier for in vitro drug delivery taking theophylline as a model drug used in asthma therapy. The crosslinking of gelatin decreased the drug release rate by 10–20% depending upon the extent of crosslinking. The modeled drug release characteristics revealed an anomalous transport mechanism. The release rates for ampicillin sodium, 5-fluorouracil and theophylline drugs in a typical crosslinked gelatin carrier were found to depend on the solubility and hydrophobicity of the drugs, and the pH of the fluid. The observed results indicated that this material can prove its mettle as a viable carrier matrix in drug delivery applications. PMID:24493973

  3. Early drug discovery and the rise of pharmaceutical chemistry.

    PubMed

    Jones, Alan Wayne

    2011-06-01

    Studies in the field of forensic pharmacology and toxicology would not be complete without some knowledge of the history of drug discovery, the various personalities involved, and the events leading to the development and introduction of new therapeutic agents. The first medicinal drugs came from natural sources and existed in the form of herbs, plants, roots, vines and fungi. Until the mid-nineteenth century nature's pharmaceuticals were all that were available to relieve man's pain and suffering. The first synthetic drug, chloral hydrate, was discovered in 1869 and introduced as a sedative-hypnotic; it is still available today in some countries. The first pharmaceutical companies were spin-offs from the textiles and synthetic dye industry and owe much to the rich source of organic chemicals derived from the distillation of coal (coal-tar). The first analgesics and antipyretics, exemplified by phenacetin and acetanilide, were simple chemical derivatives of aniline and p-nitrophenol, both of which were byproducts from coal-tar. An extract from the bark of the white willow tree had been used for centuries to treat various fevers and inflammation. The active principle in white willow, salicin or salicylic acid, had a bitter taste and irritated the gastric mucosa, but a simple chemical modification was much more palatable. This was acetylsalicylic acid, better known as Aspirin®, the first blockbuster drug. At the start of the twentieth century, the first of the barbiturate family of drugs entered the pharmacopoeia and the rest, as they say, is history.

  4. The US drug safety system: role of the pharmaceutical industry.

    PubMed

    Gibson, Brent R; Suh, Ryung; Tilson, Hugh

    2008-02-01

    Despite increasingly strident calls for improved drug safety in the United States, recent events underscore the continuing gap among manufacturers, regulators, patients, and physicians. In the period leading to the recent Institute of Medicine report on the future of drug safety, representatives from industry were given an opportunity to provide input into this report. In light of continuing concerns about drug safety and pending legislation, this original perspective provides an important context. This work consolidates the views of representatives of individual pharmaceutical companies; the large industry trade associations, the Pharmaceutical Researchers and Manufacturers of America (PhRMA) and the Biotechnology Industry Association (BIO); and those of the authors with regard to the industry role of drug safety in the United States. To ensure continued protection of the public's health, manufacturers must recognize themselves as critical to ensuring safe products; maintain corporate safety functions separate from marketing functions; provide oversight by a senior medical executive; engage in structured epidemiological research, risk assessment, and risk communication; and mandate the formation and maintenance of an internal, interdisciplinary, senior level safety council. The importance of aggressive and accountable drug safety will only become more salient as the public and their elected representatives demand better accountability from industry. Individual corporations now have the opportunity to move first to counter perceptions of profit over safety and to ensure that their business practices adequately protect the public's health. Copyright 2007 John Wiley & Sons, Ltd.

  5. Pharmaceutical drug marketing strategies and tactics: a comparative analysis of attitudes held by pharmaceutical representatives and physicians.

    PubMed

    Parker, R Stephen; Pettijohn, Charles E

    2005-01-01

    A variety of promotional strategies have been used to stimulate sales of pharmaceutical drugs. Traditionally, push techniques have been the predominant means used to encourage physicians to prescribe drugs and thus increase sales. Recently, the traditional push strategy has been supplemented by a pull strategy. Direct-to-consumer advertising is increasingly used to encourage consumers to request advertised drugs from their physicians. This research compares the attitudes of two of the most affected participants in the prescriptive sales processes; physicians and pharmaceutical sales representatives. The findings indicate differences between physicians and pharmaceutical sales representatives regarding the efficacy and ethical considerations of various promotional strategies.

  6. 75 FR 26160 - Drug and Drug-Related Supply Promotion by Pharmaceutical Company Sales Representatives at VA...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-05-11

    ... AFFAIRS 38 CFR Part 1 RIN 2900-AN42 Drug and Drug-Related Supply Promotion by Pharmaceutical Company Sales... eliminate any potential for disruption in the patient care environment, manage activities and promotions at... response to ``RIN 2900-AN42--Drug and Drug-Related Supply Promotion by Pharmaceutical Company...

  7. Micellar systems: Novel family for drug carriers

    NASA Astrophysics Data System (ADS)

    Rana, Meenakshi; Chowdhury, Papia

    2016-05-01

    Micellar systems have attracted a great deal of interest, especially in the field of biomedical sciences. The paper deals with the encapsulation behavior of Pyrrole-2-carboxyldehyde (PCL) an anti-cancer drug in different micellar systems. The inculsion capability of PCL is verified experimentally (UV-Vis, Photoluminescence and Raman spectroscopy) in polymer matrix. Two-micellar systems sodium dodecyl sulfate (SDS) and Polysorbate 80 (TWEEN 80) have been studied with a poorly water soluble PCL. The present work provides the effects of biocompatible organic PCL molecule entrap in micellar system in polymer phase due to its vast applicability in drug industry.

  8. Barriers to Alzheimer disease drug discovery and drug development in the pharmaceutical industry.

    PubMed

    Anand, Ravi

    2002-01-01

    The drug development process in the pharmaceutical industry has evolved from separate programs, specific for each country, into one coordinated, global development scheme. As a result, such a development program must meet regulatory requirements for all countries in which approval for the new drug will be sought. Barriers to Alzheimer disease (AD) drug discovery and development in the pharmaceutical industry can be categorized as (1) regulatory, (2) logistical, and (3) drug development issues. Some of the regulatory barriers could be overcome by international harmonization of guidelines for the development of antidementia drugs. The logistical issues can be reduced through international collaboration in the conduct of clinical studies, and the developmental issues can be addressed by using an expedited drug development plan that not only can reduce the time but also the resources required to develop the drug.

  9. Active Targeted Drug Delivery for Microbes Using Nano-Carriers

    PubMed Central

    Lin, Yung-Sheng; Lee, Ming-Yuan; Yang, Chih-Hui; Huang, Keng-Shiang

    2015-01-01

    Although vaccines and antibiotics could kill or inhibit microbes, many infectious diseases remain difficult to treat because of acquired resistance and adverse side effects. Nano-carriers-based technology has made significant progress for a long time and is introducing a new paradigm in drug delivery. However, it still has some challenges like lack of specificity toward targeting the infectious site. Nano-carriers utilized targeting ligands on their surface called ‘active target’ provide the promising way to solve the problems like accelerating drug delivery to infectious areas and preventing toxicity or side-effects. In this mini review, we demonstrate the recent studies using the active targeted strategy to kill or inhibit microbes. The four common nano-carriers (e.g. liposomes, nanoparticles, dendrimers and carbon nanotubes) delivering encapsulated drugs are introduced. PMID:25877093

  10. Nanoscale poly(4-hydroxybutyrate)-mPEG carriers for anticancer drugs delivery.

    PubMed

    Shah, Mohsin; Ullah, Najeeb; Choi, Mun Hwan; Yoon, Sung Chul

    2014-11-01

    Despite several advancements in chemotherapy, cancer is still the second most frequent cause of mortality worldwide. Drug delivery to solid tumors is one of the most challenging aspects in cancer therapy. In pharmaceutical industries biodegradable polymeric nanoparticles as drug carriers have attracted great research interest because of their biocompatibility, biodegradability and sustained release of drugs. In our study we prepared poly(4-hydroxybutyrate)-mPEG (P(4HB)-mPEG) nanocarriers for the delivery of cisplatin as anticancer drug to mouse hippocampal HT22 cells. P(4HB) is more suitable candidate to be utilized in pharmaceutical industries due to its wide medical applications. P(4HB) is a homopolymer of 4-hydroxybutyrate (4HB), and belongs to a diverse class of materials called polyhydroxyalkanoates (PHA) produced by microorganisms inside the cells as energy storage materials. P(4HB) has certain unique properties such as biocompatibility and rapid in vivo degradation, which differentiate it from others PHA based polymers. Novel amorphous amphiphilic block copolymer P(4HB)-mPEG nanocarriers were prepared and characterized. Flow cytometry, and confocal microscopy revealed a suppression effect by the cisplatin loaded nanocarriers on HT22 cell growth, and enhancement of apoptotic process of the cells compared to free drug treated cells. The amorphous polymeric nanocarriers could be effective vehicles for the sustained delivery of toxic anticancer drugs for the therapy of cancer.

  11. Raman microscopy for cellular investigations--From single cell imaging to drug carrier uptake visualization.

    PubMed

    Kann, Birthe; Offerhaus, Herman L; Windbergs, Maike; Otto, Cees

    2015-07-15

    Progress in advanced therapeutic concepts requires the development of appropriate carrier systems for intracellular drug delivery. Consequently, analysis of interaction between carriers, drugs and cells as well as their uptake and intracellular fate is a current focus of research interest. In this context, Raman spectroscopy recently became an emerging analytical technique, due to its non-destructive, chemically selective and label-free working principle. In this review, we briefly present the state-of-the-art technologies for cell visualization and drug internalization. Against this background, Raman microscopy is introduced as a versatile analytical technique. An overview of various Raman spectroscopy investigations in this field is given including interactions of cells with drug molecules, carrier systems and other nanomaterials. Further, Raman instrumentations and sample preparation methods are discussed. Finally, as the analytical limit is not reached yet, a future perspective for Raman microscopy in pharmaceutical and biomedical research on the single cell level is given. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. The Role of Carrier Geometry in Overcoming Biological Barriers to Drug Delivery.

    PubMed

    Jordan, Carolyn; Shuvaev, Vladimir V; Bailey, Mark; Muzykantov, Vladimir R; Dziubla, Thomas D

    2016-01-01

    For a variety of diseases, effective therapy is severely limited or rendered impossible due to an inability to deliver medications to the intended sites of action. Multiple barriers exist through the body, which have evolved over time to limit the migration of foreign compounds from entering the tissues. Turning toward biology as inspiration, it has been the general goal of drug delivery to create carrier strategies that mimic, in part, features of bacteria/ viruses that allow them overcome these barriers. By packaging drugs into nano and micron scale vehicles, it should be possible to completely change the biodistribution and residence times of pharmaceutically active compounds. Recently, due to advances in formulation technologies, it has become possible to control not just the material selection, surface chemistry, and/or size, but also the overall geometry and plasticity of the drug carriers. These approaches aid in the formulation of nonspherical particles such as, discs, rods, and even unique structures such as cubes and nanodiamonds. The adjustment of size and shape can be used for the aid or prevention in cellular uptake and also to overcome the vascular and mucosal barrier. In this review, we present a summary of some approaches used to control carrier shape and the impact these geometries have upon drug transport across biological barriers.

  13. Cyclodextrin-functionalized polymers as drug carriers for cancer therapy.

    PubMed

    Wei, Hua; Yu, Cui-yun

    2015-07-01

    Cyclodextrins (CDs) represent the most extensively investigated cyclic molecules due to their wide availability, facile functionalization, unique amphiphilicity and inclusion capacity. The marriage of CD chemistry with polymer science has generated novel biomaterials by integrating supermolecular host-guest chemistry and state-of-the-art polymer chemistry techniques. The current mini-review focuses on the recent progress in CD-functionalized polymers as drug carriers for cancer therapy. CD-functionalized polymers with different structures are summarized. Their application as drug carriers for cancer therapy is then highlighted. In the end, the future directions of this rapidly developing research field are discussed.

  14. Drug Carrier for Photodynamic Cancer Therapy

    PubMed Central

    Debele, Tilahun Ayane; Peng, Sydney; Tsai, Hsieh-Chih

    2015-01-01

    Photodynamic therapy (PDT) is a non-invasive combinatorial therapeutic modality using light, photosensitizer (PS), and oxygen used for the treatment of cancer and other diseases. When PSs in cells are exposed to specific wavelengths of light, they are transformed from the singlet ground state (S0) to an excited singlet state (S1–Sn), followed by intersystem crossing to an excited triplet state (T1). The energy transferred from T1 to biological substrates and molecular oxygen, via type I and II reactions, generates reactive oxygen species, (1O2, H2O2, O2*, HO*), which causes cellular damage that leads to tumor cell death through necrosis or apoptosis. The solubility, selectivity, and targeting of photosensitizers are important factors that must be considered in PDT. Nano-formulating PSs with organic and inorganic nanoparticles poses as potential strategy to satisfy the requirements of an ideal PDT system. In this review, we summarize several organic and inorganic PS carriers that have been studied to enhance the efficacy of photodynamic therapy against cancer. PMID:26389879

  15. Intellectual property and pharmaceutical drugs: an ethical analysis.

    PubMed

    De George, Richard T

    2005-10-01

    The pharmaceutical industry has in recent years come under attack from an ethical point of view concerning its patents and the non-accessibility of life-saving drugs for many of the poor in both less developed countries and in the United States. The industry has replied with economic and legal justifications for its actions. The result has been a communication gap between the industry on the one hand and poor nations and American critics on the other. This paper attempts to present and evaluate the arguments on all sides and suggests a possible way out of the current impasse. It attempts to determine the ethical responsibility of the drug industry in making drugs available to the needy, while at the same time developing the parallel responsibilities of individuals, governments, and NGOs. It concludes with the suggestion that the industry develop an international code for its self-regulation.

  16. Recurring Epidemics of Pharmaceutical Drug Abuse in America: Time for an All-Drug Strategy

    PubMed Central

    Guarino, Honoria; Mateu-Gelabert, Pedro; Bennett, Alex S.

    2016-01-01

    Observers describe today’s “epidemic” of pharmaceutical drug abuse as a recent phenomenon, but we argue that it is only the most recent of three waves stretching back more than a century. During each wave, policies have followed a similar pattern: voluntary educational campaigns, followed by supply-side policing and—sometimes—public health responses that would today be understood as “harm reduction.” These experiences suggest that only broad-based application of all three approaches to users of all drugs (not just pharmaceutical drugs) can produce a reduction in drug-related harm rather than merely shifting it from one type of drug to another. This has rarely happened because policy has been shaped by the racially charged division of drug users into deserving and morally salvageable victims, or fearsome and morally repugnant criminals. PMID:26794163

  17. Recurring Epidemics of Pharmaceutical Drug Abuse in America: Time for an All-Drug Strategy.

    PubMed

    Herzberg, David; Guarino, Honoria; Mateu-Gelabert, Pedro; Bennett, Alex S

    2016-03-01

    Observers describe today's "epidemic" of pharmaceutical drug abuse as a recent phenomenon, but we argue that it is only the most recent of three waves stretching back more than a century. During each wave, policies have followed a similar pattern: voluntary educational campaigns, followed by supply-side policing and--sometimes--public health responses that would today be understood as "harm reduction." These experiences suggest that only broad-based application of all three approaches to users of all drugs (not just pharmaceutical drugs) can produce a reduction in drug-related harm rather than merely shifting it from one type of drug to another. This has rarely happened because policy has been shaped by the racially charged division of drug users into deserving and morally salvageable victims, or fearsome and morally repugnant criminals.

  18. Impurities in Drug Products and Active Pharmaceutical Ingredients.

    PubMed

    Kątny, M; Frankowski, M

    2016-09-29

    Analytical methods should be selective and fast. In modern times, scientists strive to meet the criteria of green chemistry, so they choose analytical procedures that are as short as possible and use the least toxic solvents. It is quite obvious that the products intended for human consumption should be characterized as completely as possible. The safety of a drug is dependent mainly on the impurities that it contains. High pressure liquid chromatography and ultra-high pressure liquid chromatography have been proposed as the main techniques for forced degradation and impurity profiling. The aim of this article was to characterize the relevant classification of drug impurities and to review the methods of impurities determination for atorvastatin (ATV) and duloxetine (DLX) (both in active pharmaceutical ingredients and in different dosage forms). These drugs have an impact on two systems of the human body: cardiac and nervous. Simple characteristics of ATV and DLX, their properties and specificity of action on the human body, are also included in this review. The analyzed pharmaceuticals-ATV (brand name Lipiron) and DLX (brand name Cymbalta)-were selected for this study based on annual rankings prepared by Information Medical Statistics.

  19. Preparation and application of functionalized nano drug carriers.

    PubMed

    Gong, Rudong; Chen, Gaimin

    2016-05-01

    Targeting at category memory characteristics and preparation methods of functionalized nano drugs, preparation technology of functionalized nano drug carriers is studied, and then important role of functionalized nano drug carrier in preparation of medicine is studied. Carry out the relevant literature search with computer, change limited language in the paper to Chinese and necessarily remove repetitive studies. After first review of 1260 retrieved literature, it can be found that nano drug is with accurate quantity, relatively good targeting, specificity and absorbency. Necessary research of nano drug carriers can prevent and treat disease to a certain extent. Preparation of functionalized nanocarrier is simple and convenient, which can improve frequency of use of nano preparation technology and provide better development space for medical use. Therefore, nanocarriers should be combined with drugs with relatively strong specificity in clinics, in order to be able to conduct effective research on nanometer intelligent drug, effectively promote long-term development of nano biotechnology, and then provide favorable, reliable basis for clinical diagnosis and treatment.

  20. Carrier particle design for stabilization and isolation of drug nanoparticles.

    PubMed

    Tierney, Teresa; Bodnár, Katalin; Rasmuson, Åke; Hudson, Sarah

    2017-02-25

    Nanoparticles of poorly water-soluble drugs were prepared in suspension via antisolvent precipitation in order to improve their dissolution behaviour. Insoluble, surface-functionalized, micron-range, clay carrier particles were employed for the dual purpose of stabilizing the nanoparticles in suspended state, and facilitating their unhindered isolation to solid state; often a challenging step in nanoparticle production. The carrier particles, which were functionalized with an optimal level of cationic polymer (protamine), attracted negatively-charged nanoparticles to their surface as a uniform and segregated nanoparticle layer, at drug loadings up to 9% w/w. By using carrier particles to stabilise the nanoparticles on their surface, the traditionally used solubilised nanosuspension stabilisers could be eliminated, thus avoiding time-consuming stabiliser screening tests. The carrier particle system facilitated stabilisation of nanoparticles in suspension, isolation of nanoparticles to the solid state via filtration, and preservation of fast nanoparticle-induced dissolution rates of the dried nanoparticle-carrier composites, indicating preservation of their high surface area during drying. The process was validated with two poorly water-soluble BCS Class II drugs, fenofibrate and mefenamic acid, both of which demonstrated negative surface charge in aqueous suspension.

  1. Pharmaceutical approaches to colon targeted drug delivery systems.

    PubMed

    Chourasia, M K; Jain, S K

    2003-01-01

    Although oral delivery has become a widely accepted route of administration of therapeutic drugs, the gastrointestinal tract presents several formidable barriers to drug delivery. Colonic drug delivery has gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon but also for its potential for the delivery of proteins and therapeutic peptides. To achieve successful colonic delivery, a drug needs to be protected from absorption and /or the environment of the upper gastrointestinal tract (GIT) and then be abruptly released into the proximal colon, which is considered the optimum site for colon-targeted delivery of drugs. Colon targeting is naturally of value for the topical treatment of diseases of colon such as Chron's diseases, ulcerative colitis, colorectal cancer and amebiasis. Peptides, proteins, oligonucleotides and vaccines pose potential candidature for colon targeted drug delivery. The various strategies for targeting orally administered drugs to the colon include covalent linkage of a drug with a carrier, coating with pH-sensitive polymers, formulation of timed released systems, exploitation of carriers that are degraded specifically by colonic bacteria, bioadhesive systems and osmotic controlled drug delivery systems. Various prodrugs (sulfasalazine, ipsalazine, balsalazine and olsalazine) have been developed that are aimed to deliver 5-amino salicylic acid (5-ASA) for localized chemotherapy of inflammatory bowl disease (IBD). Microbially degradable polymers especially azo crosslinked polymers have been investigated for use in targeting of drugs to colon. Certain plant polysaccharides such as amylose, inulin, pectin and guar gum remains unaffected in the presence of gastrointestinal enzymes and pave the way for the formulation of colon targeted drug delivery systems. The concept of using pH as a rigger to release a drug in the colon is based on the pH conditions that vary continuously

  2. Carbon Nanotubes: An Emerging Drug Carrier for Targeting Cancer Cells

    PubMed Central

    Bhattacharya, Shiv Sankar; Mishra, Arun Kumar; Verma, Navneet; Verma, Anurag; Pandit, Jayanta Kumar

    2014-01-01

    During recent years carbon nanotubes (CNTs) have been attracted by many researchers as a drug delivery carrier. CNTs are the third allotropic form of carbon-fullerenes which were rolled into cylindrical tubes. To be integrated into the biological systems, CNTs can be chemically modified or functionalised with therapeutically active molecules by forming stable covalent bonds or supramolecular assemblies based on noncovalent interactions. Owing to their high carrying capacity, biocompatibility, and specificity to cells, various cancer cells have been explored with CNTs for evaluation of pharmacokinetic parameters, cell viability, cytotoxicty, and drug delivery in tumor cells. This review attempts to highlight all aspects of CNTs which render them as an effective anticancer drug carrier and imaging agent. Also the potential application of CNT in targeting metastatic cancer cells by entrapping biomolecules and anticancer drugs has been covered in this review. PMID:24872894

  3. Microemulsion utility in pharmaceuticals: Implications for multi-drug delivery.

    PubMed

    Callender, Shannon P; Mathews, Jessica A; Kobernyk, Katherine; Wettig, Shawn D

    2017-06-30

    Emulsion technology has been utilized extensively in the pharmaceutical industry. This article presents a comprehensive review of the literature on an important subcategory of emulsions, microemulsions. Microemulsions are optically transparent, thermodynamically stable colloidal systems, 10-100nm diameter, that form spontaneously upon mixing of oil, water and emulsifier. This review is the first to address advantages and disadvantages, as well as considerations and challenges in multi-drug delivery. For the period 1 January 2011-30 April 2016, 431 publications related to microemulsion drug delivery were identified and screened according to microemulsion, drug classification, and surfactant types. Results indicate the use of microemulsions predominantly in lipophilic drug delivery (79.4%) via oil-in-water microemulsions and non-ionic surfactants (90%) for oral or topical administration. Cancer is the disease state most targeted followed by inflammatory diseases, microbial infections and cardiovascular disease. Key generalizations from this analysis include: 1) microemulsion formulation is largely based on trial-and-error despite over 1200 publications related to microemulsion drug delivery since their discovery in 1943; 2) characterization using methods including interfacial tension, droplet size, electrical conductivity, turbidity and viscosity may provide additional information for greater predictability; 3) microemulsion drug delivery publications arise primarily from China (27%) and India (21%) suggesting additional research opportunities elsewhere. Copyright © 2017 Elsevier B.V. All rights reserved.

  4. Sodium Montmorillonite/Amine-Containing Drugs Complexes: New Insights on Intercalated Drugs Arrangement into Layered Carrier Material

    PubMed Central

    Vieira, Bárbara A.; Dias, Luiza R. S.; de Sousa, Valéria P.; Castro, Helena C.; Rodrigues, Carlos R.; Cabral, Lucio M.

    2015-01-01

    Layered drug delivery carriers are current targets of nanotechnology studies since they are able to accommodate pharmacologically active substances and are effective at modulating drug release. Sodium montmorillonite (Na-MMT) is a clay that has suitable properties for developing new pharmaceutical materials due to its high degree of surface area and high capacity for cation exchange. Therefore Na-MMT is a versatile material for the preparation of new drug delivery systems, especially for slow release of protonable drugs. Herein, we describe the intercalation of several amine-containing drugs with Na-MMT so we can derive a better understanding of how these drugs molecules interact with and distribute throughout the Na-MMT interlayer space. Therefore, for this purpose nine sodium montmorillonite/amine-containing drugs complexes (Na-MMT/drug) were prepared and characterized. In addition, the physicochemical properties of the drugs molecules in combination with different experimental conditions were assessed to determine how these factors influenced experimental outcomes (e.g. increase of the interlayer spacing versus drugs arrangement and orientation). We also performed a molecular modeling study of these amine-containing drugs associated with different Na-MMT/drug complex models to analyze the orientation and arrangement of the drugs molecules in the complexes studied. Six amine-containing drugs (rivastigmine, doxazosin, 5-fluorouracil, chlorhexidine, dapsone, nystatin) were found to successfully intercalate Na-MMT. These findings provide important insights on the interlayer aspect of the molecular systems formed and may contribute to produce more efficient drug delivery nanosystems. PMID:25803292

  5. Preparation, characterization, and potential application of chitosan, chitosan derivatives, and chitosan metal nanoparticles in pharmaceutical drug delivery

    PubMed Central

    Ahmed, Tarek A; Aljaeid, Bader M

    2016-01-01

    Naturally occurring polymers, particularly of the polysaccharide type, have been used pharmaceutically for the delivery of a wide variety of therapeutic agents. Chitosan, the second abundant naturally occurring polysaccharide next to cellulose, is a biocompatible and biodegradable mucoadhesive polymer that has been extensively used in the preparation of micro-as well as nanoparticles. The prepared particles have been exploited as a potential carrier for different therapeutic agents such as peptides, proteins, vaccines, DNA, and drugs for parenteral and nonparenteral administration. Therapeutic agent-loaded chitosan micro- or nanoparticles were found to be more stable, permeable, and bioactive. In this review, we are highlighting the different methods of preparation and characterization of chitosan micro- and nanoparticles, while reviewing the pharmaceutical applications of these particles in drug delivery. Moreover, the roles of chitosan derivatives and chitosan metal nanoparticles in drug delivery have been illustrated. PMID:26869768

  6. Polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers for cancer therapy.

    PubMed

    Prakash, Satya; Malhotra, Meenakshi; Shao, Wei; Tomaro-Duchesneau, Catherine; Abbasi, Sana

    2011-11-01

    The scope of nanotechnology to develop target specific carriers to achieve higher therapeutic efficacy is gaining importance in the pharmaceutical and other industries. Specifically, the emergence of nanohybrid materials is posed to edge over chemotherapy and radiation therapy as cancer therapeutics. This is primarily because nanohybrid materials engage controlled production parameters in the making of engineered particles with specific size, shape, and other essential properties. It is widely expressed that these materials will significantly contribute to the next generation of medical care technology and pharmaceuticals in areas of disease diagnosis, disease prevention and many other treatment procedures. This review focuses on the currently used nanohybrid materials, polymeric nanoparticles and nanotubes, which show great potential as effective drug delivery systems for cancer therapy, as they can be grafted with cell-specific receptors and intracellular targeting molecules for the targeted delivery of therapeutics. Specifically, this article focuses on the current status, recent advancements, potentials and limitations of polymeric nanohybrids and functionalized carbon nanotubes as drug delivery carriers.

  7. [Separation of chiral pharmaceutical drugs by chromatographic and electrophoretic techniques].

    PubMed

    Morin, P

    2009-07-01

    A large number of pharmaceutical drugs possess one or more centers of asymmetry giving rise to enantiomers whose pharmacological properties and toxicity are often different. At successive stages of drug discovery, the enantiomers of any chiral molecule must be isolated and analyzed and their enantiomeric purity determined. The electrophoretic and chromatographic techniques have become the most important tools to routinely determine the enantiomeric purity of pharmaceutical molecules. Liquid chromatography (LC) is the most widely used because of the large number of columns marketed, the variety of selectivities available and the ease at which analytical results can be scaled up to the preparative level. In particular, more than 80% of enantioseparations of pharmaceutical molecules are successful with polysaccharide-derivative stationary phases (cellulose, amylose) for multiple system solvents (normal phase, polar organic phase or reverse phase). Complementary selectivities can be achieved more rapidly with other types of stationary phase (glycopeptides, Pirkle, cyclodextrins) but their application is hindered by problems of stability (proteins) or transfer to the preparative scale (cyclodextrins). At the present time, glycopeptide phases offer very promising prospects for the separation of amino acids (and derivatives) and peptide enantiomers. In addition, because of its faster analysis and environmental benefits, supercritical chromatography (SFC) has given rise to renewed interest. Capillary electrophoresis (CE) is an orthogonal technique complementary to chromatographic methods. Its principle involves the formation of diastereoisomer complexes after addition of anionic (HS-beta-CD, HS-gamma-CD CM-beta-CD) or neutral (TM-beta -CD, HP-beta-CD, DM-beta-CD, HP-gamma-CD) cyclodextrins to the running buffer. Compared to LC, CE analyses are cheaper (no chiral column, no solvent, low consumption of chiral selector) and peak efficiencies are higher by one order of

  8. Novel application of hydrophobin in medical science: a drug carrier for improving serum stability

    PubMed Central

    Zhao, Liqiang; Xu, Haijin; Li, Ying; Song, Dongmin; Wang, Xiangxiang; Qiao, Mingqiang; Gong, Min

    2016-01-01

    Multiple physiological properties of glucagon-like peptide-1 (GLP-1) ensure that it is a promising drug candidate for the treatment of type 2 diabetes. However, the in vivo half-life of GLP-1 is short because of rapid degradation by dipeptidyl peptidase-IV (DPP-IV) and renal clearance. The poor serum stability of GLP-1 has significantly limited its clinical utility, although many studies are focused on extending the serum stability of this molecule. Hydrophobin, a self-assembling protein, was first applied as drug carrier to stabilize GLP-1 against protease degradation by forming a cavity. The glucose tolerance test clarified that the complex retained blood glucose clearance activity for 72 hours suggesting that this complex might be utilized as a drug candidate administered every 2–3 days. Additionally, it was found that the mutagenesis of hydrophobin preferred a unique pH condition for self-assembly. These findings suggested that hydrophobin might be a powerful tool as a drug carrier or a pH sensitive drug-release compound. The novel pharmaceutical applications of hydrophobin might result in future widespread interest in hydrophobin. PMID:27212208

  9. Particles from preformed polymers as carriers for drug delivery

    PubMed Central

    Miladi, K.; Ibraheem, D.; Iqbal, M.; Sfar, S.; Fessi, H.; Elaissari, A.

    2014-01-01

    Biodegradable and biocompatible polymers are widely used for the encapsulation of drug molecules. Various particulate carriers with different sizes and characteristics have been prepared by miscellaneous techniques. In this review, we reported the commonly used preformed polymer based techniques for the preparation of micro and nano-structured materials intended for drug encapsulation. A description of polymer-solvent interaction was provided. The most widely used polymers were reported and described and their related research studies were mentioned. Moreover, principles of each technique and its crucial operating conditions were described and discussed. Recent applications of all the reported techniques in drug delivery were also reviewed. PMID:26417241

  10. The interaction between carrier rugosity and carrier payload, and its effect on drug particle redispersion from adhesive mixtures during inhalation.

    PubMed

    Dickhoff, B H J; de Boer, A H; Lambregts, D; Frijlink, H W

    2005-01-01

    The effectiveness of press-on forces (defined as the adhesive forces between drug and carrier particles) in relation to carrier payload as the result of collisions between carrier particles during the mixing process of an adhesive mixture, has been investigated. Three different carriers of the same size fraction (250-355 microm), but with completely different surface rugosity were studied. It could be shown that this effectiveness depends on the carrier rugosity. The fraction of drug detached from the carrier particles during inhalation appeared to decrease faster with increasing carrier payload for crystalline carriers than for granular carriers. Apparently, increasing the volume of the carrier surface cavities increases the drug mass that can find shelter from the press-on forces during mixing. By measuring the size distribution in the aerosol, it could also be shown that the press-on forces may increase the size of the particles that are detached. This seems to be the result of drug particle re-agglomeration on the carrier surface during mixing. On the other hand, when press-on forces are highly ineffective, an increase in the size of detached particles may also be the result of incomplete break-up of natural drug agglomerates. Finally, it could be shown that when the press-on forces are highly effective, the effect of mixing time is small.

  11. Biochemical effects of the pharmaceutical drug paracetamol on Anguilla anguilla.

    PubMed

    Nunes, Bruno; Verde, Maria Francisca; Soares, Amadeu M V M

    2015-08-01

    The ever-increasing presence of pharmaceutical drugs in the environment is a motif of concern, and human-use drugs are of particular importance. This is the case of paracetamol, a widely employed drug in human therapeutics, as analgesic and antipyretic, whose toxicity on aquatic organisms is still not fully characterized. The present study aimed to assess the toxic deleterious effects of paracetamol on European eel, Anguila anguilla, by using a comprehensive battery of antioxidant biomarkers (activities of enzymes such as catalase (CAT) and glutathione S-transferases (GSTs)), and the quantification of oxidative damage (measurement of levels of lipid peroxidation (thiobarbituric acid reactive substances (TBARS) assay)). Other biochemical effects elicited by this substance were also quantified, in terms of anaerobic respiration (activity of lactate dehydrogenase, LDH) and neurotoxicity (acetylcholinesterase, AChE, activity). The obtained results showed the occurrence of an oxidative base response, and paracetamol also seemed to inhibit AChE, showing that this drug can also elicit neurotoxicity. The lack of response by both CAT and LDH show that, despite the occurrence of toxicity, eels have detoxification mechanisms that are effective to cope with paracetamol, preventing additional deleterious alterations, including in the main pathway by which they obtain energy.

  12. Adaptive Chitosan Hollow Microspheres as Efficient Drug Carrier.

    PubMed

    Fu, Ya-Nan; Li, Yongsan; Li, Guofeng; Yang, Lei; Yuan, Qipeng; Tao, Lei; Wang, Xing

    2017-07-10

    Smart drug carrier with function-oriented adaptations is highly desired due to its unique properties in medical applications. Herein, adaptive chitosan hollow microspheres (CHM) are fabricated by employing interfacial Schiff-base bonding reaction. Hydrophilic macromolecules of glycol chitosan are fixed at the oil/water interface through numerous hydrophobic small molecules of borneol 4-formylbenzoate, forming the CHM with a positively charged surface and lipophilic cavity. These CHM have an average size of 400-1000 nm after passing through the 0.22 μm apertures of filter paper. This phenomenon combined with SEM measurements demonstrates its remarkable shape-adaptive behavior. Furthermore, the CHM present a pH-dependence of structural stability. When pH value reduces from 7.06 to 5.01, the CHM begin to lose their integrity. All those characteristics make the CHM an intelligent drug carrier, especially for water-insoluble anticancer drugs, paclitaxel (PTX) in particular. Both cell uptake and cell cytotoxicity assays suggest that the PTX-loaded CHM are highly efficient on HepG2 and A549 cells. Therefore, rather than most of the traditional materials, these adaptive CHM show great potential as a novel drug carrier.

  13. Drug carriers for the delivery of therapeutic peptides.

    PubMed

    Du, Alice W; Stenzel, Martina H

    2014-04-14

    Peptides take on an increasingly important role as therapeutics in areas including diabetes, oncology, and metabolic, cardiovascular, and infectious diseases. In addition, many peptides such as insulin have been employed for many years. A challenge in the administration of peptide drugs is their often low hydrolytic stability, as well as other problems that are common to any drug treatment such as systemic distribution. There is a significant attention in the literature of protein drugs and their delivery strategies, but not many overviews are specifically dedicated to peptides. In this review, the different approaches to deliver peptides have been summarized where the focus is only on drug carriers based on organic materials. Initial discussion is on different methods of polymer-peptide conjugation before being followed by physical encapsulation techniques, which is divided into surfactant-based techniques and polymer carriers. Surfactant-based techniques are dominated by liposome, microemulsions and solid-lipid nanoparticles. The field widens further in the polymer field. The delivery of peptides has been enhanced using polymer-decorated liposomes, solid microspheres, polyelectrolyte complex, emulsions, hydrogels, and injectable polymers. The aim of this article is to give the reader an overview over the different types of carriers.

  14. [Liposomes as non-viral carriers for genetic drugs].

    PubMed

    Meissner, Justyna M; Toporkiewicz, Monika; Matusewicz, Lucyna; Machnicka, Beata

    2016-03-16

    Methods in cancer therapy particularly in recent years, are rapidly changing, due to the need of design of new, more effective therapeutic strategies. Very promising approach to treatment of the neoplastic diseases is antisense gene therapy. Due to the low toxicity of treatment and eliminating not only the symptoms but also the molecular causes of the disease it may represent a breakthrough in cancer therapies. Delivery of a therapeutic DNA or RNA oligonucleotides to the target cells in vivo requires suitable carrier system. Non-viral drug carriers are increasingly used in new systems of targeted gene therapy. This review presents new generation of non-viral carriers, and is focused on immunoliposomes finding potential application in targeted gene therapy.

  15. The effect of carrier surface and bulk properties on drug particle detachment from crystalline lactose carrier particles during inhalation, as function of carrier payload and mixing time.

    PubMed

    Dickhoff, B H J; de Boer, A H; Lambregts, D; Frijlink, H W

    2003-09-01

    The effect of carrier payload and mixing time on the redispersion of drug particles from adhesive mixtures during inhalation for two different drugs (budesonide and disodium cromoglycate) has been investigated. A special test inhaler which retains carrier crystals during inhalation was used at 30 and 60 l/min. The special inhaler enabled the analysis of residual drug on the carrier yielding so called carrier residue (CR) values. Mixtures with carrier size fractions of 32-45; 150-200 and 250-355 microm, derived from marketed lactose brands, with increasing carrier payload (0.4-6.0% w/w of drug) were prepared. It was found that with increasing carrier payload, the CR increases for the coarse carrier fraction, decreases for the fine fraction and remains roughly constant for the intermediate fraction at 30 l/min. At 60 l/min, the CR decreased for all carrier fractions with increasing payload. The effect of powder bulk properties on the adhesive forces between drug and carrier (during mixing) as well as changes in the balance between adhesion and separation forces (during inhalation) explain the results found. An improved understanding of the different effects is obtained through the recently introduced force distribution concept. The ratio of (mean) separation force to (mean) adhesion force increases with the flow rate. The adhesive forces (during mixing) increase with increasing carrier diameter (higher press-on and kneading forces) and longer mixing time.

  16. Pharmaceutical drug promotion: how it is being practiced in India?

    PubMed

    Lal, A

    2001-02-01

    The pharmaceutical industries (PI) throughout the World are heavily involved in aggressive drug promotions, with a clear aim to change the prescribing habits of physicians and to encourage the self-medication of patients. Broadly, drug promotion refers to all the informational and persuasive activities of the PI, the effect of which is to induce prescription, supply, purchase, and use of medicinal drugs. It includes the activities of medical representatives, drug advertisements to physicians, provision of gifts and samples, drug package inserts, direct-to-consumer advertisements, periodicals, telemarketing, holding of conferences, symposium and scientific meetings, sponsoring of medical education and conduct of promotional trials. The PI has the right to promote its products, but it should do so in a fair, accurate, and ethical manner. The promotional claims need to be reliable, truthful, informative, balanced, up-to-date, and capable of substantiation in good taste. However, now a days, whilst the promotional methods have become very sophisticated and effective, it was found that while promoting their products, the PI does not adhere to these ethical principles. Hence, in most situations, these lead to irrational use of drugs. This unfortunate situation could be tackled only by the multiple prong strategy involving government, PI, doctors, medical associations and consumers. The government is required to formulate some guidelines in addition to developing their own code. The doctors and consumers are required to be educated on the promotional practices and abuses committed by the PI and different ways to tackle those. Various medical and consumer groups should also intervene to improve the scenario of promotion.

  17. Aqueous boundary layers related to oral absorption of a drug: from dissolution of a drug to carrier mediated transport and intestinal wall metabolism.

    PubMed

    Sugano, Kiyohiko

    2010-10-04

    The aqueous boundary layer (ABL) affects various aspects of oral absorption of a drug, from dissolution of the drug to the apparent K(m) value of intestinal wall metabolism and carrier mediated transport. However, the importance of ABL has often been entirely ignored in oral absorption investigation. In this minireview, the effect of ABL on oral absorption of a drug is discussed in an easy-to-understand manner. This review starts with an introduction of the boundary layer theory with many illustrations (and links to public web movies visualizing the ABL), and then discusses some specific cases of interest in pharmaceutical science, such as dissolution of floating drug particles in the USP paddle apparatus. The effect of the boundary layer on the membrane permeation is also discussed from the viewpoint of structure permeability relationship, carrier mediated transport/metabolism and estimation of the fraction of a dose absorbed for poor solubility compounds.

  18. Pharmaceutical and Toxicological Properties of Engineered Nanomaterials for Drug Delivery

    PubMed Central

    Palombo, Matthew; Deshmukh, Manjeet; Myers, Daniel; Gao, Jieming; Szekely, Zoltan; Sinko, Patrick J.

    2014-01-01

    Novel engineered nanomaterials (ENMs) are being developed to enhance therapy. The physicochemical properties of ENMs can be manipulated to control/direct biodistribution and target delivery, but these alterations also have implications for toxicity. It is well known that size plays a significant role in determining ENM effects since simply nanosizing a safe bulk material can render it toxic. However, charge, shape, rigidity, and surface modifications also have a significant influence on the biodistribution and toxicity of nanoscale drug delivery systems (NDDSs). In this review, NDDSs are considered in terms of platform technologies, materials, and physical properties that impart their pharmaceutical and toxicological effects. Moving forward, the development of safe and effective nanomedicines requires standardized protocols for determining the physical characteristics of ENMs as well as assessing their potential long-term toxicity. When such protocols are established, the remarkable promise of nanomedicine to improve the diagnosis and treatment of human disease can be fulfilled. PMID:24160695

  19. Mucoadhesive drug carrier based on functional-modified cellulose as poorly water-soluble drug delivery system.

    PubMed

    Songsurang, Kultida; Siraleartmukul, Krisana; Muangsin, Nongnuj

    2015-01-01

    The purpose of this study was to design and characterise an oral mucoadhesive micellar drug carrier. In this regard, a mucoadhesive hydrophobic cationic aminocellulose was easily synthesised under mild homogeneous conditions with high yield. The cellulose derivative resulted in strongly improved mucoadhesive properties but was pH dependent. Furthermore, the hydrophobic anticancer drug camptothecin was successfully encapsulated into the mucoadhesive cellulose derivative micelles with spherical shape stability of 233 nm in diameter and low particle size distribution. The CPT-loaded nanocarriers provided high encapsulation efficiency about 86.4%. In vitro release, CPT-loaded cellulose derivative micelles showed a reduction in release rate compared with physically pure CPT solution. The release results also indicated that a sustained release of CPT to >80% over 4 d for pH 6.8 and 7.4. Therefore, mucoadhesive hydrophobic cationic aminocellulose micelles seem to be a promising carrier for various pharmaceutical applications especially for poorly water-soluble drug delivery system.

  20. Molecular Mechanisms of Pharmaceutical Drug Binding into Calsequestrin

    PubMed Central

    Subra, Arun K.; Nissen, Mark S.; Lewis, Kevin M.; Muralidharan, Ashwin K.; Sanchez, Emiliano J.; Milting, Hendrik; Kang, ChulHee

    2012-01-01

    Calsequestrin (CASQ) is a major Ca2+-storage/buffer protein present in the sarcoplasmic reticulum of both skeletal (CASQ1) and cardiac (CASQ2) muscles. CASQ has significant affinity for a number of pharmaceutical drugs with known muscular toxicities. Our approach, with in silico molecular docking, single crystal X-ray diffraction, and isothermal titration calorimetry (ITC), identified three distinct binding pockets on the surface of CASQ2, which overlap with 2-methyl-2,4-pentanediol (MPD) binding sites observed in the crystal structure. Those three receptor sites based on canine CASQ1 crystal structure gave a high correlation (R2 = 0.80) to our ITC data. Daunomycin, doxorubicin, thioridazine, and trifluoperazine showed strong affinity to the S1 site, which is a central cavity formed between three domains of CASQ2. Some of the moderate-affinity drugs and some high-affinity drugs like amlodipine and verapamil displayed their binding into S2 sites, which are the thioredoxin-like fold present in each CASQ domain. Docking predictions combined with dissociation constants imply that presence of large aromatic cores and less flexible functional groups determines the strength of binding affinity to CASQ. In addition, the predicted binding pockets for both caffeine and epigallocatechin overlapped with the S1 and S2 sites, suggesting competitive inhibition by these natural compounds as a plausible explanation for their antagonistic effects on cardiotoxic side effects. PMID:23203067

  1. Pharmaceutical penetration of new drug and pharmaceutical market structure in Taiwan: hospital-level prescription of thiazolidinediones for diabetes.

    PubMed

    Tsai, Yi-Wen; Wen, Yu-Wen; Huang, Weng-Foung; Kuo, Ken N; Chen, Pei-Fen; Shih, Hsin-Wei; Lee, Yue-Chune

    2010-06-01

    This study used Taiwan's National Health Insurance claim database (years 2000-2005) to examine how thiazolidinediones (TZD), a new class of drugs for diabetes, penetrated into Taiwan's hospitals, and its association with the concentration of all diabetes drugs at the hospital level. We collected 72 monthly summaries of diabetes prescriptions from all hospitals in Taiwan. Hospital-level pharmaceutical concentration was measured by penetration of TZD, defined as monthly market share of TZD in each hospital. Concentration of diabetes drugs was measured by Herfindahl-Hirschman indices. We found a negative association (coefficient = -0.3610) between TZD penetration and concentration of diabetes drug but a positive association between penetration of TZD and the volume of prescribed diabetes drugs (coefficient = 0.4088). In conclusion, hospital characteristics and volume of services determined the concentration of pharmaceuticals at the institution level, reflecting the heterogeneous competition between pharmaceutical companies within each hospital. Institution-level pharmaceutical concentration influences the adoption and penetration of new drugs.

  2. Evolution of drug reimbursement in Canada: the Pan-Canadian Pharmaceutical Alliance for new drugs.

    PubMed

    Husereau, Don; Dempster, William; Blanchard, Adrienne; Chambers, Johanne

    2014-12-01

    Canada has a unique system of public drug coverage and reimbursement characterized by a centralized review agency that makes funding recommendations along with decentralized authority for delivering health care across 10 provinces and three territories. There has been a significant increase in price negotiation for new pharmaceuticals in the past 10 years, first by individual provinces and now through a collective price negotiation process called the "Pan-Canadian Pharmaceutical Alliance." As of February 2014, the Pan-Canadian Pharmaceutical Alliance has already completed 32 negotiations despite still being in a formative stage; it is anticipated that a formal process will be developed in the coming year. In this article, we describe the evolution of price negotiation in Canada and identify several opportunities for improvement of the current process, including the incorporation of economic considerations into price negotiation.

  3. Preparation and characterization of PEGylated chitosan nanocapsules as a carrier for pharmaceutical application

    NASA Astrophysics Data System (ADS)

    Najafabadi, Alireza Hassani; Abdouss, Majid; Faghihi, Shahab

    2014-03-01

    A new method to conjugate methoxy polyethylene glycol (mPEG) to C6 position of chitosan under the mild condition is introduced that improves the biocompatibility and water solubility of chitosan. Harsh deprotecting step and several purification cycles are two major disadvantages of the current methods for preparing PEGylated chitosan. In this study, the amine groups at C2 position of chitosan are protected using SDS followed by grafting the PEG. The protecting group of chitosan is simply removed by dialyzing against Tris solution. The chemical structure of the prepared polymer is characterized by FTIR and 1H NMR spectroscopy. Fourier transformed-infrared (FT-IR) and 1H NMR spectra confirmed that the mPEG is successfully grafted to C6 position of chitosan. Prepared methoxy polyethylene glycol (mPEG) is then employed to prepare the nanocapsules for the encapsulation of poor water-soluble drug, propofol. The TEM, AFM, and DLS techniques are used to characterize the prepared nanocapsules size and morphology. The results show a size of about 80 nm with spherical shape for nanocapsules. In vitro drug release is carried out to evaluate the potential of nanocarriers for the intravenous delivery of drugs. The profile of release from formulated nanocapsules is similar to those of commercial lipid emulsion (CLE). In vivo animal sleep-recovery test on rats shows a close similarity between the time of unconsciousness and recovery of righting reflex between nanoparticles and CLE. This study provides an efficient, novel, and easy method for preparing a carrier system that requires less intensive reaction conditions, fewer reaction steps, and less purification steps. In addition, the nanocapsules introduced here could be a promising nano carrier for the delivery of poor water-soluble drugs.

  4. Recent advances in medicinal chemistry and pharmaceutical technology--strategies for drug delivery to the brain.

    PubMed

    Denora, Nunzio; Trapani, Adriana; Laquintana, Valentino; Lopedota, Angela; Trapani, Giuseppe

    2009-01-01

    This paper provides a mini-review of some recent approaches for the treatment of brain pathologies examining both medicinal chemistry and pharmaceutical technology contributions. Medicinal chemistry-based strategies are essentially aimed at the chemical modification of low molecular weight drugs in order to increase their lipophilicity or the design of appropriate prodrugs, although this review will focus primarily on the use of prodrugs and not analog development. Recently, interest has been focused on the design and evaluation of prodrugs that are capable of exploiting one or more of the various endogenous transport systems at the level of the blood brain barrier (BBB). The technological strategies are essentially non-invasive methods of drug delivery to malignancies of the central nervous system (CNS) and are based on the use of nanosystems (colloidal carriers) such as liposomes, polymeric nanoparticles, solid lipid nanoparticles, polymeric micelles and dendrimers. The biodistribution of these nanocarriers can be manipulated by modifying their surface physico-chemical properties or by coating them with surfactants and polyethylene-glycols (PEGs). Liposomes, surfactant coated polymeric nanoparticles, and solid lipid nanoparticles are promising systems for delivery of drugs to tumors of the CNS. This mini-review discusses issues concerning the scope and limitations of both the medicinal chemistry and technological approaches. Based on the current findings, it can be concluded that crossing of the BBB and drug delivery to CNS is extremely complex and requires a multidisciplinary approach such as a close collaboration and common efforts among researchers of several scientific areas, particularly medicinal chemists, biologists and pharmaceutical technologists.

  5. Nanoparticles and nanostructured carriers for drug delivery and contrast enhancement

    NASA Astrophysics Data System (ADS)

    Godage, Olga S.; Bucharskaya, Alla B.; Navolokin, Nikita A.; German, Sergey V.; Zuev, Viktor V.; Terentyuk, Georgy S.; Maslyakova, Galina N.; Gorin, Dmitry A.

    2016-04-01

    Currently, nanotechnologies are widely used in science and industry. It is known that the application of drug delivery nanostructured carriers for biomedicine is one of the promising areas of nanotechnology. Nanostructured carriers can be used in the diagnosis process for detecting a neoplastic tumor cells in peripheral blood, for contrast enhancement on magnetic resonance imaging (MRI), as well as for targeted drug delivery to tumor tissues. Agents for the targeted delivery (nanoparticles, liposomes, microcapsules, and etc) can affect the healthy tissues and organs, cause side effects and have a toxic effect. Therefore, it necessary to study the morphological changes that occur not only in the "target", such as a tumor, but also the internal organs, taking place under the influence of both the agents for targeted drug delivery and physical impact induced remote controlled drug release. Thus , the aim of our work is selection of the most promising agents for targeted drug delivery to tumor and contrast agents for in vivo visualization of tumor tissue boundaries , as well as their impact on the organs and tissues as results of nanostructured object biodistribution.

  6. Biocompatibility of Chitosan Carriers with Application in Drug Delivery

    PubMed Central

    Rodrigues, Susana; Dionísio, Marita; Remuñán López, Carmen; Grenha, Ana

    2012-01-01

    Chitosan is one of the most used polysaccharides in the design of drug delivery strategies for administration of either biomacromolecules or low molecular weight drugs. For these purposes, it is frequently used as matrix forming material in both nano and micron-sized particles. In addition to its interesting physicochemical and biopharmaceutical properties, which include high mucoadhesion and a great capacity to produce drug delivery systems, ensuring the biocompatibility of the drug delivery vehicles is a highly relevant issue. Nevertheless, this subject is not addressed as frequently as desired and even though the application of chitosan carriers has been widely explored, the demonstration of systems biocompatibility is still in its infancy. In this review, addressing the biocompatibility of chitosan carriers with application in drug delivery is discussed and the methods used in vitro and in vivo, exploring the effect of different variables, are described. We further provide a discussion on the pros and cons of used methodologies, as well as on the difficulties arising from the absence of standardization of procedures. PMID:24955636

  7. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 3 2014-10-01 2014-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... DRUG BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical prices...

  8. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 3 2012-10-01 2012-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... DRUG BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical prices...

  9. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 3 2013-10-01 2013-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... DRUG BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical prices...

  10. Drug carrier systems for solubility enhancement of BCS class II drugs: a critical review.

    PubMed

    Kumar, Sumit; Bhargava, Deepak; Thakkar, Arti; Arora, Saahil

    2013-01-01

    Poor aqueous solubility impedes a drug's bioavailability and challenges its pharmaceutical development. Pharmaceutical development of drugs with poor water solubility requires the establishment of a suitable formulation layout among various techniques. Various approaches have been investigated extensively to improve the aqueous solubility and poor dissolution rate of BCS class II and IV drugs. In this literature review, novel formulation options, particularly for class II drugs designed for applications such as micronization, self-emulsification, cyclodextrin complexation, co-crystallisation, super critical fluid technology, solubilisation by change in pH, salt formation, co-solvents, melt granulation, and solid dispersion, liposomal/niosomal formulations, are discussed in detail to introduce biopharmaceutical challenges and recent approaches to facilitate more efficient drug formulation and development.

  11. Design of Nanoparticle-Based Carriers for Targeted Drug Delivery

    PubMed Central

    Ren, Muqing; Duval, Kayla; Guo, Xing; Chen, Zi

    2016-01-01

    Nanoparticles have shown promise as both drug delivery vehicles and direct antitumor systems, but they must be properly designed in order to maximize efficacy. Computational modeling is often used both to design new nanoparticles and to better understand existing ones. Modeled processes include the release of drugs at the tumor site and the physical interaction between the nanoparticle and cancer cells. In this article, we provide an overview of three different targeted drug delivery methods (passive targeting, active targeting and physical targeting), compare methods of action, advantages, limitations, and the current stage of research. For the most commonly used nanoparticle carriers, fabrication methods are also reviewed. This is followed by a review of computational simulations and models on nanoparticle-based drug delivery. PMID:27398083

  12. Electrosprayed nanoparticles and electrospun nanofibers based on natural materials: applications in tissue regeneration, drug delivery and pharmaceuticals.

    PubMed

    Sridhar, Radhakrishnan; Lakshminarayanan, Rajamani; Madhaiyan, Kalaipriya; Amutha Barathi, Veluchamy; Lim, Keith Hsiu Chin; Ramakrishna, Seeram

    2015-02-07

    Nanotechnology refers to the fabrication, characterization, and application of substances in nanometer scale dimensions for various ends. The influence of nanotechnology on the healthcare industry is substantial, particularly in the areas of disease diagnosis and treatment. Recent investigations in nanotechnology for drug delivery and tissue engineering have delivered high-impact contributions in translational research, with associated pharmaceutical products and applications. Over the past decade, the synthesis of nanofibers or nanoparticles via electrostatic spinning or spraying, respectively, has emerged as an important nanostructuring methodology. This is due to both the versatility of the electrospinning/electrospraying process and the ensuing control of nanofiber/nanoparticle surface parameters. Electrosprayed nanoparticles and electrospun nanofibers are both employed as natural or synthetic carriers for the delivery of entrapped drugs, growth factors, health supplements, vitamins, and so on. The role of nanofiber/nanoparticle carriers is substantiated by the programmed, tailored, or targeted release of their contents in the guise of tissue engineering scaffolds or medical devices for drug delivery. This review focuses on the nanoformulation of natural materials via the electrospraying or electrospinning of nanoparticles or nanofibers for tissue engineering or drug delivery/pharmaceutical purposes. Here, we classify the natural materials with respect to their animal/plant origin and macrocyclic, small molecule or herbal active constituents, and further categorize the materials according to their proteinaceous or saccharide nature.

  13. Drugs and pharmaceuticals: management of intoxication and antidotes.

    PubMed

    Smith, Silas W

    2010-01-01

    The treatment of patients poisoned with drugs and pharmaceuticals can be quite challenging. Diverse exposure circumstances, varied clinical presentations, unique patient-specific factors, and inconsistent diagnostic and therapeutic infrastructure support, coupled with relatively few definitive antidotes, may complicate evaluation and management. The historical approach to poisoned patients (patient arousal, toxin elimination, and toxin identification) has given way to rigorous attention to the fundamental aspects of basic life support--airway management, oxygenation and ventilation, circulatory competence, thermoregulation, and substrate availability. Selected patients may benefit from methods to alter toxin pharmacokinetics to minimize systemic, target organ, or tissue compartment exposure (either by decreasing absorption or increasing elimination). These may include syrup of ipecac, orogastric lavage, activated single- or multi-dose charcoal, whole bowel irrigation, endoscopy and surgery, urinary alkalinization, saline diuresis, or extracorporeal methods (hemodialysis, charcoal hemoperfusion, continuous venovenous hemofiltration, and exchange transfusion). Pharmaceutical adjuncts and antidotes may be useful in toxicant-induced hyperthermias. In the context of analgesic, anti-inflammatory, anticholinergic, anticonvulsant, antihyperglycemic, antimicrobial, antineoplastic, cardiovascular, opioid, or sedative-hypnotic agents overdose, N-acetylcysteine, physostigmine, L-carnitine, dextrose, octreotide, pyridoxine, dexrazoxane, leucovorin, glucarpidase, atropine, calcium, digoxin-specific antibody fragments, glucagon, high-dose insulin euglycemia therapy, lipid emulsion, magnesium, sodium bicarbonate, naloxone, and flumazenil are specifically reviewed. In summary, patients generally benefit from aggressive support of vital functions, careful history and physical examination, specific laboratory analyses, a thoughtful consideration of the risks and benefits of

  14. GELATIN CARRIERS FOR DRUG AND CELL DELIVERY IN TISSUE ENGINEERING

    PubMed Central

    Santoro, Marco; Tatara, Alexander M.; Mikos, Antonios G.

    2014-01-01

    The ability of gelatin to form complexes with different drugs has been investigated for controlled release applications. Gelatin parameters, such as crosslinking density and isoelectric point, have been tuned in order to optimize gelatin degradation and drug delivery kinetics. In recent years, focus has shifted away from the use of gelatin in isolation towards the modification of gelatin with functional groups and the fabrication of material composites with embedded gelatin carriers. In this review, we highlight some of the latest work being performed in these areas and comment on trends in the field. Specifically, we discuss gelatin modifications for immune system evasion, drug stabilization, and targeted delivery, as well as gelatin composite systems based on ceramics, naturally-occurring polymers, and synthetic polymers. PMID:24746627

  15. Carrier-free, functionalized pure drug nanorods as a novel cancer-targeted drug delivery platform

    NASA Astrophysics Data System (ADS)

    Li, Yanan; Yang, Yinlong; An, Feifei; Liu, Zhuang; Zhang, Xiujuan; Zhang, Xiaohong

    2013-01-01

    A one-dimensional drug delivery system (1D DDS) is highly attractive since it has distinct advantages such as enhanced drug efficiency and better pharmacokinetics. However, drugs in 1D DDSs are all encapsulated in inert carriers, and problems such as low drug loading content and possible undesirable side effects caused by the carriers remain a serious challenge. In this paper, a novel, carrier-free, pure drug nanorod-based, tumor-targeted 1D DDS has been developed. Drugs are first prepared as nanorods and then surface functionalized to achieve excellent water dispersity and stability. The resulting drug nanorods show enhanced internalization rates mainly through energy-dependent endocytosis, with the shape-mediated nanorod (NR) diffusion process as a secondary pathway. The multiple endocytotic mechanisms lead to significantly improved drug efficiency of functionalized NRs with nearly ten times higher cytotoxicity than those of free molecules and unfunctionalized NRs. A targeted drug delivery system can be readily achieved through surface functionalization with targeting group linked amphipathic surfactant, which exhibits significantly enhanced drug efficacy and discriminates between cell lines with high selectivity. These results clearly show that this tumor-targeting DDS demonstrates high potential toward specific cancer cell lines.

  16. Bacterial Magnetosome: A Novel Biogenetic Magnetic Targeted Drug Carrier with Potential Multifunctions

    PubMed Central

    Sun, Jianbo; Li, Ying; Liang, Xing-Jie; Wang, Paul C.

    2012-01-01

    Bacterial magnetosomes (BMs) synthesized by magnetotactic bacteria have recently drawn great interest due to their unique features. BMs are used experimentally as carriers for antibodies, enzymes, ligands, nucleic acids, and chemotherapeutic drugs. In addition to the common attractive properties of magnetic carriers, BMs also show superiority as targeting nanoscale drug carriers, which is hardly matched by artificial magnetic particles. We are presenting the potential applications of BMs as drug carriers by introducing the drug-loading methods and strategies and the recent research progress of BMs which has contributed to the application of BMs as drug carriers. PMID:22448162

  17. Comparison of pharmaceutical nanoformulations for curcumin: Enhancement of aqueous solubility and carrier retention.

    PubMed

    Allijn, Iris E; Schiffelers, Raymond M; Storm, Gert

    2016-06-15

    Curcumin, originally used in traditional medicine and as a spice, is one of the most studied and most popular natural products of the past decade. It has been described to be an effective anti-inflammatory and anti-cancer drug and protects against chronic diseases such as rheumatoid arthritis and atherosclerosis. Despite these promising pharmacological properties, curcumin is also very lipophilic, which makes its formulation challenging. Ideally the nanocarrier should additionally also retain the encapsulated curcumin to provide target tissue accumulation. In this study we aimed to tackle this aqueous solubility and carrier retention challenge of curcumin by encapsulating curcumin in different nanoparticles. We successfully loaded LDL (30nm), polymeric micelles (80nm), liposomes (180nm) and Intralipid (280nm) with curcumin. The relative loading capacity was inversely related to the size of the particle. The stability for all formulations was determined in fetal bovine serum over a course of 24h. Although all curcumin-nanoparticles were stable in buffer solution, all leaked more than 70% of curcumin under physiological conditions. Altogether, tested nanoparticles do solve the aqueous insolubility problem of curcumin, however, because of their leaky nature, the challenge of carrier retention remains. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Reconsidering Japan's underperformance in pharmaceuticals: evidence from Japan's anticancer drug sector.

    PubMed

    Umemura, Maki

    2010-01-01

    Unlike its automobile or electronics industries, Japan's pharmaceutical industry did not become a global leader. Japan remains a net importer of pharmaceuticals and has introduced few global blockbuster drugs. Alfred Chandler argued that Japan's pharmaceutical firms remained relatively weak because Western firms enjoyed an insurmountable first first-mover advantage. However, this case study of the anticancer drug sector illustrates that Chandler's explanation is incomplete. Japanese medical culture, government policy, and research environment also played a substantial role in shaping the industry. In the 1970s and 1980s, these factors encouraged firms to develop little few effective drugs with low side effects, and profit from Japan's domestic market. But, these drugs were unsuitable to foreign markets with more demanding efficacy standards. As a result, Japan not only lost more than a decade in developing ineffective drugs, but also neglected to create the infrastructure necessary to develop innovative drugs and build a stronger pharmaceutical industry.

  19. Natural polysaccharide functionalized gold nanoparticles as biocompatible drug delivery carrier.

    PubMed

    Pooja, Deep; Panyaram, Sravani; Kulhari, Hitesh; Reddy, Bharathi; Rachamalla, Shyam S; Sistla, Ramakrishna

    2015-09-01

    Biocompatibility is one of the major concerns with inorganic nanoparticles for their applications as drug delivery system. Natural compounds such as sugars, hydrocolloids and plant extracts have shown potential for the green synthesis of biocompatible gold nanoparticles. In this study, we report the synthesis of gum karaya (GK) stabilized gold nanoparticles (GKNP) and the application of prepared nanoparticles in the delivery of anticancer drugs. GKNP were characterized using different analytical techniques. GKNP exhibited high biocompatibility during cell survival study against CHO normal ovary cells and A549 human non-small cell lung cancer cells and during hemolytic toxicity studies. Gemcitabine hydrochloride (GEM), an anticancer drug, was loaded on the surface of nanoparticles with 19.2% drug loading efficiency. GEM loaded nanoparticles (GEM-GNP) showed better inhibition of growth of cancer cells in anti-proliferation and clonogenic assays than native GEM. This effect was correlated with higher reactive oxygen species generation by GEM-GNP in A549 cells than native GEM. In summary, GK has significant potential in the synthesis of biocompatible gold nanoparticles that could be used as prospective drug delivery carrier for anticancer drugs.

  20. Self-assembling cyclic systems as drug carriers

    NASA Astrophysics Data System (ADS)

    Banerjee, A.; Yadav, A.

    2013-12-01

    Self-assembling cyclic systems have been of interest to researchers for over a decade now, and their wide variety applications have been explored from electronic devices to medicinal purposes. But still their discovery for newer innovative applications remains as valuable as before. In this study, ab initio Hartree-Fock molecular orbital calculations have been performed on peptidic and peptidomimetic cyclic compounds to identify characteristics required in compounds for efficient self-aggregation. The effect of these characteristics in determining the pore size and length of nanotube has been studied. Effect of backbone and substituents on environment of outer and inner surface and carriage properties has been studied in detail. Self-aggregating compounds (Ala)12 and (Ala)10 have been predicted to form a tubular structure with dimensions in nanoscale. They have been predicted to work as novel drug carriers having inert outer wall and inner pore. A peptidic self-aggregating compound (Ala)12 has been studied and suggested as carrier for antibiotic gentamicin to exemplify carriage properties of the designed compound. Such novel self-aggregatory systems are expected to help simplify the drug delivery process and increase bioavailability of various drugs.

  1. Acrylate-tethering drug carrier: covalently linking carrier to biological surface and application in the treatment of Helicobacter pylori infection.

    PubMed

    Tachaprutinun, Amornset; Pan-In, Porntip; Samutprasert, Pawatsanai; Banlunara, Wijit; Chaichanawongsaroj, Nuntaree; Wanichwecharungruang, Supason

    2014-11-10

    The development of carriers to sustain drugs at stomach surface is an attractive strategy to increase drug bioavailability locally and systematically. So far, the only reported carrier that can form a covalent bond with mucus, the thiolated carrier, relies on a reversible disulfide exchange reaction between thiols on the carrier and disulfide bridges on the mucus. Here we show the design and fabrication of a cellulose carrier with tethering acrylate groups (denoted here as clickable carrier) that, under a nontoxic condition, can efficiently react with thiols on biomaterials in situ through the thermodynamically driven and kinetically probable Michael thiol-ene click reaction. Here we show the attachments of the clickable carriers to a mucin protein, a surface of human laryngeal carcinoma cells, and a surface of a fresh porcine stomach. We also show that the required thiol moieties can be generated in situ by reducing existing cystine disulfide bridges with either the edible vitamin C or the relatively nontoxic tris(2-carboxyethyl) phosphine. Comparing to a control carrier, the clickable carrier can increase some drug concentrations in an ex vivo stomach tissue, and improve the Helicobacter pylori treatment in infected C57BL/6 mice.

  2. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research.

    PubMed

    Orzan, G; Zara, I A; Purcarea, V L

    2012-12-15

    Recent years have seen an "explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer's thoughts and tailor specific marketing messages.

  3. Scanning ion images; analysis of pharmaceutical drugs at organelle levels

    NASA Astrophysics Data System (ADS)

    Larras-Regard, E.; Mony, M.-C.

    1995-05-01

    With the ion analyser IMS 4F used in microprobe mode, it is possible to obtain images of fields of 10 × 10 [mu]m2, corresponding to an effective magnification of 7000 with lateral resolution of 250 nm, technical characteristics that are appropriate for the size of cell organelles. It is possible to characterize organelles by their relative CN-, P- and S- intensities when the tissues are prepared by freeze fixation and freeze substitution. The recognition of organelles enables correlation of the tissue distribution of ebselen, a pharmaceutical drug containing selenium. The various metabolites characterized in plasma, bile and urine during biotransformation of ebselen all contain selenium, so the presence of the drug and its metabolites can be followed by images of Se. We were also able to detect the endogenous content of Se in tissue, due to the increased sensitivity of ion analysis in microprobe mode. Our results show a natural occurrence of Se in the border corresponding to the basal lamina of cells of proximal but not distal tubules of the kidney. After treatment of rats with ebselen, an additional site of Se is found in the lysosomes. We suggest that in addition to direct elimination of ebselen and its metabolites by glomerular filtration and urinary elimination, a second process of elimination may occur: Se compounds reaching the epithelial cells via the basal lamina accumulate in lysosomes prior to excretion into the tubular fluid. The technical developments of using the IMS 4F instrument in the microprobe mode and the improvement in preparation of samples by freeze fixation and substitution further extend the limit of ion analysis in biology. Direct imaging of trace elements and molecules marked with a tracer make it possible to determine their targets by comparison with images of subcellular structures. This is a promising advance in the study of pathways of compounds within tissues, cells and the whole organism.

  4. Effect of drug solubility and lipid carrier on drug release from lipid nanoparticles for dermal delivery.

    PubMed

    Zoubari, Gaith; Staufenbiel, Sven; Volz, Pierre; Alexiev, Ulrike; Bodmeier, Roland

    2017-01-01

    Lipid nanoparticles have gained increased interest in the field of dermal products because of various advantages such as improved drug absorption and controlled drug release. The main objective was to investigate the influence of drug solubility and type of lipid carrier on the in vitro drug release. Drugs of different solubilities in the release medium PBS pH 7.4 (dexamethasone: 0.1mg/ml and diclofenac sodium: 5.0mg/ml) and three different lipids (in which the drugs had the highest solubility), Gelucire® 50/13 (solid lipid, mp: 50°C), Witepsol® S55 (solid lipid, mp: 33.5-35.5°C) and Capryol® 90 (liquid lipid) were chosen. The lipid nanoparticles were prepared by high shear homogenization. All nanosuspensions were in the nanometer range (up to 400nm) and the drug encapsulation efficiency was between 84% and 95%. The drug release was prolonged over 48h without an initial burst release and was dependent on the lipid carrier. Formulations containing a higher amount of solid Gelucire® 50/13 released the drugs slower due to the high affinity of the drugs to this lipid product. Inclusion of the liquid lipid Capryol® 90 resulted in a less organized lipidic structures (softer particles) and therefore a faster drug release. Despite its higher water solubility, diclofenac was released slower than dexamethasone because of its higher solubility in the lipid carriers. DSC studies indicated a partial miscibility between the solid lipids and a good miscibility between the solid and liquid lipids. Primary studies using total internal reflection fluorescence (TIRF) microscopy indicated that it is possible to detect individual fluorescently labeled dexamethasone (DXM-F) molecules dissolved in the liquid lipid Capryol® 90. These studies will allow for the precise determination of the drug distribution within the lipid carrier, and the changes upon drug release. In conclusion, lipid carrier type and drug solubility in the lipid have a large influence on the in vitro drug

  5. Tuberculosis: from molecular pathogenesis to effective drug carrier design.

    PubMed

    Dube, Devyani; Agrawal, Govind P; Vyas, Suresh P

    2012-07-01

    In the past two decades, tuberculosis has gone from being a forgotten disease to a modern and recrudescent pathology. Tuberculosis is a curable infection and most of the negative therapeutic outcomes are related to poor patient compliance, which could be solved by new drug delivery approaches. By using such approaches the technological drawbacks of the currently used therapeutic agents could be addressed. In addition, optimum effectiveness of the drug by targeting the infection reservoirs could be achieved. In this article we compile the general physiological aspects of the infection along with new research updates especially on novel carriers used in the prevention of tuberculosis which might enhance therapeutic efficacy and patient compliance. Copyright © 2012 Elsevier Ltd. All rights reserved.

  6. Methods for reduction of cohesive forces between carrier and drug in DPI formulation.

    PubMed

    Desai, Swapnil S; Aher, Abhijeet A; Kadaskar, Preeti T

    2013-11-01

    Dry powder inhaler (DPI) has become a well accepted drug delivery for pulmonary system to treat many related diseases including symptomatic and life threatening diseases. Successful delivery of dry powder to the lung requires careful consideration of powder production process, formulation and inhaler device. The formulation of DPI mostly comprises of lactose as a carrier for drug delivery. In DPI formulation, particulate interactions within the formulation govern both the drug dissociation from carrier particles and the disaggregation of drug into primary particles with a capacity to penetrate deep into lung. Two contradictory requirements must be fulfilled for this type of dry powder formulation. On one hand, adhesion between carrier and drug must be sufficient for the blend drug/carrier to be stable. On the other hand, adhesion drug/carrier has to be weak enough to enable the release of drug from carrier during patient inhalation. Thus the carrier use restricted due to detachment problem. Different methods are proposed to reduce the cohesive forces between drug and carrier to desired level. Various studies conducted for understanding the mechanism of deposition into lungs and making formulation with optimum carrier drug cohesive force. This review provides information on various processes involved in reducing the cohesive forces between drug and carrier, to a required level.

  7. Critical evaluation of the claims made by pharmaceutical companies in drug promotional material in Pakistan.

    PubMed

    Rohra, Dileep Kumar; Gilani, Anwarul Hassan; Memon, Ismail Kamal; Perven, Ghazala; Khan, Muhammad Talha; Zafar, Hina; Kumar, Rakesh

    2006-01-01

    In Pakistan, there is no mechanism to monitor the drug promotional campaign by pharmaceutical industry despite the fact that there is enough evidence that irrational pharmacotherapy is increasingly encountered even in the developed countries due to unethical practices of pharmaceutical promotion. Objectives. To audit the drug promotional claims made by the pharmaceutical companies in Pakistan. Drug promotional pamphlets and brochures containing claims for the drugs, which were circulated by the pharmaceutical representatives were collected from 122 general practitioners (GPs) from Karachi and Larkana cities of the Sindh Province. The claims were critically analyzed and audited with the help of currently available evidence in the medical literature. 345 distinct advertisements covering 182 drugs from different manufacturers were critically analyzed for information content. Sixty two out of 345 (18%) of the reviewed advertisements were adjudged to be misleading / unjustifiable, which were again classified as, exaggerated (32%), ambiguous (21%), false (26%), and controversial (21%). The primary source of information (approximately 78%) about the newly launched drugs for the GPs was found to be the pharmaceutical representatives followed by hospital doctors (5%) and colleagues (5%). Furthermore, 110 (90%) GPs were of the view that the drug promotion has definitely an influence on their prescribing pattern. Since GPs in Pakistan rate pharmaceutical companies as their primary source of information regarding drugs, it can be anticipated that inappropriate advertisement claims would lead to irrational prescribing if physicians had no any other information to follow.

  8. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical prices for...

  9. 42 CFR 423.132 - Public disclosure of pharmaceutical prices for equivalent drugs.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 3 2011-10-01 2011-10-01 false Public disclosure of pharmaceutical prices for equivalent drugs. 423.132 Section 423.132 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT... BENEFIT Benefits and Beneficiary Protections § 423.132 Public disclosure of pharmaceutical prices for...

  10. Thermally Responsive Hydrogel Blends: A General Drug Carrier Model for Controlled Drug Release.

    PubMed

    Ma, Chongbo; Shi, Ye; Pena, Danilo A; Peng, Lele; Yu, Guihua

    2015-06-15

    Thermally responsive hydrogels have drawn significant research attention recently because of their simple use as drug carrier at human body temperature. Here we design a hybrid hydrogel that incorporates a hydrophilic polymer, polyethyleneimine (PEI), into the thermally responsive hydrogel poly(N-isopropylacrylamide) (PNIPAm), as a general drug carrier model for controlled drug release. In this work, on one hand, PEI modifies the structure and the size of the pores in the PNIPAm hydrogel. On the other hand, PEI plays an important role in tuning the water content in the hydrogel and controls the water release rate of the hydrogel below the lower critical solution temperature (LCST), resulting in a tunable release rate of the drugs at human body temperature (37 °C). Different release rates are shown as different amounts of PEI are incorporated. PEI controls the release rate, dependent on the charge characteristics of the drugs. The hydrogel blends described in this work extend the concept of a general drug carrier for loading both positively and negatively charged drugs, as well as the controlled release effect.

  11. [The list of drugs in the Popular Pharmacy Program and the Brazilian National Pharmaceutical Care Policy].

    PubMed

    Yamauti, Sueli Miyuki; Barberato-Filho, Silvio; Lopes, Luciane Cruz

    2015-08-01

    This study aimed to analyze the list of drugs in the Popular Pharmacy Program in Brazil (PFPB) in relation to the country's pharmaceutical care policy. The list of drugs in the PFPB was compared to the Brazilian and international reference lists of essential medicines, the components of pharmaceutical care in Brazilian Unified National Health System (SUS), and drug production by the country's government pharmaceutical laboratories. The PFPB list includes 119 drugs, of which 19.3% and 47.1% were not selected on the Brazilian and international reference lists, respectively; 16.8% are not used in primary care, and 40.3% are not produced by the country's government laboratories. A revision of the PFPB list based on the essential medicines concept (World Health Organization), alignment of pharmaceutical care policies, and production by government laboratories are essential to improve quality of health care, management, training of prescribers, and information for the population.

  12. Big data analysis of global advances in pharmaceutics and drug delivery 1980-2014.

    PubMed

    Zhang, Weixiang; Zhao, Qianqian; Deng, Junling; Hu, Yuanjia; Wang, Yitao; Ouyang, Defang

    2017-08-01

    This review provides a comprehensive perspective of the global research advances and frontiers in pharmaceutics from 1980 to 2014. Furthermore, a historical view and future prospects of drug delivery are discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. An update on pharmaceutical film coating for drug delivery.

    PubMed

    Felton, Linda A; Porter, Stuart C

    2013-04-01

    Pharmaceutical coating processes have generally been transformed from what was essentially an art form in the mid-twentieth century to a much more technology-driven process. This review article provides a basic overview of current film coating processes, including a discussion on polymer selection, coating formulation additives and processing equipment. Substrate considerations for pharmaceutical coating processes are also presented. While polymeric coating operations are commonplace in the pharmaceutical industry, film coating processes are still not fully understood, which presents serious challenges with current regulatory requirements. Novel analytical technologies and various modeling techniques that are being used to better understand film coating processes are discussed. This review article also examines the challenges of implementing process analytical technologies in coating operations, active pharmaceutical ingredients in polymer film coatings, the use of high-solids coating systems and continuous coating and other novel coating application methods.

  14. [Pharmaceutical drugs containing lactose can as a rule be used by persons with lactose intolerance].

    PubMed

    Vinther, Siri; Rumessen, Jöri Johannes; Christensen, Mikkel

    2015-03-09

    Lactose is often used as an excipient in pharmaceutical drugs. Current evidence indicates that the amount of lactose in most drugs is not sufficient to cause symptoms in persons with lactose intolerance, although interindividual differences in sensitivity probably exist. Patient preferences and/or suboptimal treatment adherence could be reasons for considering lactose-free drug alternatives.

  15. Application of ion chromatography in pharmaceutical and drug analysis.

    PubMed

    Jenke, Dennis

    2011-08-01

    Ion chromatography (IC) has developed and matured into an important analytical methodology in a number of diverse applications and industries, including pharmaceuticals. This manuscript provides a review of IC applications for the determinations of active and inactive ingredients, excipients, degradation products, and impurities relevant to pharmaceutical analyses and thus serves as a resource for investigators looking for insights into the use of the IC methodology in this field of application.

  16. Synthesis and use of organic biodegradable aerogels as drug carriers.

    PubMed

    Veronovski, Anja; Novak, Zoran; Knez, Željko

    2012-01-01

    Aerogels of natural polysaccharides possess both biocharacteristics of polysaccharides, such as good biological compatibility and cell or enzyme-controlled degradability, and aerogel characteristics, such as very high porosity and specific surface areas that makes them highly attractive in drug delivery. Biodegradable alginate aerogels were synthesized via a sol-gel process. In the present work two methods of ionic cross-linking were used to prepare alginate hydrogels as monoliths and spheres, which can be further easily converted to high surface area aerogels. The aerogels obtained were further used as drug carriers. We investigated the effect of process parameters, such as starting concentration and viscosity of alginate solution, on synthesis products and on model drug (nicotinic acid) release. The results indicate that by using the internal setting cross-linking method for obtaining monolithic aerogels nicotinic acid was released in a more controlled manner. The aerogels thus obtained also exhibited smaller volume shrinkage than the ones described in other publications. However, with increasing alginate concentration in both types of synthesis more compact and cross-linked aerogels were formed.

  17. Bacterial ghosts as drug carrier and targeting vehicles.

    PubMed

    Huter, V; Szostak, M P; Gampfer, J; Prethaler, S; Wanner, G; Gabor, F; Lubitz, W

    1999-08-27

    A novel system for the packaging of drugs as well as vaccines is presented. Bacterial ghosts are intact, non-denatured bacterial envelopes that are created by lysis of bacteria through the expression of cloned phage PhiX174 gene E. Inhibition of induced E-mediated lysis by MgSO(4), harvesting of cells by centrifugation, and resuspension in low-ionic-strength buffers leads to rapid, violent lysis and results in empty bacterial envelopes with large (approximately 1 microm in diameter) openings. The construction of plasmid pAV1, which encodes a streptavidin fusion protein with an N-terminal membrane anchor sequence, allows the loading of the inner side of the cytoplasmic membrane with streptavidin. The functionality and efficacy of binding of even large biotinylated compounds in such streptavidin ghosts (SA-ghosts) was assessed using the enzyme alkaline phosphatase. The successful binding of biotinylated fluorescent dextran, as well as fluorescent DNA complexed with biotinylated polylysine, was demonstrated microscopically. The display by bacterial ghosts of morphological and antigenic surface structures of their living counterparts permits their attachment to target tissues such as the mucosal surfaces of the gastrointestinal and respiratory tract, and their uptake by phagocytes and M cells. In consequence, SA-ghosts are proposed as drug carriers for site-specific drug delivery.

  18. Rhodamine/Nanodiamond as a System Model for Drug Carrier.

    PubMed

    Reina, G; Orlanducci, S; Cairone, C; Tamburri, E; Lenti, S; Cianchetta, I; Rossi, M; Terranova, M L

    2015-02-01

    In this paper we present some strategies that are being developed in our labs towards enabling nanodiamond-based applications for drug delivery. Rhodamine B (RhB) has been choosen as model molecule to study the loading of nanodiamonds with active moieties and the conditions for their controlled release. In order to test the chemical/physical interactions between functionalized detonation nanodiamond (DND) and complex molecules, we prepared and tested different RhB@DND systems, with RhB adsorbed or linked by ionic bonding to the DND surface. The chemical state of the DND surfaces before conjugation with the RhB molecules, and the chemical features of the DND-RhB interactions have been deeply analysed by coupling DND with Au nanoparticles and taking advantage of surface enhanced Raman spectroscopy SERS. The effects due to temperature and pH variations on the process of RhB release from the DND carrier have been also investigated. The amounts of released molecules are consistent with those required for effective drug action in conventional therapeutic applications, and this makes the DND promising nanostructured cargos for drug delivery applications.

  19. Stability of drug-carrier emulsions containing phosphatidylcholine mixtures.

    PubMed

    Trotta, Michele; Pattarino, Franco; Ignoni, Terenzio

    2002-03-01

    Lipid emulsion particles containing 10% of medium chain triglycerides were prepared using 2% w/w of a mixture 1:1 w/w of purified soya phosphatidylcholine and 2-hexanoyl phosphatidylcholine as emulsifier mixture, for use as drug carriers. The mean droplet sizes of emulsions, prepared using an Ultra Turrax or a high-pressure homogenizer, were about 288 and 158 nm, respectively, compared with 380 and 268 nm for emulsions containing lecithin, or 325 and 240 nm for those containing 6-phosphatidylcholine. The stability of the emulsions, determined by monitoring the decrease of a lipophilic marker at a specified level within the emulsion, and observing coalescence over time, was also greatly increased using the emulsifier mixture. The emulsion stability did not notably change in the presence of a model destabilizing drug, indomethacin. The use of a second hydrophilic surfactant to adjust the packing properties of the lecithin at the oil-water interface provided an increase in the stability of lipid emulsions, and this may be of importance in the formulation of drug delivery systems.

  20. Nanostructured lipid carriers as vehicles for transdermal iontophoretic drug delivery.

    PubMed

    Liu, W; Yang, X; Zhu, Y; Chen, H; Xu, H

    2005-01-01

    The aim of the present work was to assess the merits of nanostructured lipid carriers (NLCs) as vehicles for transdermal iontophoretic drug delivery. For the measurements, either a model drug (triamcinolone acetonide acetate, TAA) or a lipophilic fluorescent probe (nile red, NR) was encapsulated into NLCs. The NLCs with sizes of 100 nm and 350 nm diameter were prepared by high-pressure homogenization technique. The particle size with polydispersity index (PDI), zeta potential and morphology were examined by photon correlation spectroscopy (PCS) and atomic force microscopy (AFM). In vitro penetration studies involved passive penetration and iontophoresis for control (TAA ethanol solution) and TAA-NLCs formulations. Confocal laser scanning microscopy (CLSM) was employed to visualize the distribution of NR-NLCs after skin permeation. The overall results reveal the benefits of the combined use of iontophoresis and NLCs in improving skin penetration parameters. The NLCs with a size of 100 nm seem to be promising for iontophoretic delivery as they have shown maximum enhancement ratio and skin deposition. This is the first report of the use of NLCs as vehicles for transdermal iontophoretic drug delivery.

  1. Physico-chemical characterization of liposomes and drug substance-liposome interactions in pharmaceutics using capillary electrophoresis and electrokinetic chromatography.

    PubMed

    Franzen, Ulrik; Østergaard, Jesper

    2012-12-07

    Liposomes are self-assembled phospholipid vesicles and have numerous research and therapeutic applications. In the pharmaceutical and biomedical sciences liposomes find use as models of biological membranes, partitioning medium and as drug carriers. The present review addresses the use of capillary electrophoresis and liposome electrokinetic chromatography for the characterization of liposomes in a pharmaceutical context. Capillary electrophoretic techniques have been used for the measurement of electrophoretic mobility, which provides information on liposome surface charge, size and membrane permeability of liposomes. The use of liposome electrokinetic chromatography and capillary electrophoresis for determination of liposome/water partitioning and characterization of drug-liposome interactions is reviewed. A number of studies indicate that capillary electrophoresis may have a role in the characterization of liposome drug delivery systems, e.g., for the investigation of encapsulation efficiency and drug leakage. The well-known characteristics of capillary electrophoresis, i.e., low sample volume requirement, high separation efficiency in aqueous media without a stationary phase, minimal sample preparation, and a high degree of automation, makes it an attractive approach in liposome research.

  2. DNA nanostructure-based imaging probes and drug carriers.

    PubMed

    Zhan, Pengfei; Jiang, Qiao; Wang, Zhen-Gang; Li, Na; Yu, Haiyin; Ding, Baoquan

    2014-09-01

    Self-assembled DNA nanostructures are well-defined nanoscale shapes, with uniform sizes, precise spatial addressability, and excellent biocompatibility. With these features, DNA nanostructures show great potential for biomedical applications; various DNA-based biomedical imaging probes or payload delivery carriers have been developed. In this review, we summarize the recent developments of DNA-based nanostructures as tools for diagnosis and cancer therapy. The biological effects that are brought about by DNA nanostructures are highlighted by in vitro and in vivo imaging, antitumor drug delivery, and immunostimulatory therapy. The challenges and perspectives of DNA nanostructures in the field of nanomedicine are discussed. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  3. Magnetically Stimulated Release of a Model Drug From a Magnetic Drug Carrier

    NASA Astrophysics Data System (ADS)

    Riley, Tom; Evans, Ben

    The use of particles in the micro and nanometer ranges has become increasingly important as therapeutic tools in medicine. In particular, magnetically-active particles may allow for magnetically-controlled release of drugs at targeted locations. The drugs can be delivered directly to cancerous tumors at desired concentrations. While hydrogel-based microspheres have been commonly proposed for such purposes, there is also a need for a lipophilic magnetic microsphere for delivery of poorly-soluble pharmaceuticals. We have created a well-dispersed suspension of iron oxide nanoparticles in a silicone matrix, and have used the material to manufacture microspheres in sizes ranging from 100nm to 50 microns. Our spheres are stable in aqueous suspensions, yet their silicone matrix is uniquely suited for the transport and delivery of hydrophobic pharmaceuticals. A high concentration of magnetic nanoparticles (50% wt.) enables magnetic localization, magnetic heating (hyperthermia), and magnetic stimulation to trigger drug release. Using fluorescein as a model drug, we use UV-visible spectroscopy to show a slow native release rate of the hydrophobic fluorescein from the spheres. We use these measurements to quantify the loading capacity of the microspheres, and we show results of magnetically-stimulated drug release using a DM100 field applicator (nanoScale Biomagnetics).

  4. A Novel Magnetic Nanoparticle Drug Carrier for Enhanced Cancer Chemotherapy

    PubMed Central

    Guo, Lili; Zhu, Jingjing; Peng, Mingli; Vermorken, Alphonsus J. M.; Van de Ven, Wim J. M.; Chen, Chao; Cui, Yali

    2012-01-01

    Background Magnetic nanoparticles (NPs) loaded with antitumor drugs in combination with an external magnetic field (EMF)-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1) to investigate application of PEG modified GMNPs (PGMNPs) as a drug carrier of the chemotherapy compound doxorubicin (DOX) in vitro; 2) to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs) using an EMF-guided delivery in vivo. Methods First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues) was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M). Results The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each p<0.05), following treatment for 33 days. The life span of tumor-bearing mice treated with DOX-PGMNPs-M, DOX-PGMNPs, and DOX were 74.8±9.95, 66.1±13.5, and 31.3±3.31 days, respectively (each p<0.05). Conclusion This simple and adaptive nanoparticle design may accommodate chemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future. PMID:23056167

  5. A novel magnetic nanoparticle drug carrier for enhanced cancer chemotherapy.

    PubMed

    Chao, Xu; Zhang, Zhuoli; Guo, Lili; Zhu, Jingjing; Peng, Mingli; Vermorken, Alphonsus J M; Van de Ven, Wim J M; Chen, Chao; Cui, Yali

    2012-01-01

    Magnetic nanoparticles (NPs) loaded with antitumor drugs in combination with an external magnetic field (EMF)-guided delivery can improve the efficacy of treatment and may decrease serious side effects. The purpose of this study was 1) to investigate application of PEG modified GMNPs (PGMNPs) as a drug carrier of the chemotherapy compound doxorubicin (DOX) in vitro; 2) to evaluate the therapeutic efficiency of DOX-conjugated PGMNPs (DOX-PGMNPs) using an EMF-guided delivery in vivo. First, DOX-PGMNPs were synthesized and the cytotoxicity of DOX-PGMNPs was assessed in vitro. Second, upon intravenous administration of DOX-PMGPNs to H22 hepatoma cell tumor-bearing mice, the DOX biodistribution in different organs (tissues) was measured. The antitumor activity was evaluated using different treatment strategies such as DOX-PMGPNs or DOX-PMGPNs with an EMF-guided delivery (DOX-PGMNPs-M). The relative tumor volumes in DOX-PGMNPs-M, DOX-PGMNPs, and DOX groups were 5.46±1.48, 9.22±1.51, and 14.8±1.64, respectively (each p<0.05), following treatment for 33 days. The life span of tumor-bearing mice treated with DOX-PGMNPs-M, DOX-PGMNPs, and DOX were 74.8±9.95, 66.1±13.5, and 31.3±3.31 days, respectively (each p<0.05). This simple and adaptive nanoparticle design may accommodate chemotherapy for drug delivery optimization and in vivo drug-target definition in system biology profiling, increasing the margin of safety in treatment of cancers in the near future.

  6. Swellable Microparticles as Carriers for Sustained Pulmonary Drug Delivery

    PubMed Central

    EL-SHERBINY, IBRAHIM M.; MCGILL, SHAYNA; SMYTH, HUGH D.C.

    2012-01-01

    In this investigation, novel biodegradable physically crosslinked hydrogel micro-particles were developed and evaluated in vitro as potential carriers for sustained pulmonary drug delivery. To facilitate sustained release in the lungs, aerosols must first navigate past efficient aerodynamic filtering to penetrate to the deep lung (requires small particle size) where they must then avoid rapid macrophage clearance (enhanced by large particle size). The strategy suggested in this study to solve this problem is to deliver drug-loaded hydrogel microparticles with aerodynamic characteristics allowing them to be respirable when dry but attain large swollen sizes once deposited on moist lung surfaces to reduce macrophage uptake rates. The microparticles are based on PEG graft copolymerized onto chitosan in combination with Pluronic® F-108 and were prepared via cryomilling. The synthesized polymers used in preparation of the microparticles were characterized using FTIR, EA, 2D-XRD, and differential scanning calorimetry (DSC). The microparticles size, morphology, moisture content, and biodegradation rates were investigated. Swelling studies and in vitro drug release profiles were determined. An aerosolization study was conducted and macrophage uptake rates were evaluated against controls. The microparticles showed a respirable fraction of approximately 15% when prepared as dry powders. Enzymatic degradation of microparticles started within the first hour and about 7–41% weights were remaining after 240 h. Microparticles showed sustained release up to 10 and 20 days in the presence and absence of lysozyme, respectively. Preliminary macrophage interaction studies indicate that the developed hydrogel microparticles significantly delayed phagocytosis and may have the potential for sustained drug delivery to the lung. PMID:19967777

  7. The Effect of Pharmaceutical Patent Term Length on Research and Development and Drug Expenditures in Canada

    PubMed Central

    Grootendorst, Paul; Matteo, Livio Di

    2007-01-01

    While pharmaceutical patent terms have increased in Canada, increases in patented drug spending have been mitigated by price controls and retrenchment of public prescription drug subsidy programs. We estimate the net effects of these offsetting policies on domestic pharmaceutical R&D expenditures and also provide an upper-bound estimate on the effects of these policies on Canadian pharmaceutical spending over the period 1988–2002. We estimate that R&D spending increased by $4.4 billion (1997 dollars). Drug spending increased by $3.9 billion at most and, quite likely, by much less. Cutbacks to public drug subsidies and the introduction of price controls likely mitigated drug spending growth. In cost–benefit terms, we suspect that the patent extension policies have been beneficial to Canada. PMID:19305720

  8. Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history.

    PubMed

    Nagaich, Upendra; Sadhna, Divya

    2015-01-01

    There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall.

  9. Drug recall: An incubus for pharmaceutical companies and most serious drug recall of history

    PubMed Central

    Nagaich, Upendra; Sadhna, Divya

    2015-01-01

    There has been an increasing trend in the number of prescribed and over-the-counter drug recall over the last few years. The recall is usually due to company's discovery, customer's complaint or Food and Drug Administration (FDA) observation. The process of recall involves a planned specific course of action, which addresses the depth of recall, need for public warning, and the extent of effectiveness checks for the recall. The FDA review and/or recommend changes to the firm's recall strategy, as appropriate. The critical recall information list includes the identity of the product; summary of the failure; amount of product produced in the distribution chain and direct account. Product recalls clashes thousands of companies every year affecting: sales, testing customer relationships and disrupting supply chains. Drug recall is incubus for pharmaceutical companies. It effects the reputation of the company. The reason for the recall can be divided into two categories: manufacturing affined and safety/efficacy affined. It is essential to follow all the guidelines related to drug development and manufacturing procedure so as to minimize drug recall. PMID:25599028

  10. Graphene oxide: a carrier for pharmaceuticals and a scaffold for cell interactions.

    PubMed

    Durán, Nelson; Martinez, Diego Stéfani T; Silveira, Camila P; Durán, Marcela; de Moraes, Ana C M; Simões, Mateus B; Alves, Oswaldo L; Fávaro, Wagner J

    2015-01-01

    During the last ten years, graphene oxide has been explored in many applications due to its remarkable electroconductivity, thermal properties and mobility of charge carriers, among other properties. As discussed in this review, the literature suggests that a total characterization of graphene oxide must be conducted because oxidation debris (synthesis impurities) present in the graphene oxides could act as a graphene oxide surfactant, stabilizing aqueous dispersions. It is also important to note that the structure models of graphene oxide need to be revisited because of significant implications for its chemical composition and its direct covalent functionalization. Another aspect that is discussed is the need to consider graphene oxide surface chemistry. The hemolysis assay is recommended as a reliable test for the preliminary assessment of graphene oxide toxicity, biocompatibility and cell membrane interaction. More recently, graphene oxide has been extensively explored for drug delivery applications. An important increase in research efforts in this emerging field is clearly represented by the hundreds of related publications per year, including some reviews. Many studies have been performed to explore the graphene oxide properties that enable it to deliver more than one activity simultaneously and to combine multidrug systems with photothermal therapy, indicating that graphene oxide is an attractive tool to overcome hurdles in cancer therapies. Some strategic aspects of the application of these materials in cancer treatment are also discussed. In vitro studies have indicated that graphene oxide can also promote stem cell adhesion, growth and differentiation, and this review discusses the recent and pertinent findings regarding graphene oxide as a valuable nanomaterial for stem cell research in medicine. The protein corona is a key concept in nanomedicine and nanotoxicology because it provides a biomolecular identity for nanomaterials in a biological environment

  11. RGD based peptide amphiphiles as drug carriers for cancer targeting

    NASA Astrophysics Data System (ADS)

    Saraf, Poonam S.

    Specific interactions of ligands with receptors is one of the approaches for active targeting of anticancer drugs to cancer cells. Over expression of integrin receptors is a physiological manifestation in several cancers and is associated with cancer progression and metastasis, which makes it an attractive target for cancer chemotherapy. The peptide sequence for this integrin recognition is the Arg-Gly-Asp (RGD). Self-assembly offers a unique way of presenting ligands to target receptors for recognition and binding. This study focuses on development of integrin specific peptide amphiphile self-assemblies as carriers for targeted delivery of paclitaxel to αvbeta 3 integrin overexpressing cancers. Amphiphiles composed of conjugates of different analogs of RGD (linear, cyclic or glycosylated) and aliphatic fatty acid with or without 8-amino-3,6-dioxaoctanoic acid (ADA) as linker were synthesized and characterized. The amphiphiles exhibited Critical Micellar Concentration in the range of 7-30 μM. Transmission electron microscopy images revealed the formation of spherical micelles in the size range of 10-40 nm. Forster Resonance Energy Transfer studies revealed entrapment of hydrophobic dyes within a tight micellar core and provided information regarding the cargo exchange within micelles. The RGD micelles exhibited competitive binding with 55% displacement of a bound fluorescent probe by the cyclic RGD micelles. The internalization of fluorescein isothiocynate (FITC) loaded RGD micelles was significantly higher in A2058 melanoma cells compared to free FITC within 20 minutes of incubation at 37°C. The same micelles showed significantly lower internalization at 4°C and on pretreatment with 0.45M sucrose confirming endocytotic uptake of the RGD micellar carriers. The IC50 of paclitaxel in A2058 melanoma cells was lower when treated within RGD micelles as compared to treatment of free drug. On the other hand, IC50 values increased by 2 to 9 fold for micellar treatment

  12. Peering into the Pharmaceutical “Pipeline”: Investigational Drugs, Clinical Trials, and Industry Priorities

    PubMed Central

    Cottingham, Marci D.; Kalbaugh, Corey A.

    2014-01-01

    In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry’s investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding – and often problematic – role of pharmaceuticals in society. To access the pharmaceutical industry’s pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2,477 different drugs in 4,182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline were being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered. PMID:25159693

  13. Peering into the pharmaceutical "pipeline": investigational drugs, clinical trials, and industry priorities.

    PubMed

    Fisher, Jill A; Cottingham, Marci D; Kalbaugh, Corey A

    2015-04-01

    In spite of a growing literature on pharmaceuticalization, little is known about the pharmaceutical industry's investments in research and development (R&D). Information about the drugs being developed can provide important context for existing case studies detailing the expanding--and often problematic--role of pharmaceuticals in society. To access the pharmaceutical industry's pipeline, we constructed a database of drugs for which pharmaceutical companies reported initiating clinical trials over a five-year period (July 2006-June 2011), capturing 2477 different drugs in 4182 clinical trials. Comparing drugs in the pipeline that target diseases in high-income and low-income countries, we found that the number of drugs for diseases prevalent in high-income countries was 3.46 times higher than drugs for diseases prevalent in low-income countries. We also found that the plurality of drugs in the pipeline was being developed to treat cancers (26.2%). Interpreting our findings through the lens of pharmaceuticalization, we illustrate how investigating the entire drug development pipeline provides important information about patterns of pharmaceuticalization that are invisible when only marketed drugs are considered.

  14. Natural attenuation of pharmaceuticals and an illicit drug in a laboratory column experiment.

    PubMed

    Greenhagen, Andrew M; Lenczewski, Melissa E; Carroll, Monica

    2014-11-01

    Trace amounts of pharmaceutical compounds have been detected in waters across the United States. Many compounds are released as the result of human ingestion and subsequent excretion of over-the-counter and prescription medications, and illicit drugs. This research utilized columns (30×30cm) of sand and undisturbed fine-grained sediments to simulate injection of wastewater containing pharmaceuticals and an illicit drug, such as would be found in a septic system, leaky sewer, or landfill. The columns were placed in a temperature-controlled laboratory and each was injected with natural groundwater containing known concentrations of caffeine, methamphetamine, and acetaminophen. Natural attenuation of each chemical was observed in all columns. The highest amount removed (approximately 90%) occurred in the undisturbed column injected with methamphetamine, compared with little reduction in the sand column. When the suite of drugs was injected, loss of methamphetamine was less than when methamphetamine was injected alone. The subsurface sediments exhibit the ability to remove a substantial amount of the injected pharmaceuticals and illicit drug; however, complete removal was not achieved. There was little attenuation of injected pharmaceuticals in the sand column which demonstrates a concern for water quality in the environment if pharmaceuticals were to contaminate a sandy aquifer. Understanding the transport of pharmaceuticals in the subsurface environment is an important component of protecting drinking water supplies from contamination. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Why trash don't pass? pharmaceutical licensing and safety performance of drugs.

    PubMed

    Banerjee, Tannista; Nayak, Arnab

    2017-01-01

    This paper examines how asymmetric information in pharmaceutical licensing affects the safety standards of licensed drugs. Pharmaceutical companies often license potential drug molecules at different stages of drug development from other pharmaceutical or biotechnology companies and complete the remaining of research stages before submitting the new drug application(NDA) to the food and drug administration. The asymmetric information associated with the quality of licensed molecules might result in the molecules which are less likely to succeed to be licensed out, while those with greater potential of success being held internally for development. We identify the NDAs submitted between 1993 and 2004 where new molecular entities were acquired through licensing. Controlling for other drug area specific and applicant firm specific factors, we investigate whether drugs developed with licensed molecules face higher probability of safety based recall and ultimate withdrawal from the market than drugs developed internally. Results suggest the opposite of Akerlof's (Q J Econ 84:488-500, 1970) lemons problem. Licensed molecules rather have less probability of facing safety based recalls and ultimate withdrawal from the market comparing to internally developed drug molecules. This suggests that biotechnology and small pharmaceutical firms specializing in pharmaceutical research are more efficient in developing good potential molecules because of their concentrated research. Biotechnology firms license out good potential molecules because it increases their market value and reputation. In addition, results suggest that both the number of previous approved drugs in the disease area, and also the applicant firms' total number of previous approvals in all disease areas reduce the probability that an additional approved drug in the same drug area will potentially be harmful.

  16. Commentary: Why Pharmaceutical Scientists in Early Drug Discovery Are Critical for Influencing the Design and Selection of Optimal Drug Candidates.

    PubMed

    Landis, Margaret S; Bhattachar, Shobha; Yazdanian, Mehran; Morrison, John

    2017-07-28

    This commentary reflects the collective view of pharmaceutical scientists from four different organizations with extensive experience in the field of drug discovery support. Herein, engaging discussion is presented on the current and future approaches for the selection of the most optimal and developable drug candidates. Over the past two decades, developability assessment programs have been implemented with the intention of improving physicochemical and metabolic properties. However, the complexity of both new drug targets and non-traditional drug candidates provides continuing challenges for developing formulations for optimal drug delivery. The need for more enabled technologies to deliver drug candidates has necessitated an even more active role for pharmaceutical scientists to influence many key molecular parameters during compound optimization and selection. This enhanced role begins at the early in vitro screening stages, where key learnings regarding the interplay of molecular structure and pharmaceutical property relationships can be derived. Performance of the drug candidates in formulations intended to support key in vivo studies provides important information on chemotype-formulation compatibility relationships. Structure modifications to support the selection of the solid form are also important to consider, and predictive in silico models are being rapidly developed in this area. Ultimately, the role of pharmaceutical scientists in drug discovery now extends beyond rapid solubility screening, early form assessment, and data delivery. This multidisciplinary role has evolved to include the practice of proactively taking part in the molecular design to better align solid form and formulation requirements to enhance developability potential.

  17. Generic gas chromatography-flame ionization detection method for quantitation of volatile amines in pharmaceutical drugs and synthetic intermediates.

    PubMed

    Graffius, Gabriel C; Jocher, Brandon M; Zewge, Daniel; Halsey, Holst M; Lee, Gary; Bernardoni, Frank; Bu, Xiaodong; Hartman, Robert; Regalado, Erik L

    2017-10-06

    Volatile amines are among the most frequently used chemicals in organic and pharmaceutical chemistry. Synthetic route optimization often involves the evaluation of several different amines requiring the development and validation of analytical methods for quantitation of residual amine levels. Herein, a simple and fast generic GC-FID method on an Agilent J&W CP-Volamine capillary column (using either He or H2 as the carrier gas) capable of separating over 25 volatile amines and other basic polar species commonly used in pharmaceutical chemistry workflows is described. This 16min method is successfully applied to the analysis and quantitation of volatile amines in a variety of pharmaceutically-related drugs and synthetic intermediates. Method validation experiments showed excellent analytical performance in linearity, recovery, repeatability, and limit of quantitation and detection. In addition, diverse examples for the application of this method to the simultaneous determination of other amine-related chemicals in reaction mixtures are illustrated, thereby indicating that these GC-FID method conditions can be effectively used as starting point during method development for the analysis of other basic polar species beyond the validated list of amines described in this study. Copyright © 2017 Elsevier B.V. All rights reserved.

  18. Pharmaceutical Companies and Their Drugs on Social Media: A Content Analysis of Drug Information on Popular Social Media Sites

    PubMed Central

    2015-01-01

    Background Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Objective Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Methods Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. Results From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies’ social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers

  19. Pharmaceutical companies and their drugs on social media: a content analysis of drug information on popular social media sites.

    PubMed

    Tyrawski, Jennifer; DeAndrea, David C

    2015-06-01

    Many concerns have been raised about pharmaceutical companies marketing their drugs directly to consumers on social media. This form of direct-to-consumer advertising (DTCA) can be interactive and, because it is largely unmonitored, the benefits of pharmaceutical treatment could easily be overemphasized compared to the risks. Additionally, nonexpert consumers can share their own drug product testimonials on social media and illegal online pharmacies can market their services on popular social media sites. There is great potential for the public to be exposed to misleading or dangerous information about pharmaceutical drugs on social media. Our central aim was to examine how pharmaceutical companies use social media to interact with the general public and market their drugs. We also sought to analyze the nature of information that appears in search results for widely used pharmaceutical drugs in the United States on Facebook, Twitter, and YouTube with a particular emphasis on the presence of illegal pharmacies. Content analyses were performed on (1) social media content on the Facebook, Twitter, and YouTube accounts of the top 15 pharmaceutical companies in the world and (2) the content that appears when searching on Facebook, Twitter, and YouTube for the top 20 pharmaceutical drugs purchased in the United States. Notably, for the company-specific analysis, we examined the presence of information similar to various forms of DTCA, the audience reach of company postings, and the quantity and quality of company-consumer interaction. For the drug-specific analysis, we documented the presence of illegal pharmacies, personal testimonials, and drug efficacy claims. From the company-specific analysis, we found information similar to help-seeking DTCA in 40.7% (301/740) of pharmaceutical companies' social media posts. Drug product claims were present in only 1.6% (12/740) of posts. Overall, there was a substantial amount of consumers who interacted with pharmaceutical

  20. Neuromarketing techniques in pharmaceutical drugs advertising. A discussion and agenda for future research

    PubMed Central

    Orzan, G; Zara, IA; Purcarea, VL

    2012-01-01

    Recent years have seen an “explosion" in the abilities of scientists to use neuroscience in new domains. Unfortunately, it is little known and reported on how advertising companies make more effective pharmaceutical drugs commercials. The purpose of this paper is to analyze how neuromarketing techniques may impact the consumer response to pharmaceutical advertising campaigns. The result shows that using neuromarketing methods a pharmaceutical company can better understand the conscious and unconscious consumer’s thoughts and tailor specific marketing messages. PMID:23346245

  1. Physiologically based pharmacokinetic modeling in drug discovery and development: a pharmaceutical industry perspective.

    PubMed

    Jones, H M; Chen, Y; Gibson, C; Heimbach, T; Parrott, N; Peters, S A; Snoeys, J; Upreti, V V; Zheng, M; Hall, S D

    2015-03-01

    The application of physiologically based pharmacokinetic (PBPK) modeling has developed rapidly within the pharmaceutical industry and is becoming an integral part of drug discovery and development. In this study, we provide a cross pharmaceutical industry position on "how PBPK modeling can be applied in industry" focusing on the strategies for application of PBPK at different stages, an associated perspective on the confidence and challenges, as well as guidance on interacting with regulatory agencies and internal best practices.

  2. The effect of carrier surface treatment on drug particle detachment from crystalline carriers in adhesive mixtures for inhalation.

    PubMed

    Dickhoff, B H J; de Boer, A H; Lambregts, D; Frijlink, H W

    2006-12-11

    In this study, the effect of lactose carrier surface treatment on drug particle detachment during inhalation has been investigated. Crystals of marketed brands of alpha lactose monohydrate brands normally exhibit a certain surface rugosity and contain natural fines and impurities on their surface, which influence the drug-to-carrier interaction in adhesive mixtures for inhalation. Submersion treatment may change these surface characteristics. Two different sieve fractions (63-90 and 250-355microm) were submerged in mixtures of ethanol and water (96 and 80% v/v, respectively). Microscopic observation and laser diffraction analysis revealed that neither the shape nor the size of the carrier particles was changed by the submersion treatment. However, the specific surface area and the amount of impurities appeared to decrease substantially after submersion, and the magnitude of the decrease was different for the different ethanol-water mixtures. The reduction in specific surface area was attributed particularly to the removal of the adhering lactose fines from the carrier surface. Mixtures with budesonide (in a wide range of carrier payloads) were prepared before and after treatment. Drug particle detachment from the various mixtures was studied with a sieve test and with a cascade impactor analysis at 30 and 60l/min. Two different types of inhalers were used, one generating lift- and drag-forces (ISF inhaler) and one generating inertial forces (test inhaler), respectively. The cascade impactor and sieve test experiments showed that an increase in carrier surface smoothness results in a reduced drug particle detachment during inhalation, which was independent of the type of inhaler used. This reduction could be attributed to the removal of the adhering lactose fines which may provide shelter for the drug particles from press-on forces during mixing.

  3. The interaction of a model active pharmaceutical with cationic surfactant and the subsequent design of drug based ionic liquid surfactants.

    PubMed

    Qamar, Sara; Brown, Paul; Ferguson, Steven; Khan, Rafaqat Ali; Ismail, Bushra; Khan, Abdur Rahman; Sayed, Murtaza; Khan, Asad Muhammad

    2016-11-01

    Interactions of active pharmaceutical ingredients (API) with surfactants remain an important research area due to the need to improve drug delivery systems. In this study, UV-Visible spectrophotometry was used to investigate the interactions between a model low molecular weight hydrophilic drug sodium valproate (SV) and cationic surfactant cetyltrimethylammonium bromide (CTAB). Changes in the spectra of SV were observed in pre- and post-micellar concentrations of CTAB. The binding constant (Kb) values and the number of drug molecules encapsulated per micelle were calculated, which posed the possibility of mixed micelle formation and strong complexation between SV and CTAB. These results were compared to those of a novel room temperature surface active ionic liquid, which was synthesized by the removal of inorganic counterions from a 1:1 mixture of CTAB and SV. In this new compound the drug now constitutes a building block of the carrier and, as such, has considerably different surfactant properties to its building blocks. In addition, enhanced solubility in a range of solvents, including simulated gastric fluid, was observed. The study provides valuable experimental evidence concerning the performance of drug based surfactant ionic liquids and how their chemical manipulation, without altering the architecture of the API, leads to control of surfactant behavior and physicochemical properties. In turn, this should feed through to improved and controlled drug release rates and delivery mechanisms, and the prevention of precipitation or formation of polymorphs typical of crystalline form APIs.

  4. Preparation and characterization of a drug carrier for hepatocellular carcinoma targeting

    NASA Astrophysics Data System (ADS)

    Ma, Yuxiang; Chen, Yuqi; Cui, Sisi; Zhao, Juan; Chen, Wei R.; Gu, Yueqing

    2013-02-01

    Asialoglycoprotein receptors distributing on the surface of hepatic parenchymal cells could specifically recognize galactose residues. Therefore, galactose residues can be applied in hepatocellar carcinoma targeted therapy through binding to the asialoglycoprotein receptors. A drug carrier containing of near infrared (NIR) fluorescence dye (MPA) and galactose was constructed by covalently conjugation process and named as GAL-MPA. The optical properties, cell viability, cell affinity and in vivo bio-distribution of this drug carrier were evaluated respectively. The results demonstrated that the drug carrier was provided with NIR fluorescence after conjugated with MPA. The low bio-toxicity and high hepatic cells affinity facilitated this drug carrier for in vivo biomedical application. Finally, the in vivo dynamic distribution of GAL-MPA confirmed this drug carrier was a promising candidate for tumor-targeting imaging and therapy.

  5. Thermoresponsive hyaluronic acid nanogels as hydrophobic drug carrier to macrophages.

    PubMed

    Fernandes Stefanello, Talitha; Szarpak-Jankowska, Anna; Appaix, Florence; Louage, Benoit; Hamard, Lauriane; De Geest, Bruno G; van der Sanden, Boudewijn; Nakamura, Celso Vataru; Auzély-Velty, Rachel

    2014-11-01

    Delivery systems for macrophages are particularly attractive since these phagocytic cells play a important role in immunological and inflammatory responses, also acting as host cells for microorganisms that are involved in deadly infectious diseases, such as leishmaniasis. Hyaluronic acid (HA) is specifically recognized by macrophages that are known to express HA receptors. Therefore, in this study, we focused on HA-based nanogels as drug carriers for these cells. The drug delivery was validated in an in vivo study on mice using intravital two-photon laser scanning microscopy. HA derivatives were modified with a biocompatible oligo(ethylene glycol)-based thermoresponsive polymer to form nanogels. These HA conjugates were readily prepared by varying the molar mass of initial HA and the degree of substitution via radical-mediated thiol-ene chemistry in aqueous solution. The derivatives were shown to self-assemble into spherical gel particles with diameters ranging from 150 to 214 nm above 37 °C. A poorly water-soluble two-photon dye was successfully loaded into the nanogels during this self-assembly process. In vitro cellular uptake tests using a RAW 264.7 murine macrophage cell line showed successful intracellular delivery of the hydrophobic dye. After intravenous injection in mice, the nanogels circulated freely in the blood but were rapidly phagocytized within 13 min by circulating macrophages and stored in the liver and spleen, as observed by two-photon microscopy. Benefit can be thus expected in using such a delivery system for the liver and spleen macrophage-associated diseases.

  6. Fluency of pharmaceutical drug names predicts perceived hazardousness, assumed side effects and willingness to buy.

    PubMed

    Dohle, Simone; Siegrist, Michael

    2014-10-01

    The impact of pharmaceutical drug names on people's evaluations and behavioural intentions is still uncertain. According to the representativeness heuristic, evaluations should be more positive for complex drug names; in contrast, fluency theory suggests that evaluations should be more positive for simple drug names. Results of three experimental studies showed that complex drug names were perceived as more hazardous than simple drug names and negatively influenced willingness to buy. The results are of particular importance given the fact that there is a worldwide trend to make more drugs available for self-medication. © The Author(s) 2013.

  7. Discovery of peptide drug carrier candidates for targeted multi-drug delivery into prostate cancer cells.

    PubMed

    Bashari, O; Redko, B; Cohen, A; Luboshits, G; Gellerman, G; Firer, M A

    2017-09-06

    Metastatic castration-resistant prostate cancer (mCRPC) remains essentially incurable. Targeted Drug Delivery (TDD) systems may overcome the limitations of current mCRPC therapies. We describe the use of strict criteria to isolate novel prostate cancer cell targeting peptides that specifically deliver drugs into target cells. Phage from a libraries displaying 7mer peptides were exposed to PC-3 cells and only internalized phage were recovered. The ability of these phage to internalize into other prostate cancer cells (LNCaP, DU-145) was validated. The displayed peptides of selected phage clones were synthesized and their specificity for target cells was validated in vitro and in vivo. One peptide (P12) which specifically targeted PC-3 tumors in vivo was incorporated into mono-drug (Chlorambucil, Combretastatin or Camptothecin) and dual-drug (Chlorambucil/Combretastatin or Chlorambucil/Camptothecin) PDCs and the cytotoxic efficacy of these conjugates for target cells was tested. Conjugation of P12 into dual-drug PDCs allowed discovery of new drug combinations with synergistic effects. The use of strict selection criteria can lead to discovery of novel peptides for use as drug carriers for TDD. PDCs represent an effective alternative to current modes of free drug chemotherapy for prostate cancer. Copyright © 2017. Published by Elsevier B.V.

  8. Drug policy in China: pharmaceutical distribution in rural areas.

    PubMed

    Dong, H; Bogg, L; Rehnberg, C; Diwan, V

    1999-03-01

    In 1978, China decided to reform its economy and since then has gradually opened up to the world. The economy has grown rapidly at an average of 9.8% per year from 1978 to 1994. Medical expenditure, especially for drugs, has grown even more rapidly. The increase in medical expenditure can be attributed to changing disease patterns, a higher proportion of older people in the population and fee-for-service incentives for hospitals. Due to the changing economic system and higher cost of health care, the Chinese government has reformed its health care system, including its health and drug policy. The drug policy reform has led to more comprehensive policy elements, including registration, production, distribution, utilization and administration. As a part of drug policy reform, the drug distribution network has also been changed, from a centrally controlled supply system (push system) to a market-oriented demand system (pull system). Hospitals can now purchase drugs directly from drug companies, factories and retailers, leading to increased price competition. Patients have easier access to drugs as more drugs are available on the market. At the same time, this has also entailed negative effects. The old drug administrative system is not suitable for the new drug distribution network. It is easy for people to get drugs on the market and this can lead to overuse and misuse. Marketing factors have influenced drug distribution so strongly that there is a risk of fake or low quality drugs being distributed. The government has taken some measures to fight these negative effects. This paper describes the drug policy reform in China, particularly the distribution of drugs to health care facilities.

  9. Vaccines, Pharmaceutical Products, and Bioterrorism: Challenges for the U.S. Food and Drug Administration

    DTIC Science & Technology

    1999-08-01

    plague (Yersinia pestis), tularemia (Francisella tularensis), brucellosis ( Brucella abortus, B. melitensis , B. suis, B. canis), Q fever (Coxiella...Special Issue 20011029 090 Vaccines, Pharmaceutical Products, and Bioterrorism: Challenges for the U.S. Food and Drug Administration Kathryn C...Zoon U.S. Food and Drug Administration, Rockville, Maryland, USA In regards to bioterrorism, the goal of the U.S. Food and Drug Administration (FDA

  10. Evaluation of the microbial growth potential of pharmaceutical drug products and quality by design.

    PubMed

    Lolas, Anastasia G; Metcalfe, John W

    2011-01-01

    The microbial growth potential of a pharmaceutical drug product refers to the ability of microorganisms to survive and proliferate in the product. Each drug formulation possesses a different potential for supporting or inhibiting microbial growth. Understanding this microbial growth potential can have a significant effect on the development and design of the drug manufacturing process. This article describes how this attribute can exert this effect on manufacturing process development and design through real examples and case studies obtained from the regulatory review of new drug and biologics license applications. In addition, this article describes how understanding the microbial growth potential of a pharmaceutical drug product is an element of the Quality by Design paradigm and how this understanding can simplify the drug development process and lead to better process design. The microbial growth potential of a pharmaceutical drug product refers to the ability of microorganisms to survive and proliferate in the product formulation. Each drug product formulation possesses a different potential for supporting or inhibiting microbial growth depending on its components. Understanding this microbial growth potential can have a significant effect on the development and design of the drug manufacturing process. This article describes how this attribute can affect manufacturing process development and design through real examples and case studies obtained from the regulatory review of new drug and biologics license applications. In addition, this article describes how understanding the microbial growth potential of a pharmaceutical drug product is an element of the Quality by Design paradigm and how this understanding can simplify the drug development process and lead to better process design.

  11. Pharmaceutical equivalence by design for generic drugs: modified-release products.

    PubMed

    Raw, André Sirota; Lionberger, Robert; Yu, Lawrence X

    2011-07-01

    The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as the RLD. Drug products have increased in design complexity; as a result, approaches to ensure therapeutic equivalence must evolve to provide assurance of quality generic drug products. The Food and Drug Administration quality by design initiative (QbD) provides an enhanced evaluation approach by introducing the concept of a quality target product profile (QTPP). The QTPP introduces, within the context of the current regulatory framework, the quality concept of "pharmaceutical equivalence by design." This article illustrates through several examples how this QbD element in the evaluation of modified-release drug products enhances the current framework to ensure generic drug product equivalence. It achieves this by complementing the traditional paradigm, "equivalence by testing," where product equivalence is based upon inferences from a limited bioequivalence study, to one that also considers whether the drug product was developed to be an equivalent to the RLD, using appropriate quality surrogates that target "pharmaceutical equivalence by design."

  12. Towards improved solubility of poorly water-soluble drugs: cryogenic co-grinding of piroxicam with carrier polymers.

    PubMed

    Penkina, Anna; Semjonov, Kristian; Hakola, Maija; Vuorinen, Sirpa; Repo, Timo; Yliruusi, Jouko; Aruväli, Jaan; Kogermann, Karin; Veski, Peep; Heinämäki, Jyrki

    2016-01-01

    Amorphous solid dispersions (SDs) open up exciting opportunities in formulating poorly water-soluble active pharmaceutical ingredients (APIs). In the present study, novel catalytic pretreated softwood cellulose (CPSC) and polyvinylpyrrolidone (PVP) were investigated as carrier polymers for preparing and stabilizing cryogenic co-ground SDs of poorly water-soluble piroxicam (PRX). CPSC was isolated from pine wood (Pinus sylvestris). Raman and Fourier transform infrared (FTIR) spectroscopy, X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) were used for characterizing the solid-state changes and drug-polymer interactions. High-resolution scanning electron microscope (SEM) was used to analyze the particle size and surface morphology of starting materials and final cryogenic co-ground SDs. In addition, the molecular aspects of drug-polymer interactions and stabilization mechanisms are presented. The results showed that the carrier polymer influenced both the degree of amorphization of PRX and stabilization against crystallization. The cryogenic co-ground SDs prepared from PVP showed an enhanced dissolution rate of PRX, while the corresponding SDs prepared from CPSC exhibited a clear sustained release behavior. In conclusion, cryogenic co-grinding provides a versatile method for preparing amorphous SDs of poorly water-soluble APIs. The solid-state stability and dissolution behavior of such co-ground SDs are to a great extent dependent on the carrier polymer used.

  13. [PHARMACEUTICAL INDUSTRY AND PERSONALIZED MEDICINE: A PARADIGM SHIFT IN THE DEVELOPMENT OF NEW DRUGS].

    PubMed

    Scheen, A J

    2015-01-01

    The cost of pharmacotherapy is increasing in the health care budget. The pharmaceutical industry is facing the exhaustion of medications that are largely prescribed and have a high profitability (blockbusters). Because of patient heterogeneity, there is a great interindividual variability of the responses to drug therapy. Thus, it is essential to better detect potential to avoid waste of resources resulting from the prescription of expensive drugs to poor responders. The development of personalized medicine, or precision medicine, certainly offers opportunities to the pharmaceutical industry, but also exposes it to new big challenges.

  14. High-performance thin layer chromatography: A powerful analytical technique in pharmaceutical drug discovery

    PubMed Central

    Attimarad, Mahesh; Ahmed, K. K. Mueen; Aldhubaib, Bandar E.; Harsha, Sree

    2011-01-01

    Analysis of pharmaceutical and natural compounds and newer drugs is commonly used in all the stages of drug discovery and development process. High-performance thin layer chromatography is one of the sophisticated instrumental techniques based on the full capabilities of thin layer chromatography. The advantages of automation, scanning, full optimization, selective detection principle, minimum sample preparation, hyphenation, and so on enable it to be a powerful analytical tool for chromatographic information of complex mixtures of pharmaceuticals, natural products, clinical samples, food stuffs, and so on. PMID:23781433

  15. Mechanisms of drug toxicity and relevance to pharmaceutical development.

    PubMed

    Guengerich, F Peter

    2011-01-01

    Toxicity has been estimated to be responsible for the attrition of approximately one-third of drug candidates and is a major contributor to the high cost of drug development, particularly when not recognized until late in clinical trials or post-marketing. The causes of drug toxicity can be classified in several ways and include mechanism-based (on-target) toxicity, immune hypersensitivity, off-target toxicity, and bioactivation/covalent modification. In addition, idiosyncratic responses are rare but can be one of the most problematic issues; several hypotheses for these have been advanced. Although covalent binding of drugs to proteins was described almost 40 years ago, the significance to toxicity has been difficult to establish; recent literature in this field is considered. The development of more useful biomarkers and short-term assays for rapid screening of drug toxicity early in the drug discovery/development process is a major goal, and some progress has been made using "omics" approaches.

  16. Difficulties in the production of identical drug products from a pharmaceutical technology viewpoint.

    PubMed

    Genazzani, Armando A; Pattarino, Franco

    2008-01-01

    Generic products reduce healthcare expenditure and create market competition, and it is broadly assumed that these drugs are identical to the original branded reference drug product. In practice, despite legislation demanding demonstration of pharmaceutical equivalence and bioequivalence, thereby ensuring the safety and efficacy of the product, generic products can differ significantly from the reference drug and amongst themselves, particularly in terms of pharmacokinetic properties. These differences most often relate to pharmaceutical technical differences in production of the active principle ingredient (e.g. different crystalline forms or particle size), to use of excipients (such as sugars) or to the manufacturing process itself (such as tablet manufacture). Furthermore, from the patient's perspective, changing from branded to generic drugs can give rise to concerns about switching. Although sufficient safeguards exist to ensure patient safety and generic drug efficacy, it should not be assumed that all generics are entirely identical.

  17. Tamoxifen nanostructured lipid carriers: enhanced in vivo antitumor efficacy with reduced adverse drug effects.

    PubMed

    Shete, Harshad K; Selkar, Nilakash; Vanage, Geeta R; Patravale, Vandana B

    2014-07-01

    A novel approach of enhancing the Tamoxifen uptake via Intestinal Lymphatic System is executed by developing long chain lipid and oil based nanostructured lipid carrier system (Tmx-NLC). The aim was to achieve improved systemic bioavailability of Tamoxifen, prevent systemic and hepatotoxicity and enhance antitumor efficacy. Following the proof of concept achieved in cell culture experiments and in vivo pharmacokinetic and biodistribution study, the current work focuses on investigation of antitumor efficacy and treatment associated toxicity in murine mammary tumor mice model. The efficacy study demonstrated greater tumor suppression and 100% survival with 1.5 and 3 mg/kg Tmx-NLC compared to 3 mg/kg Tamoxifen suspension and Mamofen(®) (Khandelwal Pharmaceuticals, Mumbai, India). Tmx-NLC treatment for a month demonstrated improved systemic toxicity profile and no evidences of hepatotoxicity. Thus, developed Tmx-NLC could prove to be a promising delivery strategy to confer superior therapeutic efficacy and ability to address the biopharmaceutical and toxicity associated issues of drug. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A Collaborative Assessment Among 11 Pharmaceutical Companies of Misinformation in Commonly Used Online Drug Information Compendia

    PubMed Central

    Randhawa, Amarita S.; Babalola, Olakiitan; Henney, Zachary; Miller, Michele; Nelson, Tanya; Oza, Meerat; Patel, Chandni; Randhawa, Anupma S.; Riley, Joyce; Snyder, Scott; So, Sherri

    2016-01-01

    Background: Online drug information compendia (ODIC) are valuable tools that health care professionals (HCPs) and consumers use to educate themselves on pharmaceutical products. Research suggests that these resources, although informative and easily accessible, may contain misinformation, posing risk for product misuse and patient harm. Objective: Evaluate drug summaries within ODIC for accuracy and completeness and identify product-specific misinformation. Methods: Between August 2014 and January 2015, medical information (MI) specialists from 11 pharmaceutical/biotechnology companies systematically evaluated 270 drug summaries within 5 commonly used ODIC for misinformation. Using a standardized approach, errors were identified; classified as inaccurate, incomplete, or omitted; and categorized per sections of the Full Prescribing Information (FPI). On review of each drug summary, content-correction requests were proposed and supported by the respective product’s FPI. Results: Across the 270 drug summaries reviewed within the 5 compendia, the median of the total number of errors identified was 782, with the greatest number of errors occurring in the categories of Dosage and Administration, Patient Education, and Warnings and Precautions. The majority of errors were classified as incomplete, followed by inaccurate and omitted. Conclusion: This analysis demonstrates that ODIC may contain misinformation. HCPs and consumers should be aware of the potential for misinformation and consider more than 1 drug information resource, including the FPI and Medication Guide as well as pharmaceutical/biotechnology companies’ MI departments, to obtain unbiased, accurate, and complete product-specific drug information to help support the safe and effective use of prescription drug products. PMID:26917822

  19. A Collaborative Assessment Among 11 Pharmaceutical Companies of Misinformation in Commonly Used Online Drug Information Compendia.

    PubMed

    Randhawa, Amarita S; Babalola, Olakiitan; Henney, Zachary; Miller, Michele; Nelson, Tanya; Oza, Meerat; Patel, Chandni; Randhawa, Anupma S; Riley, Joyce; Snyder, Scott; So, Sherri

    2016-05-01

    Online drug information compendia (ODIC) are valuable tools that health care professionals (HCPs) and consumers use to educate themselves on pharmaceutical products. Research suggests that these resources, although informative and easily accessible, may contain misinformation, posing risk for product misuse and patient harm. Evaluate drug summaries within ODIC for accuracy and completeness and identify product-specific misinformation. Between August 2014 and January 2015, medical information (MI) specialists from 11 pharmaceutical/biotechnology companies systematically evaluated 270 drug summaries within 5 commonly used ODIC for misinformation. Using a standardized approach, errors were identified; classified as inaccurate, incomplete, or omitted; and categorized per sections of the Full Prescribing Information (FPI). On review of each drug summary, content-correction requests were proposed and supported by the respective product's FPI. Across the 270 drug summaries reviewed within the 5 compendia, the median of the total number of errors identified was 782, with the greatest number of errors occurring in the categories of Dosage and Administration, Patient Education, and Warnings and Precautions. The majority of errors were classified as incomplete, followed by inaccurate and omitted. This analysis demonstrates that ODIC may contain misinformation. HCPs and consumers should be aware of the potential for misinformation and consider more than 1 drug information resource, including the FPI and Medication Guide as well as pharmaceutical/biotechnology companies' MI departments, to obtain unbiased, accurate, and complete product-specific drug information to help support the safe and effective use of prescription drug products. © The Author(s) 2016.

  20. Muco-inert nanoparticle probes and drug carriers

    NASA Astrophysics Data System (ADS)

    Wang, Ying-Ying

    2011-12-01

    Mucus coats the exposed surfaces of the eyes and respiratory, gastrointestinal (GI) and cervicovaginal (CV) tracts, and protects mucosal tissues against pathogens and other foreign particulates. Most foreign particles are effectively trapped in mucus through steric and adhesive interactions, and are rapidly eliminated by different mucus clearance mechanisms. Nevertheless, mucus also immobilizes conventional drug and gene carriers, thereby precluding sustained and targeted drug delivery to mucosal sites. Synthetic particles engineered with muco-inert surfaces, and some viruses, can readily penetrate mucus gel, and may serve as useful probes to understand the biophysical barrier properties of mucus. Improved understanding of the mucus barrier could provide insights into methods to enhance drug and gene delivery at mucosal surfaces, as well as understanding the occasional failure of mucus to protect against infection or injury. Recently, muco-inert nanoparticles were developed by conjugating a dense layer of low MW polyethylene glycol to particle surfaces. Since they are slowed only by steric obstruction from the mucus mesh, various sized muco-inert nanoparticles can be used to probe the microstructure and microrheology of mucus. I applied this technique to determine whether the mucus barrier may be altered by exogenous factors, including the presence of detergent, pH changes and synthetic nanoparticles. I first studied the microrheology of native human cervicovaginal mucus (CVM), and found that CVM behaves as a viscoelastic solid at length scales ≥ 1 microm (preventing large particles from diffusing through) but as a viscoelastic liquid at length scales up to at least 500 nm (allowing smaller particles to diffuse through low viscosity fluid-filled pores). Treating CVM with a nonionic detergent, N9, shifted the viscoelastic liquid-solid transition point to < 200 nm, suggesting hydrophobic interactions between mucin fibers play an important role in regulating the

  1. Pharmaceutical-grade albumin: impaired drug-binding capacity in vitro

    PubMed Central

    Olsen, Harald; Andersen, Anders; Nordbø, Arve; Kongsgaard, Ulf E; Børmer, Ole P

    2004-01-01

    Background Albumin is the most abundant protein in blood plasma, and due to its ligand binding properties, serves as a circulating depot for endogenous and exogenous (e.g. drugs) compounds. Hence, the unbound drug is the pharmacologically active drug. Commercial human albumin preparations are frequently used during surgery and in critically ill patients. Recent studies have indicated that the use of pharmaceutical-grade albumin is controversial in critically ill patients. In this in vitro study we investigated the drug binding properties of pharmaceutical-grade albumins (Baxter/Immuno, Octapharma, and Pharmacia & Upjohn), native human serum, and commercially available human serum albumin from Sigma Chemical Company. Methods The binding properties of the various albumin solutions were tested in vitro by means of ultrafiltration. Naproxen, warfarin, and digitoxin were used as ligands. HPLC was used to quantitate the total and free drug concentrations. The data were fitted to a model of two classes of binding sites for naproxen and warfarin and one class for digitoxin, using Microsoft Excel and Graphpad Prism. Results The drugs were highly bound to albumin (95–99.5%). The highest affinity (lowest K1) was found with naproxen. Pharmaceutical-grade albumin solutions displayed significantly lower drug-binding capacity compared to native human serum and Sigma albumin. Thus, the free fraction was considerably higher, approximately 40 times for naproxen and 5 and 2 times for warfarin and digitoxin, respectively. The stabilisers caprylic acid and N-acetyl-DL-tryptophan used in the manufacturing procedure seem to be of importance. Adding the stabilisers to human serum and Sigma albumin reduced the binding affinity whereas charcoal treatment of the pharmaceutical-grade albumin from Octapharma almost restored the specific binding capacity. Conclusion This in vitro study demonstrates that the specific binding for warfarin and digitoxin is significantly reduced and for naproxen

  2. Modeling Drug-Carrier Interaction in the Drug Release from Nanocarriers

    PubMed Central

    Zeng, Like; An, Lingling; Wu, Xiaoyi

    2011-01-01

    Numerous nanocarriers of various compositions and geometries have been developed for the delivery and release of therapeutic and imaging agents. Due to the high specific surface areas of nanocarriers, different mechanisms such as ion pairing and hydrophobic interaction need to be explored for achieving sustained release. Recently, we developed a three-parameter model that considers reversible drug-carrier interaction and first-order drug release from liposomes. A closed-form analytical solution was obtained. Here, we further explore the ability of the model to capture the release of bioactive molecules such as drugs and growth factors from various nanocarriers. A parameter study demonstrates that the model is capable of resembling major categories of drug release kinetics. We further fit the model to 60 sets of experimental data from various drug release systems, including nanoparticles, hollow particles, fibers, and hollow fibers. Additionally, bootstrapping is used to evaluate the accuracy of parameter determination and validate the model in selected cases. The simplicity and universality of the model and the clear physical meanings of each model parameter render the model useful for the design and development of new drug delivery systems. PMID:21845225

  3. Physicochemical properties of structured phosphatidylcholine in drug carrier lipid emulsions for drug delivery systems.

    PubMed

    Kawaguchi, Emi; Shimokawa, Ken-ichi; Ishii, Fumiyoshi

    2008-03-15

    Drug carrier emulsions were prepared with structured phosphatidylcholine (PC-LM) which has both a long hydrocarbon chain and a medium hydrocarbon chain, and the characteristics of PC-LM as an emulsifier were investigated by measuring the creaming ratio, the surface tension of the emulsion system, and the mean particle size and zeta potential of the oil droplets in emulsions. The emulsion prepared with PC-LM as an emulsifier kept the condition and the ratio of separation was lower than those with purified egg yolk lecithin (PEL). The mean particle size of the emulsion prepared with PC-LM was smaller than that with PEL when using only sonication, approximately 250 nm. When using a high-pressure homogenizer after sonication, the mean emulsion size with PC-LM was also smaller than with PEL, approximately 150 nm. The surface tension of the various emulsions and the zeta potential of the emulsion droplets were measured to investigate the stability of the systems. In emulsions with PC-LM or PEL, the surface tension as an index of stability increased as the pressure of the homogenizer increased. Moreover, the zeta potential of the emulsion droplets prepared with PC-LM also increased with an increase in pressure of the homogenizer. As a result, it was found that the drug carrier emulsion prepared with PC-LM had significant advantages in terms of stability and mean diameter. We considered it could be used for the preparations of nanoparticle dispersion systems in drug delivery systems.

  4. Synthesis of a smart pH-responsive magnetic nanocomposite as high loading carrier of pharmaceutical agents.

    PubMed

    Berah, Razieh; Ghorbani, Mohsen; Moghadamnia, Ali Akbar

    2017-06-01

    To create facile external controlled drug delivery system, a magnetic porous carrier based on Tin oxide nanoparticles was synthesized by an inexpensive and versatile hydrothermal strategy and used for in-vitro process. Magnetic nanocomposites were qualified by Fourier Transform Infrared (FTIR), Scanning Electron Microscopy (SEM), X-Ray Diffraction (XRD), Vibrational Sample Magnetometer (VSM) and Transmission Electron Microscopy (TEM). Results showed that nanoparticles were synthesized successfully with good dispersion of magnetic nanoparticles in cavity, uniform particle size distribution with average size of 65nm and high magnetization of 33.75 emu/mg. Furthermore, the nano-porosity and magnetism allowed high efficiency and remote controlled drug release. In this study, anti-migraine Sumatriptan was used as drug sample and the effect of drug concentration, Fe/Sn ratio and loading time on drug absorption were investigated. The best result was checked for stability at body temperature and different body pH. The sample with drug concentration of 0.25(mg/ml), Fe/Sn=0.22 and loading time of 1.5h had the highest drug efficiency (70%). Finally, in order to simulate the in vivo process for in-vitro step, Amnion was used and drug diffusion rate was measured in different intervals and different pH values. The result illustrated that after 25h, diffusion reached 65% at pH=2 and 56% at pH=7, and then became constant. Based on the above mentioned results, the carrier has an acceptable in vitro yield and therefore could be chosen for future in vivo researches. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Amorphous Silica Based Nanomedicine with Safe Carrier Excretion and Enhanced Drug Efficacy

    NASA Astrophysics Data System (ADS)

    Zhang, Silu

    With recent development of nanoscience and nanotechnology, a great amount of efforts have been devoted to nanomedicine development. Among various nanomaterials, silica nanoparticle (NP) is generally accepted as non-toxic, and can provide a versatile platform for drug loading. In addition, the surface of the silica NP is hydrophilic, being favorable for cellular uptake. Therefore, it is considered as one of the most promising candidates to serve as carriers for drugs. The present thesis mainly focuses on the design of silica based nanocarrier-drug systems, aiming at achieving safe nanocarrier excretion from the biological system and enhanced drug efficacy, which two are considered as most important issues in nanomedicine development. To address the safe carrier excretion issue, we have developed a special type of selfdecomposable SiO2-drug composite NPs. By creating a radial concentration gradient of drug in the NP, the drug release occurred simultaneously with the silica carrier decomposition. Such unique characteristic was different from the conventional dense SiO2-drug NP, in which drug was uniformly distributed and can hardly escape the carrier. We found that the controllable release of the drug was primarily determined by diffusion, which was caused by the radial drug concentration gradient in the NP. Escape of the drug molecules then triggered the silica carrier decomposition, which started from the center of the NP and eventually led to its complete fragmentation. The small size of the final carrier fragments enabled their easy excretion via renal systems. Apart from the feature of safe carrier excretion, we also found the controlled release of drugs contribute significantly to the drug efficacy enhancement. By loading an anticancer drug doxorubicin (Dox) to the decomposable SiO 2-methylene blue (MB) NPs, we achieved a self-decomposable SiO 2(MB)-Dox nanomedicine. The gradual escape of drug molecules from NPs and their enabled cytosolic release by optical

  6. Analysis of pharmaceutical impurities in the methamphetamine crystals seized for drug trafficking in Korea.

    PubMed

    Choe, Sanggil; Heo, Sewoong; Choi, Hyeyoung; Kim, Eunmi; Chung, Heesun; Lee, Jaesin

    2013-04-10

    Some methamphetamine (MA) crystals contain pharmaceutical impurities. They often come from the co-ingredients of cold drugs used for extracting ephedrine or pseudoephedrine. Though these impurities are not so commonly encountered, they reflect the trends in precursor chemicals and manufacturing sources. As a result of monitoring impurities in the MA crystals seized in Korea during 2006-2011, 10 species of pharmaceutical impurities were identified by gas chromatography-flame ionization detection and gas chromatography-mass spectrometry. They may be co-ingredients of the legal drugs used as a source of ephedrine or pseudoephedrine. In contrast, some of them are presumed to be adulterants added during or after clandestine synthesis. It is interesting that some of these have been identified in the MA crystals seized in other countries in the same year. Species of pharmaceutical impurities in the MA crystals increased particularly in 2010, indicating a change in precursor chemicals and/or manufacturing sources.

  7. Drug delivery systems improve pharmaceutical profile and facilitate medication adherence.

    PubMed

    Wertheimer, Albert I; Santella, Thomas M; Finestone, Albert J; Levy, Richard A

    2005-01-01

    Innovations in dosage forms and dose delivery systems across a wide range of medications offer substantial clinical advantages, including reduced dosing frequency and improved patient adherence; minimized fluctuation of drug concentrations and maintenance of blood levels within a desired range; localized drug delivery; and the potential for reduced adverse effects and increased safety. The advent of new large-molecule drugs for previously untreatable or only partially treatable diseases is stimulating the development of suitable delivery systems for these agents. Although advanced formulations may be more expensive than conventional dosage forms, they often have a more favorable pharmacologic profile and can be cost-effective. Inclusion of these dosage forms on drug formulary lists may help patients remain on therapy and reduce the economic and social burden of care.

  8. Pharmaceutical versatility of cationic niosomes derived from amino acid-based surfactants: Skin penetration behavior and controlled drug release.

    PubMed

    Muzzalupo, Rita; Pérez, Lourdes; Pinazo, Aurora; Tavano, Lorena

    2017-08-30

    The natural capability shown by cationic vesicles in interacting with negatively charged surfaces or biomolecules has recently attracted increased interest. Important pharmacological advantages include the selective targeting of the tumour vasculature, the promotion of permeation across cell membranes, as well as the influence of cationic vesicles on drug delivery. Accordingly, cationic amphiphiles derived from amino acids may represent an alternative to traditional synthetic cationic surfactants due to their lower cytotoxicity. The importance of a synthesized lysine-based gemini surfactant (labelledC6(LL)2) was evaluated in drug delivery by designing cationic niosomes as usable pharmaceutical tools of chemotherapeutics and antibiotics, respectively like methotrexate and tetracycline. The influence of formulation factors on the vesicles' physical-chemical properties, drug entrapment efficiency, in vitro release and ex-vivo skin permeation were investigated. A niosomal gel containing the gemini surfactant was also tested as a viable multi-component topical formulation. Results indicate that in the presence of cholesterol, C6(LL)2 was able to form stable and nanosized niosomes, loading hydrophilic or hydrophobic molecules. Furthermore, in vitro release studies and ex-vivo permeation profiles showed that C6(LL)2-based vesicles behave as sustained and controlled delivery systems in the case of parenteral administration, and as drug percutaneous permeation enhancers after topical application. Finally, cationic C6(LL)2 acts as a carrier constituent, conferring peculiar and interesting functionality to the final formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  9. [Drugs and pharmaceutical episodes in "Sazae-San": Japanese comic strips in 1940s-1970s].

    PubMed

    Goino, Masahiko

    2009-01-01

    This is a report on episodes with references to drugs and pharmaceuticals in one of the most famous Japanese comic strips, "Sazae-san", in the period from 1945 to 1974. There were 111 episodes of "Sazae-san" including references to drugs and pharmaceuticals in this period. In the period from 1945 to 1954, there were some references to pharmacists and pharmacies but only a small number of references in the period from 1965 to 1974. In the period from 1945 to 1954, there were references to disinfectants and insecticides in the hygienic chemistry field. However, in the period from 1965 to 1974, there were references to environmental problems, food additives and agricultural chemicals. As drug development has progressed, the number of references to practical drugs in "Sazae-san" has decreased over the period from 1945-1974.

  10. Atomic scale surface engineering of micro- to nano-sized pharmaceutical particles for drug delivery applications.

    PubMed

    Zhang, D; Quayle, M J; Petersson, G; van Ommen, J R; Folestad, S

    2017-08-17

    Atomic layer deposition on pharmaceutical particles for drug delivery applications is demonstrated using assisted fluidized bed dry powder processing. Complete and conformal layering is achieved on particle sizes from the lower micron to upper nanometer range under near ambient conditions. As few as 2-14 atomic alumina layers alter particle properties: dissolution, dispersibility and heat transfer.

  11. Drug and drug-related supply promotion by pharmaceutical company representatives at VA facilities. Final rule.

    PubMed

    2012-03-05

    This final rule amends the Department of Veterans Affairs (VA) regulations regarding access to VA facilities by pharmaceutical company representatives. The purposes of the rule are to reduce or eliminate any potential for disruption in the patient care environment, manage activities and promotions at VA facilities, and provide pharmaceutical company representatives with a consistent standard of permissible business practice at VA facilities. The amendments will facilitate mutually beneficial relationships between VA and pharmaceutical company representatives.

  12. Fast dissolution of poorly water soluble drugs from fluidized bed coated nanocomposites: Impact of carrier size.

    PubMed

    Azad, Mohammad; Moreno, Jacqueline; Bilgili, Ecevit; Davé, Rajesh

    2016-11-20

    Formation of core-shell nanocomposites of Fenofibrate and Itraconazole, model poorly water soluble drugs, via fluidized bed (FB) coating of their well-stabilized high drug loaded nanosuspensions is investigated. Specifically, the extent of dissolution enhancement, when fine carrier particles (sub-50μm) as opposed to the traditional large carrier particles (>300μm) are used, is examined. This allows testing the hypothesis that greatly increased carrier surface area and more importantly, thinner shell for finer carriers at the same drug loading can significantly increase the dissolution rate when spray-coated nanosuspensions are well-stabilized. Fine sub-50μm lactose (GranuLac(®) 200) carrier particles were made fluidizable via dry coating with nano-silica, enabling decreased cohesion, fluidization and subsequent nanosuspension coating. For both drugs, 30% drug loaded suspensions were prepared via wet-stirred media milling using hydroxypropyl methyl cellulose and sodium dodecyl sulfate as stabilizers. The stabilizer concentrations were varied to affect the milled particle size and prepare a stable nanosuspension. The suspensions were FB coated onto hydrophilic nano-silica (M-5P) dry coated sub-50μm lactose (GranuLac(®) 200) carrier particles or larger carrier particles of median size >300μm (PrismaLac(®)40). The resulting finer composite powders (sub-100μm) based on GranuLac(®) 200 were freely flowing, had high bulk density, and had much faster, immediate dissolution of the poorly water-soluble drugs, in particular for Itraconazole. This is attributed to a much higher specific surface area of the carrier and corresponding thinner coating layer for fine carriers as opposed to those for large carrier particles. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. 'Pro et contra' ionic liquid drugs - Challenges and opportunities for pharmaceutical translation.

    PubMed

    Balk, Anja; Holzgrabe, Ulrike; Meinel, Lorenz

    2015-08-01

    Ionic liquids (ILs) are organic salts with a melting point below 100°C. Active pharmaceutical ingredients (APIs) are transformed into ILs by combining them with typically large yet charged counterions. ILs hold promise to build a large design space for relevant pharmaceutical parameters, particularly for poorly water soluble drugs. It is for this wide design space that ILs may be the entry into the fascinating vision of modifying physico-chemical properties without the need to structurally modify the active pharmaceutical ingredient itself. This extremely intriguing pharmaceutical option is critically discussed including its potential and limitations. The review is starting off with an introduction to the metathesis and characterization of ILs, and leads over to examples for pharmaceutical application, including enhancement of dissolution rate and kinetic solubility and hygroscopicity adaptation, respectively. Tuning biopharmaceutics and toxicology by proper IL design is another focus. The review connects the interrelated chemical, physical, pharmaceutical, and toxicological outcome of API-ILs, serving as guidance for the formulation scientist who aims at expanding ones armamentarium for poorly water soluble APIs while avoiding structural modification, thereof.

  14. [Rheologic properties of some pharmaceutical excipients in drug forms and cosmetic preparation technology].

    PubMed

    Tsagareishvili, G V; Bashura, A A; Alekseeva, M A; Bashura, G S

    2012-06-01

    The establishment of mechanisms and principles of the formation of deformation (fracture) of spatial structure of bentonite solutions and various solutions and disperse systems is one or the most important problems of modern pharmaceutical technology. The article presents the results of a long-term research of influence of high-molecular compounds and surfactants on the properties of designed dosage drug forms and cosmetic preparation. Research data, as the basis for drug combinations "gel" with dekamitoksin, extract Aesculus hippocastanum L and probiotics.

  15. A review of the effect of pharmaceutical firm drug announcements on stock option pricing.

    PubMed

    Younis, Mustafa Mike Z; Younies, Hassan; Kisa, Adnan; Hartmann, Michael; Hussain, Ali Al Sayed; Al-Amro, Abdulla

    2009-01-01

    Since the Black and Sholes published their work in option pricing in 1973, there have been a great number of dissertations, theses, and articles published on options pricing. Several articles discussed American options and European options. Many articles where empirical in nature. In this article, we review some of the literature in this area and then discuss in a descriptive way the effect of pharmaceutical companies' announcements of new drugs on the market or drug withdrawals from the market on their stock options. This article should be the beginning of the discussion on how stock prices might affect the cost of drugs and the affect of the affordability of drug prices, if any.

  16. The teaching of drug development to medical students: collaboration between the pharmaceutical industry and medical school.

    PubMed

    Stanley, A G; Jackson, D; Barnett, D B

    2005-04-01

    Collaboration between the medical school at Leicester and a local pharmaceutical company, AstraZeneca, led to the design and implementation of an optional third year special science skills module teaching medical students about drug discovery and development. The module includes didactic teaching about the complexities of the drug discovery process leading to development of candidate drugs for clinical investigation as well as practical experience of the processes involved in drug evaluation preclinically and clinically. It highlights the major ethical and regulatory issues concerned with the production and testing of novel therapies in industry and the NHS. In addition it helps to reinforce other areas of the medical school curriculum, particularly the understanding of clinical study design and critical appraisal. The module is assessed on the basis of a written dissertation and the critical appraisal of a drug advertisement. This paper describes the objectives of the module and its content. In addition we outline the results of an initial student evaluation of the module and an assessment of its impact on student knowledge and the opinion of the pharmaceutical industry partner. This module has proven to be popular with medical students, who acquire a greater understanding of the work required for drug development and therefore reflect more favourably on the role of pharmaceutical companies in the UK.

  17. The teaching of drug development to medical students: collaboration between the pharmaceutical industry and medical school

    PubMed Central

    Stanley, A G; Jackson, D; Barnett, D B

    2005-01-01

    Collaboration between the medical school at Leicester and a local pharmaceutical company, AstraZeneca, led to the design and implementation of an optional third year special science skills module teaching medical students about drug discovery and development. The module includes didactic teaching about the complexities of the drug discovery process leading to development of candidate drugs for clinical investigation as well as practical experience of the processes involved in drug evaluation preclinically and clinically. It highlights the major ethical and regulatory issues concerned with the production and testing of novel therapies in industry and the NHS. In addition it helps to reinforce other areas of the medical school curriculum, particularly the understanding of clinical study design and critical appraisal. The module is assessed on the basis of a written dissertation and the critical appraisal of a drug advertisement. This paper describes the objectives of the module and its content. In addition we outline the results of an initial student evaluation of the module and an assessment of its impact on student knowledge and the opinion of the pharmaceutical industry partner. This module has proven to be popular with medical students, who acquire a greater understanding of the work required for drug development and therefore reflect more favourably on the role of pharmaceutical companies in the UK. PMID:15801942

  18. General public knowledge, perceptions and practice towards pharmaceutical drug advertisements in the Western region of KSA.

    PubMed

    Al-Haddad, Mahmoud S; Hamam, Fayez; Al-Shakhshir, Sami M

    2014-04-01

    This study aims to examine general public knowledge and behavior toward pharmaceutical advertisements in the Western part of KSA. A cross sectional convenience sampling technique was used in this study. A total of 1445 valid questionnaires were received and analyzed using SPSS version 16 at alpha value of 0.05. Majority of respondents were aware of different types of drugs to be advertised and drug advertisements should seek approval from the health authorities. Television and Internet showed the highest effect on consumers. Almost half of the participants preferred an advertised drug over non-advertised one. Most of the respondents indicated that the quality of frequently advertised drugs is not better than those prescribed by the doctors. Majority of participants had positive beliefs toward advertised drugs concerning their role in education and spreading of awareness among the public. Pharmaceutical advertisements harm the doctor-patient relationship as evidenced by one-third of the investigated sample. Moreover, majority of the participants mentioned that they would consult another doctor or even change the current doctor if he/she refused to prescribe an advertised medication. Results of this study could be used to develop awareness programs for the general public and try to enforce the regulations and policies to protect the general public and patients from the business oriented pharmaceutical companies and drug suppliers.

  19. General public knowledge, perceptions and practice towards pharmaceutical drug advertisements in the Western region of KSA

    PubMed Central

    Al-Haddad, Mahmoud S.; Hamam, Fayez; AL-Shakhshir, Sami M.

    2013-01-01

    This study aims to examine general public knowledge and behavior toward pharmaceutical advertisements in the Western part of KSA. A cross sectional convenience sampling technique was used in this study. A total of 1445 valid questionnaires were received and analyzed using SPSS version 16 at alpha value of 0.05. Majority of respondents were aware of different types of drugs to be advertised and drug advertisements should seek approval from the health authorities. Television and Internet showed the highest effect on consumers. Almost half of the participants preferred an advertised drug over non-advertised one. Most of the respondents indicated that the quality of frequently advertised drugs is not better than those prescribed by the doctors. Majority of participants had positive beliefs toward advertised drugs concerning their role in education and spreading of awareness among the public. Pharmaceutical advertisements harm the doctor–patient relationship as evidenced by one-third of the investigated sample. Moreover, majority of the participants mentioned that they would consult another doctor or even change the current doctor if he/she refused to prescribe an advertised medication. Results of this study could be used to develop awareness programs for the general public and try to enforce the regulations and policies to protect the general public and patients from the business oriented pharmaceutical companies and drug suppliers. PMID:24648823

  20. Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier

    PubMed Central

    Hayashida, Kayoko; Higashi, Taishi; Kono, Daichi; Motoyama, Keiichi; Wada, Koki

    2014-01-01

    Summary Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products. PMID:25550741

  1. Preparation and evaluation of cyclodextrin polypseudorotaxane with PEGylated liposome as a sustained release drug carrier.

    PubMed

    Hayashida, Kayoko; Higashi, Taishi; Kono, Daichi; Motoyama, Keiichi; Wada, Koki; Arima, Hidetoshi

    2014-01-01

    Cyclodextrins (CDs) can form polypseudorotaxanes (PPRXs) with drugs or drug carriers possessing linear polymers such as polyethylene glycol (PEG). On the other hand, PEGylated liposomes have been utilized as a representative anticancer drug carrier. However, little is known about the formation of CD PPRX with PEGylated liposome. In the present study, we first report the formation of CD PPRX with PEGylated liposome and evaluate it as a sustained release drug carrier. PEGylated liposome encapsulating doxorubicin was disrupted by the addition of α-CD. Meanwhile, γ-CD included two PEG chains and/or one bending PEG chain of PEGylated liposome and formed PPRX without the disruption of the membrane integrity of the PEGylated liposome. Moreover, the release of doxorubicin and/or PEGylated liposome encapsulating doxorubicin from the PPRX was prolonged in accordance with the matrix type release mechanism. These findings suggest the potential of γ-CD PPRX as sustained release carriers for PEGylated liposome products.

  2. Vesicles: a recently developed novel carrier for enhanced topical drug delivery.

    PubMed

    Akhtar, Nida

    2014-01-01

    As skin is one of the crucial and important organs of the human body, delivering the drug across it requires an effective development in the field of research. Topical drug delivery system is specifically designed with the objective to accomplish the delivery of therapeutically active drugs across the skin. Though skin is considered to be a multifunctional organ of a human body, it has the limitation of lesser permeability across the stratum corneum. As this layer constitutes an effective barrier for the drugs, various carrier systems have been developed to overcome this barrier. Vesicular carriers are one of the recently invented carriers. Liposomes, niosomes, transferosomes and ethosomes constitute the major part of these vesicles that have been sufficiently employed for the treatment of variety of topical skin diseases. In the past few years various research reports on the development of topical carrier systems showed that these carriers have emerged as a novel vesicular carrier. These are considered to be effective enough for the enhanced and safe delivery of both hydrophilic and lipophilic drugs. The present review focuses on the topical delivery via these vesicles, emphasizing on various aspects of all these carriers.

  3. Recent Techniques and Patents on Solid Lipid Nanoparticles as Novel Carrier for Drug Delivery.

    PubMed

    Khatak, Sunil; Dureja, Harish

    2015-01-01

    The various approaches have been utilized in the treatment of a variety of diseases by applying drug delivery system such as polymeric nanoparticles, self-emulsifying delivery systems, liposomes, microemulsions and micellar solutions. Recently, solid lipid nanoparticles (SLNs), nanostructured lipid carriers (NLCs) and lipid-drug conjugates (LDCs) have been exploited as a carrier of lipophilic and hydrophilic/amphiphilic substances for invasive and non-invasive routes of delivery. SLNs are colloidal drug carrier system and are like nanoemulsion, however, the lipid content in SLNs is solid in nature. These novel type of lipid nanoparticles with solid matrix offers to develop new prototype therapeutics in drug delivery, which could be used for controlled release, drug targeting, gene therapy, physical and chemical stability and site-specific drug delivery and thereby attracted the research groups worldwide. This manuscript overviews the recent patents, advantages, formulation techniques, stability aspects and applications of SLNs.

  4. Interfacing materials science and biology for drug carrier design.

    PubMed

    Such, Georgina K; Yan, Yan; Johnston, Angus P R; Gunawan, Sylvia T; Caruso, Frank

    2015-04-08

    Over the last ten years, there has been considerable research interest in the development of polymeric carriers for biomedicine. Such delivery systems have the potential to significantly reduce side effects and increase the bioavailability of poorly soluble therapeutics. The design of carriers has relied on harnessing specific variations in biological conditions, such as pH or redox potential, and more recently, by incorporating specific peptide cleavage sites for enzymatic hydrolysis. Although much progress has been made in this field, the specificity of polymeric carriers is still limited when compared with their biological counterparts. To synthesize the next generation of carriers, it is important to consider the biological rationale for materials design. This requires a detailed understanding of the cellular microenvironments and how these can be harnessed for specific applications. In this review, several important physiological cues in the cellular microenvironments are outlined, with a focus on changes in pH, redox potential, and the types of enzymes present in specific regions. Furthermore, recent studies that use such biologically inspired triggers to design polymeric carriers are highlighted, focusing on applications in the field of therapeutic delivery.

  5. Radiopharmaceuticals for oncology drug development: a pharmaceutical industry perspective.

    PubMed

    Murphy, Philip S; Bergström, Mats

    2009-01-01

    Oncology remains an increasingly important focus of therapeutic development yet there remain many scientific and operational bottlenecks to deliver optimum treatments efficiently. Radiopharmaceuticals constitute a group of methodologies able to support the many stages of drug development. Methods such as [(18)F]-FDG-PET continue to have a role, evaluating early metabolic response to treatment and supporting more conventional assessments of disease response. Improvements over such tracers (for example, use of [(18)F]-FLT) in certain settings can also widen the impact radiotracers have on clinical development. New categories of tracers able to provide molecular insight into therapeutic intervention are likely grow and aim to remove the ambiguity of how effective a new drug is. It is likely that newer tracers able to define processes such as angiogenesis and apoptosis will supplement other methods in supporting early development decision-making and de-risking expensive, late-stage programs. Labeled drugs themselves also offer the ability to study localised pharmacokinetics in vivo and study issues such as therapeutic combinations. Owing to the significant cost, resource and time investment in developing novel tracers, new opportunities need to be closely matched with emerging drug development needs.

  6. The CTSA Pharmaceutical Assets Portal – a public–private partnership model for drug repositioning

    PubMed Central

    Marusina, Kate; Welsch, Dean J.; Rose, Lynn; Brock, Doug; Bahr, Nathan

    2011-01-01

    The Pharmaceutical Assets Portal aims to facilitate industry-academic collaborations for discovery of new indications for compounds no longer being developed by pharmaceutical companies, through eliminating barriers to access such compounds. The Portal’s enabling infrastructure includes a national investigator database; a Foci-of-Expertise browser; a material transfer agreement template; and a funding partner. Whereas the goal of creating a shared compound repository remains to be achieved, the Portal has established a mechanism to facilitate future drug repositioning opportunities. PMID:22768020

  7. Attitudes and beliefs regarding direct-to-consumer advertising of pharmaceutical drugs: an exploratory comparison of physicians and pharmaceutical sales representatives.

    PubMed

    Schulz, Steven A; Broekemier, Gregory M; Burkink, Tim J

    2014-01-01

    Even with many changes in regulation in recent years, direct-to-consumer advertising (DTCA) of pharmaceutical drugs remains a complicated and contentious issue. Many in our society argue for increased legislation of DTCA while others believe that DTCA serves a useful purpose and should not be overregulated. This study was designed to compare attitudes and beliefs regarding DTCA held by two key stakeholder groups, physicians and pharmaceutical sales representatives. A questionnaire was created, pretested, and administered to 30 physicians and 30 pharmaceutical sales representatives to investigate these issues. Significant differences between these two groups were found and implications for DTCA are discussed.

  8. An iterative approach for compound detection in an unknown pharmaceutical drug product: Application on Raman microscopy.

    PubMed

    Boiret, Mathieu; Gorretta, Nathalie; Ginot, Yves-Michel; Roger, Jean-Michel

    2016-02-20

    Raman chemical imaging provides both spectral and spatial information on a pharmaceutical drug product. Even if the main objective of chemical imaging is to obtain distribution maps of each formulation compound, identification of pure signals in a mixture dataset remains of huge interest. In this work, an iterative approach is proposed to identify the compounds in a pharmaceutical drug product, assuming that the chemical composition of the product is not known by the analyst and that a low dose compound can be present in the studied medicine. The proposed approach uses a spectral library, spectral distances and orthogonal projections to iteratively detect pure compounds of a tablet. Since the proposed method is not based on variance decomposition, it should be well adapted for a drug product which contains a low dose product, interpreted as a compound located in few pixels and with low spectral contributions. The method is tested on a tablet specifically manufactured for this study with one active pharmaceutical ingredient and five excipients. A spectral library, constituted of 24 pure pharmaceutical compounds, is used as a reference spectral database. Pure spectra of active and excipients, including a modification of the crystalline form and a low dose compound, are iteratively detected. Once the pure spectra are identified, multivariate curve resolution-alternating least squares process is performed on the data to provide distribution maps of each compound in the studied sample. Distributions of the two crystalline forms of active and the five excipients were in accordance with the theoretical formulation.

  9. Multi-residue screening of prioritised human pharmaceuticals, illicit drugs and bactericides in sediments and sludge.

    PubMed

    Langford, Katherine H; Reid, Malcolm; Thomas, Kevin V

    2011-08-01

    A robust multi-residue method was developed for the analysis of a selection of pharmaceutical compounds, illicit drugs and personal care product bactericides in sediments and sludges. Human pharmaceuticals were selected for analysis in Scottish sewage sludge and freshwater sediments based on prescription, physico-chemical and occurrence data. The method was suitable for the analysis of the selected illicit drugs amphetamine, benzoylecgonine, cocaine, and methamphetamine, the pharmaceuticals atenolol, bendroflumethiazide, carbamazepine, citalopram, diclofenac, fluoxetine, ibuprofen, and salbutamol, and the bactericides triclosan and triclocarban in sewage sludge and freshwater sediment. The method provided an overall recovery of between 56 and 128%, RSDs of between 2 and 19% and LODs of between 1 and 50 ng g(-1). Using the methodology the human pharmaceuticals atenolol, carbamazepine and citalopram and the bactericides triclosan and triclocarban were detected in Scottish sewage sludge. The illicit drugs cocaine, its metabolite benzoylecgonine, amphetamine and methamphetamine were not detected in any of the samples analysed. Triclosan and triclocarban were present at the highest concentrations with triclocarban detected in all but one sample and showing a pattern of co-occurrence in both sludge and sediment samples.

  10. [Active ingredients, pharmaceutic aids and efficacy of topical drugs].

    PubMed

    Zesch, A

    1988-05-01

    In local therapy, in contrast to all other forms of therapy, the galenic vehicle or various so-called inactive ingredients can influence the efficacy of the preparations to a great extent. This means that when such drugs are licensed, i.e. when their efficacy and safety are investigated, the therapeutic effects of the total compound under clinical conditions should form the basis for judgement, and not the pharmacological profile of the active substance alone. Taking these point into consideration, the value of application in phases, vehicle tolerance and the therapeutic properties of inactive ingredients, as compared with active ingredients, are assessed in relation to the range of indications of drugs. In this connection, the efficacy of generic products and the declaration of so-called inactive ingredients are discussed.

  11. A comprehensive system of pharmaceutical care for drug misusers

    PubMed Central

    Roberts, Kay; Hunter, Carole

    2004-01-01

    This article outlines the evolution of a community pharmacy-based supervised consumption of methadone program in Grater Glasgow. The formalization of this program in 1994 promoted full patient compliance with the methadone regimen and reduced seepage of the drug to the illicit market. 184 of the area's 215 community pharmacies now dispense methadone for the treatment of opiate dependence. Of these, 173 have a supplementary contract with the local health board to supervise the consumption of methadone on their premises. In addition 15 of "methadone" pharmacists are involved in the provision of a pharmacy based needle exchange scheme. This has been shown to be the most efficient and cost effective method of delivering clean injecting equipment to injecting drug users in the Greater Glasgow area. Glasgow's pharmacists' have now been involved in the methadone and needle exchange programs for more than ten years. The support needed by pharmacists and the steps that have been put in place to provide this level of commitment are described. The development of the Glasgow pharmacy based services to drug users has had a major impact on practice elsewhere in the United Kingdom. PMID:15169565

  12. Interpretation of pharmaceutical drug concentrations in young children's head hair.

    PubMed

    Chatterton, Craig; Turner, Kirsten; Klinger, Nadine; Etter, Matthieu; Duez, Mathieu; Cirimele, Vincent

    2014-01-01

    Three separate cases of child administration of prescription drugs are described. Following liquid-liquid extraction, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was used to identify and quantify methadone, 2-ethylidene-1,5-dimethyl-3,3-diphenyl-1-pyrrolidine (EDDP), tramadol, amitriptyline, and nortriptyline in children's hair. The children's age ranged from 14 months to 7 years; in all three cases, the drug in question was detected in more than one section of hair. Methadone was detected in the concentration range of 0.65-0.99 and 0.04-0.4 ng/mg; tramadol was detected in the concentration range of 1.5-2.2 ng/mg; amitriptyline and nortriptyline were detected in the concentration range of 0.18-1.06 and 0.38-2.0 ng/mg, respectively. In each case, the children's parents admitted to or were found guilty of drug administration to the child. These cases demonstrate the added value of hair testing and emphasize the importance of using hair samples to complement conventional analyses.

  13. Biophysical methods in drug discovery from small molecule to pharmaceutical.

    PubMed

    Holdgate, Geoffrey; Geschwindner, Stefan; Breeze, Alex; Davies, Gareth; Colclough, Nicola; Temesi, David; Ward, Lara

    2013-01-01

    Biophysical methods have become established in many areas of drug discovery. Application of these methods was once restricted to a relatively small number of scientists using specialized, low throughput technologies and methods. Now, automated high-throughput instruments are to be found in a growing number of laboratories. Many biophysical methods are capable of measuring the equilibrium binding constants between pairs of molecules crucial for molecular recognition processes, encompassing protein-protein, protein-small molecule, and protein-nucleic acid interactions, and several can be used to measure the kinetic or thermodynamic components controlling these biological processes. For a full characterization of a binding process, determinations of stoichiometry, binding mode, and any conformational changes associated with such interactions are also required. The suite of biophysical methods that are now available represents a powerful toolbox of techniques which can effectively deliver this full characterization.The aim of this chapter is to provide the reader with an overview of the drug discovery process and how biophysical methods, such as surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), nuclear magnetic resonance, mass spectrometry (MS), and thermal unfolding methods can answer specific questions in order to influence project progression and outcomes. The selection of these examples is based upon the experiences of the authors at AstraZeneca, and relevant approaches are highlighted where they have utility in a particular drug discovery scenario.

  14. Between confidentiality and scientific exchange: the place of publication in drug discovery and pharmaceutical research.

    PubMed

    Clozel, Martine

    2011-01-26

    To continue to improve life expectancy and quality of life, the discovery of innovative therapies should be among the prime goals of the life sciences. The large majority of the drugs that are discovered and successfully developed to the point of being used by patients come from the drug industry, but publications from this sector are rare among life sciences research publications. Publications in the field of pharmaceutical drug discovery should take into account the confidentiality inherent to the protection of the intellectual property rights of a discovery, but they are fundamentally important because they can enhance scientific knowledge, improve the care and safety of patients, provide information for prescribers, and educate the public about the pharmaceutical industry.

  15. Use of near-infrared spectroscopy and multipoint measurements for quality control of pharmaceutical drug products.

    PubMed

    Boiret, Mathieu; Chauchard, Fabien

    2017-01-01

    Near-infrared (NIR) spectroscopy is a non-destructive analytical technique that enables better-understanding and optimization of pharmaceutical processes and final drug products. The use in line is often limited by acquisition speed and sampling area. This work focuses on performing a multipoint measurement at high acquisition speed at the end of the manufacturing process on a conveyor belt system to control both the distribution and the content of active pharmaceutical ingredient within final drug products, i.e., tablets. A specially designed probe with several collection fibers was developed for this study. By measuring spectral and spatial information, it provides physical and chemical knowledge on the final drug product. The NIR probe was installed on a conveyor belt system that enables the analysis of a lot of tablets. The use of these NIR multipoint measurement probes on a conveyor belt system provided an innovative method that has the potential to be used as a new paradigm to ensure the drug product quality at the end of the manufacturing process and as a new analytical method for the real-time release control strategy. Graphical abstract Use of near-infrared spectroscopy and multipoint measurements for quality control of pharmaceutical drug products.

  16. Analysis of pharmaceutical preparations containing antihistamine drugs by micellar liquid chromatography.

    PubMed

    Martínez-Algaba, C; Bermúdez-Saldaña, J M; Villanueva-Camañas, R M; Sagrado, S; Medina-Hernández, M J

    2006-02-13

    Rapid chromatographic procedures for analytical quality control of pharmaceutical preparations containing antihistamine drugs, alone or together with other kind of compounds are proposed. The method uses C18 stationary phases and micellar mobile phases of cetyltrimethylammonium bromide (CTAB) with either 1-propanol or 1-butanol as organic modifier. The proposed procedures allow the determination of the antihistamines: brompheniramine, chlorcyclizine, chlorpheniramine, diphenhydramine, doxylamine, flunarizine, hydroxyzine, promethazine, terfenadine, tripelennamine and triprolidine, in addition to caffeine, dextromethorphan, guaifenesin, paracetamol and pyridoxine in different pharmaceutical presentations (tablets, capsules, suppositories, syrups and ointments). The methods require minimum handling sample and are rapid (between 3 and 12 min at 1 mLmin(-1) flow rate) and reproducible (R.S.D. values<5%). Limits of detection are lower than 1 microgmL(-1) and the recoveries of the analytes in the pharmaceutical preparations are in the range 100+/-10%.

  17. Parelectric spectroscopy of drug-carrier-systems--distribution of carrier masses or activation energies.

    PubMed

    Sivaramakrishnan, R; Kankate, L; Niehus, H; Kramer, K D

    2005-04-22

    The answer of a high-frequency electromagnetic wave to a sample as termination of an open-ended coaxial line gives the mobility and the density of permanent electric dipole moments in the substance under test. As long as these dipoles are attached to carrier molecules of well defined masses, both parameters can be extracted from the reflected wave in a quick manner giving unambiguous results. The corresponding algorithm has been applied to solid lipid nanoparticles with glucocorticoid molecules attached to or incorporated in the carrier molecules. The results from measurements in the frequency region (0.1-100) MHz have recently been published. As soon as we have to envisage a distribution in carrier masses and/or in activation energies of the attached molecules, we have to apply a more sophisticated evaluation algorithm. The need for a more generalised algorithm is clear as well, when we have to deal with more than one dipole-carrying constituent in the samples. All these evaluation algorithms shall be presented together with the mathematical basis in a short but exact form.

  18. Current drug therapy and pharmaceutical challenges for Chagas disease.

    PubMed

    Bermudez, José; Davies, Carolina; Simonazzi, Analía; Real, Juan Pablo; Palma, Santiago

    2016-04-01

    One of the most significant health problems in the American continent in terms of human health, and socioeconomic impact is Chagas disease, caused by the protozoan parasite Trypanosoma cruzi. Infection was originally transmitted by reduviid insects, congenitally from mother to fetus, and by oral ingestion in sylvatic/rural environments, but blood transfusions, organ transplants, laboratory accidents, and sharing of contaminated syringes also contribute to modern day transmission. Likewise, Chagas disease used to be endemic from Northern Mexico to Argentina, but migrations have earned it global. The parasite has a complex life cycle, infecting different species, and invading a variety of cells - including muscle and nerve cells of the heart and gastrointestinal tract - in the mammalian host. Human infection outcome is a potentially fatal cardiomyopathy, and gastrointestinal tract lesions. In absence of a vaccine, vector control and treatment of patients are the only tools to control the disease. Unfortunately, the only drugs now available for Chagas' disease, Nifurtimox and Benznidazole, are relatively toxic for adult patients, and require prolonged administration. Benznidazole is the first choice for Chagas disease treatment due to its lower side effects than Nifurtimox. However, different strategies are being sought to overcome Benznidazole's toxicity including shorter or intermittent administration schedules-either alone or in combination with other drugs. In addition, a long list of compounds has shown trypanocidal activity, ranging from natural products to specially designed molecules, re-purposing drugs commercialized to treat other maladies, and homeopathy. In the present review, we will briefly summarize the upturns of current treatment of Chagas disease, discuss the increment on research and scientific publications about this topic, and give an overview of the state-of-the-art research aiming to produce an alternative medication to treat T. cruzi infection.

  19. Spectrophotometric determination of dopaminergic drugs used for Parkinson's disease, cabergoline and ropinirole, in pharmaceutical preparations.

    PubMed

    Onal, Armağan; Cağlar, Sena

    2007-04-01

    Simple and reproducible spectrophotometric methods have been developed for determination of dopaminergic drugs used for Parkinson's disease, cabergoline (CAB) and ropinirole hydrochloride (ROP), in pharmaceutical preparations. The methods are based on the reactions between the studied drug substances and ion-pair agents [methyl orange (MO), bromocresol green (BCG) and bromophenol blue (BPB)] producing yellow colored ion-pair complexes in acidic buffers, after extracting in dichloromethane, which are spectrophotometrically determined at the appropriate wavelength of ion-pair complexes. Beer's law was obeyed within the concentration range from 1.0 to 35 microg ml(-1). The developed methods were applied successfully for the determination of these drugs in tablets.

  20. [Me-too pharmaceuticals -- marketing-strategies of drug producers and drug purchasers. Example: non-ionic contrast media].

    PubMed

    Wild, C; Puig, S

    2004-11-01

    In the context of increasing economic pressure upon on hospital budgets, it is inevitable that central and standardized purchasing of pharmaceuticals must be considered. It was the aim of this assessment to analyse the many different non-ionic contrast media/CM products on the actual "clinical relevance of the differences" in order to give advice for a more concerted purchasing of CM. The assessment was commissioned by a large scale Austrian hospital cooperation; it can be regarded as the beginning of a broad strategy against the many new, only rarely innovative, but nevertheless patent-protected pharmaceuticals. Eight different non-ionic contrast media - used in routine care - were compared for their physico-chemical characteristics: osmolality, nephrotoxicity, viscosity, hydrophilicity and electric charge. In a systematic review 193 publications were analysed. The examined CM show similar pharmacokinetic and -dynamic attributes, and no differences of clinical relevance. An optimisation of purchasing pharmaceuticals by standardisation of the range of products takes place in the context of common strategies of producers and buying agents in marketing-economies. The strategies of the pharmaceutical industry (patent protection of me-too drugs, high-price-policy, extensive marketing of up to 40 % of revenue) and the counter-strategies of the central hospital purchasers (market concentration, drug commissions, institutional measures to disentangle interests) are presented - exemplified by contrast media - in this article.

  1. Particle Shape: A New Design Parameter for Micro- and Nanoscale Drug Delivery Carriers

    PubMed Central

    Champion, Julie A.; Katare, Yogesh K.; Mitragotri, Samir

    2014-01-01

    Encapsulation of therapeutic agents in polymer particles has been successfully used in the development of new drug carriers. A number of design parameters that govern the functional behavior of carriers, including the choice of polymer, particle size and surface chemistry, have been tuned to optimize their performance in vivo. However, particle shape, which may also have a strong impact on carrier performance, has not been investigated. This is perhaps due to the limited availability of techniques to produce non-spherical polymer particles. In recent years, a number of reports have emerged to directly address this bottleneck and initial studies have indeed confirmed that particle shape can significantly impact the performance of polymer drug carriers. This article provides a review of this field with respect to methods of particle preparation and the role of particle shape in drug delivery. PMID:17544538

  2. Ionic liquid-in-oil microemulsion as a potential carrier of sparingly soluble drug: characterization and cytotoxicity evaluation.

    PubMed

    Moniruzzaman, Muhammad; Tamura, Miki; Tahara, Yoshiro; Kamiya, Noriho; Goto, Masahiro

    2010-11-15

    Pharmaceutical industries have posed challenges in the topical and transdermal administration of drugs which are poorly soluble or insoluble in water and most of organic solvents. In an approach to overcome this limitation, ionic liquid-in-oil (IL/o) microemulsions (MEs) were employed to increase the solubility of a sparingly soluble drug to enhance its topical and transdermal delivery. The formulation of MEs was composed of a blend of nonionic surfactants, polyoxyethylene sorbitan monooleate (Tween-80) and sorbitan laurate (Span-20), isopropyl myristate (IPM) as an oil phase, and IL [C(1)mim] [(CH(3)O)(2)PO(2)] (dimethylimidazolium dimethylphosphate) as a pseudophase. Among various weight ratios of Tween-80 to Span-20 investigated in the ME systems, the ratio 3:2 showed excellent solubility and skin permeation enhancing effect for acyclovir (ACV) used as a model sparingly soluble drug. The size and size distribution of the ME droplets with and without drug were determined by dynamic light scattering. The permeability study of ACV incorporated in IL droplets as well as other formulations was performed into and across the Yucatan micropig (YMP) porcine skin, and the use of IL/o MEs has been shown to dramatically increase ACV administration. Finally, the cytotoxicity of the new carrier was evaluated in vitro using the reconstructed human epidermal model LabCyte™ EPI-MODEL12. It was found that the cell viability of IL/o MEs containing 4wt% IL was over 80% compared to Dulbecco's Phosphate-Buffered Salines, indicating low cytotoxicity of the carrier. Taken together these results, it can be assumed that IL-assisted nonaqueous ME could serve as a versatile and efficient nanodelivery system for insoluble or sparingly soluble drug molecules that require solubilizing agents for delivery.

  3. Magnetic Nanoparticle Drug Carriers and their Study by Quadrupole Magnetic Field-Flow Fractionation

    PubMed Central

    Williams, P. Stephen; Carpino, Francesca; Zborowski, Maciej

    2009-01-01

    Magnetic nanoparticle drug carriers continue to attract considerable interest for drug targeting in the treatment of cancers and other pathological conditions. The efficient delivery of therapeutic levels of drug to a target site while limiting nonspecific, systemic toxicity requires optimization of the drug delivery materials, the applied magnetic field, and the treatment protocol. The history and current state of magnetic drug targeting is reviewed. While initial studies involved micron-sized and larger carriers, and work with these microcarriers continues, it is the sub-micron carriers or nanocarriers that are of increasing interest. An aspect of magnetic drug targeting using nanoparticle carriers that has not been considered is then addressed. This aspect involves the variation in the magnetic properties of the nanocarriers. Quadrupole magnetic field-flow fractionation (QMgFFF) is a relatively new technique for characterizing magnetic nanoparticles. It is unique in its capability of determining the distribution in magnetic properties of a nanoparticle sample in suspension. The development and current state of this technique is also reviewed. Magnetic nanoparticle drug carriers have been found by QMgFFF analysis to be highly polydisperse in their magnetic properties, and the strength of response of the particles to magnetic field gradients is predicted to vary by orders of magnitude. It is expected that the least magnetic fraction of a formulation will contribute the most to systemic toxicity, and the depletion of this fraction will result in a more effective drug carrying material. A material that has a reduced systemic toxicity will allow higher doses of cytotoxic drugs to be delivered to the tumor with reduced side effects. Preliminary experiments involving a novel method of refining a magnetic nanoparticle drug carrier to achieve this result are described. QMgFFF is used to characterize the refined and unrefined material. PMID:19591456

  4. [Approval of drugs by national and European agencies--sequelae for the pharmaceutical industry].

    PubMed

    Zierenberg, O

    1997-11-01

    The research-based pharmaceutical industry supports the European harmonization process for the granting of pharmaceutical registrations. In order to improve consumer protection and the therapeutic options available to physicians in comparison to nationally registered products, the harmonization must be carried out on schedule and transparently a high scientific standard. It must not lead to the adoption of all national restrictions regarding data sheets and patient leaflets. Pharmaceutical products with the same ingredients can be registered either through the national or through the European procedure. This situation can only be remedied by the harmonization of core SPCs. This process must be agreed in consultation between pharmaceutical companies and regulatory authorities. With regard to measures to avert drug risks, professional associations and the pharmaceutical companies affected should be heard by the national authorities and their arguments given due consideration. In addition, national authorities and the CPMP must coordinate their decisions before they are published. In particular, the basis of these decisions should be made clear and therapeutic alternatives should be known.

  5. 78 FR 3900 - Generic Drug User Fee-Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-17

    ... HUMAN SERVICES Food and Drug Administration Generic Drug User Fee--Active Pharmaceutical Ingredient and Finished Dosage Form Facility Fee Rates for Fiscal Year 2013 AGENCY: Food and Drug Administration, HHS. ACTION: Notice. SUMMARY: The Food and Drug Administration (FDA) is announcing the rate for the generic...

  6. The pharmaceutical economics of child psychiatric drug treatment.

    PubMed

    Schlander, Michael

    2010-01-01

    The last decade, the number of health economic evaluations has increased substantially in the field of child psychiatry. The objective of the present paper is to offer an overview of economic evaluations of child psychiatric drug treatment. Major electronic databases, as well as abstract booklets from international clinical and health economics conferences with an external peer review process, were examined to search for comparative economic evaluations of child and adolescent psychiatric drug treatment. Most studies of pharmacotreatment were cost effectiveness analyses (CEAs) concerned with attention-deficit/hyperactivity disorder (ADHD). Three evaluations were done by or on behalf of agencies as part of ADHD-related health technology assessments. A number of economic studies used patient-level data from specific randomized clinical trials, especially the NIMH-initiated MTA (in childhood ADHD) and TADS (in adolescent major depression) studies. Almost all studies relied on narrow scale symptom scales to assess effects of treatment, even when quality-adjusted life years (QALYs) were reported. In many cases, effectiveness data came from short-term studies, and extrapolation to a one-year time horizon was usually based on assumptions. Even those evaluations attempting to address longer time horizons by way of modeling did not include the impact of treatment on long-term sequelae of the conditions studied, mainly due to a paucity of robust clinical data. Nevertheless, currently available health economic evaluations broadly suggest an acceptable to attractive cost effectiveness of medication management of ADHD, whereas there is no such evidence for child psychiatric disorders other than ADHD.

  7. A new chapter in pharmaceutical manufacturing: 3D-printed drug products.

    PubMed

    Norman, James; Madurawe, Rapti D; Moore, Christine M V; Khan, Mansoor A; Khairuzzaman, Akm

    2017-01-01

    FDA recently approved a 3D-printed drug product in August 2015, which is indicative of a new chapter for pharmaceutical manufacturing. This review article summarizes progress with 3D printed drug products and discusses process development for solid oral dosage forms. 3D printing is a layer-by-layer process capable of producing 3D drug products from digital designs. Traditional pharmaceutical processes, such as tablet compression, have been used for decades with established regulatory pathways. These processes are well understood, but antiquated in terms of process capability and manufacturing flexibility. 3D printing, as a platform technology, has competitive advantages for complex products, personalized products, and products made on-demand. These advantages create opportunities for improving the safety, efficacy, and accessibility of medicines. Although 3D printing differs from traditional manufacturing processes for solid oral dosage forms, risk-based process development is feasible. This review highlights how product and process understanding can facilitate the development of a control strategy for different 3D printing methods. Overall, the authors believe that the recent approval of a 3D printed drug product will stimulate continual innovation in pharmaceutical manufacturing technology. FDA encourages the development of advanced manufacturing technologies, including 3D-printing, using science- and risk-based approaches.

  8. Pharmaceutical cocrystals: a novel approach for oral bioavailability enhancement of drugs.

    PubMed

    Chadha, Renu; Saini, Anupam; Arora, Poonam; Bhandari, Swati

    2012-01-01

    Solid dosage forms are by far the preferred drug delivery systems. However, these often face the problem of poor and erratic bioavailability during the drug development process. Numerous formulation strategies for drug delivery are currently under development, among which the solid forms such as polymorphs, solvates, salts, and cocrystals have been considered to be the most important for improving dissolution rate and bioavailability. Cocrystallization is a fairly new approach in pharmaceutical industry that can improve the solubility and, consequently, the bioactivity of the active pharmaceutical ingredient (API) without compromising its structural integrity. Pharmaceutical cocrystals have found their place in drug delivery, primarily due to their ability to produce alternative, viable solid forms when a more standard approach of salt and polymorph formation fails to deliver the desired objectives. Over the past few years, a number of papers have been published focusing on a broad range of subjects, from traditional crystal engineering to structure-property relationships of cocrystals. The present review, however, illustrates how the cocrystalline forms of APIs have improved their in vitro dissolution rate and in vivo bioavailability, often correlating well with their improved solubility as well.

  9. Integration of active pharmaceutical ingredient solid form selection and particle engineering into drug product design.

    PubMed

    Ticehurst, Martyn David; Marziano, Ivan

    2015-06-01

    This review seeks to offer a broad perspective that encompasses an understanding of the drug product attributes affected by active pharmaceutical ingredient (API) physical properties, their link to solid form selection and the role of particle engineering. While the crucial role of active pharmaceutical ingredient (API) solid form selection is universally acknowledged in the pharmaceutical industry, the value of increasing effort to understanding the link between solid form, API physical properties and drug product formulation and manufacture is now also being recognised. A truly holistic strategy for drug product development should focus on connecting solid form selection, particle engineering and formulation design to both exploit opportunities to access simpler manufacturing operations and prevent failures. Modelling and predictive tools that assist in establishing these links early in product development are discussed. In addition, the potential for differences between the ingoing API physical properties and those in the final product caused by drug product processing is considered. The focus of this review is on oral solid dosage forms and dry powder inhaler products for lung delivery.

  10. Drug discovery market exclusivity after KSR: the challenge to pharmaceutical scientists and the US congress.

    PubMed

    Wolff, Manfred E

    2011-08-01

    The Hatch-Waxman Act provides 180 days of market exclusivity to encourage generic companies to challenge the validity of pharmaceutical patents issued to innovator pharmaceutical companies. The consequent patent losses have been exacerbated owing to the application of holdings of the 2007 Supreme Court KSR decision to questions of pharmaceutical patentability by the judiciary and the US Patent Office. The resulting negative effect on support for new drug and formulation discovery by pharmaceutical scientists is discussed. To counteract the societal detriment of this negative effect, the adoption of a 12-year US Food and Drug Administration (FDA) market exclusivity paradigm for all approved new chemical entities including prodrugs is proposed. Such market exclusivities have already been enacted in the United States for follow-on biologicals and are in substantial harmony with those of the European Union, Japan, and Canada. An extension of the existing 3-year FDA market exclusivity for new formulations under 21 U.S.C. (United States Code) §505(b)(2) to 5 years should also be considered.

  11. A novel strategy to achieve effective drug delivery: exploit cells as carrier combined with nanoparticles.

    PubMed

    Pang, Liang; Zhang, Chun; Qin, Jing; Han, Limei; Li, Ruixiang; Hong, Chao; He, Huining; Wang, Jianxin

    2017-11-01

    Cell-mediated drug delivery systems employ specific cells as drug vehicles to deliver drugs to targeted sites. Therapeutics or imaging agents are loaded into these cells and then released in diseased sites. These specific cells mainly include red blood cells, leukocytes, stem cells and so on. The cell acts as a Trojan horse to transfer the drug from circulating blood to the diseased tissue. In such a system, these cells keep their original properties, which allow them to mimic the migration behavior of specific cells to carry drug to the targeted site after in vivo administration. This strategy elegantly combines the advantages of both carriers, i.e. the adjustability of nanoparticles (NPs) and the natural functions of active cells, which therefore provides a new perspective to challenge current obstacles in drug delivery. This review will describe a fundamental understanding of these cell-based drug delivery systems, and discuss the great potential of combinational application of cell carrier and NPs.

  12. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy.

    PubMed

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-12-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

  13. The Research and Applications of Quantum Dots as Nano-Carriers for Targeted Drug Delivery and Cancer Therapy

    NASA Astrophysics Data System (ADS)

    Zhao, Mei-Xia; Zhu, Bing-Jie

    2016-04-01

    Quantum dots (QDs), nano-carriers for drugs, can help realize the targeting of drugs, and improve the bioavailability of drugs in biological fields. And, a QD nano-carrier system for drugs has the potential to realize early detection, monitoring, and localized treatments of specific disease sites. In addition, QD nano-carrier systems for drugs can improve stability of drugs, lengthen circulation time in vivo, enhance targeted absorption, and improve the distribution and metabolism process of drugs in organization. So, the development of QD nano-carriers for drugs has become a hotspot in the fields of nano-drug research in recent years. In this paper, we review the advantages and applications of the QD nano-carriers for drugs in biological fields.

  14. Enhanced cytotoxicity of anticancer drug delivered by novel nanoscale polymeric carrier

    NASA Astrophysics Data System (ADS)

    Stoika, R.; Boiko, N.; Senkiv, Y.; Shlyakhtina, Y.; Panchuk, R.; Finiuk, N.; Filyak, Y.; Bilyy, R.; Kit, Y.; Skorohyd, N.; Klyuchivska, O.; Zaichenko, A.; Mitina, N.; Ryabceva, A.

    2013-04-01

    We compared in vitro action of highly toxic anticancer drug doxorubicin under its delivery to the mammalian tumor cells in free form and after encapsulation in novel bio-functionalized nanoscale polymeric carrier. Such encapsulation was found to enhance significantly drug uptake by the targeted cells, as well as its cytotoxic action. 10 times higher cytotoxicity of the carrier-immobilized doxorubicin comparing to its free form was demonstrated by direct cell counting, and 5 times higher cytotoxicity of encapsulated doxorubicin was shown by FACS analysis. The polymeric carrier itself did not possess significant toxicity in vitro or in vivo (laboratory mice). The carrier protected against negative side effects of doxorubicin in mice with experimental NK/Ly lymphoma. The life duration of tumor-bearing animals treated with doxorubicin-carrier complex was significantly longer than life duration in animals treated with free doxorubicin. Besides, the effective treatment dose of the carrier-delivered doxorubicin in tumor-bearing mice was 10 times lower than such dose of free doxorubicin. Thus, novel nanoscale polymers possess high potential as drug carrier.

  15. Investigation of pharmaceutical drugs and caffeine-containing foods using Fourier and terahertz time-domain spectroscopy

    NASA Astrophysics Data System (ADS)

    KaraliÅ«nas, Mindaugas; Venckevičius, Rimvydas; Kašalynas, Irmantas; Puc, Uroš; Abina, Andreja; Jeglič, Anton; Zidanšek, Aleksander; Valušis, Gintaras

    2015-08-01

    Several pharmaceutical drugs, such as alprazolam, ibuprofen, acetaminophen, activated carbon and others, and caffeine-containing foods were tested using terahertz (THz) time domain spectroscopy in the range from 0.3 to 2 THz. The dry powder of pharmaceutical drugs was mixed with HDPE and pressed into the pellets using hydraulic press. The coffee grounds were also pressed into the pellets after ball-milling and mixing with HDPE. The caffeine containing liquid foods were dried out on the paper strips of various stacking. Experiments allow one to determine characteristic spectral signatures of the investigated substances within THz range caused by active pharmaceutical ingredients, like in the case of caffeine, as well as supporting pharmaceutical ingredients. Spectroscopic THz imaging approach is considered as a possible option to identify packaged pharmaceutical drugs. The caffeine spectral features in the tested caffeine containing foods are difficult to observed due to the low caffeine concentration and complex caffeine chemical surrounding.

  16. The synthesis and application of heparin-based smart drug carrier.

    PubMed

    Li, Qingxuan; Gan, Lu; Tao, Hong; Wang, Qian; Ye, Lin; Zhang, Aiying; Feng, Zengguo

    2016-04-20

    Heparin based polymer drug which could self-assemble into sphere micelle in water was firstly prepared by grafting paclitaxel (PTX) into the hydroxyl of heparin via aconitic bond as pH sensitive spacer. Positive charged drug DOX·HCl and cationic folic acid (CFA) can be further loaded into the polymer drug via electrostatic interaction in aqueous solution so as to prepare smart drug carrier. The drug carrier was able to release more PTX and DOX at pH 4.8 than that at pH 7.4, exhibiting pH sensitivity for two drugs. Furthermore, tumor cell cytotoxicity test proved it possessed significant cytotoxicity against tumor cells MDA-MB-231 as well as its active tumor targeting ability resulting from the loading of CFA. Cellular uptake and intracellular distribution were further revealed by confocal laser scanning microscopy (CLSM). In conclusion, this paper not only provided a simple strategy but also indicated heparin is a versatile platform for the design of smart drug carrier. The as-prepared drug carrier also showed promising potential in chemotherapy.

  17. Nanostructured lipid carriers and their current application in targeted drug delivery.

    PubMed

    Jaiswal, Piyush; Gidwani, Bina; Vyas, Amber

    2016-01-01

    In the last few decades, various drug-delivery technologies have emerged and a fascinating part of this has been the development of nanoscale drug delivery devices. Nanoparticles (NPs) and other colloidal drug-delivery systems modify the kinetics, drug distribution in the body and release profile of an associated drug. Nanostructured lipid carriers (NLCs) have been reported to be an alternative system to emulsions, liposomes, microparticles, solid lipid nanoparticles (SLNs) and their polymeric counterparts due to their numerous advantages. This paper basically reviews the types of NLCs, mechanism of skin penetration, stability related issues along with their production techniques, characterisation and applications towards targeted drug delivery.

  18. Biodegradable long circulating cellular carrier for antimalarial drug pyrimethamine.

    PubMed

    Agnihotri, Jaya; Jain, Narendra Kumar

    2013-10-01

    The objective of the present study was to develop targeted engineered nanoerythrosomes based intravenous formulation of antimalarial drug pyrimethamine. The nanoerythrosomes formulation was developed by sonication method and optimized for effective drug loading at variable drug concentration, surface morphology, viscosity and sedimentation volume. The in vitro drug release of formulated product was found to be delayed after 8 hours, having good stability at 4 ± 1°C and showing controlled in vivo release. Tissue distribution studies showed higher accumulation of drug in the liver (18.71 ± 1.4 μg/ml) (P < 0.05) at 1 hour in case of pyrimethamine-loaded nanoerythrosomes as compared to that in free drug (12.82 ± 0.7 μg/ml). Higher amount of drug, i.e. 14.18 ± 0.9 μg/ml (P < 0.05), was found after 24 hours in the liver in case of pyrimethamine-loaded nanoerythrosomes as compared to free drug concentration of 9.72 ± 0.5 μg/ml). Data showed that developed pyrimethamine-loaded nanoerythrosomes hold promise for targeting and controlling the release of drug and for improving treatment of malaria when they are combined with rapid acting antimalarials such as artemisinin. A decrease in the concentration of pyrimethamine in kidneys and lungs after 24 hours was observed as compared to that observed after 1 hour, showing no or little involvement of these organs in the clearance of drug-loaded nanoerythrosomes.

  19. Application of DPD in the design of polymeric nano-micelles as drug carriers.

    PubMed

    Ramezani, Mohammad; Shamsara, Jamal

    2016-05-01

    Developing new drug carrier systems are of a great importance in the treatment approach for a wide range of diseases. The simulation techniques can be valuable for decreasing the time and cost of developing novel drug carriers. Among the simulation methods there are a vast number of studies using dissipative particle dynamics (DPD) method for the prediction of different aspects of polymeric nano-micelles for encapsulating drugs. Here, we reviewed the results of the studies employing DPD for the simulation of drug loading and release in different polymeric micelles carriers. In some cases the simulation results were compared with the experimental results by the authors that were demonstrated the reliability of the DPD predictions.

  20. 77 FR 24723 - AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a New Drug Application for IRESSA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-04-25

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration AstraZeneca Pharmaceuticals LP; Withdrawal of Approval of a... IRESSA (gefitinib) Tablets held by AstraZeneca Pharmaceuticals LP (AstraZeneca), 1800 Concord Pike, P.O...

  1. 77 FR 40367 - Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New Drug Application for DURACT Capsules

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-07-09

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Wyeth Pharmaceuticals, Inc.; Withdrawal of Approval of a New... DURACT (bromfenac sodium) Capsules, held by Wyeth Pharmaceuticals, Inc. (Wyeth), P.O. Box 8299...

  2. Occurrence of illicit drugs and selected pharmaceuticals in Slovak municipal wastewater.

    PubMed

    Bodík, Igor; Mackuľak, Tomáš; Fáberová, Milota; Ivanová, Lucia

    2016-10-01

    We analyzed illicit drugs and their metabolites and pharmaceuticals in wastewater from 15 selected wastewater treatment plants (WWTPs) in Slovakia. Our results indicate that methamphetamine is one of the most commonly used illegal drugs in all the regions of Slovakia monitored in this study. Compared with the international results, the Slovak cities of Dunajská Streda (479 mg/day/1000inh) and Trnava (354 mg/day/1000inh) are among the cities with the largest numbers of methamphetamine users in Europe. These results indicate an increase in the incidence of drugs in big cities and in the satellite cities (Trnava and Dunajská Streda) near Bratislava. These results also confirm the police statistics about production and use of illicit drugs in Slovakia. The highest specific loads of cocaine were found in Bratislava (112 mg/day/1000inh), followed by Petržalka (74 mg/day/1000inh). Compared with other European cities, Bratislava and the other Slovak cities in this study have a relatively low number of COC consumers. The ecstasy load in wastewater from larger cities also significantly increased over the weekend and during music festivals. The highest 2-year mean concentrations of THC-COOH, a cannabis biomarker, were observed in the sewage from BA-Petržalka and BA-Central (191 and 171 ng/L, respectively). A first complex monitoring of pharmaceuticals in all therapeutic groups was also realized in selected Slovak WWTPs. Occurrence of wide spectrum of pharmaceuticals with very high concentrations as well as consumptions were observed mainly in small Slovak cities. Considering all 120 monitored pharmaceuticals, Valsartan had the highest concentrations: 6000 ng/L, on average.

  3. A versatile, quantitative analytical method for pharmaceutical relevant lipids in drug delivery systems.

    PubMed

    Jeschek, Dominik; Lhota, Gabriele; Wallner, Jakob; Vorauer-Uhl, Karola

    2016-02-05

    Over the past few years, liposomal formulations as drug carrier systems have markedly advanced in pharmaceutical research and development. Therefore, analytical methods to characterize liposome-based formulations are required. One particular issue in liposome analysis is the imbalance of lipid ratios within the vesicle formulations and the detectability of degradation products such as lysophospholipids and fatty acids caused by hydrolysis, especially in low molar ranges. Here, a highly sensitive and selective reversed-phase high-performance liquid chromatography (rp-HPLC) method is described by the combination of an organic solvent/trifluoroacetic acid (TFA) triggered gradient and the application of an evaporative light scattering detector (ELSD). Gain setting adjustments of the ELSD were applied to obtain an optimal detection profile of the analyzed substances. This optimization provides simultaneous separation and quantification of 16 components, including different phosphatidylcholines, phosphatidylglycerols and their degradation products, as well as cholesterol. Parameters such as limit of detection (LOD) and limit of quantification (LOQ) were determined for each of the components and had ranges from 0.25-1.00mg/mL (LOD) and 0.50-2.50μg/mL (LOQ), respectively. The intra-day precision for all analytes is less than 3% (RSD) and inter-day precision is about 8%. The applicability of the method was verified by analyzing two different liposome formulations consisting of DSPC:DPPC:DSPG:Chol (35:35:20:10) and DSPC:DPPC:DSPG (38:38:24). For degradation studies, both formulations were stored at 4°C and at ambient temperature. Additionally, forced degradation experiments were performed to determine hydrolysis mass balances. A total recovery of 96-102% for phospholipid compounds was found. Analytical data revealed that the sensitivity, selectivity, accuracy, and resolution are appropriate for the detection and quantification of phospholipids and their hydrolysis products

  4. Overview on zein protein: a promising pharmaceutical excipient in drug delivery systems and tissue engineering.

    PubMed

    Labib, Gihan

    2017-07-06

    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.

  5. Pharmaceutical pricing: a review of proposals to improve access and affordability of prescription drugs.

    PubMed

    Tironi, Paula

    2010-01-01

    This article discusses how pharmaceutical innovation achieves remarkable improvements in human health but a significant portion of the U.S. population cannot afford prescription drugs. The author examines ways that patent protection, generics, supply chain complexity, and the cost of innovation and promotion affect access and affordability. The author then looks at the influences of marketing strategies and industry trends such as the patent cliff and pipeline for new drugs, innovations in biotechnology and genomics, comparative effectiveness analysis, and payor and employer strategies on drug prices. An analysis of reform proposals in the context of industry trends suggests that promoting generic drug use and availability through education, prohibiting authorized generics, and restricting the practice of developing follow-on drugs and discontinuing the original formulations upon patent expiration could improve access and affordability most quickly and significantly.

  6. Second generation lipid nanoparticles (NLC) as an oral drug carrier for delivery of lercanidipine hydrochloride.

    PubMed

    Ranpise, Nisharani S; Korabu, Swati S; Ghodake, Vinod N

    2014-04-01

    Lercanidipine hydrochloride is a calcium channel blocker used in the treatment of hypertension. It is a poor water soluble drug with absolute bioavailability of 10%. The aim of this study was to design lercanidipine hydrochloride-loaded nanostructured lipid carriers to investigate whether the bioavailability of the same can be improved by oral delivery. Lercanidipine hydrochloride nanostructured lipid carriers were prepared by the method of solvent evaporation at a high temperature and solidification by freeze drying. The nanostructured lipid carriers were evaluated for particle size analysis, zeta potential, entrapment efficiency, in vitro drug diffusion, ex vivo permeation studies and pharmacodynamic study. The resultant nanostructured lipid carriers had a mean size of 214.97 nm and a zeta potential of -31.6 ± 1.5 mV. More than 70% lercanidipine hydrochloride was entrapped in the NLCs. The SEM studies indicated the formation of type 2 nanostructured lipid carriers. The in vitro release studies demonstrated 19.36% release in acidic buffer pH 1.2 indicating that the drug entrapped in the nanostructured lipid carriers remains entrapped at acidic pH. The ex vivo studies indicated that the drug release was enhanced from 10% to 60.54% at blood pH in 24h. The in vivo pharmacodynamic study showed that NLCs released lercanidipine hydrochloride in a controlled manner for a prolonged period of time as compared to plain drug. These results clearly indicate that nanostructured lipid carriers are a potential controlled release formulation for lercanidipine hydrochloride and may be a promising drug delivery system for the treatment of hypertension.

  7. The Compendium of Pharmaceuticals and Specialties as a Drug Information Resource for Treatment of Acute Drug Overdose

    PubMed Central

    Parker, William A.

    1979-01-01

    A study was undertaken to determine the extent to which family physicians consult the Compendium of Pharmaceuticals and Specialties (CPS) as an information resource for acute drug ingestions and to evaluate the scope and consistency of the informational content contained in the CPS Product monographs. Ninety percent of family physicians were found to consult the CPS as their first resource in a suspected acute drug ingestion. Although the CPS is a useful reference because of its universal distribution and annual updating, standardization of informational content and consistency between product monographs are necessary. Presently, major inconsistencies exist and some information is outdated.

  8. Study of Rheology and Polymer Adsorption Onto Drug Nanoparticles in Pharmaceutical Suspensions Produced by Nanomilling.

    PubMed

    Negrini, Renata; Aleandri, Simone; Kuentz, Martin

    2017-07-18

    Nanosuspensions provide a drug delivery approach to cope with erratic absorption of poorly water-soluble compounds. Despite extensive research over the last years, there are still open pharmaceutical challenges so it is often unclear how quality attributes such as viscosity and physical stability are generated, which requires a more thorough study of the colloidal structures and interactions in nanosuspensions. In this study, diffusing wave spectroscopy and microfluidics-based rheology were used for the first time to assess pharmaceutical nanosuspensions that were obtained by wet milling. Further sample characterization following centrifugation was based on optical rotatory dispersion and conductivity experiments. Ketoconazole was selected as model drug in the presence of sodium dodecyl sulfate and hydroxypropyl cellulose as anionic and steric stabilizer, respectively. The results unexpectedly showed that the investigated nanosuspensions did not behave as Einstein-like suspensions because a viscosity decrease was evidenced for increased drug load. This effect was attributed to the polymer that formed a dominating network in the bulk solution from where adsorption occurred onto particle surfaces. This depletion of bulk polymer caused the observed rheological finding. Further colloidal research should be invested into different pharmaceutical nanosuspensions to gain a more complete structural understanding and to harness their full technological potential. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  9. Protein Nanoparticles as Drug Delivery Carriers for Cancer Therapy

    PubMed Central

    Lohcharoenkal, Warangkana; Wang, Liying; Chen, Yi Charlie

    2014-01-01

    Nanoparticles have increasingly been used for a variety of applications, most notably for the delivery of therapeutic and diagnostic agents. A large number of nanoparticle drug delivery systems have been developed for cancer treatment and various materials have been explored as drug delivery agents to improve the therapeutic efficacy and safety of anticancer drugs. Natural biomolecules such as proteins are an attractive alternative to synthetic polymers which are commonly used in drug formulations because of their safety. In general, protein nanoparticles offer a number of advantages including biocompatibility and biodegradability. They can be prepared under mild conditions without the use of toxic chemicals or organic solvents. Moreover, due to their defined primary structure, protein-based nanoparticles offer various possibilities for surface modifications including covalent attachment of drugs and targeting ligands. In this paper, we review the most significant advancements in protein nanoparticle technology and their use in drug delivery arena. We then examine the various sources of protein materials that have been used successfully for the construction of protein nanoparticles as well as their methods of preparation. Finally, we discuss the applications of protein nanoparticles in cancer therapy. PMID:24772414

  10. Alginate drug delivery systems: application in context of pharmaceutical and biomedical research.

    PubMed

    Jain, Dharmendra; Bar-Shalom, Daniel

    2014-12-01

    Alginates are natural polymers widely used in the food industry because of their biocompatible, biodegradable character, nontoxicity and easy availability. The bioadhesive character of alginates makes them useful in the pharmaceutical industry as well. The application areas of sodium alginate-based drug delivery systems are many and these systems can be formulated as gels, matrices, membranes, nanospheres, microspheres, etc. Worldwide researchers are exploring possible applications of alginates as coating material, preparation of controlled-release drug delivery systems such as microspheres, beads, pellets, gels, fibers, membranes, etc. In the present review, such applications of alginates are discussed.

  11. Pharmaceutical treatments of gastrointestinal nematode infections of sheep--future of anthelmintic drugs.

    PubMed

    Sargison, N D

    2012-09-30

    Various interacting factors have been identified to explain why health plans for nematode parasite control, based on conventional epidemiological knowledge and involving pharmaceutical treatments of their sheep hosts have become unsustainable. Of these, the emergence of anthelmintic resistance has had a major impact on the economics of sheep farming, necessitating fundamental managemental changes. This review focusses on the use of anthelmintic drugs for the control of gastrointestinal nematode infections in sheep, emphasising the need to develop sustainable strategies in the face of inevitable parasite evolution in response to exposure to anthelmintic drugs and other noxious stimuli, or favourable opportunities resulting from changing animal management and climatic factors.

  12. Adequacy of pharmacological information provided in pharmaceutical drug advertisements in African medical journals.

    PubMed

    Oshikoya, Kazeem A; Senbanjo, Idowu O; Soipe, Ayo

    2009-04-01

    Pharmaceutical advertisement of drugs is a means of advocating drug use and their selling but not a substitute for drug formulary to guide physicians in safe prescribing. To evaluate drug advertisements in Nigerian and other African medical journals for their adequacy of pharmacological information. Twenty four issues from each of West African Journal of Medicine (WAJM), East African Medical Journal (EAMJ), South African Medical Journal (SAMJ), Nigerian Medical Practitioner (NMP), Nigerian Quarterly Journal of Hospital Medicine (NQJHM) and Nigerian Postgraduate Medical Journal (NPMJ) were reviewed. While EAMJ, SAMJ and NMP are published monthly, the WAJM, NQJHM and NPMJ are published quarterly. The monthly journals were reviewed between January 2005 and December 2006, and the quarterly journals between January 2001 and December 2006. The drug information with regards to brand/non-proprietary name, pharmacological data, clinical information, pharmaceutical information and legal aspects was evaluated as per World Health Organisation (WHO) criteria. Counts in all categories were collated for each advertiser. Forty one pharmaceutical companies made 192 advertisements. 112 (58.3%) of these advertisements were made in the African medical journals. Pfizer (20.3%) and Swipha (12.5%) topped the list of the advertising companies. Four (2.1%) adverts mentioned generic names only, 157 (81.8%) mentioned clinical indications. Adults and children dosage (39.6%), use in special situations such as pregnancy and renal or liver problems (36.5%), adverse effects (30.2%), average duration of treatment (26.0%), and potential for interaction with other drugs (18.7%) were less discussed. Pharmaceutical information such as available dosage forms and product and package information {summary of the generic and proprietary names, the formulation strength, active ingredient, route of administration, batch number, manufactured and expiry dates, and the manufacturer on both the container and

  13. Enhancing the pharmaceutical properties of protein drugs by ancestral sequence reconstruction

    PubMed Central

    Zakas, Philip M.; Brown, Harrison C.; Knight, Kristopher; Meeks, Shannon L.; Spencer, H. Trent; Gaucher, Eric A.; Doering, Christopher B.

    2016-01-01

    Optimization of a protein’s pharmaceutical properties is usually carried out by rational design and/or directed evolution. Here we test an alternative approach based on ancestral sequence reconstruction. Using available genomic sequence data on coagulation factor VIII and predictive models of molecular evolution, we engineer protein variants with improved activity, stability. biosynthesis potential, and reduced inhibition by clinical anti-drug antibodies. In principle, this approach can be applied to any protein drug based on a conserved gene sequence. PMID:27669166

  14. Cardiovascular Drug Discovery: A Perspective from a Research-Based Pharmaceutical Company

    PubMed Central

    Gromo, G.; Mann, J.; Fitzgerald, J.D.

    2014-01-01

    The theme of this review is to summarize the evolving processes in cardiovascular drug discovery and development within a large pharmaceutical company. Emphasis is placed on the contrast between the academic and industrial research operating environments, which can influence the effectiveness of research collaboration between the two constituencies, but which plays such an important role in drug innovation. The strategic challenges that research directors face are also emphasized. The need for improved therapy in many cardiovascular indications remains high, but the feasibility in making progress, despite the advances in molecular biology and genomics, is also assessed. PMID:24890831

  15. Adequacy of pharmacological information provided in pharmaceutical drug advertisements in African medical journals

    PubMed Central

    Oshikoya, Kazeem A.; Senbanjo, Idowu O.; Soipe, Ayo

    2008-01-01

    Pharmaceutical advertisement of drugs is a means of advocating drug use and their selling but not a substitute for drug formulary to guide physicians in safe prescribing. Objectives: To evaluate drug advertisements in Nigerian and other African medical journals for their adequacy of pharmacological information. Methods: Twenty four issues from each of West African Journal of Medicine (WAJM), East African Medical Journal (EAMJ), South African Medical Journal (SAMJ), Nigerian Medical Practitioner (NMP), Nigerian Quarterly Journal of Hospital Medicine (NQJHM) and Nigerian Postgraduate Medical Journal (NPMJ) were reviewed. While EAMJ, SAMJ and NMP are published monthly, the WAJM, NQJHM and NPMJ are published quarterly. The monthly journals were reviewed between January 2005 and December 2006, and the quarterly journals between January 2001 and December 2006. The drug information with regards to brand/non-proprietary name, pharmacological data, clinical information, pharmaceutical information and legal aspects was evaluated as per World Health Organisation (WHO) criteria. Counts in all categories were collated for each advertiser. Results: Forty one pharmaceutical companies made 192 advertisements. 112 (58.3%) of these advertisements were made in the African medical journals. Pfizer (20.3%) and Swipha (12.5%) topped the list of the advertising companies. Four (2.1%) adverts mentioned generic names only, 157 (81.8%) mentioned clinical indications. Adults and children dosage (39.6%), use in special situations such as pregnancy and renal or liver problems (36.5%), adverse effects (30.2%), average duration of treatment (26.0%), and potential for interaction with other drugs (18.7%) were less discussed. Pharmaceutical information such as available dosage forms and product and package information {summary of the generic and proprietary names, the formulation strength, active ingredient, route of administration, batch number, manufactured and expiry dates, and the manufacturer

  16. "Inactive" ingredients in pharmaceutical products: update (subject review). American Academy of Pediatrics Committee on Drugs.

    PubMed

    1997-02-01

    Because of an increasing number of reports of adverse reactions associated with pharmaceutical excipients, in 1985 the Committee on Drugs issued a position statement recommending that the Food and Drug Administration mandate labeling of over-the-counter and prescription formulations to include a qualitative list of inactive ingredients. However, labeling of inactive ingredients remains voluntary. Adverse reactions continue to be reported, although some are no longer considered clinically significant, and other new reactions have emerged. The original statement, therefore, has been updated and its information expanded.

  17. Bolaamphiphiles: A Pharmaceutical Review

    PubMed Central

    Fariya, Mayur; Jain, Ankitkumar; Dhawan, Vivek; Shah, Sanket; Nagarsenker, Mangal S.

    2014-01-01

    The field of drug discovery is ever growing and excipients play a major role in it. A novel class of amphiphiles has been discussed in the review. The review focuses on natural as well as synthetic bolaamphiphiles, their chemical structures and importantly, their ability to self assemble rendering them of great use to pharmaceutical industry. Recent reports on their ability to be used in fabrication of suitable nanosized carriers for drug as well as genes to target site, has been discussed substantially to understand the potential of bolaamphiphiles in field of drug delivery. PMID:25671179

  18. White opioids: Pharmaceutical race and the war on drugs that wasn't.

    PubMed

    Netherland, Julie; Hansen, Helena

    2017-06-01

    The US 'War on Drugs' has had a profound role in reinforcing racial hierarchies. Although Black Americans are no more likely than Whites to use illicit drugs, they are 6-10 times more likely to be incarcerated for drug offenses. Meanwhile, a very different system for responding to the drug use of Whites has emerged. This article uses the recent history of White opioids - the synthetic opiates such as OxyContin(®) that gained notoriety starting in the 1990s in connection with epidemic prescription medication abuse among White, suburban and rural Americans and Suboxone(®) that came on the market as an addiction treatment in the 2000s - to show how American drug policy is racialized, using the lesser known lens of decriminalized White drugs. Examining four 'technologies of whiteness' (neuroscience, pharmaceutical technology, legislative innovation and marketing), we trace a separate system for categorizing and disciplining drug use among Whites. This less examined 'White drug war' has carved out a less punitive, clinical realm for Whites where their drug use is decriminalized, treated primarily as a biomedical disease, and where their whiteness is preserved, leaving intact more punitive systems that govern the drug use of people of color.

  19. [Plasma lipoproteins as drug carriers. Effect of phospholipid formulations].

    PubMed

    Torkhovskaia, T I; Ipatova, O M; Medvedeva, N V; Ivanov, V S; Ivanova, L I

    2010-01-01

    The extensive development of nanotechnologies in the last two decades has brought about new understanding of plasma lipoproteins (LP) as natural drug nanocarriers that escape interaction with immune and reticuloendothelial systems. Drugs bound to LP (especially LDL) can more actively penetrate into cells of many cancer and inflammation tissues with enhanced expression or/and dysregulation of B,E receptors or possibly scavenger SR-BI receptors. Relevant studies are focused on the development of new dosage forms by conjugating lipophilic drugs either with isolated plasma LP or with their model formulations, such as nanoemulsions, mimetics, lipid nanospheres, etc. Some authors include in these particles serum or recombinant apoproteins, peptides, and modified polymer products. As shown recently, protein-free lipid nanoemulsions in plasma take up free apoA and apoE. Complexes with various LP also form after direct administration of lypophilic drugs into blood especially those enclosed in phospholipid formulations, e.g. liposomes. Results of evaluation of some lipophilic dugs (mainly cytostatics, amphotericin B, cyclosporine A, etc.) are discussed. Original data are presented on the influence of phospholipid formulations on the distribution of doxorubicin and indomethacin between LP classes after in vitro incubation in plasma. On the whole, the review illustrates the importance of research on LP and phospholi pid forms as drug nanocarriers to be used to enhance effect of therapy.

  20. Glycyrrhetinic Acid Mediated Drug Delivery Carriers for Hepatocellular Carcinoma Therapy.

    PubMed

    Cai, Yuee; Xu, Yingqi; Chan, Hon Fai; Fang, Xiaobin; He, Chengwei; Chen, Meiwan

    2016-03-07

    Glycyrrhetinic acid (GA), the main hydrolysate of glycyrrhizic acid extracted from the root of licorice, has been used in hepatocellular carcinoma (HCC) therapy. Particularly, GA as a ligand in HCC therapy has been widely explored in different drug delivery systems, including liposomes, micelles, and nanoparticles. There is considerable interest worldwide with respect to the development of GA-modified drug delivery systems due to the extensive presence of GA receptors on the surface of hepatocyte. Up until now, much work has been focused on developing GA-modified drug delivery systems which bear good liver- or hepatocyte-targeted efficiency both in vitro and in vivo. Owing to its contribution in overcoming the limitations of low lipophilicity and poor bioavailability as well as its ability to promote receptor-mediated endocytosis, GA-modified drug delivery systems play an important role in enhancing liver-targeting efficacy and thus are focused on the treatment of HCC. Moreover, since GA-modified delivery systems present more favorable pharmacokinetic properties and hepatocyte-targeting effects, they may be a promising formulation for GA in the treatment of HCC. In this review, we will give an overview of GA-modified novel drug delivery systems, paying attention to their efficacy in treating HCC and discussing their mechanism and the treatment effects.

  1. [Access to drugs and the situation of the pharmaceutical market in Ecuador].

    PubMed

    Ortiz-Prado, Esteban; Galarza, Claudio; León, Fernando Cornejo; Ponce, Jorge

    2014-07-01

    In the area of public health, it is fundamental to understand the structure and dynamics of the Ecuadorian pharmaceutical market, its segmentation between the public and private sectors, and its relationship with supply and demand, both for generic and brand-name drugs. To achieve this, an observational descriptive study was conducted with information obtained from the available scientific, institutional, technical-administrative, and economic databases. Furthermore, the scientific information concerning the Ecuadorian and regional pharmaceutical market was reviewed through the PubMed and Ovid search engines. In Ecuador, 69.6% of dispensed drugs are brand-name and 30.4% are generics. Of all registered drugs in the country, 1,829 (13.6%) are considered over-the-counter and 11,622 (86.4%) are for sale under medical prescription. In terms of sales, 93.15% correspond to brand-name drugs and only 6.85% to generics. Ninety percent of the pharmacies are located in urban areas and only 10% in rural areas. In the last five years, prices have increased by 12.5% for brand-name drugs and 0.86% for generics. Brand-name drugs are dispensed and consumed 2.3 times more than generics. The majority of pharmacies are located in urban areas, showing that there is a relationship between purchasing power and access to drugs. Although the regulatory authority stipulates that 13% of drugs should be over-the-counter, approximately 60% of the population acquires drugs without a medical prescription.

  2. Charge-reversal nanoparticles: novel targeted drug delivery carriers.

    PubMed

    Chen, Xinli; Liu, Lisha; Jiang, Chen

    2016-07-01

    Spurred by significant progress in materials chemistry and drug delivery, charge-reversal nanocarriers are being developed to deliver anticancer formulations in spatial-, temporal- and dosage-controlled approaches. Charge-reversal nanoparticles can release their drug payload in response to specific stimuli that alter the charge on their surface. They can elude clearance from the circulation and be activated by protonation, enzymatic cleavage, or a molecular conformational change. In this review, we discuss the physiological basis for, and recent advances in the design of charge-reversal nanoparticles that are able to control drug biodistribution in response to specific stimuli, endogenous factors (changes in pH, redox gradients, or enzyme concentration) or exogenous factors (light or thermos-stimulation).

  3. A porphyrin-based metal-organic framework as a pH-responsive drug carrier

    NASA Astrophysics Data System (ADS)

    Lin, Wenxin; Hu, Quan; Jiang, Ke; Yang, Yanyu; Yang, Yu; Cui, Yuanjing; Qian, Guodong

    2016-05-01

    A low cytotoxic porphyrin-based metal-organic framework (MOF) PCN-221, which exhibited high PC12 cell viability via 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium (MTT) assay, was selected as an oral drug carrier. Methotrexate (MTX) was chosen as the model drug molecule which was absorbed into inner pores and channels of MOFs by diffusion. PCN-221 showed high drug loading and sustained release behavior under physiological environment without "burst effect". The controlled pH-responsive release of drugs by PCN-221 revealed its promising application in oral drug delivery.

  4. Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA).

    PubMed

    do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura; Gratieri, Tais

    2017-01-01

    Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products.

  5. Main Reasons for Registration Application Refusal of Generic and Similar Pharmaceutical Drug Products by the Brazilian Health Regulatory Agency (ANVISA)

    PubMed Central

    do Carmo, Ana Cerúlia Moraes; Piras, Stefânia Schimaneski; Rocha, Nayrton Flávio Moura

    2017-01-01

    Objective. The marketing authorization of generic and similar pharmaceutical drug products involves the analysis of proposing company's administrative aspects as well as drug product technical description and scientific evaluations. This study evaluated the main reasons for registration refusal of generic and similar pharmaceutical drug products in Brazil. The aim is to help future applicants to better organize the proposal. Methods. A retrospective search of drug products registration processes was performed on the Brazilian Government Official Gazette from January 1, 2015, and December 31, 2015. Results. Drug product quality control, drug product stability study, deadline accomplishment, API quality control made by drug manufacturer, active pharmaceutical ingredient (API), and production report were the main reasons for marketing authorization application refusal of generic and similar pharmaceutical drug products in 2015. Conclusion. Disclosure of the reasons behind failed applications is a step forward on regulatory transparency. Sharing of experiences is essential to international regulatory authorities and organizations to improve legislation requirements for the marketing authorization of generic and similar pharmaceutical drug products. PMID:28280742

  6. Physicochemical characterisation and investigation of the bonding mechanisms of API-titanate nanotube composites as new drug carrier systems.

    PubMed

    Sipos, Barbara; Pintye-Hódi, Klára; Kónya, Zoltán; Kelemen, András; Regdon, Géza; Sovány, Tamás

    2017-02-25

    Titanate nanotube (TNT) has recently been explored as a new carrier material for active pharmaceutical ingredients (API). The aim of the present work was to reveal the physicochemical properties of API-TNT composites, focusing on the interactions between the TNTs and the incorporated APIs. Drugs belonging to different Biopharmaceutical Classification System (BCS) classes were loaded into TNTs: diltiazem hydrochloride (BCS I.), diclofenac sodium (BCS II.), atenolol (BCS III.) and hydrochlorothiazide (BCS IV.). Experimental results demonstrated that it is feasible for spiral cross-sectioned titanate nanotubes to carry drugs and maintain their bioactivity. The structural properties of the composites were characterized by a range of analytical techniques, including FT-IR, DSC, TG-MS, etc. The interactions between APIs and TNTs were identified as electrostatic attractions, mainly dominated by hydrogen bonds. Based on the results, it can be stated that the strength of the association depends on the hydrogen donor strength of the API. The drug release of incorporated APIs was evaluated from compressed tablets and compared to that of pure APIs. Differences noticed in the dissolution profiles due to incorporation showed a correlation with the strength of interactions between the APIs and the TNTs observed in the above analytical studies. Copyright © 2016 Elsevier B.V. All rights reserved.

  7. Lymphatic system: a prospective area for advanced targeting of particulate drug carriers.

    PubMed

    Singh, Indu; Swami, Rajan; Khan, Wahid; Sistla, Ramakrishna

    2014-02-01

    The lymphatic system has a critical role in the immune system's recognition and response to disease and it is an additional circulatory system throughout the entire body. Extensive multidisciplinary investigations have been carried out in the area of lymphatic delivery, and lymphatic targeting has attracted a lot of attention for providing preferential chemotherapy and improving bioavailability of drugs that undergo hepatic first-pass metabolism. This review focuses on progress in the field of lymphatic therapeutics and diagnosis. Moreover, the anatomy and physiology of the lymphatic system, particulate drug carriers and different physicochemical parameters of both modified and unmodified particulate drug carriers and their effect on lymphatic targeting are addressed. Particulate drug carriers have encouraged lymphatic targeting, but there are still challenges in targeting drugs and bioactives to specific sites, maintaining desired action and crossing all the physiological barriers. Lymphatic therapy using drug-encapsulated lipid carriers, especially liposomes and solid lipid nanoparticles, emerges as a new technology to provide better penetration into the lymphatics where residual disease exists. Size is the most important criteria when designing nanocarriers for targeting lymphatic vessels as the transportation of these particles into lymphatic vessels is size dependent. By increasing our understanding of lymphatic transport and uptake, and the role of lymphatics in various diseases, we can design new therapeutics for effective disease control.

  8. Physical and chemical stability of nanostructured lipid drug carriers (NLC) based on natural lipids from Baikal region (Siberia, Russia).

    PubMed

    Averina, E S; Müller, R H; Popov, D V; Radnaeva, L D

    2011-05-01

    At the turn of the millennium, a new generation of lipid nanoparticles for pharmacology was developed, nanostructured lipid carriers (NLC). The features of NLC structure which allow the inclusion of natural biologically active lipids in the NLC matrix open a wide prospect for the creation of high performance drug carriers. In this study NLC formulations were developed based on natural lipids from the Siberia region (Russia): fish oil from Lake Baikal fish; polyunsaturated fatty acid fractions and monounsaturated and saturated fatty acid fractions from fish oil and Siberian pine seed oil. Formulation parameters of NLC such as as type of surfactant and storage conditions were evaluated. The data obtained indicated high physical stability of NLC formulated on the basis of pure fish oil stabilized by Tween 80 and NLC formulated on the basis of free fatty acids stabilized by Poloxamer 188. The good chemical stability of the lipid matrix and the high concentrations of the biologically active polyunsaturated fatty acids in the NLC developed open wide prospects for their use in pharmaceutics and cosmetics.

  9. 76 FR 59144 - Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-23

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Novartis Pharmaceuticals Corp. et al.; Withdrawal of Approval of 27 New Drug Applications and 58 Abbreviated New Drug Applications; Correction AGENCY: Food and...

  10. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations.

    PubMed

    Spinks, Crystal B; Zidan, Ahmed S; Khan, Mansoor A; Habib, Muhammad J; Faustino, Patrick J

    2017-01-01

    Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na2PO4/acetonitrile pH 7.4 (95:5 v/v). The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that calibration curves were linear with r(2) > 0.9995 over the analytical range of 1-10 µg/mL. Inter- and intraday accuracy and precision values ranged from 95% to 101% and 0.3% to 2.6%, respectively. The method was determined to be specific and robust. Regarding the potential of the prepared vectors to potentiate tenofovir permeability through the Caco-2 model, a 10-fold increase in tenofovir apparent permeability was observed compared to its oral solution. In conclusion, this novel and validated method was

  11. Pharmaceutical characterization of novel tenofovir liposomal formulations for enhanced oral drug delivery: in vitro pharmaceutics and Caco-2 permeability investigations

    PubMed Central

    Spinks, Crystal B; Zidan, Ahmed S; Khan, Mansoor A; Habib, Muhammad J; Faustino, Patrick J

    2017-01-01

    Tenofovir, currently marketed as the prodrug tenofovir disoproxil fumarate, is used clinically to treat patients with HIV/AIDS. The oral bioavailability of tenofovir is relatively low, limiting its clinical effectiveness. Encapsulation of tenofovir within modified long-circulating liposomes would deliver this hydrophilic anti-HIV drug to the reticuloendothelial system for better therapeutic efficacy. The objectives of the current study were to prepare and pharmaceutically characterize model liposomal tenofovir formulations in an attempt to improve their bioavailability. The entrapment process was performed using film hydration method, and the formulations were characterized in terms of encapsulation efficiency and Caco-2 permeability. An efficient reverse-phase high-performance liquid chromatography method was developed and validated for tenofovir quantitation in both in vitro liposomal formulations and Caco-2 permeability samples. Separation was achieved isocratically on a Waters Symmetry C8 column using 10 mM Na2PO4/acetonitrile pH 7.4 (95:5 v/v). The flow rate was 1 mL/min with a 12 min elution time. Injection volume was 10 µL with ultraviolet detection at 270 nm. The method was validated according to United States Pharmacopeial Convention category I requirements. The obtained result showed that tenofovir encapsulation within the prepared liposomes was dependent on the employed amount of the positive charge-imparting agent. The obtained results indicated that calibration curves were linear with r2 > 0.9995 over the analytical range of 1–10 µg/mL. Inter- and intraday accuracy and precision values ranged from 95% to 101% and 0.3% to 2.6%, respectively. The method was determined to be specific and robust. Regarding the potential of the prepared vectors to potentiate tenofovir permeability through the Caco-2 model, a 10-fold increase in tenofovir apparent permeability was observed compared to its oral solution. In conclusion, this novel and validated method was

  12. Transforming lipid-based oral drug delivery systems into solid dosage forms: an overview of solid carriers, physicochemical properties, and biopharmaceutical performance.

    PubMed

    Tan, Angel; Rao, Shasha; Prestidge, Clive A

    2013-12-01

    The diversity of lipid excipients available commercially has enabled versatile formulation design of lipid-based drug delivery systems for enhancing the oral absorption of poorly water-soluble drugs, such as emulsions, microemulsions, micelles, liposomes, niosomes and various self-emulsifying systems. The transformation of liquid lipid-based systems into solid dosage forms has been investigated for several decades, and has recently become a core subject of pharmaceutical research as solidification is regarded as viable means for stabilising lipid colloidal systems while eliminating stringent processing requirements associated with liquid systems. This review describes the types of pharmaceutical grade excipients (silica nanoparticle/microparticle, polysaccharide, polymer and protein-based materials) used as solid carriers and the current state of knowledge on the liquid-to-solid conversion approaches. Details are primarily focused on the solid-state physicochemical properties and redispersion capacity of various dry lipid-based formulations, and how these relate to the in vitro drug release and solubilisation, lipid carrier digestion and cell permeation performances. Numerous in vivo proof-of-concept studies are presented to highlight the viability of these dry lipid-based formulations. This review is significant in directing future research work in fostering translation of dry lipid-based formulations into clinical applications.

  13. Principles and applications of Raman spectroscopy in pharmaceutical drug discovery and development.

    PubMed

    Gala, Urvi; Chauhan, Harsh

    2015-02-01

    In recent years, Raman spectroscopy has become increasingly important as an analytical technique in various scientific areas of research and development. This is partly due to the technological advancements in Raman instrumentation and partly due to detailed fingerprinting that can be derived from Raman spectra. Its versatility of applications, rapidness of collection and easy analysis have made Raman spectroscopy an attractive analytical tool. The following review describes Raman spectroscopy and its application within the pharmaceutical industry. The authors explain the theory of Raman scattering and its variations in Raman spectroscopy. The authors also highlight how Raman spectra are interpreted, providing examples. Raman spectroscopy has a number of potential applications within drug discovery and development. It can be used to estimate the molecular activity of drugs and to establish a drug's physicochemical properties such as its partition coefficient. It can also be used in compatibility studies during the drug formulation process. Raman spectroscopy's immense potential should be further investigated in future.

  14. Homopolymer vesicles with a gradient bilayer membrane as drug carriers.

    PubMed

    Fan, Lang; Lu, Hang; Zou, Kaidian; Chen, Jing; Du, Jianzhong

    2013-12-21

    We report an unusual homopolymer vesicle, which has a soft bilayer membrane composed of oligo(ethyleneoxy) side chains (OEs) with a gradually decreased packing density from the centre of the membrane to both margins, exhibiting thermo-responsive zeta potential and dispersibility and showing potential applications for anti-cancer drug delivery.

  15. White opioids: Pharmaceutical race and the war on drugs that wasn’t

    PubMed Central

    Netherland, Julie; Hansen, Helena

    2016-01-01

    The US ‘War on Drugs’ has had a profound role in reinforcing racial hierarchies. Although Black Americans are no more likely than Whites to use illicit drugs, they are 6–10 times more likely to be incarcerated for drug offenses. Meanwhile, a very different system for responding to the drug use of Whites has emerged. This article uses the recent history of White opioids – the synthetic opiates such as OxyContin® that gained notoriety starting in the 1990s in connection with epidemic prescription medication abuse among White, suburban and rural Americans and Suboxone® that came on the market as an addiction treatment in the 2000s – to show how American drug policy is racialized, using the lesser known lens of decriminalized White drugs. Examining four ‘technologies of whiteness’ (neuroscience, pharmaceutical technology, legislative innovation and marketing), we trace a separate system for categorizing and disciplining drug use among Whites. This less examined ‘White drug war’ has carved out a less punitive, clinical realm for Whites where their drug use is decriminalized, treated primarily as a biomedical disease, and where their whiteness is preserved, leaving intact more punitive systems that govern the drug use of people of color. PMID:28690668

  16. Recent national and regional drug reforms in Sweden: implications for pharmaceutical companies in Europe.

    PubMed

    Wettermark, Björn; Godman, Brian; Andersson, Karolina; Gustafsson, Lars L; Haycox, Alan; Bertele, Vittorio

    2008-01-01

    With an aging population and increased prevalence of chronic diseases, such as obesity and diabetes mellitus, drug reforms are needed across Europe to ensure the continued provision of comprehensive healthcare. It is also a challenge, with the limited resources available, to fund new innovative drugs that significantly improve patient health. Recent national and regional reforms in Sweden have moderated the rate of increase in drug expenditure, despite increased volumes of drug use and the launch of new, expensive drugs. National reforms include the adoption of economic principles when assessing the value and subsequent reimbursement of new and existing drugs, as well as reforms to obtain low prices for generic drugs. Regional reforms aim to encourage the rational use of medicines through the establishment of drug and therapeutic committees, development of guidelines, academic detailing, continuous benchmarking of prescribing patterns, and financial incentives. Some of these reforms provide examples to other European countries, whilst others duplicate existing measures. As such, we believe other European countries can benefit from an analysis of the Swedish reforms. We believe the pharmaceutical industry can also benefit from this analysis by working with key regional payers involved with developing and implementing the reforms as they moderate and refine their future activities, including finding acceptable ways of introducing new expensive drugs.

  17. Positively Charged Nanostructured Lipid Carriers and Their Effect on the Dissolution of Poorly Soluble Drugs.

    PubMed

    Choi, Kyeong-Ok; Choe, Jaehyeog; Suh, Seokjin; Ko, Sanghoon

    2016-05-20

    The objective of this study is to develop suitable formulations to improve the dissolution rate of poorly water soluble drugs. We selected lipid-based formulation as a drug carrier and modified the surface using positively charged chitosan derivative (HTCC) to increase its water solubility and bioavailability. Chitosan and HTCC-coated lipid particles had higher zeta-potential values than uncoated one over the whole pH ranges and improved encapsulation efficiency. In vitro drug release showed that all NLC formulations showed higher in vitro release efficiency than drug particle at pH 7.4. Furthermore, NLC formulation prepared with chitosan or HTCC represented good sustained release property. The results indicate that chitosan and HTCC can be excellent formulating excipients of lipid-based delivery carrier for improving poorly water soluble drug delivery.

  18. Superparamagnetic iron oxide nanoparticles: magnetic nanoplatforms as drug carriers

    PubMed Central

    Wahajuddin; Arora, Sumit

    2012-01-01

    A targeted drug delivery system is the need of the hour. Guiding magnetic iron oxide nanoparticles with the help of an external magnetic field to its target is the principle behind the development of superparamagnetic iron oxide nanoparticles (SPIONs) as novel drug delivery vehicles. SPIONs are small synthetic γ-Fe2O3 (maghemite) or Fe3O4 (magnetite) particles with a core ranging between 10 nm and 100 nm in diameter. These magnetic particles are coated with certain biocompatible polymers, such as dextran or polyethylene glycol, which provide chemical handles for the conjugation of therapeutic agents and also improve their blood distribution profile. The current research on SPIONs is opening up wide horizons for their use as diagnostic agents in magnetic resonance imaging as well as for drug delivery vehicles. Delivery of anticancer drugs by coupling with functionalized SPIONs to their targeted site is one of the most pursued areas of research in the development of cancer treatment strategies. SPIONs have also demonstrated their efficiency as nonviral gene vectors that facilitate the introduction of plasmids into the nucleus at rates multifold those of routinely available standard technologies. SPION-induced hyperthermia has also been utilized for localized killing of cancerous cells. Despite their potential biomedical application, alteration in gene expression profiles, disturbance in iron homeostasis, oxidative stress, and altered cellular responses are some SPION-related toxicological aspects which require due consideration. This review provides a comprehensive understanding of SPIONs with regard to their method of preparation, their utility as drug delivery vehicles, and some concerns which need to be resolved before they can be moved from bench top to bedside. PMID:22848170

  19. Drug production with a social conscience, the experience of Gonoshasthaya Pharmaceuticals.

    PubMed

    Chetley, A

    1985-01-01

    In many 3rd World countries, people face shortages of the most essential drugs for primary health care and an excess of drugs which are inappropriate to their basic needs. In Bangladesh, a grassroots primary health care project has established its own pharmaceuticals factory--Gonoshasthaya Pharmaceuticals Limited (GPL)--to challenge the situation. The author of this article, a journalist, visited GPL and found that the technology to produce drugs was accessible to a poor, rural workforce with little or no formal education. Because the factory grew out of the health care project, it has been integrated into the surrounding community, and supported by the local people. GPL has played a prominent role in transforming the drug production and supply system in Bangladesh, and its example could have future impact in other 3rd World countries. The management team at GPL recognized that at all costs, the drugs produced by GPL would have to be of the very highest quality. GPL focuses on basic health and development needs rather than simply on production of drugs. GPL gave the government confidence that, even if all the transnational companies withdrew from the country, local firms could meet high standards of quality and produce at least the essential drugs. GPL's survival is largely due to its relationship with the local community. GPL is clear proof that business can operate with a social conscience. It can interact with the community around it and play a major role in fulfilling the community's needs. GPL provides essential drugs as well as employment, education, and a sense of achievement.

  20. Resistant starch as a carrier for oral colon-targeting drug matrix system.

    PubMed

    Chen, Ling; Li, Xiaoxi; Pang, Yansheng; Li, Lin; Zhang, Ximei; Yu, Long

    2007-11-01

    In this study, a novel tablet of protein drug matrix for colon targeting was developed using resistant starch as a carrier prepared by pre-gelatinization and cross-linking of starch. The effects of pre-gelatinization and cross-linking on the swelling and enzymatic degradation of maize starch as well as the release rate of drug from the matrix tablets were examined. Cross-linked pre-gelatinized maize starches were prepared by double modification of pre-gelatinization and cross-linked with POCl(3), and bovine serum albumin was used as a model drug. For in vitro drug release assays, the resistant starch matrix tablets were incubated in simulated gastric fluid, simulated intestinal fluid and simulated colonic fluid, respectively. The content of resistant starch and swelling property of maize starch were increased by pre-gelatinization and cross-linking, which retarded its enzymatic degradation. Drug release studies have shown that the matrix tablets of cross-linked pre-gelatinized maize starch could delivery the drug to the colon. These results indicate that the resistant starch carrier prepared by pre-gelatinization and cross-linking can be used for a potential drug delivery carrier for colon-targeting drug matrix delivery system.

  1. Promote potential applications of nanoparticles as respiratory drug carrier: insights from molecular dynamics simulations

    NASA Astrophysics Data System (ADS)

    Lin, Xubo; Bai, Tingting; Zuo, Yi Y.; Gu, Ning

    2014-02-01

    Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water interface. Four different NPs were considered, including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5 nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers, which have been widely used for nanoscale drug carrier systems). Our simulations showed that hydrophilic NPs can readily penetrate into the aqueous phase with little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to induce large structural disruptions, thus inhibiting the normal phase transition of the DPPC monolayer upon film compression. Our simulations also showed that this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation. Our results provide useful guidelines for molecular design of NPs as carrier systems for pulmonary drug delivery.Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs

  2. Illicit and pharmaceutical drug consumption estimated via wastewater analysis. Part A: chemical analysis and drug use estimates.

    PubMed

    Baker, David R; Barron, Leon; Kasprzyk-Hordern, Barbara

    2014-07-15

    This paper presents, for the first time, community-wide estimation of drug and pharmaceuticals consumption in England using wastewater analysis and a large number of compounds. Among groups of compounds studied were: stimulants, hallucinogens and their metabolites, opioids, morphine derivatives, benzodiazepines, antidepressants and others. Obtained results showed the usefulness of wastewater analysis in order to provide estimates of local community drug consumption. It is noticeable that where target compounds could be compared to NHS prescription statistics, good comparisons were apparent between the two sets of data. These compounds include oxycodone, dihydrocodeine, methadone, tramadol, temazepam and diazepam. Whereas, discrepancies were observed for propoxyphene, codeine, dosulepin and venlafaxine (over-estimations in each case except codeine). Potential reasons for discrepancies include: sales of drugs sold without prescription and not included within NHS data, abuse of a drug with the compound trafficked through illegal sources, different consumption patterns in different areas, direct disposal leading to over estimations when using parent compound as the drug target residue and excretion factors not being representative of the local community. It is noticeable that using a metabolite (and not a parent drug) as a biomarker leads to higher certainty of obtained estimates. With regard to illicit drugs, consistent and logical results were reported. Monitoring of these compounds over a one week period highlighted the expected recreational use of many of these drugs (e.g. cocaine and MDMA) and the more consistent use of others (e.g. methadone).

  3. Nanostructured lipid carriers versus microemulsions for delivery of the poorly water-soluble drug luteolin.

    PubMed

    Liu, Ying; Wang, Lan; Zhao, Yiqing; He, Man; Zhang, Xin; Niu, Mengmeng; Feng, Nianping

    2014-12-10

    Nanostructured lipid carriers and microemulsions effectively deliver poorly water-soluble drugs. However, few studies have investigated their ability and difference in improving drug bioavailability, especially the factors contributed to the difference. Thus, this study was aimed at investigating their efficiency in bioavailability enhancement based on studying two key processes that occur in NLC and ME during traverse along the intestinal tract: the solubilization process and the intestinal permeability process. The nanostructured lipid carriers and microemulsions had the same composition except that the former were prepared with solid lipids and the latter with liquid lipids; both were evaluated for particle size and zeta potential. Transmission electron microscopy, differential scanning calorimetry, and X-ray diffraction were performed to characterize their properties. Furthermore, in vitro drug release, in situ intestinal absorption, and in vitro lipolysis were studied. The bioavailability of luteolin delivered using nanostructured lipid carriers in rats was compared with that delivered using microemulsions and suspensions. The in vitro analysis revealed different release mechanisms for luteolin in nanostructured lipid carriers and microemulsions, although the in situ intestinal absorption was similar. The in vitro lipolysis data indicated that digestion speed and extent were higher for microemulsions than for nanostructured lipid carriers, and that more of the former partitioned to the aqueous phase. The in vivo bioavailability analysis in rats indicated that the oral absorption and bioavailability of luteolin delivered using nanostructured lipid carriers and microemulsions were higher than those of luteolin suspensions. Nanostructured lipid carriers and microemulsions improved luteolin's oral bioavailability in rats. The rapid lipid digestion and much more drug solubilized available for absorption in microemulsions may contribute to better absorption and

  4. Thiolated graphene oxide as promising mucoadhesive carrier for hydrophobic drugs.

    PubMed

    Pereira de Sousa, Irene; Buttenhauser, Katrin; Suchaoin, Wongsakorn; Partenhauser, Alexandra; Perrone, Mara; Matuszczak, Barbara; Bernkop-Schnürch, Andreas

    2016-07-25

    The aim of this study was to improve the mucoadhesive properties of graphene by conjugating thiol ligands, in order to formulate an oral delivery system for hydrophobic drugs showing long mucus residence time. Graphene oxide was obtained by oxidation of graphite and then was thiolated following two synthetic paths. On the one hand, the hydroxyl groups were conjugated with thiourea passing through the formation of a brominated intermediate. On the other hand, the carboxylic acid groups were conjugated with cysteamine via carbodiimide chemistry. The mucoadhesive properties of thiolated graphene were evaluated by rheological measurements and by residence time assay. Then, valsartan was loaded on thiolated graphene and the release profile was evaluated in simulated intestinal fluid. Following both synthetic paths it was possible to obtain thiolated graphene bearing 215-302μmol SH/g product. Both products induced after 1h incubation an increase of mucus viscosity of about 22-33-fold compared to unmodified graphite. The residence time assay confirmed that 60% of thiolated graphene could be retained on intestinal mucosa after 4h incubation, whereas just 20% of unmodified graphite could be retained. Valsartan could be loaded with a drug loading of about 31±0.3% and a sustained release profile was observed for both formulations. According to the presented data, the thiolation of graphene could improve its mucoadhesive properties. Therefore, thiolated graphene represents a promising platform for oral delivery of hydrophobic drugs, possessing a long residence time on intestinal mucosa which allows the release of the loaded drug close to the adsorptive epithelium. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Composite of magnetic drug carriers with thermo-responsive polymer for controlled drug release

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Kitamoto, Yoshitaka

    2016-02-01

    The present paper describes organic/inorganic composite nanoparticles (CNPs) with a thermal response for biomedical applications. The composite nanoparticles are composed of a thermo-responsive polymer shell of hydroxypropyl cellulose (HPC) and a magnetic FeOx/silica core that exhibits a heat-generation capability against alternating magnetic fields. The heat-generation capability of the FeOx core was improved by modifying the synthesis process of the NPs to oxidize nonmagnetic FeO to magnetic Fe3O4. The HPC shell is observed by transmission electron microscopy after coating FeOx/silica NPs with HPC; the coating is confirmed by the increase of the hydrodynamic size of NPs and the weight loss with thermogravimetry. The FeOx/silica/HPC composite NPs exhibit a thermal response, which is confirmed by the temperature-dependent hydrodynamic size of the NPs. These results indicate that the thermo-responsive FeOx/silica/HPC composite particles have a potential as a drug carrier with a capability of controlled release.

  6. Barrier or carrier? Pulmonary surfactant and drug delivery.

    PubMed

    Hidalgo, Alberto; Cruz, Antonio; Pérez-Gil, Jesús

    2015-09-01

    To consider the lung as a target for drug delivery and to optimise strategies directed at the pulmonary route, it is essential to consider the role of pulmonary surfactant, a thin lipid-protein film lining the respiratory surface of mammalian lungs. Membrane-based surfactant multilayers are essential for reducing the surface tension at the respiratory air-liquid interface to minimise the work of breathing. Different components of surfactant are also responsible for facilitating the removal of potentially pathological entities such as microorganisms, allergens or environmental pollutants and particles. Upon inhalation, drugs or nanoparticles first contact the surfactant layer, and these interactions critically affect their lifetime and fate in the airways. This review summarises the current knowledge on the possible role and effects of the pulmonary surfactant system in drug delivery strategies. It also summarises the evidence that suggests that pulmonary surfactant is far from being an insuperable barrier and could be used as an efficient shuttle for delivering hydrophobic and hydrophilic compounds deep into the lung and the organism. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Improving pharmaceutical innovation by building a more comprehensive database on drug development and use.

    PubMed

    Daniel, Gregory W; Cazé, Alexis; Romine, Morgan H; Audibert, Céline; Leff, Jonathan S; McClellan, Mark B

    2015-02-01

    New drugs and biologics have had a tremendous impact on the treatment of many diseases. However, available measures suggest that pharmaceutical innovation has remained relatively flat, despite substantial growth in research and development spending. We review recent literature on pharmaceutical innovation to identify limitations in measuring and assessing innovation, and we describe the framework and collaborative approach we are using to develop more comprehensive, publicly available metrics for innovation. Our research teams at the Brookings Institution and Deerfield Institute are collaborating with experts from multiple areas of drug development and regulatory review to identify and collect comprehensive data elements related to key development and regulatory characteristics for each new molecular entity approved over the past several decades in the United States and the European Union. Subsequent phases of our effort will add data on downstream product use and patient outcomes and will also include drugs that have failed or been abandoned in development. Such a database will enable researchers to better analyze the drivers of drug innovation, trends in the output of new medicines, and the effect of policy efforts designed to improve innovation.

  8. Canadian policy makers' views on pharmaceutical reimbursement contracts involving confidential discounts from drug manufacturers.

    PubMed

    Morgan, Steven G; Thomson, Paige A; Daw, Jamie R; Friesen, Melissa K

    2013-10-01

    Pharmaceutical policy makers are increasingly negotiating reimbursement contracts that include confidential price terms that may be affected by drug utilization volumes, patterns, or outcomes. Though such contracts may offer a variety of benefits, including the ability to tie payment to the actual performance of a product, they may also create potential policy challenges. Through telephone interviews about this type of contract, we studied the views of officials in nine of ten Canadian provinces. Use of reimbursement contracts involving confidential discounts is new in Canada and ideas about power and equity emerged as cross-cutting themes in our interviews. Though confidential rebates can lower prices and thereby increase coverage of new medicines, several policy makers felt they had little power in the decision to negotiate rebates. Study participants explained that the recent rise in the use of rebates had been driven by manufacturers' pricing tactics and precedent set by other jurisdictions. Several policy makers expressed concerns that confidential rebates could result in inter-jurisdictional inequities in drug pricing and coverage. Policy makers also noted un-insured and under-insured patients must pay inflated "list prices" even if rebates are negotiated by drug plans. The establishment of policies for disciplined negotiations, inter-jurisdictional cooperation, and provision of drug coverage for all citizens are potential solutions to the challenges created by this new pharmaceutical pricing paradigm. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  9. Dropwise additive manufacturing of pharmaceutical products for amorphous and self emulsifying drug delivery systems.

    PubMed

    Içten, Elçin; Purohit, Hitesh S; Wallace, Chelsey; Giridhar, Arun; Taylor, Lynne S; Nagy, Zoltan K; Reklaitis, Gintaras V

    2017-05-30

    The improvements in healthcare systems and the advent of the precision medicine initiative have created the need to develop more innovative manufacturing methods for the delivery and production of individualized dosing and personalized treatments. In accordance with the changes observed in healthcare systems towards more innovative therapies, this paper presents dropwise additive manufacturing of pharmaceutical products (DAMPP) for small scale, distributed manufacturing of individualized dosing as an alternative to conventional manufacturing methods A dropwise additive manufacturing process for amorphous and self-emulsifying drug delivery systems is reported, which utilizes drop-on-demand printing technology for automated and controlled deposition of melt-based formulations onto inert tablets. The advantages of drop on demand technology include reproducible production of droplets with adjustable sizing and high placement accuracy, which enable production of individualized dosing even for low dose and high potency drugs. Flexible use of different formulations, such as lipid-based formulations, allows enhancement of the solubility of poorly water soluble and highly lipophilic drugs with DAMPP. Here, DAMPP is used to produce solid oral dosage forms from melts of an active pharmaceutical ingredient and a surfactant. The dosage forms are analyzed to show the amorphous nature, self-emulsifying drug delivery system characteristics and dissolution behavior of these formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. [Role of pharmaceutical company pharmacist in provision of drug information for cancer chemotherapy].

    PubMed

    Koshida, Iori; Kubota, Kenichi; Yamashita, Masaki; Katayanagi, Hideya; Noda, Kohei; Terada, Hakaru; Yoshioka, Shinichi; Sekine, Nobuyuki; Kameda, Toshikazu; Terada, Kiyoshi

    2009-04-01

    Recently, oxaliplatin(L-OHP)and irinotecan hydrochloride hydrate(CPT-11)have gained recognition as key drugs in the treatment of advanced colorectal cancer. In this article, we describe the results of a survey of medical institutions by pharmacists working at a pharmaceutical company. First, questions from medical institutions on L-OHP and CPT-11 were totaled and analyzed. The results showed that most of these questions concerned safety, with many of these addressing side effects. Next, a questionnaire on FOLFOX and FOLFIRI regimens was administered to medical institutions. The results indicated that staff are interested in the safety and critical path of these regimens. These results suggest that a lot of medical institutions require more information from pharmaceutical companies. This indicates that pharmacists should do more to take the needs of medical institutions into account in providing improved customer support.

  11. Non-prescription Drugs and Self-medication: Features and Subjects in Pharmaceutical Education.

    PubMed

    Watanabe, Kinzo

    2016-01-01

    At the time of consultation with a patient regarding OTC drugs, a pharmacist goes through the following five steps. In Step 1 information is collected, including the patient's gender, age, health condition, living situation, etc. In Step 2, upon analyzing and evaluating this collected information, the pharmacist decides whether to recommend that the patient see a medical doctor or whether an OTC drug is sufficient. In Step 3, when an OTC drug is required, the pharmacist suggests the most suitable OTC drug. In Step 4, the pharmacist provides the patient recommendations and information about the selected OTC. In Step 5, sales record entry and aftercare are performed. In these five steps, the pharmacist is making a decision on whether the consultation recommendation is required or optional; the step of making an optimal selection of an OTC drug is distinct from prescription dispensing. In many cases, at the time of OTC drug consultation, since the patient is not consulting a medical doctor, a pharmacist becomes a "first access" health professional. In this instance, the advice of a pharmacist may have a great influence on a patient's prognosis regarding the particular health challenge. Therefore, pharmacists who perform patient consultations regarding OTC drugs are required to have broad medical knowledge and communication skills. The features of consultation and information dissemination about OTC drugs by a pharmacist, and the practice and study of this subject in present-day pharmaceutical education, are described herein.

  12. Albumin-Encapsulated Liposomes: A Novel Drug Delivery Carrier With Hydrophobic Drugs Encapsulated in the Inner Aqueous Core.

    PubMed

    Okamoto, Yuko; Taguchi, Kazuaki; Yamasaki, Keishi; Sakuragi, Mina; Kuroda, Shun'ichi; Otagiri, Masaki

    2017-08-18

    Liposomes are clinically used in drug delivery, but loading hydrophobic substances is limited to the hydrophobic space of a lipid membrane, despite the fact that it is favorable to encapsulate substances into the inner aqueous core of liposome, from a drug stability of view. We report herein on the preparation of a liposome with bovine serum albumin encapsulated (BSA-liposome). Using this system, it is possible to encapsulate hydrophobic drugs in the inner aqueous core of the liposome based on the hypothesis that the water solubility of hydrophobic drugs is increased when bound to albumin. The physicochemical properties of the prepared BSA-liposomes could be easily regulated and the loading of hydrophobic drugs in the inner aqueous core of the liposome was dramatically improved by virtue of the drug-binding properties of albumin. An in vivo safety and pharmacokinetic study showed that BSA-liposomes possess favorable properties as a drug carrier, including biocompatibility and a stealth effect. This new type of hydrophobic drug carrier, an albumin-liposome, has the potential for use in delivering numerous hydrophobic drugs that typically bind to albumin. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  13. Mucosa-plate for direct evaluation of mucoadhesion of drug carriers.

    PubMed

    Tachaprutinun, Amornset; Pan-In, Porntip; Wanichwecharungruang, Supason

    2013-01-30

    The method to prepare mucosa-plates, glass slides covalently coated with mucin, is demonstrated. The use of the plate to evaluate mucoadhesion of nanocarriers made from different four polymeric materials, N-succinylchitosan (NS-chitosan), alginate (ALG), ethylcellulose (EC), and a blend of EC and methylcellulose (EC/MC), was demonstrated. While different mucoadhesion of the four carriers could be detected using mucosa-plate, the conventional viscosity measurement could not differentiate their mucin-binding ability. ALG and NS-chitosan nanospheres showed the best attachment to the mucosa-plate compared to the EC/MC and EC spheres. Capsaicin, a model hydrophobic drug, was loaded into the carriers and the ability of the different polymeric carriers to retain capsaicin at the stomach tissue was compared using an ex vivo fresh porcine stomach assay. Ability to retain capsaicin at the stomach tissue correlated well with binding affinity toward the mucosa-plate and the loading capacity of the carriers.

  14. [Rising attention to the market to ratio meet demand of improving efficiency of pharmaceutical circulation--based on complicated variety and specification of drugs].

    PubMed

    Chen, Zhaoxing; Sun, Lihua

    2010-05-01

    Analyzing the complicated variety and specification of drugs and the objective demand of pharmaceutical circulation, to seek out the key factors in improving the efficiency of pharmaceutical circulation, for putting forward suggestions to promote the development of pharmaceutical circulation in China. The conclusion is drawed from industrial organization theory and successful experience of foreign countries, high market attention met with the demand of complicated variety and specification of drugs in pharmaceutical circulation.

  15. Molecular Aspects of Mucoadhesive Carrier Development for Drug Delivery and Improved Absorption

    PubMed Central

    Peppas, Nicholas A; Thomas, J. Brock; McGinity, James

    2011-01-01

    Although the oral route remains the most favored route of drug administration, major scientific obstacles prevent the effective and efficient delivery of low-molecular-mass drugs, peptides and proteins that exhibit poor solubility and permeability. Mucoadhesive dosage forms and the associated drug carriers have the ability to interact at a molecular level with the mucus gel layer that lines the epithelial surfaces of the major absorptive regions of the body. This interaction provides an increased residence time of the therapeutic formulation while localizing the drug at the site of administration. Such local, non-specific targeting leads to an increase in both oral absorption and bioavailability. Fundamental understanding of the biological processes encountered along the gastrointestinal tract can provide a sufficient engineer of carriers that are capable to provide this increase in residence time. Here we discuss the theoretical framework for achieving mucoadhesive systems as related to biomaterials science and the structure of the biomaterials used. PMID:19105897

  16. The politics of access to expensive drugs: INESSS and the innovative pharmaceutical industry.

    PubMed

    Hughes, David

    2012-05-01

    The innovative pharmaceutical industry employs thousands of people in Quebec and so has the ability to exert strong political pressure; the public statements of Sanofi-Aventis concerning the provincial reimbursement of certain expensive drugs are an example. "Maintaining a dynamic biopharmaceutical industry" is one of four main axes of the drug policy of Quebec's ministry of health. However, this role of government should not take precedence over the efficient and equitable management of health resources. We defend the legitimate and responsible choice of the Institut national d'excellence en santé et en services sociaux du Québec (INESSS) to require an acceptable cost-effectiveness ratio from expensive new drugs.

  17. A vision for cyclodextrin nanoparticles in drug delivery systems and pharmaceutical applications.

    PubMed

    Lakkakula, Jaya Raju; Maçedo Krause, Rui Werner

    2014-05-01

    Cyclodextrins (CDs) have brought a revolution in the pharmaceutical field over the last decade. Natural and modified CDs (α-CD and β-CD) have been studied and some have gained US FDA approval or achieved 'Generally Regarded as Safe' (GRAS) status. Another characteristic of CDs is the ease with which they can be induced to form supramolecular structures for its use in drug delivery. CDs, grafted or crosslinked with polymers, are now being developed into 'smart' systems for efficient targeted drug delivery, especially for hydrophobic drugs. Amphiphilic CDs have the ability to form nanospheres or nanocapsules via a simple nanoprecipitation technique. This review deals with different types of CDs, and their efficacy, physicochemical properties and transformation into nanoparticles with interesting in vitro and in vivo applications.

  18. Nano carriers for drug transport across the blood-brain barrier.

    PubMed

    Li, Xinming; Tsibouklis, John; Weng, Tingting; Zhang, Buning; Yin, Guoqiang; Feng, Guangzhu; Cui, Yingde; Savina, Irina N; Mikhalovska, Lyuba I; Sandeman, Susan R; Howel, Carol A; Mikhalovsky, Sergey V

    2017-01-01

    Effective therapy lies in achieving a therapeutic amount of drug to the proper site in the body and then maintaining the desired drug concentration for a sufficient time interval to be clinically effective for treatment. The blood-brain barrier (BBB) hinders most drugs from entering the central nervous system (CNS) from the blood stream, leading to the difficulty of delivering drugs to the brain via the circulatory system for the treatment, diagnosis and prevention of brain diseases. Several brain drug delivery approaches have been developed, such as intracerebral and intracerebroventricular administration, intranasal delivery and blood-to-brain delivery, as a result of transient BBB disruption induced by biological, chemical or physical stimuli such as zonula occludens toxin, mannitol, magnetic heating and ultrasound, but these approaches showed disadvantages of being dangerous, high cost and unsuitability for most brain diseases and drugs. The strategy of vector-mediated blood-to-brain delivery, which involves improving BBB permeability of the drug-carrier conjugate, can minimize side effects, such as being submicrometre objects that behave as a whole unit in terms of their transport and properties, nanomaterials, are promising carrier vehicles for direct drug transport across the intact BBB as a result of their potential to enter the brain capillary endothelial cells by means of normal endocytosis and transcytosis due to their small size, as well as their possibility of being functionalized with multiple copies of the drug molecule of interest. This review provids a concise discussion of nano carriers for drug transport across the intact BBB, various forms of nanomaterials including inorganic/solid lipid/polymeric nanoparticles, nanoemulsions, quantum dots, nanogels, liposomes, micelles, dendrimers, polymersomes and exosomes are critically evaluated, their mechanisms for drug transport across the BBB are reviewed, and the future directions of this area are fully

  19. Preparation of hierarchical hollow CaCO3 particles and the application as anticancer drug carrier.

    PubMed

    Wei, Wei; Ma, Guang-Hui; Hu, Gang; Yu, Di; McLeish, Tom; Su, Zhi-Guo; Shen, Zhe-Yu

    2008-11-26

    One-pot approach to couple the crystallization of CaCO(3) nanoparticles and the in situ symmetry-breaking assembly of these crystallites into hollow spherical shells was developed under the templating effect of a soluble starch. Further functional study using HP-a as an anticancer drug carrier (DOX) demonstrated its advantages for localizing drug release by the pH value-sensitive structure and enhancing cytotoxicity by increasing cellular uptake, perinuclear accumulation, and nuclear entry.

  20. Institutional corruption of pharmaceuticals and the myth of safe and effective drugs.

    PubMed

    Light, Donald W; Lexchin, Joel; Darrow, Jonathan J

    2013-01-01

    Over the past 35 years, patients have suffered from a largely hidden epidemic of side effects from drugs that usually have few offsetting benefits. The pharmaceutical industry has corrupted the practice of medicine through its influence over what drugs are developed, how they are tested, and how medical knowledge is created. Since 1906, heavy commercial influence has compromised congressional legislation to protect the public from unsafe drugs. The authorization of user fees in 1992 has turned drug companies into the FDA's prime clients, deepening the regulatory and cultural capture of the agency. Industry has demanded shorter average review times and, with less time to thoroughly review evidence, increased hospitalizations and deaths have resulted. Meeting the needs of the drug companies has taken priority over meeting the needs of patients. Unless this corruption of regulatory intent is reversed, the situation will continue to deteriorate. We offer practical suggestions including: separating the funding of clinical trials from their conduct, analysis, and publication; independent FDA leadership; full public funding for all FDA activities; measures to discourage R&D on drugs with few, if any, new clinical benefits; and the creation of a National Drug Safety Board.

  1. Carrier characteristics influence the kinetics of passive drug loading into lipid nanoemulsions.

    PubMed

    Göke, Katrin; Bunjes, Heike

    2017-08-11

    Passive loading as a novel screening approach is a material-saving tool for the efficient selection of a suitable colloidal lipid carrier system for poorly water soluble drug candidates. This method comprises incubation of preformed carrier systems with drug powder and subsequent determination of the resulting drug load of the carrier particles after removal of excess drug. For reliable routine use and to obtain meaningful loading results, information on the kinetics of the process is required. Passive loading proceeds via a dissolution-diffusion based mechanism, where drug surface area and drug water solubility are key parameters for fast passive loading. While the influence of the drug characteristics is mostly understood, the influence of the carrier characteristics remains unknown. The aim of this study was to examine how the lipid nanocarriers' characteristics, i.e. the type of lipid, the lipid content and the particle size, influence the kinetics of passive loading. Fenofibrate was used as model drug and the loading progress was analyzed by UV spectroscopy. The saturation solubility in the nanocarrier particles, i.e. the lipid type, did not influence the passive loading rate constant. Low lipid content in the nanocarrier and a small nanocarrier particle size both increased passive loading speed. Both variations increase the diffusivity of the nanocarrier particles, which is the primary cause for fast loading at these conditions: The quicker the carrier particles diffuse, the higher is the speed of passive loading. The influence of the diffusivity of the lipid nanocarriers and the effect of drug dissolution rate were included in an overall mechanistic model developed for similar processes (A. Balakrishnan, B.D. Rege, G.L. Amidon, J.E. Polli, Surfactant-mediated dissolution: contributions of solubility enhancement and relatively low micelle diffusivity, J. Pharm. Sci. 93 (2004) 2064-2075). The resulting mechanistic model gave a good estimate of the speed of

  2. [Generic drugs: we must cut pharmaceutical spending but undertaking drug quality].

    PubMed

    Carrillo Norte, Juan Antonio; Postigo Mota, Salvador

    2012-02-01

    The World Health Organization and all drug regulatory agencies (DRA) support the commercialization of generic medicines because they control costs and are irreplaceable therapeutic options in countries lacking the innovator product. Generic drugs are widely considered to be cost-efficient substitutes for brand-name medications. They make up about 20% of the total number of prescriptions in Spain, a figure that is still far from the use of generic drugs in USA and other European countries. Despite economical interest in this issue, in this article we review the interest of generic drugs from a pharmacological and clinical perspective that must undertake drug quality to ensure drug efficacy and safety of the patients. A generic drug (generic drugs, short: generics) is defined as "a drug product that is comparable to brand/reference listed drug product in dosage form, strength, route of administration, quality and performance characteristics, and intended use". Both the reference drug and the generic drug have to demonstrate previously they are therapeutically equivalent. With the exception of parenteral drugs, two products have demonstrated to be therapeutically equivalent if after administration in the same molar dose, their effects with respect to both efficacy and safety are essentially the same, as determined from bioequivalence studies in terms of comparison of appropriate pharmacokinetic parameters and bioavailability. Parenteral formulations, however, are not required to demonstrate therapeutic equivalence because it may be considered self-evident. Such assumptions have never been challenged, but there are reasons to do so for parenteral antimicrobials. It is interesting to highlight that although brand-name drugs and generic drugs are both approved by DRA and may be interchangeable with respect to their clinical effects, they can differ substantially in their appearance. Consumers of brand-name medications receive identical-appearing batches of pills with

  3. Liposomes coated with thiolated chitosan as drug carriers of curcumin.

    PubMed

    Li, Riwang; Deng, Li; Cai, Zhengwei; Zhang, Shuyun; Wang, Kun; Li, Lihua; Ding, Shan; Zhou, Changren

    2017-11-01

    Liposome is one of a promising delivery system to improve water solubility, stability, and bioavailability of curcumin. But its instability is not favorable for long-circulating treatment, controlled release or conservation. To overcome the disadvantages, thiol derivatised chitosan (CSSH) were synthesized and utilized to coat liposomes. The CSSH coated curcumin liposomes (Cur-Lip-CSSH) had an encapsulation efficiency (EE) of 93.95%, a drug loading (DL) of 7.95%, an average particle size of 406.0nm, and a positive zeta-potential of 36.6mV, which were all higher than that of Cur-Lip. Cur-Lip-CSSH showed slower in vitro release than Cur-Lip at pH5.5 and pH7.4, and the higher retention of curcumin would be remained for the following uptake of cells. The stability of the both liposomes at 4°C was almost the same, but Cur-Lip-CSSH displayed a higher stability at room temperature and higher temperature by DSC characterization. Curcumin can inhibit the growth of cancer cells under certain conditions. MCF-7 cell line was used to study its inhibition and proliferation after treating with curcumin and Cur-Lip-CSSH. Treatment of MCF-7 with curcumin and Cur-Lip-CSSH showed dose and time dependent cytotoxicity, with growth suppression at 200μM, 72h, obviously. These results indicate that the proper coating of liposomes is able to improve the stability of liposomes and the Lip-CSSH can function as potential drug delivery system. Copyright © 2017. Published by Elsevier B.V.

  4. Drug loading and release on tumor cells using silk fibroin-albumin nanoparticles as carriers

    NASA Astrophysics Data System (ADS)

    Subia, B.; Kundu, S. C.

    2013-01-01

    Polymeric and biodegradable nanoparticles are frequently used in drug delivery systems. In this study silk fibroin-albumin blended nanoparticles were prepared using the desolvation method without any surfactant. These nanoparticles are easily internalized by the cells, reside within perinuclear spaces and act as carriers for delivery of the model drug methotrexate. Methotrexate loaded nanoparticles have better encapsulation efficiency, drug loading ability and less toxicity. The in vitro release behavior of methotrexate from the nanoparticles suggests that about 85% of the drug gets released after 12 days. The encapsulation and loading of a drug would depend on factors such as size, charge and hydrophobicity, which affect drug release. MTT assay and conjugation of particles with FITC demonstrate that the silk fibroin-albumin nanoparticles do not affect the viability and biocompatibility of cells. This blended nanoparticle, therefore, could be a promising nanocarrier for the delivery of drugs and other bioactive molecules.

  5. In vivo-in vitro correlations: predicting pulmonary drug deposition from pharmaceutical aerosols.

    PubMed

    Byron, Peter R; Hindle, Michael; Lange, Carlos F; Longest, P Worth; McRobbie, Donald; Oldham, Michael J; Olsson, Bo; Thiel, Charles G; Wachtel, Herbert; Finlay, Warren H

    2010-12-01

    In order to answer the question "what research remains to be done?" we review the current state of the art in pharmaceutical aerosol deposition modeling and explore possible in vivo- in vitro correlations (IVIVC) linking drug deposition in the human lung to predictions made using in vitro physical airway models and in silico computer models. The use of physical replicas of portions of the respiratory tract is considered, alongside the advantages and disadvantages of the different imaging methods used to obtain their dimensions. The use of airway replicas to determine drug deposition in vitro is discussed and compared with the predictions from different empirical curve fits to long-standing in vivo deposition data for monodisperse aerosols. The use of improved computational models and three-dimensional computational fluid dynamics (CFD) to predict aerosol deposition within the respiratory tract is examined. CFD's ability to predict both drug deposition from pharmaceutical aerosol sprays and powder behavior in dry powder inhalers is examined; both were highlighted as important areas for future research. Although the authors note the abilities of current in vitro and in silico methods to predict in vivo data, a number of limitations remain. These include our present inability to either image or replicate all but the most proximal airways in sufficient spatial and temporal detail to allow full capture of the fluid and aerosol mechanics in these regions. In addition, the highly complex microscale behavior of aerosols within inhalers and the respiratory tract places extreme computational demands on in silico methods. When the complexity of variations in respiratory tract geometry is associated with additional factors such as breathing pattern, age, disease state, postural position, and patient-device interaction are all considered, it is clear that further research is required before the prediction of all aspects of inhaled pharmaceutical aerosol deposition is possible.

  6. [Psychological impacts of being a carrier of multi-drug resistant bacteria].

    PubMed

    Pires, Elisabete; Frange, Pierre; Henry, Benoît; Lortholary, Olivier; Reichert, Catherine

    2015-01-01

    Learning that they are a carrier of multi-drug resistant bacteria and being placed in isolation to prevent transmission has significant psychological repercussions for the patient and their families. Through therapeutic education, caregivers adapt their support to the patient's experience, raising their awareness of prevention. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  7. Protein encapsulated magnetic carriers for micro/nanoscale drug delivery systems.

    SciTech Connect

    Xie, Y.; Kaminski, M. D.; Mertz, C. J.; Finck, M. R.; Guy, S. G.; Chen, H.; Rosengart, A. J.; Chemical Engineering; Univ. of Chicago, Pritzker School of Medicine

    2005-01-01

    Novel methods for drug delivery may be based on nanotechnology using non-invasive magnetic guidance of drug loaded magnetic carriers to the targeted site and thereafter released by external ultrasound energy. The key building block of this system is to successfully synthesize biodegradable, magnetic drug carriers. Magnetic carriers using poly(D,L-lactide-co-glycolide) (PLGA) or poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) as matrix materials were loaded with bovine serum albumin (BSA) by a double-emulsion technique. BSA-loaded magnetic microspheres were characterized for size, morphology, surface charge, and magnetization. The BSA encapsulation efficiency was determined by recovering albumin from the microspheres using dimethyl sulfoxide and 0.05N NaOH/0.5% SDS then quantifying with the Micro-BCA protein assay. BSA release profiles were also determined by the Micro-BCA protein assay. The microspheres had drug encapsulation efficiencies up to 90% depending on synthesis parameters. Particles were spherical with a smooth or porous surface having a size range less than 5 {mu}m. The surface charge (expressed as zeta potential) was near neutral, optimal for prolonged intravascular survival. The magnetization of these BSA loaded magnetic carriers was 2 to 6 emu/g, depending on the specific magnetic materials used during synthesis.

  8. A water-soluble pillar[5]arene as a new carrier for an old drug.

    PubMed

    Barbera, Lucia; Franco, Domenico; De Plano, Laura M; Gattuso, Giuseppe; Guglielmino, Salvatore P P; Lentini, Germana; Manganaro, Nadia; Marino, Nino; Pappalardo, Sebastiano; Parisi, Melchiorre F; Puntoriero, Fausto; Pisagatti, Ilenia; Notti, Anna

    2017-04-11

    The remarkable affinity of deca-carboxylatopillar[5]arene WP5 towards the aminoglycoside antibiotic, amikacin, in aqueous media is reported; in vitro studies on Gram-positive bacteria (Staphylococcus aureus) show that drug entrapment inside WP5 also takes place in the presence of the microrganisms, thus pointing to WP5 as an appealing carrier for amikacin targeted delivery.

  9. Promote potential applications of nanoparticles as respiratory drug carrier: insights from molecular dynamics simulations.

    PubMed

    Lin, Xubo; Bai, Tingting; Zuo, Yi Y; Gu, Ning

    2014-03-07

    Nanoparticles (NPs) show great promises in biomedical applications as the respiratory drug carrier system. Once reaching the alveolar region, NPs first interact with the pulmonary surfactant (PS) film, which serves as the first biological barrier and plays an important role in maintaining the normal respiratory mechanics. Therefore, understanding the interactions between NPs and PS can help promote the NP-based respiratory drug carrier systems. Using coarse-grained molecular dynamics simulations, we studied the effect of rigid spherical NPs with different hydrophobicity and sizes on a dipalmitoylphosphatidylcholine (DPPC) monolayer at the air-water interface. Four different NPs were considered, including hydrophilic and hydrophobic NPs, each with two diameters of 3 nm and 5 nm (the sizes are comparable to that of generation 3 and 5 PAMAM dendrimers, which have been widely used for nanoscale drug carrier systems). Our simulations showed that hydrophilic NPs can readily penetrate into the aqueous phase with little or no disturbance on the DPPC monolayer. However, hydrophobic NPs tend to induce large structural disruptions, thus inhibiting the normal phase transition of the DPPC monolayer upon film compression. Our simulations also showed that this inhibitory effect of hydrophobic NPs can be mitigated through PEGylation. Our results provide useful guidelines for molecular design of NPs as carrier systems for pulmonary drug delivery.

  10. Crystal engineering of lactose using electrospray technology: carrier for pulmonary drug delivery.

    PubMed

    Patil, Sharvil; Mahadik, Abhijeet; Nalawade, Pradeep; More, Priyesh

    2017-09-05

    Dry powder inhalers (DPIs) consisting of a powder mixture containing coarse carrier particles (generally lactose) and micronized drug particles are used for lung drug delivery. The effective drug delivery to the lungs depends on size and shape of carrier particles. Thus, various methods have been proposed for engineering lactose particles to enhance drug delivery to lungs. The objective of current work was to assess suitability of electrospray technology toward crystal engineering of lactose. Further, utility of the prepared lactose particles as a carrier in DPI was evaluated. Saturated lactose solutions were electrosprayed to obtain electrosprayed lactose (EL) particles. The polymorphic form of EL was determined using Fourier transform infrared spectroscopy, powder X-ray diffractometry, and differential scanning calorimetry. In addition, morphological, surface textural, and flow properties of EL were determined using scanning electron microscopy and Carr's index, respectively. The aerosolization properties of EL were determined using twin-stage impinger and compared with commercial lactose particles [Respitose(®) (SV003, Goch, Germany)] used in DPI formulations. EL was found to contain both isomers (α and β) of lactose having flow properties comparable to Respitose(®) (SV003). In addition, the aerosolization properties of EL were found to be significantly improved when compared to Respitose(®) (SV003) which could be attributed to morphological (high elongation ratio) and surface characteristic (smooth surface) alterations induced by electrospray technology. Electrospray technology can serve as an alternative technique for continuous manufacturing of engineered lactose particles which can be used as a carrier in DPI formulations.

  11. Are Pharmaceuticals with Evolutionary Conserved Molecular Drug Targets More Potent to Cause Toxic Effects in Non-Target Organisms?

    PubMed Central

    Furuhagen, Sara; Fuchs, Anne; Lundström Belleza, Elin; Breitholtz, Magnus; Gorokhova, Elena

    2014-01-01

    The ubiquitous use of pharmaceuticals has resulted in a continuous discharge into wastewater and pharmaceuticals and their metabolites are found in the environment. Due to their design towards specific drug targets, pharmaceuticals may be therapeutically active already at low environmental concentrations. Several human drug targets are evolutionary conserved in aquatic organisms, raising concerns about effects of these pharmaceuticals in non-target organisms. In this study, we hypothesized that the toxicity of a pharmaceutical towards a non-target invertebrate depends on the presence of the human drug target orthologs in this species. This was tested by assessing toxicity of pharmaceuticals with (miconazole and promethazine) and without (levonorgestrel) identified drug target orthologs in the cladoceran Daphnia magna. The toxicity was evaluated using general toxicity endpoints at individual (immobility, reproduction and development), biochemical (RNA and DNA content) and molecular (gene expression) levels. The results provide evidence for higher toxicity of miconazole and promethazine, i.e. the drugs with identified drug target orthologs. At the individual level, miconazole had the lowest effect concentrations for immobility and reproduction (0.3 and 0.022 mg L−1, respectively) followed by promethazine (1.6 and 0.18 mg L−1, respectively). At the biochemical level, individual RNA content was affected by miconazole and promethazine already at 0.0023 and 0.059 mg L−1, respectively. At the molecular level, gene expression for cuticle protein was significantly suppressed by exposure to both miconazole and promethazine; moreover, daphnids exposed to miconazole had significantly lower vitellogenin expression. Levonorgestrel did not have any effects on any endpoints in the concentrations tested. These results highlight the importance of considering drug target conservation in environmental risk assessments of pharmaceuticals. PMID:25140792

  12. Can open-source drug R&D repower pharmaceutical innovation?

    PubMed

    Munos, B

    2010-05-01

    Open-source R&D initiatives are multiplying across biomedical research. Some of them-such as public-private partnerships-have achieved notable success in bringing new drugs to market economically, whereas others reflect the pharmaceutical industry's efforts to retool its R&D model. Is open innovation the answer to the innovation crisis? This Commentary argues that although it may likely be part of the solution, significant cultural, scientific, and regulatory barriers can prevent it from delivering on its promise.

  13. The assessment of potential for QT interval prolongation with new pharmaceuticals: impact on drug development.

    PubMed

    Gralinski, M R

    2000-01-01

    Few examinations of a single physiological variable can end the development of a putative new pharmaceutical. Prolongation of the electrocardiographic QT interval is one of these tests. Recognizing the removal of several approved and widely used medicines, worldwide regulatory authorities have raised a heightened awareness on the submission of data surrounding the ventricular repolarization process. This review will discuss the anatomy and physiology surrounding the generation of the electrocardiographic QT interval and the consequences of its alteration. In addition, relevant models of preclinical safety and general guidelines for clinical examination in this area are discussed along with the impact of incorporating these assays into the drug development process.

  14. Static headspace gas chromatography of (semi-)volatile drugs in pharmaceuticals for topical use.

    PubMed

    Sitaramaraju, Yarramraju; van Hul, Ariane; Wolfs, Kris; Van Schepdael, Ann; Hoogmartens, Jos; Adams, Erwin

    2008-08-05

    An analytical method that allows simultaneous analysis of some (semi-)volatile drugs and additives in pharmaceuticals for topical use was developed using classical static headspace as sampling technique combined with gas chromatography (HS-GC). The capillary column used, RSL-200, showed good selectivity towards all the analytes in the samples investigated. Among the different dilution media investigated, dimethyl sulfoxide in combination with sodium chloride solution showed better sensitivity. Using the optimized headspace sample dilution medium, better sensitivities for all the analytes were achieved at low thermostatting temperature (85 degrees C). The optimized HS-GC method with flame ionization detection showed good repeatability, linearity and accuracy.

  15. Patent issues in drug development: perspectives of a pharmaceutical scientist-attorney.

    PubMed

    Melethil, Srikumaran

    2005-10-27

    The major purpose of this article is to emphasize the need for pharmaceutical scientists to have a better understanding of patent fundamentals. This need is illustrated by analyses of key scientific and legal issues that arose during recent patent infringement cases involving Prozac, Prilosec, and Buspar. Economic incentives for drug discovery and development clash with societal needs for low-cost pharmaceuticals in the United States and all over the world. The Hatch-Waxman Act of 1984 was enacted to promote public health by balancing the interests of brand name and generic companies. Patent protection, which provides a monopoly for a limited time, is aimed to provide such incentives. Creation of patents requires the interaction between scientists and lawyers, an endeavor made difficult by the differing intellectual spheres of their respective disciplines. Therefore, in the first place, a thorough understanding of patent fundamentals among pharmaceutical scientists will help them work more efficiently with patent attorneys. Second, it will enable them to appreciate the strengths and weaknesses of individual patents, which is critical in developing strategies amidst the ongoing patent tug-of-war between brand-name and generic companies.

  16. Nanoparticles of hydrophobically modified dextrans as potential drug carrier systems.

    PubMed

    Aumelas, A; Serrero, A; Durand, A; Dellacherie, E; Leonard, M

    2007-09-01

    Nanoparticles combining a hydrophobically modified dextran core and a polysaccharide surface coverage were elaborated. Their suitability for applications like drug delivery was evaluated. The selected polysaccharide, dextran, was chemically modified by the covalent attachment of hydrocarbon groups (aliphatic or aromatic) via the formation of ether links. According to the extent of modification, either water-soluble or water-insoluble dextran derivatives were obtained. The latter exhibited solubility in organic solvents like tetrahydrofuran or dichloromethane saturated with water. Water-soluble dextran derivatives were used as polymeric surfactants for the control of nanoparticles surface characteristics. Nanoparticles were prepared either by o/w emulsion or solvent-diffusion methods. The size and surface properties of dextran nanoparticles were correlated to processing conditions. The stability of colloidal suspensions was examined as a function of ionic strength and related to the particle surface characteristics. The redispersability of freeze-dried suspensions without the addition of cryoprotectant was demonstrated. Finally, the degradability of modified dextrans was compared to that of starting dextran, after enzymatic hydrolysis in the presence of dextranase.

  17. Gender-based differences in the toxicity of pharmaceuticals--the Food and Drug Administration's perspective.

    PubMed

    Miller, M A

    2001-01-01

    Women experience more adverse reactions to treatment with therapeutic drugs than men. Theories proposed to explain this include overdosing, different pharmacokinetics and pharmacodynamics, women are more likely to report adverse events than men, or women take more medications than men. Food and Drug Administration (FDA) Office of Women's Health (OWH) funds research to promote including women in clinical trials and understanding the biology of sex-related differences in the safety of FDA-regulated products. Including women in clinical trials advances the understanding of drug efficacy and safety in women by providing information on drug dosing, pharmacokinetics, and pharmacodynamics. A Baysian statistical analysis of sex differences in adverse events showed that although about the same number of adverse events were reported for men and women, those reported for women were more serious. One example of a sex difference in the toxicity of pharmaceuticals is the drug-induced cardiac arrhythmia, torsades de point. OWH funded studies in animals and humans to investigate the mechanism behind this sex difference. These studies demonstrated that shortening the QT interval increases the risk of developing torsades and that androgens protect against torsades by slowing cardiac repolarization and prolonging the QT interval. Understanding the mechanisms behind other reported sex-related differences in adverse drug effects requires additional research. The preliminary studies conducted to date suggest that this sex-related difference is likely to be a multifactorial problem requiring information from several fields of study. Ideally, individuals at risk for developing an adverse event should be identified prior to therapeutic intervention. The OWH plans to fund more studies to investigate the role of hormonal variations on drug metabolism and drug-drug interactions. Animal and in vitro model systems are needed to fully understand the mechanism of how gender influences drug

  18. Acute and chronic ecotoxicological effects of four pharmaceuticals drugs on cladoceran Daphnia magna.

    PubMed

    de Oliveira, Laira L Damasceno; Antunes, Sara Cristina; Gonçalves, Fernando; Rocha, Odete; Nunes, Bruno

    2016-01-01

    The occurrence of pharmaceuticals in the aquatic environment has received increasing attention in recent years, as concerns have risen about their environmental persistence, biological activity and different effects toward nontarget organisms. Considering the magnitude of concentrations (ng L(-1) to mg L(-1)) and their often-specific modes of action, the assessment of physiological responses of exposed aquatic biota may provide significant information regarding the potential ecological consequences of exposure to these contaminants. The present study intended to assess the acute and chronic effects of four pharmaceuticals: acetaminophen, chlorpromazine, diclofenac sodium and propranolol in the cladoceran species Daphnia magna. Parameters such as immobility, total of offspring and rate of population increase were analyzed. Results of acute exposures showed a considerable variability of toxicity among pharmaceuticals, with the following ranking of toxicity: diclofenac (EC50 = 123.3 mg L(-1)) < propranolol (EC50 = 5.531 mg L(-1)) < acetaminophen (EC50 = 2.831 mg L(-1)) < chlorpromazine (EC50 = 1.805 mg L(-1)). The chronic toxicity data showed the exertion of reproductive adverse effects. The compounds chlorpromazine and propranolol caused a significant decrease in fecundity, and the rate of population increase parameter suffered a significant decrease from 0.33 mg L(-1) to 0.128 mg L(-1) onwards, respectively. The levels of exposure to which our test organism was acutely and chronically exposed were above those already reported in the wild. Nevertheless, the extensive production, prescription and release of pharmaceuticals drugs will continue to grow in the future, and consequently their loadings to the environment can result in potential long-term ecological risks to aquatic biota.

  19. Characterization of Different Functionalized Lipidic Nanocapsules as Potential Drug Carriers

    PubMed Central

    Sánchez-Moreno, Paola; Ortega-Vinuesa, Juan Luis; Martín-Rodríguez, Antonio; Boulaiz, Houría; Marchal-Corrales, Juan Antonio; Peula-García, José Manuel

    2012-01-01

    Lipid nanocapsules (LNC) based on a core-shell structure consisting of an oil-filled core with a surrounding polymer layer are known to be promising vehicles for the delivery of hydrophobic drugs in the new therapeutic strategies in anti-cancer treatments. The present work has been designed as basic research about different LNC systems. We have synthesized—and physico-chemically characterized—three different LNC systems in which the core was constituted by olive oil and the shell by different phospholipids (phosphatidyl-serine or lecithin) and other biocompatible molecules such as Pluronic® F68 or chitosan. It is notable that the olive-oil-phosphatidyl-serine LCN is a novel formulation presented in this work and was designed to generate an enriched carboxylic surface. This carboxylic layer is meant to link specific antibodies, which could facilitate the specific nanocapsule uptake by cancer cells. This is why nanoparticles with phosphatidyl-serine in their shell have also been used in this work to form immuno-nanocapsules containing a polyclonal IgG against a model antigen (C-reactive protein) covalently bounded by means of a simple and reproducible carbodiimide method. An immunological study was made to verify that these IgG-LNC complexes showed the expected specific immune response. Finally, a preliminary in vitro study was performed by culturing a breast-carcinoma cell line (MCF-7) with Nile-Red-loaded LNC. We found that these cancer cells take up the fluorescent Nile- Red molecule in a process dependent on the surface properties of the nanocarriers. PMID:22408461

  20. Preliminary thermoluminescence investigation of commercial pharmaceutical glass containers towards the sterilization dosimetry of liquid drugs.

    PubMed

    Kazakis, Nikolaos A; Tsirliganis, Nestor C; Kitis, George

    2015-11-01

    Drug sterilization with ionizing radiation is a well-established technology, which is constantly extending to several products due to its numerous advantages, since it allows the heat-free sterilization of heat-sensitive pharmaceutical preparations. In a previous study, the possibility to identify irradiated solid-state drugs by means of OSL and TL was examined with very promising findings. In the same respect, the present work aims, for the first time to the authors' best knowledge, to explore whether TL can be employed as a method for post-sterilization dosimetry on commercial liquid-state drugs, by studying the properties of their glass containers. Two different types of glass containers (bottle and ampoule) of two widely used liquid drugs, i.e., Hexalen® and Voltaren®, are used for this purpose. Both glass containers exhibit a linear TL dose response for doses up to 6kGy with a stable behavior through time, while no significant sensitization of the main peaks is observed. Thus, preliminary findings are very promising towards the post-sterilization dosimetry of liquid drugs and the use of the containers of commercial liquid drugs for normal and/or accidental dosimetry.

  1. Data-mining for sulfur and fluorine: an evaluation of pharmaceuticals to reveal opportunities for drug design and discovery.

    PubMed

    Ilardi, Elizabeth A; Vitaku, Edon; Njardarson, Jon T

    2014-04-10

    Among carbon, hydrogen, oxygen, and nitrogen, sulfur and fluorine are both leading constituents of the pharmaceuticals that comprise our medicinal history. In efforts to stimulate the minds of both the general public and expert scientist, statistics were collected from the trends associated with therapeutics spanning 12 disease categories (a total of 1969 drugs) from our new graphical montage compilation: disease focused pharmaceuticals posters. Each poster is a vibrant display of a collection of pharmaceuticals (including structural image, Food and Drug Administration (FDA) approval date, international nonproprietary name (INN), initial market name, and a color-coded subclass of function) organized chronologically and classified according to an association with a particular clinical indication. Specifically, the evolution and structural diversity of sulfur and the popular integration of fluorine into drugs introduced over the past 50 years are evaluated. The presented qualitative conclusions in this article aim to promote innovative insights into drug development.

  2. Drug delivery carriers on the fringes: natural red blood cells versus synthetic multilayered capsules.

    PubMed

    Muzykantov, Vladimir R

    2013-01-01

    Red blood cells (RBC) and synthetic multilayered nanocarriers may appear as distant 'extremes' of the continuum of diverse drug delivery systems. The former are natural, old and simple, whereas the latter are artificial, novel and sophisticated. However, juxtaposition of features of these types of carriers, offered in a review article published in this issue, is instructive. Such an analysis helps to define both their distinctions and similarities (structural, functional, technological, specific areas of utility), and illustrates perspectives of their translation into the practice. Thus, synthetic multilayered carriers (which, in some embodiments, use elements of design inspired by RBC) represent an attractive research object offering high degree of control of their features. These carriers may find utility for intracellular delivery, controlled release of multiple cargoes and imaging. On the other hand, RBC provide arguably the most attractive carriers for sustained intravascular delivery of variety of drugs including biotherapeutics, either encapsulated into the inner RBC volume or coupled to RBC surface. The discussion of specific medical utility of these carriers and comparative analysis of the factors that may affect their translation (including complexity, costs, market value and therapeutic benefit/risk ratio) is timely and likely to intensify in the near future.

  3. Advantages and challenges of the spray-drying technology for the production of pure drug particles and drug-loaded polymeric carriers.

    PubMed

    Sosnik, Alejandro; Seremeta, Katia P

    2015-09-01

    Spray-drying is a rapid, continuous, cost-effective, reproducible and scalable process for the production of dry powders from a fluid material by atomization through an atomizer into a hot drying gas medium, usually air. Often spray-drying is considered only a dehydration process, though it also can be used for the encapsulation of hydrophilic and hydrophobic active compounds within different carriers without substantial thermal degradation, even of heat-sensitive substances due to fast drying (seconds or milliseconds) and relatively short exposure time to heat. The solid particles obtained present relatively narrow size distribution at the submicron-to-micron scale. Generally, the yield% of spray-drying at laboratory scale with conventional spray-dryers is not optimal (20-70%) due to the loss of product in the walls of the drying chamber and the low capacity of the cyclone to separate fine particles (<2 μm). Aiming to overcome this crucial drawback in early development stages, new devices that enable the production of submicron particles with high yield, even for small sample amounts, have been introduced into the market. This review describes the most outstanding advantages and challenges of the spray-drying method for the production of pure drug particles and drug-loaded polymeric particles and discusses the potential of this technique and the more advanced equipment to pave the way toward reproducible and scalable processes that are critical to the bench-to-bedside translation of innovative pharmaceutical products.

  4. Design of Chitosan and Its Water Soluble Derivatives-Based Drug Carriers with Polyelectrolyte Complexes

    PubMed Central

    Wu, Qing-Xi; Lin, Dong-Qiang; Yao, Shan-Jing

    2014-01-01

    Chitosan, the cationic polysaccharide derived from the natural polysaccharide chitin, has been studied as a biomaterial for more than two decades. As a polycationic polymer with favorable properties, it has been widely used to form polyelectrolyte complexes with polyanions for various applications in drug delivery fields. In recent years, a growing number of studies have been focused on the preparation of polyelectrolyte complexes based on chitosan and its water soluble derivatives. They have been considered well-suited as biomaterials for a number of vital drug carriers with targeted/controlled release profiles, e.g., films, capsules, microcapsules. In this work, an overview highlights not only the favorable properties of chitosan and its water soluble derivatives but also the good performance of the polyelectrolyte complexes produced based on chitosan. Their various types of applications as drug carriers are reviewed in detail. PMID:25532565

  5. Drug detection in breath: non-invasive assessment of illicit or pharmaceutical drugs.

    PubMed

    Trefz, Phillip; Kamysek, Svend; Fuchs, Patricia; Sukul, Pritam; Schubert, Jochen K; Miekisch, Wolfram

    2017-03-20

    Breath analysis not only holds great potential for the development of new non-invasive diagnostic methods, but also for the identification and follow up of drug levels in breath. This is of interest for both, forensic and medical science. On the one hand, the detection of drugs of abuse in exhaled breath-similar to the well-known breath alcohol tests-would be highly desirable as an alternative to blood or urine analysis in situations such as police controls for drugged driving. The non-invasive detection of drugs and their metabolites is thus of great interest in forensic science, especially since marijuana is becoming legalized in certain parts of the US and the EU. The detection and monitoring of medical drugs in exhaled breath without the need of drawing blood samples on the other hand, is of high relevance in the clinical environment. This could facilitate a more precise medication and enable therapy control without any burden to the patient. Furthermore, it could be a step towards personalized medicine. This review gives an overview of the current state of drug detection in breath, including both volatile and non-volatile substances. The review is divided into two sections. The first section deals with qualitative detection of drugs (drugs of abuse), while the second is related to quantitative drug detection (medical drugs). Chances and limitations are discussed for both aspects. The detection of the intravenous anesthetic propofol is presented as a detailed example that demonstrates the potential, requirements, pitfalls and limitations of therapeutic drug monitoring by means of breath analysis.

  6. Potential therapeutic application of dendrimer/cyclodextrin conjugates with targeting ligands as advanced carriers for gene and oligonucleotide drugs.

    PubMed

    Arima, Hidetoshi; Motoyama, Keiichi; Higashi, Taishi

    2017-04-01

    Despite the recent approval of some gene medicines and nucleic acid drugs, further improvement of delivery techniques for these drugs is strongly required. Several delivery technologies for these drugs have been developed, in other words, viral and two types of nonviral (lipofection and polyfection) vectors. Among the polyfection system, the potential use of various cyclodextrin (CyD) derivatives and CyD-appended polymers as carriers for gene and nucleic acid drugs has been demonstrated. The polyamidoamine dendrimer (G3) conjugates with α-CyD (α-CDE (G3)) have been reported to possess noteworthy properties as DNA and nucleic acid drugs carriers. This review will focus on the attempts to develop such cell-specific drug carriers by preparing polyethylene glycol, galactose, lactose, mannose, fucose and folic acid-appended α-CDEs as tissue and cell-selective carriers of gene and nucleic acid drugs.

  7. The toxicity and pharmacokinetics of carbon nanotubes as an effective drug carrier.

    PubMed

    Luo, En; Song, Guodong; Li, Yunfeng; Shi, Pengwei; Hu, Jing; Lin, Yunfeng

    2013-10-01

    Carbon nanotubes have shown broad potential in biomedical applications, given their unique mechanical, optical, and chemical properties. Functionalized carbon nanotubes not only can deliver drug into specific organs but also can inherently produce heating by near-infrared laser radiation for cancer therapy. However, the toxicological and pharmacological profile of such carbon nanotube system will have to be determined prior to any clinical study undertaken. For providing a guide to develop safe drug carriers, this review discusses the functionalization, toxicity and pharmacokinetics of carbon nanotubes. Lastly, the drug delivery and thermal ablation on carbon nanotubes are proposed.

  8. Unwarranted claims of drug efficacy in pharmaceutical sales visits: are drugs approved on the basis of surrogate outcomes promoted appropriately?

    PubMed

    Habibi, Roojin; Lexchin, Joel; Mintzes, Barbara; Holbrook, Anne

    2017-06-29

    This study compares physicians' recall of the claims of benefits on cardiovascular disease and diabetes made by pharmaceutical sales representatives for drugs approved on the basis of a surrogate outcome, i.e., an off-label claim, compared with those approved on the basis of a serious morbidity or mortality (clinical) outcome. Physicians in primary care practices in Montreal, Vancouver, Sacramento and Toulouse, who saw sales representatives as part of their usual practice and served a non-referral population, were contacted in blocks of 25 from a randomized list of all physicians practising in the relevant metropolitan area. We compared how frequently physicians reported that sales reps made claims of serious morbidity or mortality (clinically meaningful) benefits for drugs approved on the basis of surrogate outcomes vs. drugs approved on the basis of clinical outcomes. There were 448 promotions for 58 unique brand name cardiovascular and diabetes drugs. Claims of clinically meaningful benefit were reported in 156 (45%) of the 347 promotions for surrogate outcome drugs, constituting unwarranted efficacy claims, i.e., off-label promotion. Claims of clinical benefit were reported in 72 of the 101 promotions (71%) for drugs approved on the basis of clinical outcomes, adjusted OR = 0.3 (95% CI 0.2, 0.6), P < 0.001. Claims of efficacy made in sales visit promotions for drugs approved only on the basis of surrogate outcomes extended beyond the regulator-approved efficacy information for the product in almost half of promotions. Unapproved claims of drug efficacy constitute a form of off-label promotion and merit greater attention from regulators. © 2017 The British Pharmacological Society.

  9. Rapid screening of pharmaceutical drugs using thermal desorption - SALDI mass spectrometry

    NASA Astrophysics Data System (ADS)

    Grechnikov, A. A.; Kubasov, A. E.; Georgieva, V. B.; Borodkov, A. S.; Nikiforov, S. M.; Simanovsky, Ya O.; Alimpiev, S. S.

    2012-12-01

    A novel approach to the rapid screening of pharmaceutical drugs by surface assisted laser desorption-ionization (SALDI) mass spectrometry with the rotating ball interface coupled with temperature programmed thermal desorption has been developed. Analytes were thermally desorbed and deposited onto the surface of amorphous silicon substrate attached to the rotating ball. The ball was rotated and the deposited analytes were analyzed using SALDI. The effectiveness of coupling SALDI mass spectrometry with thermal desorption was evaluated by the direct and rapid analysis of tablets containing lidocaine, diphenhydramine and propranolol without any sample pretreatment. The overall duration of the screening procedure was 30÷40 sec. Real urine samples were studied for drug analysis. It is shown that with simple preparation steps, urine samples can be quantitatively analyzed using the proposed technique with the detection limits in the range of 0.2÷0.5 ng/ml.

  10. Compliance revisited: pharmaceutical drug trials in the era of the contract research organization.

    PubMed

    Jonvallen, Petra

    2009-12-01

    Over the past decade, the management of clinical trials of pharmaceuticals has become a veritable industry, as evidenced by the emergence and proliferation of contract research organizations (CROs) that co-ordinate and monitor trials. This article focuses on work performed by one CRO involved in the introduction of new software, modelled on industrial production processes, into clinical trial practices. It investigates how this new management technique relates to the work performed in the clinic to ensure that trial participants comply with the protocol. Using an analytical distinction between 'classical' management work and invisible work, the article contextualizes the meaning of compliance in the clinic and suggests that the work involved in producing compliance should be taken into consideration by those concerned with validity of trials, as clinical trials are put under private industrial management. The article builds on participant observation at a Swedish university hospital and interviews the nurses, dieticians, doctors and a software engineer, all part of a team involved in pharmaceutical drug trials on a potential obesity drug.

  11. Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations

    NASA Astrophysics Data System (ADS)

    Hassan, Wafaa S.; El-Henawee, Magda M.; Gouda, Ayman A.

    2008-01-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of three histamine H1-antagonists drugs, e.g., chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and clemastine (CMT) in bulk and in their pharmaceutical formulations. The first method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with the cited drugs to form stable ion-pair complexes which extractable with methylene chloride, the orange red color complex was determined colorimetrically at λmax 470 nm. The second method is based on the formation of an ion-association complex with alizarin red S as chromogenic reagents in acidic medium (Method B), which is extracted into chloroform. The complexes have a maximum absorbance at 425 and 426 nm for (DPH or CMT) and CPX, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 5.0-40 and 5-70 μg mL -1 for molybdenum(V) thiocyanate (Method A) and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. Applications of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the procedure was confirmed by applying the standard addition technique and the results obtained in good agreement well with those obtained by the official method.

  12. Spectrophotometric determination of some histamine H1-antagonists drugs in their pharmaceutical preparations.

    PubMed

    Hassan, Wafaa S; El-Henawee, Magda M; Gouda, Ayman A

    2008-01-01

    Two rapid, simple and sensitive extractive specrophotometric methods has been developed for the determination of three histamine H1-antagonists drugs, e.g., chlorphenoxamine hydrochloride (CPX), diphenhydramine hydrochloride (DPH) and clemastine (CMT) in bulk and in their pharmaceutical formulations. The first method depend upon the reaction of molybdenum(V) thiocyanate ions (Method A) with the cited drugs to form stable ion-pair complexes which extractable with methylene chloride, the orange red color complex was determined colorimetrically at lambda(max) 470nm. The second method is based on the formation of an ion-association complex with alizarin red S as chromogenic reagents in acidic medium (Method B), which is extracted into chloroform. The complexes have a maximum absorbance at 425 and 426nm for (DPH or CMT) and CPX, respectively. Regression analysis of Beer-Lambert plots showed a good correlation in the concentration ranges of 5.0-40 and 5-70microgmL(-1) for molybdenum(V) thiocyanate (Method A) and alizarin red S (Method B), respectively. For more accurate analysis, Ringbom optimum concentration ranges were calculated. The molar absorptivity, Sandell sensitivity, detection and quantification limits were calculated. Applications of the procedure to the analysis of various pharmaceutical preparations gave reproducible and accurate results. Further, the validity of the procedure was confirmed by applying the standard addition technique and the results obtained in good agreement well with those obtained by the official method.

  13. Drug-conjugated polymers as gene carriers for synergistic therapeutic effect.

    PubMed

    Pofali, P A; Singh, B; Dandekar, P; Jain, R D; Maharjan, S; Choi, Y J; Arote, R B; Cho, C S

    2016-05-01

    The ability to safely and effectively transfer gene into cells is the fundamental goal of gene delivery. In spite of the best efforts of researchers around the world, gene therapy has limited success. This may be because of several limitations of delivering gene which is one of the greatest technical challenges in the modern medicine. To address these issues, many efforts have been made to bind drugs and genes together by polymers for co-delivery to achieve synergistic effect. Usually, binding interaction of drugs with polymers is either physical or chemical. In case of drug-polymer physical interaction, the efficiency of drugs generally decreases because of separation of drugs from polymers in vivo whenever it comes in contact with charged biofluid/s or cells. While chemical interaction of drug-polymer overcomes the aforementioned obstacle, several problems such as steric hindrance, solubility, and biodegradability hinder it to develop as gene carrier. Considering these benefits and pitfalls, the objective of this review is to discuss the possible extent of drug-conjugated polymers as safe and efficient gene delivery carriers for achieving synergistic effect to combat various genetic disorders.

  14. A Polypeptide Drug Carrier for Maternal Delivery and Prevention of Fetal Exposure

    PubMed Central

    George, Eric M.; Liu, Huiling; Robinson, Grant G.; Bidwell, Gene L.

    2014-01-01

    Background Pregnant females are largely overlooked in drug development due to concerns for fetal health. Additionally, pregnancy is often an exclusion criterion in clinical trials, so the safety of many drugs during pregnancy is unknown. Purpose The goal of this study was to evaluate Elastin-like Polypeptide (ELP), a synthetic protein derived from human elastin, for maternally sequestered drug delivery. ELP is a versatile drug carrier with a long plasma half life, low immunogenicity, and the ability to be fused to nearly any small molecule or protein-based therapeutic. Methods We determined the pharmacokinetics, biodistribution, and fetal exposure to the ELP drug carrier using quantitative fluorescence techniques in a rat pregnancy model. Results After either bolus IV administration or continuous infusion over five days, ELPs accumulated strongly in the kidneys, liver, and placenta, but importantly, little to no ELPs were detectable in the fetus. Within the placenta, ELPs were localized to the chorionic plate and broadly distributed within the labyrinth, but were excluded from the fetal portion of the chorionic villi. Conclusion These data indicate that ELP does not cross the placenta, and they suggest that this adaptable drug delivery system is a promising platform for prevention of fetal drug exposure. PMID:25148609

  15. DNA Polyplexes as Combinatory Drug Carriers of Doxorubicin and Cisplatin: An In Vitro Study

    PubMed Central

    Kang, Han Chang; Cho, Hana; Bae, You Han

    2015-01-01

    Double helix nucleic acids were used as a combination drug carrier for doxorubicin (DOX), which physically intercalates with DNA double helices, and cisplatin (CDDP), which binds to DNA without an alkylation reaction. DNA interacting with DOX, CDDP, or both was complexed with positively charged, endosomolytic polymers. Compared with the free drug, the polyplexes (100 ~ 170 nm in size) delivered more drug into the cytosol and the nucleus and demonstrated similar or superior (up to a 7-fold increase) in vitro cell-killing activity. Additionally, the gene expression activities of most of the chemical drug-loaded plasmid DNA (pDNA) polyplexes were not impaired by the physical interactions between the nucleic acid and DOX/CDDP. When a model reporter pDNA (luciferase) was employed, it expressed luciferase protein at 0.7- ~ 1.4-fold the amount expressed by the polyplex with no bound drugs (a control), which indicated the fast translocation of the intercalated or bound drugs from the “carrier DNA” to the “nuclear DNA” of target cells. The proposed concept may offer the possibility of versatile combination therapies of genetic materials and small molecule drugs that bind to nucleic acids to treat various diseases. PMID:26132975

  16. [The effect of generic price competition on drug consumption and health insurance pharmaceutical expenditures in Hungary].

    PubMed

    Répásy, Balázs; Endrei, Dóra; Zemplényi, Antal; Agoston, István; Hornyák, Lajos; Nagy, Zsolt; Csákvári, Tímea; Vajda, Réka; Boncz Imre

    2015-01-01

    The aim of our study was to analyze the Hungarian montelukast sodium drug market. We examined the effect of the appearance of generic drugs on the price and turnover of the brand-name drug, Singulair. Data derived from the nationwide pharmaceutical database of Hungarian National Health Insurance Fund Administration (2007-2014). We analized the turnover and price of the medicaments containing the active substance montelukast sodium. Accordingly our indicators were: consumer price, social insurance subsidy, patients' co-payment and days of treatment (DOT). First the generics started from a significantly lower price of 18 USD which was lower than the price of brand-name Singulair (32 USD). Then the prices of the generics started to diminish. While in 2007 the DOT was below 2 million, it increased over 10 million days by 2014. The increase of DOT was followed by the increase of health insurance subsidy until 2011. Then the amount of health insurance subsidy decreased from 10,5 million USD to 7 million USD in 2012. In 2013 and 2014 there was a further reduction, the amount of the health insurance subsidy decreased to 4,1 million USD in 2013, and in 2014 it was reduced to 2.2 million USD. Following the introduction of generic drugs, the price of the medicaments containing montelukast sodium was significantly reduced, while the days on treatment (DOT) increased. The patients' access to drugs containing montelukast sodium increased significantly. The annual health insurance subsidy was significantly reduced as well.

  17. Application of silicified microcrystalline cellulose (Prosolv) as a polymer carrier of Epilobium parviflorum Schreb. extract in oral solid drug form.

    PubMed

    Marczyński, Zbigniew; Zgoda, Marian Mikołaj; Jambor, Jerzy

    2007-01-01

    Direct tableting is simpler and more cost-effective from the point of view of good manufacturing practice (GMP) than wet granulation or dry compacting. Thus, pharmaceutical industry more and more frequently uses this particular process. Only few therapeutic substances form under compression tablets meeting current requirements. Very often additional adjuvants must be used. These substances have the ability of increasing plastic deformation and tablet mass liquidity. Microcrystalline cellulose belongs to the best adjuvant substances of the type. It has binding, disintegrating and improving liquidity properties. This study aims at investigating the usefulness of selected high-molecular substances with particular consideration of silici-fled microcrystalline cellulose (Prosolv) and croscarmellose sodium (Vivasol) as a carrier of E. parviflorum Schreb. extract in oral solid drug form in the process of direct tab-leting. The manufactured tablets were subjected to morphological tests and pharmaceutical availability tests of biologically active substances from a tablet to the acceptor fluid. The investigations were based on general and detailed principles of Polish Pharmacopoeia VI. The obtained results allow to state that the applied high-molecular adjuvant substances proved to be useful in adequate proportions in the production of tablets from dry extract from Epilobium parviflo-rum Schreb. Generally, a significant shortening of the tablets disintegration time was obtained as compared to earlier produced tablets with the method of initial granulation. The tablets formed from E. parviflorum Schreb. extract with silicified microcrystalline cellulose (Prosolv SMCC 50) and croscarmellose sodium can be included into preparations of short dissolution time of the therapeutic substance.

  18. Stability-indicating HPTLC determination of ambroxol hydrochloride in bulk drug and pharmaceutical dosage form.

    PubMed

    Jain, P S

    2010-01-01

    A simple, selective, precise, and stability-indicating high-performance thin-layer chromatographic (HPTLC) method for the analysis of ambroxol hydrochloride both as a bulk drug and in formulations was developed and validated. The method employed HPTLC aluminium plates precoated with silica gel 60F-254 as the stationary phase. The solvent system consisted of methanol-triethylamine (4:6 v/v). The system was found to give a compact spot for ambroxol hydrochloride (R(f) value of 0.53 +/- 0.02). Densitometric analysis of ambroxol hydrochloride was carried out in the absorbance mode at 254 nm. The linear regression analysis data for the calibration plots showed good linear relationship with r(2) = 0.9966 +/- 0.0013 with respect to peak area in the concentration range 100-1000 ng/spot. The mean value +/- standard deviation of slope and intercept were 164.85 +/- 0.72 and 1168.3 +/- 8.26 with respect to peak area. The method was validated for precision, recovery, and robustness. The limits of detection and quantitation were 10 and 30 ng/spot, respectively. Ambroxol hydrochloride was subjected to oxidation and thermal degradation. The drug undergoes degradation under oxidation and heat conditions. This indicates that the drug is susceptible to oxidation and heat. Statistical analysis proves that the method is repeatable, selective, and accurate for the estimation of said drug. Stability indicating of new chemical entities is an important part for the drug development of ambroxol hydrochloride and for its estimation in plasma and other biological fluids; the novel Statistical analysis proves that the method is repeatable and selective for the analysis of ambroxol hydrochloride as bulk drug and in pharmaceutical formulations. The proposed developed HPTLC method can be applied for identification and quantitative determination of ambroxol hydrochloride in bulk drug and dosage forms. This work is to determine the purity of the drug available from the various sources by detecting

  19. Advances in structural design of lipid-based nanoparticle carriers for delivery of macromolecular drugs, phytochemicals and anti-tumor agents.

    PubMed

    Angelova, Angelina; Garamus, Vasil M; Angelov, Borislav; Tian, Zhenfen; Li, Yawen; Zou, Aihua

    2017-04-18

    The present work highlights recent achievements in development of nanostructured dispersions and biocolloids for drug delivery applications. We emphasize the key role of biological small-angle X-ray scattering (BioSAXS) investigations for the nanomedicine design. A focus is given on controlled encapsulation of small molecular weight phytochemical drugs in lipid-based nanocarriers as well as on encapsulation of macromolecular siRNA, plasmid DNA, peptide and protein pharmaceuticals in nanostructured nanoparticles that may provide efficient intracellular delivery and triggered drug release. Selected examples of utilisation of the BioSAXS method for characterization of various types of liquid crystalline nanoorganizations (liposome, spongosome, cubosome, hexosome, and nanostructured lipid carriers) are discussed in view of the successful encapsulation and protection of phytochemicals and therapeutic biomolecules in the hydrophobic or the hydrophilic compartments of the nanocarriers. We conclude that the structural design of the nanoparticulate carriers is of crucial importance for the therapeutic outcome and the triggered drug release from biocolloids. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Development of membrane electrodes for selective determination of some antiepileptic drugs in pharmaceuticals, plasma and urine.

    PubMed

    Gupta, V K; Singh, A K; Gupta, Barkha

    2007-11-01

    Newly developed, simple, low-cost and sensitive ion-selective electrodes have been proposed for determination of some antiepileptic drugs such as lamotrigine, felbamate, and primidone in their pharmaceutical preparations as well as in biological fluids. The electrodes are based on poly(vinyl chloride) membranes doped with drug-tetraphenyl borate (TPB) or drug-phosphotungstic acid (PT) ion-pair complexes as molecular recognition materials. The novel electrodes displayed rapid Nernstian responses with detection limits of approximately 10(-7) M. Calibration graphs were linear over the ranges 5.2 x 10(-7)-1.0 x 10(-3), 1.5 x 10(-6)-1.0 x 10(-3), and 2.6 x 10(-7)-1.0 x 10(-3 )M for drug-TPB and 5.8 x 10(-7)-1.0 x 10(-3), 1.8 x 10(-7)-1.0 x 10(-3), and 6.6 x 10(-7)-1.0 x 10(-3) M for drug-PT electrodes, respectively, with slopes ranging from 52.3 to 62.3 mV/decade. The membranes developed have potential stability for up to 1 month and proved to be highly selective for the drugs investigated over other ions and excipients. The results show that the selectivity of the ion-selective electrodes is influenced significantly by the plasticizer. The proposed electrodes were successfully applied in the determination of these drugs in pharmaceutical preparations in four batches of different expiry dates. Statistical Student's t test and F test showed insignificant systematic error between the ion-selective electrode methods developed and a standard method. Comparison of the results obtained using the proposed electrodes with those found using a reference method showed that the ion-selective electrode technique is sensitive, reliable, and can be used with very good accuracy and high percentage recovery without pretreatment procedures of the samples to minimize interfering matrix effects.

  1. Drug-selective electrode for ketamine determination in pharmaceutical preparations and electrochemical study of drug with BSA.

    PubMed

    Alizadeh, Naader; Mehdipour, Rasoul

    2002-10-15

    Ion-selective membrane electrode to the drug ketamine hydrochloride has been constructed using a modified PVC membrane which has ionic end-groups as ion-exchanger sites and which was cast using plasticized with ortho-nitrophenyloctyl ether (o-NPOE) as plastisizer. This drug electrode show excellent Nernstian responses (59 mV per decade) in the concentration range 1 x 10(-5)-1 x 10(-2) M with a detection limit of 5 x 10(-6) M. Response time was about 10 s for ketamine concentrations between 1 x 10(-5) and 1 x 10(-2) M. The response is not affected by pH between 4 and 8.5. Selectivity coefficients against various organic and inorganic cations were evaluated. The electrode was applied for determination of ketamine hydrochloride in pharmaceutical preparations using direct potentiometry. The drug electrode has also been used to study the interaction of bovine serum albumin (BSA) with ketamine in buffer solution (phosphate, pH 7). The saturated quantities of ketamine binding were 114, 32 and 25 mol/mol in 0.01, 0.02 and 0.1% of protein, respectively. The Hill equations were applied to obtain co-operative drug bindings to BSA at 27 degrees C.

  2. DOTAM derivatives as active cartilage-targeting drug carriers for the treatment of osteoarthritis.

    PubMed

    Hu, Hai-Yu; Lim, Ngee-Han; Ding-Pfennigdorff, Danping; Saas, Joachim; Wendt, K Ulrich; Ritzeler, Olaf; Nagase, Hideaki; Plettenburg, Oliver; Schultz, Carsten; Nazare, Marc

    2015-03-18

    Targeted drug-delivery methods are crucial for effective treatment of degenerative joint diseases such as osteoarthritis (OA). Toward this goal, we developed a small multivalent structure as a model drug for the attenuation of cartilage degradation. The DOTAM (1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid amide)-based model structure is equipped with the cathepsin D protease inhibitor pepstatin A, a fluorophore, and peptide moieties targeting collagen II. In vivo injection of these soluble probes into the knee joints of mice resulted in 7-day-long local retention, while the drug carrier equipped with a scrambled peptide sequence was washed away within 6-8 h. The model drug conjugate successfully reduced the cathepsin D protease activity as measured by release of GAG peptide. Therefore, these conjugates represent a promising first drug conjugate for the targeted treatment of degenerative joint diseases.

  3. A mixed DFT-MD methodology for the in silico development of drug releasing macrocycles. Calix and thia-calix[N]arenes as carriers for Bosutinib and Sorafenib.

    PubMed

    Galindo-Murillo, Rodrigo; Aguilar-Suárez, Luis Enrique; Barroso-Flores, Joaquín

    2016-04-15

    Interaction energies between a family of 36 calix[n]arenes, their corresponding thia- analogues, and two commercially available second generation tyrosine kinase III inhibitors-Bosutinib and Sorafenib-were calculated through DFT methods at the B97D/6-31G(d,p) level of theory, based on Natural Population Analysis, for the in silico development of suitable drug carriers based on the aforementioned macrocycles which can increase their bioavailability and in turn their pharmaceutical efficiency. Molecular Dynamics simulations (production runs: +500 ns) using the General Amber Force Field were also carried out in order to assess the releasing process of these drugs in an explicit aqueous environment. In total, 144 host-guest complexes are examined. According to our results, five-membered -SO3H and i-Pr functionalized-calixarenes are the best candidates for Sorafenib-carriers while six-membered ones -SO3H and C2H4NH2 functionalized- are the lead candidates for Bosutinib-carriers. © 2015 Wiley Periodicals, Inc.

  4. An Atypical Mitochondrial Carrier That Mediates Drug Action in Trypanosoma brucei

    PubMed Central

    de Macêdo, Juan P.; Schumann Burkard, Gabriela; Niemann, Moritz; Barrett, Michael P.; Vial, Henri; Mäser, Pascal; Roditi, Isabel; Schneider, André; Bütikofer, Peter

    2015-01-01

    Elucidating the mechanism of action of trypanocidal compounds is an important step in the development of more efficient drugs against Trypanosoma brucei. In a screening approach using an RNAi library in T. brucei bloodstream forms, we identified a member of the mitochondrial carrier family, TbMCP14, as a prime candidate mediating the action of a group of anti-parasitic choline analogs. Depletion of TbMCP14 by inducible RNAi in both bloodstream and procyclic forms increased resistance of parasites towards the compounds by 7-fold and 3-fold, respectively, compared to uninduced cells. In addition, down-regulation of TbMCP14 protected bloodstream form mitochondria from a drug-induced decrease in mitochondrial membrane potential. Conversely, over-expression of the carrier in procyclic forms increased parasite susceptibility more than 13-fold. Metabolomic analyses of parasites over-expressing TbMCP14 showed increased levels of the proline metabolite, pyrroline-5-carboxylate, suggesting a possible involvement of TbMCP14 in energy production. The generation of TbMCP14 knock-out parasites showed that the carrier is not essential for survival of T. brucei bloodstream forms, but reduced parasite proliferation under standard culture conditions. In contrast, depletion of TbMCP14 in procyclic forms resulted in growth arrest, followed by parasite death. The time point at which parasite proliferation stopped was dependent on the major energy source, i.e. glucose versus proline, in the culture medium. Together with our findings that proline-dependent ATP production in crude mitochondria from TbMCP14-depleted trypanosomes was reduced compared to control mitochondria, the study demonstrates that TbMCP14 is involved in energy production in T. brucei. Since TbMCP14 belongs to a trypanosomatid-specific clade of mitochondrial carrier family proteins showing very poor similarity to mitochondrial carriers of mammals, it may represent an interesting target for drug action or targeting. PMID

  5. Controlled release formulations of risperidone antipsychotic drug in novel aliphatic polyester carriers: Data analysis and modelling.

    PubMed

    Siafaka, Panoraia I; Barmpalexis, Panagiotis; Lazaridou, Maria; Papageorgiou, George Z; Koutris, Efthimios; Karavas, Evangelos; Kostoglou, Margaritis; Bikiaris, Dimitrios N

    2015-08-01

    In the present study a series of biodegradable and biocompatible poly(ε-caprolactone)/poly(propylene glutarate) (PCL/PPGlu) polymer blends were investigated as controlled release carriers of Risperidone drug (RISP), appropriate for transdermal drug delivery. The PCL/PPGlu carriers were prepared in different weight ratios. Miscibility studies of blends were evaluated through differential scanning calorimetry (DSC) and X-ray diffractometry (XRD). Hydrolysis studies were performed at 37°C using a phosphate buffered saline solution. The prepared blends have been used for the preparation of RISP patches via solvent evaporation method, containing 5, 10 and 15wt% RISP. These formulations were characterized using FT-IR spectroscopy, DSC and WAXD in order to evaluate interactions taking place between polymer matrix and drug, as well as the dispersion and the physical state of the drug inside the polymer matrix. In vitro drug release studies were performed using as dissolution medium phosphate buffered saline simulating body fluids. It was found that in all cases controlled release formulations were obtained, while the RISP release varies due to the properties of the used polymer blend and the different levels of drug loading. Artificial Neural Networks (ANNs) were used for dissolution behaviour modelling showing increased correlation efficacy compared to Multi-Linear-Regression (MLR).

  6. Porous metal-organic-framework nanoscale carriers as a potential platform for drug delivery and imaging

    NASA Astrophysics Data System (ADS)

    Horcajada, Patricia; Chalati, Tamim; Serre, Christian; Gillet, Brigitte; Sebrie, Catherine; Baati, Tarek; Eubank, Jarrod F.; Heurtaux, Daniela; Clayette, Pascal; Kreuz, Christine; Chang, Jong-San; Hwang, Young Kyu; Marsaud, Veronique; Bories, Phuong-Nhi; Cynober, Luc; Gil, Sophie; Férey, Gérard; Couvreur, Patrick; Gref, Ruxandra

    2010-02-01

    In the domain of health, one important challenge is the efficient delivery of drugs in the body using non-toxic nanocarriers. Most of the existing carrier materials show poor drug loading (usually less than 5wt% of the transported drug versus the carrier material) and/or rapid release of the proportion of the drug that is simply adsorbed (or anchored) at the external surface of the nanocarrier. In this context, porous hybrid solids, with the ability to tune their structures and porosities for better drug interactions and high loadings, are well suited to serve as nanocarriers for delivery and imaging applications. Here we show that specific non-toxic porous iron(III)-based metal-organic frameworks with engineered cores and surfaces, as well as imaging properties, function as superior nanocarriers for efficient controlled delivery of challenging antitumoural and retroviral drugs (that is, busulfan, azidothymidine triphosphate, doxorubicin or cidofovir) against cancer and AIDS. In addition to their high loadings, they also potentially associate therapeutics and diagnostics, thus opening the way for theranostics, or personalized patient treatments.

  7. Red blood cells and polyelectrolyte multilayer capsules: natural carriers versus polymer-based drug delivery vehicles.

    PubMed

    Kolesnikova, Tatiana A; Skirtach, Andre G; Möhwald, Helmuth

    2013-01-01

    Red blood cells (RBCs) and lipid-based carriers on the one hand and polymeric capsules on the other hand represent two of the most widely used carriers in drug delivery. Each class of these carriers has its own set of properties, specificity and advantages. Thorough comparative studies of such systems are reported here for the first time. In this review, RBCs are described in comparison with synthetic polymeric drug delivery vehicles using polyelectrolyte multilayer capsules as an example. Lipid-based composition of the shell in the former case is particularly attractive due to their inherent biocompatibility and flexibility of the carriers. On the other hand, synthetic approaches to fabrication of polyelectrolyte multilayer capsules permit manipulation of the permeability of their shell as well as tuning their composition, mechanical properties, release methods and targeting. In conclusion, properties of RBCs and polyelectrolyte multilayer capsules are reported here highlighting similarities and differences in their preparation and applications. In addition, their advantages and disadvantages are discussed.

  8. Nanohybrid structure analysis and biomolecule release behavior of polysaccharide-CDHA drug carriers

    NASA Astrophysics Data System (ADS)

    Huang, Li-Ying; Liu, Ting-Yu; Liu, Tse-Ying; Mevold, Andreas; Hardiansyah, Andri; Liao, Hung-Chou; Lin, Chin-Ching; Yang, Ming-Chien

    2013-10-01

    Nanoscaled polymer composites were prepared from polysaccharide chitosan (CS) and Ca-deficient hydroxyapatite (CDHA). CS-CDHA nanocomposites were synthesized by in situ precipitation at pH 9, and the CS-CDHA carriers were then fabricated by ionic cross-linking methods using tripolyphosphate and chemical cross-linking methods by glutaraldehyde and genipin. Certain biomolecules such as vitamin B12, cytochrome c, and bovine serum albumin were loaded into the CS-CDHA carriers, and their release behaviors were investigated. Furthermore, these CS-CDHA carriers were examined by transmission electron microscopy, electron spectroscopy for chemical analysis, and X-ray diffraction. The release behavior of the biomolecules was controlled by the CS/CDHA ratios and cross-linked agents. By increasing the concentration of CS and the concentration of the cross-linking agents, cross-linking within carriers increases, and the release rate of the biomolecules is decreased. Moreover, the release rate of the biomolecules from the CS-CDHA carriers at pH 4 was higher than that at pH 10, displaying a pH-sensitive behavior. Therefore, these CS-CDHA hydrogel beads may be useful for intelligent drug release and accelerate bone reconstruction.

  9. Regulating drug information in Europe: a pyrrhic victory for pharmaceutical industry critics?

    PubMed

    Mulinari, Shai

    2013-06-01

    Informed by recent sociological debates on pharmaceuticalisation, this article examines the evolution of the current EU legal proposal on prescription drug information to patients, as well as the surrounding controversies. In 2008 the European Commission proposed the relaxation of the existing rules governing drug information provision to patients by the pharmaceutical industry. Critics of the industry's influence over health policy and markets, including consumer organisations, industry-independent patient organisations and health professionals, rejected the Commission's proposal, claiming that the industry cannot be considered a reliable source of patient information due to inherent financial conflicts of interest. Since these critics were at least partially successful in rallying opinion against the Commission proposal, they functioned as countervailing forces to promotion-driven pharmaceuticalisation. Even so, as a watered-down version of the proposal moved through the European Parliament it was further modified to ultimately resemble the Swedish system that was held up as a high-quality example of industry-based information provision. Yet this article contends that the Swedish system displays evidence of corporate bias. Significantly, basing EU policy on a drug information system not resistant to corporate bias risks creating practices that violate the legally mandated mission of EU drug regulation, which is to 'promote and protect public health'.

  10. Physicians' decision process for drug prescription and the impact of pharmaceutical marketing mix instruments.

    PubMed

    Campo, Katia; De Staebel, Odette; Gijsbrechts, Els; van Waterschoot, Walter

    2005-01-01

    This paper provides an in-depth, qualitative analysis of the physicians' decision process for drug prescription. Drugs in the considered therapeutic classes are mainly prescribed by specialists, treating patients with obligatory medical insurance, for a prolonged period of time. The research approach is specifically designed to capture the full complexity and sensitive nature of the physician's choice behavior, which appears to be more hybrid and less rational in nature than is often assumed in quantitative, model-based analyses of prescription behavior. Several interesting findings emerge from the analysis: (i) non-compensatory decision rules seem to dominate the decision process, (ii) consideration sets are typically small and change-resistant, (iii) drug cost is not a major issue for most physicians, (iv) detailing remains one of the most powerful pharmaceutical marketing instruments and is highly appreciated as a valuable and quick source of information, and (v) certain types of non-medical marketing incentives (such as free conference participation) may in some situations also influence drug choices.

  11. Current opinion: safety evaluation of drug metabolites in development of pharmaceuticals.

    PubMed

    Naito, Shinsaku; Furuta, Shigeru; Yoshida, Takemi; Kitada, Mitsukazu; Fueki, Osamu; Unno, Takashi; Ohno, Yasuo; Onodera, Hiroshi; Kawamura, Nobuyuki; Kurokawa, Misao; Sagami, Fumio; Shinoda, Kazutoshi; Nakazawa, Takahiro; Yamazaki, Tsuneyoshi

    2007-10-01

    Safety assessment of drug metabolites in the development of pharmaceuticals was discussed in January 2007 at the kick-off meeting of a "Drug Evaluation Forum", with reference to the views of clinicians and other academic representatives. Safety evaluation of metabolites cannot readily be based on a single theoretical framework, and basically a case-by-case approach is called for. These evaluations should be performed precisely and an accurate profile secured taking into account adverse reactions that are unpredictable from the parent compound administered in clinical studies and any signs or symptoms that may be associated with the metabolites. In addition, elimination of scientifically meaningless metabolite safety assessment studies is essential for prompt supply of high-quality drugs to the medical frontline. Preparation of an outline concept paper would be useful for achievement of shared understanding of issues of this type. Collective viewpoints obtained in this fashion are also relevant to the discussion on the need for guidance, and given a degree of flexibility may also be helpful for drug development and, in turn, society at large.

  12. An analysis of the attrition of drug candidates from four major pharmaceutical companies.

    PubMed

    Waring, Michael J; Arrowsmith, John; Leach, Andrew R; Leeson, Paul D; Mandrell, Sam; Owen, Robert M; Pairaudeau, Garry; Pennie, William D; Pickett, Stephen D; Wang, Jibo; Wallace, Owen; Weir, Alex

    2015-07-01

    The pharmaceutical industry remains under huge pressure to address the high attrition rates in drug development. Attempts to reduce the number of efficacy- and safety-related failures by analysing possible links to the physicochemical properties of small-molecule drug candidates have been inconclusive because of the limited size of data sets from individual companies. Here, we describe the compilation and analysis of combined data on the attrition of drug candidates from AstraZeneca, Eli Lilly and Company, GlaxoSmithKline and Pfizer. The analysis reaffirms that control of physicochemical properties during compound optimization is beneficial in identifying compounds of candidate drug quality and indicates for the first time a link between the physicochemical properties of compounds and clinical failure due to safety issues. The results also suggest that further control of physicochemical properties is unlikely to have a significant effect on attrition rates and that additional work is required to address safety-related failures. Further cross-company collaborations will be crucial to future progress in this area.

  13. DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic & Chemometric Approaches for Controlled Drug Delivery Systems

    PubMed Central

    Arafa, Mona G.; Ayoub, Bassam M.

    2017-01-01

    Niosomes entrapping pregabalin (PG) were prepared using span 60 and cholesterol in different molar ratios by hydration method, the remaining PG from the hydrating solution was separated from vesicles by freeze centrifugation. Optimization of nano-based carrier of pregabalin (PG) was achieved. Quality by Design strategy was successfully employed to obtain PG-loaded niosomes with the desired properties. The optimal particle size, drug release and entrapment efficiency were attained by Minitab® program using design of experiment (DOE) that predicted the best parameters by investigating the combined effect of different factors simultaneously. Pareto chart was used in the screening step to exclude the insignificant variables while response surface methodology (RSM) was used in the optimization step to study the significant factors. Best formula was selected to prepare topical hydrogels loaded with niosomal PG using HPMC and Carbopol 934. It was verified, by means of mechanical and rheological tests, that addition of the vesicles to the gel matrix affected significantly gel network. In vitro release and ex vivo permeation experiments were carried out. Delivery of PG molecules followed a Higuchi, non Fickian diffusion. The present work will be of interest for pharmaceutical industry as a controlled transdermal alternative to the conventional oral route. PMID:28134262

  14. DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic & Chemometric Approaches for Controlled Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

    Arafa, Mona G.; Ayoub, Bassam M.

    2017-01-01

    Niosomes entrapping pregabalin (PG) were prepared using span 60 and cholesterol in different molar ratios by hydration method, the remaining PG from the hydrating solution was separated from vesicles by freeze centrifugation. Optimization of nano-based carrier of pregabalin (PG) was achieved. Quality by Design strategy was successfully employed to obtain PG-loaded niosomes with the desired properties. The optimal particle size, drug release and entrapment efficiency were attained by Minitab® program using design of experiment (DOE) that predicted the best parameters by investigating the combined effect of different factors simultaneously. Pareto chart was used in the screening step to exclude the insignificant variables while response surface methodology (RSM) was used in the optimization step to study the significant factors. Best formula was selected to prepare topical hydrogels loaded with niosomal PG using HPMC and Carbopol 934. It was verified, by means of mechanical and rheological tests, that addition of the vesicles to the gel matrix affected significantly gel network. In vitro release and ex vivo permeation experiments were carried out. Delivery of PG molecules followed a Higuchi, non Fickian diffusion. The present work will be of interest for pharmaceutical industry as a controlled transdermal alternative to the conventional oral route.

  15. DOE Optimization of Nano-based Carrier of Pregabalin as Hydrogel: New Therapeutic &Chemometric Approaches for Controlled Drug Delivery Systems.

    PubMed

    Arafa, Mona G; Ayoub, Bassam M

    2017-01-30

    Niosomes entrapping pregabalin (PG) were prepared using span 60 and cholesterol in different molar ratios by hydration method, the remaining PG from the hydrating solution was separated from vesicles by freeze centrifugation. Optimization of nano-based carrier of pregabalin (PG) was achieved. Quality by Design strategy was successfully employed to obtain PG-loaded niosomes with the desired properties. The optimal particle size, drug release and entrapment efficiency were attained by Minitab(®) program using design of experiment (DOE) that predicted the best parameters by investigating the combined effect of different factors simultaneously. Pareto chart was used in the screening step to exclude the insignificant variables while response surface methodology (RSM) was used in the optimization step to study the significant factors. Best formula was selected to prepare topical hydrogels loaded with niosomal PG using HPMC and Carbopol 934. It was verified, by means of mechanical and rheological tests, that addition of the vesicles to the gel matrix affected significantly gel network. In vitro release and ex vivo permeation experiments were carried out. Delivery of PG molecules followed a Higuchi, non Fickian diffusion. The present work will be of interest for pharmaceutical industry as a controlled transdermal alternative to the conventional oral route.

  16. Measurement of the Density of Polymeric Nanoparticulate Drug Carriers by Isopycnic Centrifugation

    NASA Astrophysics Data System (ADS)

    Vauthier, C.; Schmidt, C.; Couvreur, P.

    1999-09-01

    The development of polymer nanoparticles as drug carriers requires numerous steps including several in vitro evaluations in cell cultures and biocompatibility. To perform these experiments, it is crucial to express the particle concentration as the number of particles per volume unit or as the particle surface area. Calculation of these suspension characteristics can be perfomed knowing the size and the density of the nanoparticles as well as the polymer concentration. While particle size and polymer concentration are parameters being determined routinely, this study proposes to measure the density of the nanoparticle drug carriers by isopycnic centrifugation using linear sucrose gradients. The method was found to be very reproducible and it presents the advantage of being applied on a small sample of nanoparticles.

  17. [Expectations for the education of graduate school of pharmaceutical sciences from the viewpoint of discovery and development of new drugs].

    PubMed

    Ohmori, Kenji

    2011-01-01

    For the purpose of the development of new drugs for incurable diseases, many students enter graduate school of pharmaceutical sciences every year. At first, I expect education to let it develop more and spread without forgetting this will. Recently, withdrawals from Japan of the research institutes of the foreign-affiliated pharmaceutical companies have occurred successively. It is pointed out that there is it for the study about the biomedical research that is the next step of fundamental researches having been weak. I expect the immediate construction of the cluster, which consists of pharmaceutical companies and graduate schools of pharmaceutical sciences. Time of ten several years and a cost of one hundred billion yen are necessary for the research and development of new drug. The success probability is low, besides. Many trials are accomplished to raise the success probability. The one is introduction of the project system. The best members are gathered from the fields such as medicinal chemistry, molecular biology, biochemistry, pharmacology, pharmacokinetics, pharmaceutics and toxicological sciences, etc. The project system is a system enforcing go or stop by own judgment, an authority and the responsibility of the purpose are given. It is necessary for the project leader to have great knowledge and the abilities to hold lively discussion. It is a researcher from graduate school of pharmaceutical sciences that is the most suited to be as a project leader. I expect to upbring education from the time when a leader is young.

  18. Oscillations in the kinetics of ethylcyanoacrylate nanoparticles intended as skin drug carriers

    NASA Astrophysics Data System (ADS)

    Díaz-Torres, R.; Castaño, V. M.; Ganem-Quintanar, A.; Quintanar-Guerrero, D.; Rodríguez-Romo, S.

    2005-11-01

    Ethylcyanoacrylate nanoparticles (40-100 nm) were synthesized to act as potential skin drug carriers. A novel multiscale non-linear model, based on an oscillatory mechanism, which includes polymerization, de-polymerization, re-polymerization and cluster dynamics, is shown to fit the kinetics experimental data and it is used to estimate the amount of potentially histotoxic by-products (i.e. residual monomers or very low molecular weight oligomers).

  19. A pH-responsive asymmetric lipid vesicle as drug carrier.

    PubMed

    Zhang, Xunan; Zong, Wei; Hu, Ying; Luo, Nan; Cheng, Wenlong; Han, Xiaojun

    2016-11-01

    In order to increase the loading efficiency of drug carriers, here we demonstrated a microfluidic method to fabricate an asymmetric vesicle, which contains trichloro(1H,1H,2H,2H-perfluoroocty-l)silane (TPS) inner leaflet and lipid outer leaflet. The asymmetric vesicle was characterised by fluorescence microscopy and Fourier transform infra-red spectrum. In vitro cytotoxicity of the vesicles carrying 5-fluorouacil (5-FU) has also been studied.

  20. Apoferritin Modified Magnetic Particles as Doxorubicin Carriers for Anticancer Drug Delivery

    PubMed Central

    Blazkova, Iva; Nguyen, Hoai Viet; Dostalova, Simona; Kopel, Pavel; Stanisavljevic, Maja; Vaculovicova, Marketa; Stiborova, Marie; Eckschlager, Tomas; Kizek, Rene; Adam, Vojtech

    2013-01-01

    Magnetic particle mediated transport in combination with nanomaterial based drug carrier has a great potential for targeted cancer therapy. In this study, doxorubicin encapsulation into the apoferritin and its conjugation with magnetic particles was investigated by capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). The quantification of encapsulated doxorubicin was performed by fluorescence spectroscopy and compared to CE-LIF. Moreover, the significant enhancement of the doxorubicin signal was observed by addition of methanol into the sample solution. PMID:23807501

  1. Acute toxicities of pharmaceuticals toward green algae. mode of action, biopharmaceutical drug disposition classification system and quantile regression models.

    PubMed

    Villain, Jonathan; Minguez, Laetitia; Halm-Lemeille, Marie-Pierre; Durrieu, Gilles; Bureau, Ronan

    2016-02-01

    The acute toxicities of 36 pharmaceuticals towards green algae were estimated from a set of quantile regression models representing the first global quantitative structure-activity relationships. The selection of these pharmaceuticals was based on their predicted environmental concentrations. An agreement between the estimated values and the observed acute toxicity values was found for several families of pharmaceuticals, in particular, for antidepressants. A recent classification (BDDCS) of drugs based on ADME properties (Absorption, Distribution, Metabolism and Excretion) was clearly correlated with the acute ecotoxicities towards algae. Over-estimation of toxicity from our QSAR models was observed for classes 2, 3 and 4 whereas our model results were in agreement for the class 1 pharmaceuticals. Clarithromycin, a class 3 antibiotic characterized by weak metabolism and high solubility, was the most toxic to algae (molecular stability and presence in surface water). Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Thermoresponsive copolymer/SiO2 nanoparticles with dual functions of thermally controlled drug release and simultaneous carrier decomposition.

    PubMed

    Li, Aihua; Zhang, Jizhen; Xu, Yuanhong; Liu, Jingquan; Feng, Shengyu

    2014-09-26

    The preparation of thermoresponsive drug carriers with a self-destruction property is presented. These drug carriers were fabricated by incorporation of drug molecules and thermoresponsive copolymer, poly(N-isopropylacrylamide-co-acrylamide), into silica nanoparticles in a one-pot preparation process. The enhanced drug release was primarily attributed to faster molecule diffusion resulting from the particle decomposition triggered by phase transformation of the copolymer upon the temperature change. The decomposition of the drug carriers into small fragments should benefit their fast excretion from the body. In addition, the resulting drug-loaded nanoparticles showed faster drug release in an acidic environment (pH 5) than in a neutral one. The controlled drug release of methylene blue and doxorubicin hydrochloride and the self-decomposition of the drug carriers were successfully characterized by using TEM, UV/Vis spectroscopy, and confocal microscopy. Together with the nontoxicity and excellent biocompatibility of the copolymer/SiO2 composite, the features of controlled drug release and simultaneous carrier self-destruction provided a promising opportunity for designing various novel drug-delivery systems.

  3. Competitive pricing within pharmaceutical classes: evidence on "follow-on" drugs in Germany 1993-2008.

    PubMed

    Mueller, Michael T; Frenzel, Alexander

    2015-01-01

    Competition from "follow-on" drugs has been a highly controversial issue. Manufacturers launching new molecules in existing drug classes have often been criticized for inflating health systems' expenses, but it has been argued that such drugs increase therapeutic options. Economic theory suggests that follow-on drugs induce price competition. We contribute to this discussion by addressing the topic of pricing at market entry and price development in the German market. We measure determinants of price strategies of follow-on drugs using regression analyses, considering all new molecules launched in the German market from 1993 to 2008. Prices of products are standardized on defined daily dosages controlling for sales volumes based on data from the IMS Health DPM database and for the therapeutic quality of a new product using ratings by Fricke/Klaus as a proxy for innovation. We identify prices correlating with therapeutic value at market entry. While the first two molecules engage in quality competition, price discounts below the market price can be observed from the third entrant on. Price discounts are even more distinct in development races with several drugs entering the market within 2 years and in classes with a low degree of therapeutic differentiation. Prices remain relatively constant over time. This study contributes to assessments of competition in pharmaceutical markets focusing on price strategies of new market entrants. After an initial phase of market building, further follow-on products induce price competition. Largely unchanged prices after 4 years may be interpreted as quality competition and can be attributed to prices in Germany being anchor points for international price referencing.

  4. Comparison of mesoporous silicon and non-ordered mesoporous silica materials as drug carriers for itraconazole.

    PubMed

    Kinnari, Päivi; Mäkilä, Ermei; Heikkilä, Teemu; Salonen, Jarno; Hirvonen, Jouni; Santos, Hélder A

    2011-07-29

    Mesoporous materials have an ability to enhance dissolution properties of poorly soluble drugs. In this study, different mesoporous silicon (thermally oxidized and thermally carbonized) and non-ordered mesoporous silica (Syloid AL-1 and 244) microparticles were compared as drug carriers for a hydrophobic drug, itraconazole (ITZ). Different surface chemistries pore volumes, surface areas, and particle sizes were selected to evaluate the structural effect of the particles on the drug loading degree and on the dissolution behavior of the drug at pH 1.2. The results showed that the loaded ITZ was apparently in amorphous form, and that the loading process did not change the chemical structure/morphology of the particles' surface. Incorporation of ITZ in both microparticles enhanced the solubility and dissolution rate of the drug, compared to the pure crystalline drug. Importantly, the physicochemical properties of the particles and the loading procedure were shown to have an effect on the drug loading efficiency and drug release kinetics. After storage under stressed conditions (3 months at 40 °C and 70% RH), the loaded silica gel particles showed practically similar dissolution profiles as before the storage. This was not the case with the loaded mesoporous silicon particles due to the almost complete chemical degradation of ITZ after storage.

  5. A Comprehensive Review on Cyclodextrin-Based Carriers for Delivery of Chemotherapeutic Cytotoxic Anticancer Drugs

    PubMed Central

    Gidwani, Bina; Vyas, Amber

    2015-01-01

    Most of the cytotoxic chemotherapeutic agents have poor aqueous solubility. These molecules are associated with poor physicochemical and biopharmaceutical properties, which makes the formulation difficult. An important approach in this regard is the use of combination of cyclodextrin and nanotechnology in delivery system. This paper provides an overview of limitations associated with anticancer drugs, their complexation with cyclodextrins, loading/encapsulating the complexed drugs into carriers, and various approaches used for the delivery. The present review article aims to assess the utility of cyclodextrin-based carriers like liposomes, niosomes, nanoparticles, micelles, millirods, and siRNA for delivery of antineoplastic agents. These systems based on cyclodextrin complexation and nanotechnology will camouflage the undesirable properties of drug and lead to synergistic or additive effect. Cyclodextrin-based nanotechnology seems to provide better therapeutic effect and sustain long life of healthy and recovered cells. Still, considerable study on delivery system and administration routes of cyclodextrin-based carriers is necessary with respect to their pharmacokinetics and toxicology to substantiate their safety and efficiency. In future, it would be possible to resolve the conventional and current issues associated with the development and commercialization of antineoplastic agents. PMID:26582104

  6. Peptides in Cancer Nanomedicine: Drug Carriers, Targeting Ligands and Protease Substrates

    PubMed Central

    Zhang, Xiao-Xiang; Eden, Henry S.; Chen, Xiaoyuan

    2011-01-01

    Peptides are attracting increasing attention as therapeutic agents, as the technologies for peptide development and manufacture continue to mature. Concurrently, with booming researches in nanotechnology for biomedical applications, peptides have been studied as an important class of components in nanomedicine, and they have been used either alone or in combination with nanomaterials of every reported composition. Peptides possess many advantages, such as smallness, ease of synthesis and modification, and good biocompatibility. Their functions in cancer nanomedicine, discussed in this review, include serving as drug carriers; as targeting ligands; and as protease-responsive substrates for drug delivery. PMID:22056916

  7. Modified local diatomite as potential functional drug carrier--A model study for diclofenac sodium.

    PubMed

    Janićijević, Jelena; Krajišnik, Danina; Čalija, Bojan; Vasiljević, Bojana Nedić; Dobričić, Vladimir; Daković, Aleksandra; Antonijević, Milan D; Milić, Jela

    2015-12-30

    Diatomite makes a promising candidate for a drug carrier because of its high porosity, large surface area, modifiable surface chemistry and biocompatibility. Herein, refined diatomite from Kolubara coal basin, which complied with the pharmacopoeial requirements for heavy metals content and microbiological quality, was used as a starting material. Inorganic modification of the starting material was performed through a simple, one-step procedure. Significant increase in adsorbent loading with diclofenac sodium (DS) was achieved after the modification process (∼373mg/g) which enabled the preparation of comprimates containing therapeutic dose of the adsorbed drug. Adsorption of DS onto modified diatomite resulted in the alteration of the drug's XRD pattern and FTIR spectrum. In vitro drug release studies in phosphate buffer pH 7.5 demonstrated prolonged DS release over 8h from comprimates containing DS adsorbed on modified diatomite (up to 37% after 8h) and those containing physical mixture of the same composition (up to 45% after 8h). The results of in vivo toxicity testing on mice pointed on potential safety of both unmodified (starting) and modified diatomite. All these findings favor the application of diatomite as a potential functional drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

  8. Pharmaceutical residues in the drinking water supply: modeling residue concentrations in surface waters of drugs prescribed in the United States.

    PubMed

    Guerrero-Preston, Rafael; Brandt-Rauf, Paul

    2008-09-01

    Pharmaceutical residues and other organic wastewater contaminants (OWC) have been shown to survive conventional water-treatment processes and persist in potable water supplies. To estimate the geographical distribution of the Predicted Environmental Concentration (PEC) of selected drugs prescribed by office based physicians in the United States (US), after non-metabolized residues have been excreted and processed in wastewater treatment plants. The geographical distribution of the PEC in surface waters of pharmaceutical residues was calculated, in four regions of the US. Prescription drug data was obtained from the National Ambulatory Medical Care Survey (NAMCS). The PEC of three drugs prescribed by office based physicians in the US between 1998 and 2000 was compared to the concentrations of these pharmaceuticals found in a surface water characterization project conducted by the United States Geological Survey between 1999 and 2000. There were 803,185,420 medications prescribed by office-based physicians in the US between 1998 and 2000. Relief of pain, hormonal, cardiovascular and antimicrobial medications followed very similar prescription patterns, both in terms of quantity and geographical distribution. Together these four types of medications account for more than half of the medications prescribed between 1998 and 2000. The concentration of pharmaceutical residues found in the drinking water supply was not significantly correlated to the PEC of pharmaceuticals prescribed by office-based physicians. The geographical distribution of medications prescribed by office based physicians in the US underlines the need to implement effective public health strategies.

  9. Preparation of hollow magnetite microspheres and their applications as drugs carriers

    PubMed Central

    2012-01-01

    Hollow magnetite microspheres have been synthesized by a simple process through a template-free hydrothermal approach. Hollow microspheres were surface modified by coating with a silica nanolayer. Pristine and modified hollow microparticles were characterized by field-emission electron microscopy, transmission electron microscopy, X-ray diffraction, X-ray photoelectron spectroscopy, FT-IR and Raman spectroscopy, and VSM magnetometry. The potential application of the modified hollow magnetite microspheres as a drug carrier was evaluated by using Rhodamine B and methotrexate as model drugs. The loading and release kinetics of both molecules showed a clear pH and temperature dependent profile. Graphical abstract Hollow magnetite microspheres have been synthesized. Load-release experiments with Rhodamine-B as a model drug and with Methotrexate (chemotherapy drug used in treating certain types of cancer) demonstrated the potential applications of these nanostructures in biomedical applications. PMID:22490731

  10. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    PubMed Central

    2014-01-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders. PMID:25114637

  11. Bovine serum albumin nanoparticles as controlled release carrier for local drug delivery to the inner ear

    NASA Astrophysics Data System (ADS)

    Yu, Zhan; Yu, Min; Zhang, Zhibao; Hong, Ge; Xiong, Qingqing

    2014-07-01

    Nanoparticles have attracted increasing attention for local drug delivery to the inner ear recently. Bovine serum albumin (BSA) nanoparticles were prepared by desolvation method followed by glutaraldehyde fixation or heat denaturation. The nanoparticles were spherical in shape with an average diameter of 492 nm. The heat-denatured nanoparticles had good cytocompatibility. The nanoparticles could adhere on and penetrate through the round window membrane of guinea pigs. The nanoparticles were analyzed as drug carriers to investigate the loading capacity and release behaviors. Rhodamine B was used as a model drug in this paper. Rhodamine B-loaded nanoparticles showed a controlled release profile and could be deposited on the osseous spiral lamina. We considered that the bovine serum albumin nanoparticles may have potential applications in the field of local drug delivery in the treatment of inner ear disorders.

  12. Non-polymeric nano-carriers in HIV/AIDS drug delivery and targeting.

    PubMed

    Gupta, Umesh; Jain, Narendra K

    2010-03-18

    Development of an effective drug delivery approach for the treatment of HIV/AIDS is a global challenge. The conventional drug delivery approaches including Highly Active Anti Retroviral Therapy (HAART) have increased the life span of the HIV/AIDS patient. However, the eradication of HIV is still not possible with these approaches due to some limitations. Emergence of polymeric and non-polymeric nanotechnological approaches can be opportunistic in this direction. Polymeric carriers like, dendrimers and nanoparticles have been reported for the targeting of anti HIV drugs. The synthetic pathways as well polymeric framework create some hurdles in their successful formulation development as well as in the possible drug delivery approaches. In the present article, we have discussed the general physiological aspects of the infection along with the relevance of non-polymeric nanocarriers like liposomes, solid lipid nanoparticles (SLN), ethosomes, etc. in the treatment of this disastrous disease.

  13. 3D printing in pharmaceutics: A new tool for designing customized drug delivery systems.

    PubMed

    Goole, Jonathan; Amighi, Karim

    2016-02-29

    Three-dimensional printing includes a wide variety of manufacturing techniques, which are all based on digitally-controlled depositing of materials (layer-by-layer) to create freeform geometries. Therefore, three-dimensional printing processes are commonly associated with freeform fabrication techniques. For years, these methods were extensively used in the field of biomanufacturing (especially for bone and tissue engineering) to produce sophisticated and tailor-made scaffolds from patient scans. This paper aims to review the processes that can be used in pharmaceutics, including the parameters to be controlled. In practice, it not straightforward for a formulator to be aware of the various technical advances made in this field, which is gaining more and more interest. Thus, a particular aim of this review is to give an overview on the pragmatic tools, which can be used for designing customized drug delivery systems using 3D printing. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Fenton-like reaction: a possible way to efficiently remove illicit drugs and pharmaceuticals from wastewater.

    PubMed

    Mackuľak, Tomáš; Mosný, Michal; Grabic, Roman; Golovko, Oksana; Koba, Olga; Birošová, Lucia

    2015-03-01

    We analyzed 13 psychoactive pharmaceuticals, illicit drugs and their metabolites in wastewater treatment plant influent and effluent and the possibility of their degradation by biological and chemical processes. Tramadol (413-853 ng/L) and methamphetamine (460-682 ng/L) were the most concentrated compounds in the wastewater in winter and summer, respectively. A significant decrease in the concentration of tramadol in wastewater was measured during the summer. The lowest efficiency was observed for tramadol, venlafaxine, citalopram and oxazepam (∼ 10%) and the highest efficiency was observed for amphetamine and THC-COOH (∼ 80%). The efficiency of compound degradation via the Fenton reaction, a modified Fenton reaction and different degradation (by algae, wood-rotting fungi and enzymes at influent versus effluent) was determined. The Fenton reaction and its modification were efficient at eliminating these substances in comparison with the tested biological processes.

  15. The Impact of Chemical Probes in Drug Discovery: A Pharmaceutical Industry Perspective.

    PubMed

    Garbaccio, Robert M; Parmee, Emma R

    2016-01-21

    Chemical probes represent an important component of both academic and pharmaceutical drug discovery research. As a complement to prior reviews that have defined this scientific field, we aim to provide an industry perspective on the value of having high-quality chemical probes throughout the course of preclinical research. By studying examples from the internal Merck pipeline, we recognize that these probes require significant collaborative investment to realize their potential impact in clarifying the tractability and translation of a given therapeutic target. This perspective concludes with recommendations for chemical probe discovery aimed toward maximizing their potential to identify targets that result in the successful delivery of novel therapeutics. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Caveat medicus: consequences of federal investigations of marketing activities of pharmaceutical suppliers of prostate cancer drugs.

    PubMed

    McKoy, June M; Lyons, E Allison; Obadina, Eniola; Carson, Kenneth; Pickard, A Simon; Schellhammer, Paul; McLeod, David; Boyd, Cynthia E; McWilliams, Norene; Sartor, Oliver; Schumock, Glen T; McCaffery, Kathryn; Bennett, Charles L

    2005-12-01

    In the course of recent health care fraud investigations against TAP Pharmaceuticals (Lake Forest, IL) and AstraZeneca International (London, United Kingdom), each pled guilty to one violation of the Prescription Drug Marketing Act, settled claims related to alleged violations of the False Claims Act without admitting guilt, and paid fines, settlements for liabilities, and reimbursements of dollar 850 million and dollar 355 million, respectively. In a unique aspect of these cases, federal investigators brought criminal charges against 14 TAP employees and investigated the billing practices of several urologists. These investigations resulted in guilty pleas from both urologists and industry employees relative to the Prescription Drug Marketing Act or the False Claims Act and probationary sentences with payments of fines and restitution to the government for urologists who cooperated with federal investigations. One uncooperative urologist was found guilty of violating the Federal False Claims Act and sentenced to 6 months of home arrest, excluded from Medicare for 5 years, required to provide 600 hours of free medical care to indigent patients and patients covered by Medicare or Medicaid, and paid fines and restitution to the government. The cases against TAP and AstraZeneca have been followed by federal and state investigations of allegedly illegal marketing practices of other pharmaceutical firms and have resulted in negotiated settlements of dollar 3.8 billion and dollar 71.5 million, respectively. Believing that an Average Wholesale Price-based reimbursement system was an important driving factor for these marketing activities, Medicare has shifted to an Average Sales Price-based reimbursement system. This is expected to greatly impact the practice of outpatient oncology nationwide.

  17. Gradient HPLC-DAD determination of two pharmaceutical mixtures containing the antihistaminic drug ebastine.

    PubMed

    Haggag, Rim S; Belal, Tarek S

    2012-01-01

    This work describes the development, validation and application of a simple and reliable high-performance liquid chromatography-diode array detection (HPLC-DAD) procedure for the analysis of two pharmaceutical mixtures. The first mixture contains the antihistaminic drug ebastine (EBS) and the famous sympathomimetic drug pseudoephedrine hydrochloride (PSD), and the second mixture is composed of EBS and another sympathomimetic agent, phenylephrine hydrochloride (PHR). Effective chromatographic separation of EBS, PSD and PHR was achieved using a Zorbax SB-C8 (4.6 × 250 mm, 5 μm) column with gradient elution of the mobile phase composed of 0.05M phosphoric acid and acetonitrile. The gradient elution started with 20% (by volume) acetonitrile, ramped up linearly to 90% in 5 min, then kept constant until the end of the run. The mobile phase was pumped at a flow rate of 1 mL/min. The multiple wavelength detector was set at 254 (for EBS and PSD) and 274 nm (for PHR) and quantification of the analytes was based on measuring their peak areas. The retention times for PHR, PSD and EBS were approximately 2.5, 2.9 and 7.1 min, respectively. The reliability and analytical performance of the proposed HPLC procedure were statistically validated with respect to linearity, ranges, precision, accuracy, selectivity, robustness and detection and quantification limits. Calibration curves were linear in the ranges 5-100, 100-1,000 and 10-200 µg/mL for EBS, PSD and PHR, respectively, with correlation coefficients > 0.9996. The validated HPLC method was applied to the analysis of the two pharmaceutical mixtures in laboratory-made tablets in which the analytes were successfully quantified with good recovery values and no interfering peaks were encountered from the inactive ingredients. Finally, the proposed method made use of DAD as a tool for peak identity and purity confirmation.

  18. Slurry photocatalytic membrane reactor technology for removal of pharmaceutical compounds from wastewater: Towards cytostatic drug elimination.

    PubMed

    Janssens, Raphael; Mandal, Mrinal Kanti; Dubey, Kashyap Kumar; Luis, Patricia

    2017-12-01

    The potential of photocatalytic membrane reactors (PMR) to degrade cytostatic drugs is presented in this work as an emerging technology for wastewater treatment. Cytostatic drugs are pharmaceutical compounds (PhCs) commonly used in cancer treatment. Such compounds and their metabolites, as well as their degraded by-products have genotoxic and mutagenic effects. A major challenge of cytostatic removal stands in the fact that most drugs are delivered to ambulant patients leading to diluted concentration in the municipal waste. Therefore safe strategies should be developed in order to collect and degrade the micro-pollutants using appropriate treatment technologies. Degradation of cytostatic compounds can be achieved with different conventional processes such as chemical oxidation, photolysis or photocatalysis but the treatment performances obtained are lower than the ones observed with slurry PMRs. Therefore the reasons why slurry PMRs may be considered as the next generation technology will be discussed in this work together with the limitations related to the mechanical abrasion of polymeric and ceramic membranes, catalyst suspension and interferences with the water matrix. Furthermore key recommendations are presented in order to develop a renewable energy powered water treatment based on long lifetime materials. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Analysis of some antifungal drugs by spectrophotometric and spectrofluorimetric methods in different pharmaceutical dosage forms.

    PubMed

    Khashaba, P Y; El-Shabouri, S R; Emara, K M; Mohamed, A M

    2000-03-01

    Simple spectrophotometric and spectrofluorimetric methods are suggested for the determination of antifungal drugs; clotrimazole, econazole nitrate, ketoconazole, miconazole and tolnaftate. Spectrophotometric one depends on the interaction between imidazole antifungal drugs as n-electron donor with the pi acceptor 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in methanol or with p-chloranilic acid (p-CA) in acetonitrile. The produced chromogens obey Beer's law at lambda(max) 460, and 520 nm in the concentration range 22.5-200 and 7.9-280 microg ml(-1) for DDQ, and p-CA, respectively. Spectrofluorimetric method is based on the measurement of the native fluorescence of ketoconazole at 375 nm with excitation at 288 nm and or the induced fluorescence after alkaline hydrolysis of tolnaftate with 5 M NaOH solution at 420 nm with excitation at 344 nm. Fluorescence intensity versus concentration is linear for ketoconazole at 49.7-800 ng ml(-1) while for tolnaftate, it is in the range of 20.4-400 ng ml(-1). The proposed methods were applied successfully for the determination of all the studied drugs in their pharmaceutical formulations.

  20. Magnetic nanoparticles-loaded PLA/PEG microspheres as drug carriers.

    PubMed

    Frounchi, Masoud; Shamshiri, Soodeh

    2015-05-01

    Surface-modified magnetite (Fe3 O4 ) nanoparticles with an average size of 22 nm were prepared. The nanoparticles had a saturation magnetization of 50.7 emu g(-1) . Then magnetite and drug-loaded microspheres of poly (lactic acid)/poly (ethylene glycol) were prepared at various compositions. The microspheres were spherical in shape and had smooth surface. The diameter size of the microspheres ranged between about 0.2 and 4 μm. Doxorubicin hydrochloride for cancer treatment was the drug that loaded into the microspheres. The prepared microspheres were characterized by FTIR, XRD, VSM, SEM and drug-release measurements. It was found that the drug cumulative release percentage was proportional to (time) (n) where 0.61 < n < 0.75 depending on PEG and Fe3 O4 contents. The drug release was controlled through a combination of diffusion and PLA hydrolysis and obeyed a non-fickian mechanism. The drug release was facilitated by presence of poly (ethylene glycol) as PLA plasticizer and was higher under applied external magnetic field. The obtained magnetic microspheres could be used as drug carriers for targeted drug delivery purposes.

  1. Stacking-cyclodextrin-microchip electrokinetic chromatographic determination of gabapentinoid drugs in pharmaceutical and biological matrices.

    PubMed

    Zeid, Abdallah M; Kaji, Noritada; Nasr, Jenny Jeehan M; Belal, Fathalla F; Baba, Yoshinobu; Walash, Mohamed I

    2017-06-23

    A facile, rapid, and highly sensitive microchip-based electrokinetic chromatographic method was developed for the simultaneous analysis of two gabapentinoid drugs, gabapentin (GPN) and pregabalin (PGN). Both drugs were first reacted with 4-fluoro-7-nitro-2,1,3-benzoxadiazole (NBD-F) via nucleophilic substitution reactions to yield highly fluorescent products with λex/em 470/540nm. Analyses of both fluorescently labeled compounds were achieved within 200s in a poly(methyl methacrylate) (PMMA) microchip with a 30mm separation channel. Optimum separation was achieved using a borate buffer (pH 9.0) solution containing methylcellulose and β-cyclodextrin (β-CD) as buffer additives. Methylcellulose acted as a dynamic coating to prevent adsorption of the studied compounds on the inner surfaces of the microchannels, while β-CD acted as a pseudo-stationary phase to improve the separation efficiency between the labeled drugs with high resolution (Rs>7). The fluorescence intensities of the labeled drugs were measured using a light emitting diode-induced fluorescence detector at 540nm after excitation at 470nm. The sensitivity of the method was enhanced 14- and 17-fold for PGN and GPN, respectively by field-amplified stacking relative to traditional pinched injection so that it could quantify 10ngmL(-1) for both analytes, with a detection limit lower than 3ngmL(-1). The developed method was efficiently applied to analyze PGN and GPN in their pharmaceutical dosage forms and in biological fluids. The extraction recoveries of the studied drugs from plasma and urine samples were more than 89% with%RSD values lower than 6.2. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. [Do pharmaceutical waste and drug residue pose a risk to public health?].

    PubMed

    Haguenoer, Jean-Marie

    2010-01-01

    Recently, awareness has developed of the environmental consequences of drug waste and disposal. These residues are identified as coming from either diffuse sources, the most significant of which is via the discharge of these residues in urine and feces, and thus the sewage system and water contains these drug remnants and their metabolites, or from point sources, sometimes with very high levels of concentration in waste from chemical and pharmaceutical industries, health care settings, but also from intensive livestock farming and aquaculture. Depending on their physical chemistry properties, these substances are more or less naturally biodegradable and easily treated in sewage purification plants. The effectiveness of these treatment processes is highly random and unpredictable, but is overall around 60%, nevertheless with variations of 2-99% according to the molecules. The silt from these treatment plants, sometimes very rich in lipophilic substances is on occasion reused for agricultural application as fertilizer, paving the way for a possible contamination of crops. Furthermore, the use of veterinary drugs in animals can lead to soil contamination either directly or through manure and slurry. The contamination can equally reach and affect surface water, groundwater and sometimes the water intended for human consumption. The National academy of Pharmacy has established some general recommendations on the proper use of drugs, environmental monitoring and surveillance, risk assessment for humans and the environment, prevention and the need for prevention. Several categories of drugs are more worrying: cancer treatments, antibiotics as well as transfers of anti-bio-resistance, and hormonal derivatives which has been previously demonstrated to contribute, along with other molecules, to detrimental effects on endocrines.

  3. [Advances in the use of instrumental measurement of colour in the development, production and quality control of drugs, medicinal preparations and pharmaceutical auxiliary substances I ].

    PubMed

    Subert, Jan; Cižmárik, Jozef

    2013-04-01

    Colour is one of the important indices of the quality of drugs, medicinal preparations and pharmaceutical auxiliary substances. The paper summarizes the development and use of instrumental measurement of colour in pharmacy in recent ten years focusing on the drugs of synthetic origin and pharmaceutical auxiliary substances including their control.

  4. Biosafe nanoscale pharmaceutical adjuvant materials.

    PubMed

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C; Zhang, Xin; Liang, Xing-Jie

    2014-09-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes.

  5. Biosafe Nanoscale Pharmaceutical Adjuvant Materials

    PubMed Central

    Jin, Shubin; Li, Shengliang; Wang, Chongxi; Liu, Juan; Yang, Xiaolong; Wang, Paul C.; Zhang, Xin; Liang, Xing-Jie

    2014-01-01

    Thanks to developments in the field of nanotechnology over the past decades, more and more biosafe nanoscale materials have become available for use as pharmaceutical adjuvants in medical research. Nanomaterials possess unique properties which could be employed to develop drug carriers with longer circulation time, higher loading capacity, better stability in physiological conditions, controlled drug release, and targeted drug delivery. In this review article, we will review recent progress in the application of representative organic, inorganic and hybrid biosafe nanoscale materials in pharmaceutical research, especially focusing on nanomaterial-based novel drug delivery systems. In addition, we briefly discuss the advantages and notable functions that make these nanomaterials suitable for the design of new medicines; the biosafety of each material discussed in this article is also highlighted to provide a comprehensive understanding of their adjuvant attributes. PMID:25429253

  6. A novel drug carrier based on functional modified nanofiber cellulose and the control release behavior

    NASA Astrophysics Data System (ADS)

    Shi, Xiangning; Zheng, Yudong; Zhang, Wei; Zhang, Zeyu; Peng, Yunling

    2013-08-01

    This study developed a novel drug carrier based on functional modified bacterial cellulose(BC) which was conjugated with Ibuprofen(IBU) by esterification. BC-Ibuprofen as the macro- molecular prodrugs and drug carrier used to improve the short half-life of the drug, and was able to control release through the hydrolysis of ester bond between the hydroxyl groups of BC with Ibuprofen under different condition. Fourier transform infrared analysis revealed that Ibuprofen had been successfully grafted onto the bacterial cellulose (BC). Thermal and morphological characterization indicated the formation of the BC-Ibuprofen system incompletely reacted maintained the bulk structure of the pristine material such as crystallinity, 3-dimentional network and so on. The drug release behaviours were affected by the ester bond hydrolysis as well as the microstructure characteristics of the modified nanofiber. The release of BC-IBU showed an apparent pH-dependent, fast in alkaline and acid solution but slow relatively in neutral. Such pH-responsiveness, in addition to its morphological characteristics, in this paper suggested a great potential of BC-IBU as a more effective, safe, and stable prodrug candidate.

  7. Safety and toxicity concerns of orally delivered nanoparticles as drug carriers.

    PubMed

    Araújo, Francisca; Shrestha, Neha; Granja, Pedro L; Hirvonen, Jouni; Santos, Hélder A; Sarmento, Bruno

    2015-03-01

    The popularity of nanotechnology is increasing and revolutionizing extensively the drug delivery field. Nanoparticles, as carriers for oral delivery of drugs, have been claimed as the perfect candidates to overcome the poor bioavailability of most of the drugs by improving their solubility and/or permeability across biological barriers. However, this is still a promise to be fulfilled. In this review, several nanosystems used as oral drug carriers are described along with their toxicological profiles. A number of nanoparticles based on different types of materials such as polymers, lipids, silica, silicon, carbon and metals are reviewed. Both in vitro and in vivo-based toxicological studies are discussed in this paper. Toxicological concerns have been raised in the past few years regarding the safety of the developed nanosystems. Assuming that most of the materials used are biocompatible and biodegradable, the toxicity caused by them when formulated into nanoparticles is usually neglected by the scientific community, existing only a few number of studies that approach the toxicity of the nanosystems. This is particularly important, because the materials that composed of the nanoparticles as well as their features such as size, charge and surface properties, will influence their pharmacokinetics after oral administration.

  8. In vivo study of liposomes as drug carriers to oral mucosa using EPR oximetry.

    PubMed

    Erjavec, V; Pavlica, Z; Sentjurc, M; Petelin, M

    2006-01-03

    The purpose of this study was to select the best types of liposomes for use as drug carriers for topical treatment of oral mucosal lesions. Electron paramagnetic resonance (EPR) oximetry, using the paramagnetic probe lithium phthalocyanine, was used in vivo to measure the effects of a hyperemic drug, benzyl nicotinate (BN) which was incorporated into liposomes of varying size and composition. The liposomes were made from either hydrogenated or non-hydrogenated soy lecithin and mixed with polymethyl methacrylate ointment for application. EPR oximetry was used to measure the partial pressure of oxygen (pO2) in the oral mucosa before and after application of liposomes. It was found that the most pronounced changes of pO2 in oral mucosa and also the longest action of the drug occurred after the topical application of BN in multi-lamellar liposomes made from hydrogenated soy lecithin (p<0.0001). When these liposomes were applied to oral mucosa over 3 successive days it was found that pO2 increased the most on the first day, the effect gradually decreased following application on the second and third days. The duration of the resulting hyperemia was the longest on the second day (p<0.01). Among the examined carriers, multi-lamellar liposomes made from hydrogenated soy lecithin appear to be the most appropriate for local drug delivery to oral mucosa.

  9. Cellulose nanocrystals from passion fruit peels waste as antibiotic drug carrier.

    PubMed

    Wijaya, Christian J; Saputra, Stephanie N; Soetaredjo, Felycia E; Putro, Jindrayani N; Lin, Chun X; Kurniawan, Alfin; Ju, Yi-Hsu; Ismadji, Suryadi

    2017-11-01

    Due to its excellent chemical and physical properties, cellulose nanocrystals (CNC) possess many potential advanced functional applications. In this study, CNC was extracted from natural product by hydrolyzing cellulose segment of passionfruit peels using sulphuric acid solution. The capability of CNC as drug carrier was tested toward tetracycline antibiotic. The drug loading processes were carried out at various pH (3-7) with the optimum uptake of tetracycline achieved at pH 3. The in vitro release of tetracycline drug was carried out in phosphoric buffer medium with two different pH conditions at 37°C. The highest release of tetracycline (82.21%) was achieved at pH 7.2, while the lowest one (25.1%) was achieved at pH 2.1, where the release pattern follow a second order kinetic model. This study highlight the potential application of CNC derived from natural resources as drug carrier without harmful chemical excipients that comply with health safety, biocompatible, biodegradable. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Polydopamine-coated liposomes as pH-sensitive anticancer drug carriers.

    PubMed

    Zong, Wei; Hu, Ying; Su, Yingchun; Luo, Nan; Zhang, Xunan; Li, Qingchuan; Han, Xiaojun

    2016-05-01

    Stimuli-responsive drug carriers are considered to play important roles in chemotherapy. We fabricated pH-sensitive polydopamine-protected liposomes (liposome@PDA) drug delivery systems, which were characterised with microscope, scanning electron microscope (SEM), UV-vis spectrometer and Fourier transform infrared (FTIR) technieques. The typical chemotherapeutic agent, 5-fluorouracil (5-FU), was loaded into liposome@PDA capsules. The maximum release percentages of 5-FU are 3.2%, 29.5%, 52.7%, 76.7% in the solution with pH 7.42, 6.87, 4.11 and 3.16, respectively. The in vitro cell cytotoxity experiments were carried out using 5-FU-loaded capsules at pH 6.87 solution, which simulate the true pH around cancerous cells. At 1.5 μM concentration, the free 5-FU, 5-FU-loaded liposome capsules and 5-FU-loaded capsules showed the cell viability of 50.56%, 22.66% and 21.63%, respectively. It confirms that drug-loaded capsules performed better than free drug. The results demonstrate the great potential of liposome@PDA capsules as carriers in biomedical applications.

  11. A Laboratory Experiment in Pharmaceutical Analysis: Determination of Drugs of Abuse in Human Urine by Thin-Layer Chromatography.

    ERIC Educational Resources Information Center

    Bailey, Leonard C.

    1979-01-01

    An experiment is described that was developed for a course in Inorganic and Analytical Pharmaceutical Chemistry at Rutgers University to provide pharmacy students with practical experience in the thin-layer chromatography used for the analysis of urine to monitor patient compliance with drug abuse treatment programs. (JMD)

  12. A Laboratory Experiment in Pharmaceutical Analysis: Determination of Drugs of Abuse in Human Urine by Thin-Layer Chromatography.

    ERIC Educational Resources Information Center

    Bailey, Leonard C.

    1979-01-01

    An experiment is described that was developed for a course in Inorganic and Analytical Pharmaceutical Chemistry at Rutgers University to provide pharmacy students with practical experience in the thin-layer chromatography used for the analysis of urine to monitor patient compliance with drug abuse treatment programs. (JMD)

  13. Folic acid-grafted bovine serum albumin decorated graphene oxide: An efficient drug carrier for targeted cancer therapy.

    PubMed

    Ma, Naxin; Liu, Jing; He, Wenxiu; Li, Zhonghao; Luan, Yuxia; Song, Yunmei; Garg, Sanjay

    2017-03-15

    Targeting drug carrier systems based on graphene oxide (GO) are of great interest, since it can selectively deliver anticancer drugs to tumor cells, and enhance therapeutic activities with minimized side effects. However, direct grafting target molecules on GO usually results in aggregation of physiological fluid, limiting its biomedical applications. Here, we propose a new strategy to construct targeting GO drug carrier using folic acid grafted bovine serum albumin (FA-BSA) as both the stabilizer and targeting agent. FA-BSA decorated graphene oxide-based nanocomposite (FA-BSA/GO) was fabricated by the physical adsorption of FA-BSA on GO, which was developed as a targeting drug delivery carrier. FA-BSA/GO as the drug carrier was associated with anticancer drug doxorubicin (DOX) through π-π and hydrogen-bond interactions, resulting in high drug loading (up to 437.43μgDOX/mgFA-BSA/GO). FA-BSA/GO/DOX systems demonstrated pH responsive and sustained drug release. The hemolysis ratio of FA-BSA/GO was less than 5%, demonstrating its safety as drug carrier for intravenous injection. Moreover, in vitro cell cytotoxicity and cellular uptake analysis suggested that the constructed FA-BSA/GO/DOX nanohybrids could significantly enhance the anticancer activity. The present work has confirmed the potential for fabrication of highly stable and dispersible GO-based targeting delivery systems for efficient cancer therapy.

  14. Resuscitation and rescue of the pharmaceutical detail: a prescriber-drug representative collaboration.

    PubMed

    Kale, Scott A; Barkin, Robert L

    2009-01-01

    The traditional pharmaceutical detail must be revised to meet current prescriber presentation and interaction needs. Best practice and evidence-based clinical strategies demands, an expanded database describing prescribable pharmaceutical therapies. We present a format for the structure of a functional database for pharmaceuticals and a means by which the data can be introduced, updated and instituted.

  15. Oncology drug clinical development and approval in Japan: the role of the pharmaceuticals and medical devices evaluation center (PMDEC).

    PubMed

    Fujiwara, Yasuhiro; Kobayashi, Ken

    2002-05-01

    In 1996 the Japanese Diet amended the Pharmaceutical Affairs Law (PAL) and its related laws based on 1996 report of the ad-hoc Committee for Drug Safety Ensuring Measures. Between 1996 and 2000, the drug approval system in Japan underwent a series of radical reforms. We describe in this paper the current system for drug approval, discuss the post-approval reexamination and reevaluation system, conditions under which development and review may be expedited, and mechanisms for approval of off-label usage. Finally, we discuss the impact of the International Conference on Harmonization (ICH) agreement on drug development and review in Japan.

  16. Nanostructured lipid carriers: An emerging platform for improving oral bioavailability of lipophilic drugs

    PubMed Central

    Khan, Saba; Baboota, Sanjula; Ali, Javed; Khan, Sana; Narang, Ramandeep Singh; Narang, Jasjeet Kaur

    2015-01-01

    Nowadays exploration of novel lipid-based formulations is akin to a magnet for researchers worldwide for improving the in vivo performance of highly lipophilic drugs. Over the last few years, new compositions of lipids have been developed, and the probable bioavailability enhancement has been investigated. We reviewed the most recent data dealing with backlogs of conventional lipid-based formulations such as physical instability, limited drug loading capacities, drug expulsion during storage along with all the possible hindrances resulting in poor absorption of highly lipophilic drugs such as P-glycoprotein efflux, extensive metabolism by cytochrome P450 etc. In tandem with these aspects, an exclusive formulation approach has been discussed in detail in this paper. Therefore, this review focuses on resolving the concerned ambiguity with successful oral administration of highly lipophilic drugs through designing novel lipidic formulations (nanostructured lipid carriers [NLC]) that constitute a blend of solid and liquid lipids. The article highlights the potential role of such formulation in normalizing the in vivo fate of poorly soluble drugs. Finally, the present manuscript discusses the dominance of NLC over other lipid-based formulations and provides a perspective of how they defeat and overcome the barriers that lead to the poor bioavailability of hydrophobic drugs. PMID:26682188

  17. The anti-bacterial poly(caprolactone)-poly(quaternary ammonium salt) as drug delivery carriers.

    PubMed

    Leng, Mengtian; Hu, Shaodong; Lu, Aijing; Cai, Mengtan; Luo, Xianglin

    2016-04-01

    Anti-bacterial materials play significant role in biomedical field. Researches and applications of new anti-bacterial materials are necessary. Novel linear and star-shaped copolymers of poly(caprolactone)-poly(quaternary ammonium salt) (PCL-PJDMA) were synthesized by a combination of ring-opening polymerization and atom transfer radical polymerization. The structures of the copolymers were confirmed by nuclear magnetic resonance ((1)H-NMR) and Fourier transform infrared spectroscopy. The copolymers self-assembled into ball-shaped micelles with low critical micelle concentration (10(-4) ∼ 10(-3) mg/ml). An anti-bacterial drug, triclosan, was chosen as a model drug to investigate the potential application of the copolymers in drug-controlled release. The anti-bacterial experiments against Escherichia coli indicated that all the copolymer micelles had anti-bacterial ability and drug-loaded star-shaped PCL-PJDMA micelles were the best. The slow release of the drug from the drug-loaded micelles prolonged anti-bacterial effect. Therefore, PCL-PJDMA themselves have not only anti-bacterial ability but also the copolymer micelles can be used as carriers for anti-bacterial drugs.

  18. A porphyrin-based metal–organic framework as a pH-responsive drug carrier

    SciTech Connect

    Lin, Wenxin; Hu, Quan; Jiang, Ke; Yang, Yanyu; Yang, Yu; Cui, Yuanjing; Qian, Guodong

    2016-05-15

    A low cytotoxic porphyrin-based metal–organic framework (MOF) PCN-221, which exhibited high PC12 cell viability via 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyl tetrazolium (MTT) assay, was selected as an oral drug carrier. Methotrexate (MTX) was chosen as the model drug molecule which was absorbed into inner pores and channels of MOFs by diffusion. PCN-221 showed high drug loading and sustained release behavior under physiological environment without “burst effect”. The controlled pH-responsive release of drugs by PCN-221 revealed its promising application in oral drug delivery. - Graphical abstract: The porous crystals PCN-221 with pore openings (MOF) PCN-221 was prepared exhibiting low cytotoxicity. PCN-221 showed high drug Methotrexate loading and controlled pH-responsive release of Methotrexate. - Highlights: • A porphyrin-based metal–organic framework (MOF) PCN-221 was prepared showing low cytotoxicity. • PCN-221 showed high drug Methotrexate loading. • PCN-221 showed controlled pH-responsive release of Methotrexate.

  19. Novel self-assembly graft copolymers as carriers for anti-inflammatory drug delivery.

    PubMed

    Bury, Katarzyna; Neugebauer, Dorota

    2014-01-02

    Indomethacin (IMC) and quercetin (QUE) as typical models of anti-inflammatory drugs were loaded into the micelles of new amphiphilic graft copolymers, comprising caprolactone 2-(methacryloyloxy)ethyl ester (CLMA) units in the main chain and poly(meth)acrylic acid side chains (PAA/PMAA), which were studied as the carriers of drugs. The macromolecules were self-assembled by solvent evaporation or dialysis. The critical micelle concentration (CMC) ranged from 0.015 to 0.199 mg/ml. The copolymer composition, grafting degree and length of side chains, nature and content of hydrophobic/hydrophilic part, were investigated as the main parameters responsible for the properties of nanoparticles including their stability, core-drug interactions, improved drug solubility, and in consequence the efficiency of drug-loading and drug release profiles. The hydrodynamic diameters of particles measured by dynamic light scattering (DLS) ranged from 50 to 275 nm, and increased after loading with drug. In vitro release experiments performed at various pH (5.0 and 7.4) indicated faster release behavior from nanoparticles in acidic conditions (55-95% vs. 25-45% within 75 h).

  20. A novel polyethylene glycol mediated lipid nanoemulsion as drug delivery carrier for paclitaxel.

    PubMed

    Jing, Xiaolong; Deng, Li; Gao, Baoan; Xiao, Lin; Zhang, Yingying; Ke, Xingfa; Lian, Jianhao; Zhao, Qiang; Ma, Lulu; Yao, Jianzhong; Chen, Jianming

    2014-02-01

    A novel polyethylene glycol 400 (PEG400) mediated lipid nanoemulsion as drug-delivery carrier for paclitaxel (PTX) was successfully developed. The formulation comprised a PEG400 solution of the drug (25mg/mL) that would be mixed with commercially 20% lipid emulsion to form PTX-loaded nanoemulsion (1mg/mL) prior to use. This two-vial formulation of PTX-loaded lipid nanoemulsion (TPLE) could significantly reduce extraction of reticuloendothelial system (RES) organs and increase tumor uptake, and exhibited more potent antitumor efficacy on bearing A2780 or Bcap-37 tumor nude mice compared to conventional PTX-loaded lipid nanoemulsion (CPLE). TPLE did not cause haematolysis and intravenous irritation response yet, and showed the same cytotoxicity against HeLa cells as Taxol®, and its LD50 was 2.7-fold higher than that of Taxol®, suggesting its good safety and druggability. In addition, TPLE displayed distinctly faster release of PTX, a greater proportion of PTX in phospholipids layer and a smaller share in oil phase than CPLE. From the Clinical Editor: This study demonstrates the feasibility and potential advantage of a novel PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in clinical application for the cancer therapy. This team of investigators convincingly demonstrates the feasibility and potential advantage of a PEG400-mediated two-vial formulation of lipid nanoemulsion as drug carrier for PTX in cancer therapy, documenting superior safety and faster release of PTX compared to commercially available formulations. © 2014.

  1. Conception, preparation and properties of functional carrier particles for pulmonary drug delivery.

    PubMed

    Odziomek, Marcin; Sosnowski, Tomasz R; Gradoń, Leon

    2012-08-20

    The effectiveness of aerosol therapy is significantly reduced by the mucus layer covering the airways of the tracheobronchial tree. According to the present concept, drug particles are delivered to the lung together with the functional carrier particle that facilitates both the drug transport into the lungs and the penetration of deposited particles through the mucus. The approach of manufacturing multi-component powders with mucoactive compounds and anti-asthmatic medicines (DSCG) bound together in a single particle is additionally considered. Powders were produced with the spray-drying technique from aqueous precursor solutions containing pure low molecular weight dextran, pure mannitol and dextran/mannitol-N-acetyl cysteine (NAC) mixtures (4:1 and 1:1). NAC has been selected for this purpose as a compound, which is known to be mucolytic. Dextran and mannitol are potentially applicable in the field of inhalation drug delivery. They have been used as stabilizers of functional carrier particles. Powders were characterized for their yield and physicochemical properties including: morphology (SEM), moisture content and thermal properties (DSC). Aerosol performance was determined with NGI impactor after standardized aerosolization of the produced powders in a commercial DPI. Particle size distributions of dextran-NAC powders were characterized by high fine particle fraction (45-62%), which assures good particle deposition in the lower airways. The thermodynamic properties of the powders based on the temperature of the glass transition T(g) (50-63 °C) suggest the required stability during storage at moderate humidity. Preliminary examination of the required properties of these particles confirms their potential as functional carriers for pulmonary drug delivery. Copyright © 2012 Elsevier B.V. All rights reserved.

  2. Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals

    PubMed Central

    Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

    2015-01-01

    Introduction Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Objectives Trends in FDA approved FDC in the period 1980–2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. Materials and Methods New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. Results During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. Conclusion FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination. PMID:26469277

  3. Fixed-Dose Combination Drug Approvals, Patents and Market Exclusivities Compared to Single Active Ingredient Pharmaceuticals.

    PubMed

    Hao, Jing; Rodriguez-Monguio, Rosa; Seoane-Vazquez, Enrique

    2015-01-01

    Fixed-dose combinations (FDC) contain two or more active ingredients. The effective patent and exclusivity life of FDC compared to single active ingredient has not been assessed. Trends in FDA approved FDC in the period 1980-2012 and time lag between approval of FDC and single active ingredients in the combination were assessed, and the effective patent and exclusivity life of FDC was compared with their single active ingredients. New molecular entities (NMEs), new therapeutic biologics license applications (BLAs) and FDC data were collected from the FDA Orange Book and Drugs@FDA. Analysis included FDC containing one or more NMEs or BLAs at first FDA approval (NMEs-FDC) and only already marketed drugs (Non-NMEs-FDC). Descriptive, Kruskal-Wallis and Wilcoxon Rank Sum analyses were performed. During the study period, the FDA approved 28 NMEs-FDC (3.5% of NMEs) and 117 non-NMEs-FDC. FDC approvals increased from 12 in the 1980s to 59 in the 2000s. Non-NMEs-FDC entered the market at a median of 5.43 years (interquartile range 1.74, 10.31) after first FDA approval of single active ingredients in the combination. The Non-NMEs-FDC entered the market at a median of 2.33 years (-7.55, 2.39) before approval of generic single active ingredient. Non-NME-FDC added a median of 9.70 (2.75, 16.24) years to the patent and exclusivity life of the single active ingredients in the combination. FDC approvals significantly increased over the last twenty years. Pharmaceutical companies market FDC drugs shortly before the generic versions of the single ingredients enter the market extending the patent and exclusivity life of drugs included in the combination.

  4. Transglycosylated stevia and hesperidin as pharmaceutical excipients: dramatic improvement in drug dissolution and bioavailability.

    PubMed

    Uchiyama, Hiromasa; Tozuka, Yuichi; Imono, Masaaki; Takeuchi, Hirofumi

    2010-10-01

    The capability of transglycosylated materials, α-glycosyltransferase-treated stevia (Stevia-G) and α-glycosyl hesperidin (Hsp-G), to enhance the bioavailability of poorly water-soluble drugs was investigated. Spray-dried particles (SDPs) of drug/transglycosylated material, such as, flurbiprofen (FP)/Stevia-G, probucol (PRO)/Stevia-G, FP/Hsp-G, and PRO/Hsp-G were prepared. All SDPs showed pronounced improvement in both dissolution rate and apparent drug solubility. The amount of dissolved PRO was significantly improved to that of untreated PRO crystals when prepared as SDPs of PRO/Stevia-G or PRO/Hsp-G. There was no cytotoxicity to Caco-2 cells at levels of 10% Stevia-G or Hsp-G solution. Values for the area under the plasma concentration-time curve (AUC) of untreated PRO, SDPs of PRO/Hsp-G and PRO/Stevia-G after oral administration to rats were 4.94±2.06, 26.08±4.52 and 48.79±9.97μgh/mL, respectively. Interestingly, AUC values in cases of the FP system were in the order of untreated FPdrug absorption enhancement may depend on the type of transglycosylated materials used. Stevia-G, a newly investigated material for this purpose, was found to have good potential for use as a pharmaceutical excipient. Copyright © 2010 Elsevier B.V. All rights reserved.

  5. Pharmaceutical drugs supporting regeneration of small-intestinal mucosa severely damaged by ionizing radiation in mice

    PubMed Central

    Ishihara, Hiroshi; Tanaka, Izumi; Yakumaru, Haruko; Tanaka, Mika; Yokochi, Kazuko; Akashi, Makoto

    2013-01-01

    Accidental exposure of the abdomen to high-dose radiation leads to severe consequences initiated by disruption of the mucosa in the small intestine. Therapeutic options are limited, even though various treatments have been investigated, particularly in the field of regenerative therapy. In order to identify readily available treatment methods, we included several current pharmaceutical drugs, for which the clinical trials have already been completed, in tests on mice that had undergone severe mucosal damage by radiation. The drugs were injected into mice 24 h after exposure to 15.7 Gy X-rays. The effects of the drugs on the damaged mucosa of the small intestine were evaluated using early regeneration indices [the expression of c-myb mRNA, and proliferation of epithelial cells in the form of microcolonies (MCs) by Days 4 and 5 post-irradiation] and the survival rate of the mice. Enhancement of mucosal regeneration at Day 4 (c-myb: P < 0.01, MC: P < 0.05) and improvement of the survival rate (P < 0.05) were observed when a clinical dose of gonadotropin, a stimulator of androgen, was injected. Similarly, a clinical dose of thiamazole (which prevents secretion of thyroid hormone) stimulated mucosal growth by Day 5 (c-myb: P < 0.01, MC: P < 0.05) and also improved the survival rate (P < 0.05). The nonclinical drugs histamine and high-dose octreotide (a growth hormone antagonist) also gave significant survival-enhancing benefits (P < 0.01 and P < 0.05, respectively). These results can be used to construct therapeutic programs and applied in various experimental studies to control the regeneration of damaged mucosa. PMID:23728323

  6. Direct analysis in real time--high resolution mass spectrometry as a valuable tool for the pharmaceutical drug development.

    PubMed

    Srbek, Jan; Klejdus, Bořivoj; Douša, Michal; Břicháč, Jiří; Stasiak, Pawel; Reitmajer, Josef; Nováková, Lucie

    2014-12-01

    In this study, direct analysis in real time-mass spectrometry (DART-MS) was assessed for the analysis of various pharmaceutical formulations with intention to summarize possible applications for the routine pharmaceutical development. As DART is an ambient ionization technique, it allows direct analysis of pharmaceutical samples in solid or liquid form without complex sample preparation, which is often the most time-consuming part of the analytical method. This makes the technique suitable for many application fields, including pharmaceutical drug development. DART mass spectra of more than twenty selected tablets and other common pharmaceutical formulations, i.e. injection solutions, ointments and suppositories developed in the pharmaceutical industry during several recent years are presented. Moreover, as thin-layer chromatography (TLC) is still very popular for the monitoring of the reactions in the synthetic chemistry, several substances were analyzed directly from the TLC plates to demonstrate the simplicity of the technique. Pure substance solutions were spotted onto a TLC plate and then analyzed with DART without separation. This was the first DART-MS study of pharmaceutical dosage forms using DART-Orbitrap combination. The duration of sample analysis by the DART-MS technique lasted several seconds, allowing enough time to collect sufficient number of data points for compound identification. The experimental setup provided excellent mass accuracy and high resolution of the mass spectra which allowed unambiguous identification of the compounds of interest. Finally, DART mass spectrometry was also used for the monitoring of the selected impurity distribution in the atorvastatin tablets. These measurements demonstrated DART to be robust ionization technique, which provided easy-to-interpret mass spectra for the broad range of compounds. DART has high-throughput potential for various types of pharmaceutical analyses and therefore eliminates the time for sample

  7. Co-suppression of vitamin C composite nano-drug carrier and its drug delivery to nidus in tumor cells.

    PubMed

    Liu, H Z; Liu, X M; Liu, X C; Zhang, C Z; Liu, H Q

    2016-01-01

    This study aimed to discuss the co-suppression of vitamin C-contained composite nano-drug carrier and its drug delivery to nidus in tumor cells. Amphiphilic polymers PLA-block-PAAA and block polymer PLA-PEG4000-Maleimide, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelles were prepared, and, PLA-block-PAAA polymer-coated Nile red nano-micelle, PLA-block-PAA and PLA-PEG4000-Maleimide composite nano-micelles as well as paclitaxel-carrying composite nano-micelle in different molar ratios were given stability tests. Lastly, PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle cancer cells and paclitaxel-carrying composite nano-micelle cancer cells were given toxicity tests. Stability tests showed that self stability of PLA-block-PAAA (63/8) nano-micelle was not sufficient; the stability was good when the molar ratio of PLA-block-PAAA and PLA-PEG4000-Maleimide composite nano-micelle was 3:1; paclitaxel-carrying composite nano-micelle had good stability within 48 hours; PAAA segment had an inhibiting effect on C6 cancer cells and paclitaxel-carrying composite nano-micelle had a strong inhibiting effect also on tumors. After 24 hours, with the continuous release of paclitaxel, the tumor inhibiting effect of paclitaxel-carrying composite nano-micelle enhanced gradually, and the controlled-release of drugs had continuous inhibiting effect on tumor cells. Therefore, PAAA segment and paclitaxel had time-postponed synergistic effect. In conclusion, vitamin C-contained composite nanometer drug carrier materials can deliver anti-cancer drugs to nidus and thus inhibit tumor cells.

  8. Preparation of keratin hydrogel/hydroxyapatite composite and its evaluation as a controlled drug release carrier.

    PubMed

    Nakata, Ryo; Tachibana, Akira; Tanabe, Toshizumi

    2014-08-01

    Infection after artificial joint replacement is a serious problem, which requires the re-implantation of prosthesis. To aim at developing bone filling materials having both osteoconductivity and ability as a sustained drug release carrier, composites of wool keratin or carboxymethylated (CM) keratin hydrogels with hydroxyapatite were prepared and evaluated as a sustained drug release carrier. CM-keratin was prepared by the reaction of keratin extracted from wool with iodoacetic acid. Hydrogels were obtained by dropping keratin or CM-keratin solution into CaCl2 solution. The composites were obtained by immersing hydrogels in simulated body fluid (SBF). The introduction of carboxymethyl groups to keratin facilitated the deposition of hydroxyapatite on hydrogel. After 7 days of immersion in SBF, a 4-5 times higher amount of hydroxyapatite was accumulated on CM-keratin hydrogel than that on keratin hydrogel. When salicylic acid was loaded on keratin and CM-keratin hydrogels, a good sustained release was observed; that is, 90% of a drug was released up to 14 days after 60 and 45% of the initial burst in 1 day. On the other hand, initial release within 1 day was suppressed by forming a composite with hydroxyapatite and the release was almost ceased at 3 days when 60% of the drug was released. Although further improvement to prolong drug release might be necessary, CaKHA and CaCMKHA are expected to be a promising novel type of bone filling materials which has both osteoconductivity and sustained drug release ability. Copyright © 2014 Elsevier B.V. All rights reserved.

  9. Comparison of Nanogel Drug Carriers and Their Formulations with Nucleoside 5′-Triphosphates

    PubMed Central

    Vinogradov, Serguei V.; Kohli, Ekta; Zeman, Arin D.

    2006-01-01

    Purpose To synthesize and characterize nanogel carriers composed of amphiphilic polymers and cationic polyethylenimine for encapsulation and delivery of cytotoxic nucleoside analogs 5′-triphosphates (NTP) into cancer cells. Methods Nanogels were synthesized by a novel micellar approach and compared with carriers prepared by the emulsification/evaporation method. Complexes of nanogels with NTP were prepared; particle size and in vitro drug release were characterized. Resistance of the nanogel-encapsulated NTP to enzymatic hydrolysis was analyzed by ion-pair HPLC. Binding to isolated cellular membranes, cellular accumulation and cytotoxicity were compared using breast carcinoma cell lines CL-66, MCF-7 and MDA-MB-231. In vivo biodistribution of the 3H-labeled NTP encapsulated in different types of nanogels was evaluated in comparison to the injected NTP alone. Results Nanogels with a particle size of 100–300 nm in the unloaded form and less than 140 nm in the NTP-loaded form were prepared. An in vitro release of NTP was ≥50% during the first 24 h. Nanogel formulations ensured increased NTP drug stability against enzymatic hydrolysis as compared to the drug alone. Pluronic®-based nanogels NG(F68), NG(F127), NG(P85) and NGM(P123) demonstrated 2–2.5 times enhanced interaction with cellular membranes and association with various cancer cells compared to NG(PEG). Among them NG(F68) and NG(F127) exhibited the lowest cytotoxicity. Injection of nanogel-formulated NTP significantly modulated the drug accumulation in different mouse organs. Conclusions Nanogels composed of Pluronic® F68 and P123 were shown to display certain advanced properties compared to NG(PEG) as a drug delivery system for NTP analogs. Formulations of nucleoside analogs in active NTP form with these nanogels will improve the delivery of these cytotoxic drugs to cancer cells and the therapeutic potential of this anti-cancer chemotherapy. PMID:16715382

  10. Computational Study of Nanosized Drug Delivery from Cyclodextrins, Crown Ethers and Hyaluronan in Pharmaceutical Formulations.

    PubMed

    Torrens, Francisco; Castellano, Gloria

    2015-01-01

    The problem in this work is the computational characterization of cyclodextrins, crown ethers and hyaluronan (HA) as hosts of inclusion complexes for nanosized drug delivery vehicles in pharmaceutical formulations. The difficulty is addressed through a computational study of some thermodynamic, geometric and topological properties of the hosts. The calculated properties of oligosaccharides of D-glucopyranoses allow these to act as co-solvents of polyanions in water. In crown ethers, the central channel is computed. Mucoadhesive polymer HA in formulations releases drugs in mucosas. Geometric, topological and fractal analyses are carried out with code TOPO. Reference calculations are performed with code GEPOL. From HA to HA·3Ca and hydrate, the hydrophilic solvent-accessible surface varies with the count of H-bonds. The fractal dimension rises. The dimension of external atoms rises resulting 1.725 for HA. It rises going to HA·3Ca and hydrate. Nonburied minus molecular dimension rises and decays. Hydrate globularity is lower than O(water), Ca(2+) and O(HA). Ca(2+) rugosity is smaller than for hydrate, O(HA) and O(water). Ca(2+) and O(water) accessibilities are greater than hydrate. Conclusions are drawn on: (1) the relative stability of linear/cyclic and shorter/larger polymers; (2) the atomic analysis of properties allows determining the atoms with maximum reactivity.

  11. The Slow Relaxation Dynamics in the Amorphous Pharmaceutical Drugs Cimetidine, Nizatidine, and Famotidine.

    PubMed

    Viciosa, M Teresa; Moura Ramos, Joaquim J; Diogo, Hermínio P

    2016-12-01

    The slow molecular mobility in the amorphous solid state of 3 active pharmaceutical drugs (cimetidine, nizatidine, and famotidine) has been studied using differential scanning calorimetry and the 2 dielectric-related techniques of dielectric relaxation spectroscopy and thermally stimulated depolarization currents. The glass-forming ability, the glass stability, and the tendency for crystallization from the equilibrium melt were investigated by differential scanning calorimetry, which also provided the characterization of the main relaxation of the 3 glass formers. The chemical instability of famotidine at the melting temperature and above it prevented the preparation of the amorphous for dielectric studies. In contrast, for cimetidine and nizatidine, the dielectric study yielded the main kinetic features of the α relaxation and of the secondary relaxations. According to the obtained results, nizatidine displays the higher fragility index of the 3 studied glass-forming drugs. The thermally stimulated depolarization current technique has proved useful to identify the Johari-Goldstein relaxation and to measure τβJG in the amorphous solid state, that is, in a frequency range which is not easily accessible by dielectric relaxation spectroscopy. Copyright © 2016 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  12. A dynamic perspective on pharmaceutical competition, drug development and cost effectiveness.

    PubMed

    Refoios Camejo, Rodrigo; McGrath, Clare; Herings, Ron

    2011-04-01

    Limited healthcare budgets result in payers adopting policies at national, regional or local level to achieve allocative efficiency in drug spending. Some of these aim at creating a link between pharmaceutical prices and the value they provide by setting a cost effectiveness (CE) threshold as the maximum acceptable ratio between incremental costs and effects of new drugs. The clinical effectiveness of the comparator used in those CE analyses tends to be greater over time, whilst, due to market competition and loss of exclusivity, their price is expected to be lower. At the same time, research and development (R&D) costs increase with inflation and with efforts to address regulation towards increased safety concerns. As effective patent times decrease, a minimum price constraint raises for the new entrant. These features occur at different rates across disease areas and are expected to result in differently shaped innovation curves. In this scenario, we demonstrate that a general arbitrary threshold may prevent further efficient R&D. Investment may be withdrawn before the optimum innovation point is reached and affordable clinical effectiveness may be lost. We conclude that disease-specific characteristics are an additional consideration in CE decision rules to accommodate the particularities of innovation across disease areas.

  13. A simple and sensitive spectrofluorimetric method for analysis of some nitrofuran drugs in pharmaceutical preparations.

    PubMed

    Belal, Tarek Saied

    2008-09-01

    A simple, rapid, selective and sensitive spectrofluorimetric method was described for the analysis of three nitrofuran drugs, namely, nifuroxazide (NX), nitrofurantoin (NT) and nitrofurazone (NZ). The method involved the alkaline hydrolysis of the studied drugs by warming with 0.1 M sodium hydroxide solution then dilution with distilled water for NX or 2-propanol for NT and NZ. The formed fluorophores were measured at 465 nm (lambda (Ex) 265 nm), 458 nm (lambda (Ex) 245 nm) and 445 nm (lambda (Ex) 245 nm) for NX, NT and NZ, respectively. The reaction pathway was discussed and the structures of the fluorescent products were proposed. The different experimental parameters were studied and optimized. Regression analysis showed good correlation between fluorescence intensity and concentration over the ranges 0.08-1.00, 0.02-0.24 and 0.004-0.050 microg ml(-1) for NX, NT and NZ, respectively. The limits of detection of the method were 8.0, 1.9 and 0.3 ng ml(-1) for NX, NT and NZ, respectively. The proposed method was validated in terms of accuracy, precision and specificity, and it was successfully applied for the assay of the three nitrofurans in their different dosage forms. No interference was observed from common pharmaceutical adjuvants. The results were favorably compared with those obtained by reference spectrophotometric methods.

  14. Self-organized nanoparticles based on drug-interpolyelectrolyte complexes as drug carriers

    NASA Astrophysics Data System (ADS)

    Palena, M. C.; Manzo, R. H.; Jimenez-Kairuz, A. F.

    2012-06-01

    Potential applications in drug delivery from nanostructures composed of two oppositely charged polymethacrylates, eudragit® L100 (EL) and eudragit® EPO (EE), loaded with three model basic drugs (D), atenolol, propranolol, and metroclopramide were evaluated. The self-organized nanoparticles based on drug-interpolyelectrolyte complexes (DIPEC), (EL-D50)-EEX, were obtained by mixing the aqueous dispersions of both polyelectrolytes at room temperature in an ultrasound bath. Dispersions of (EL-D50) neutralized with increasing proportions of EE exhibited a rise of turbidity, particle sizes in the range of 150-400 nm, and high negative zeta potential. The sign of zeta potential was shifted from negative to positive by changes in composition of DIPEC. Freeze dried DIPEC were easily redispersed in water yielding nearly the same parameters of fresh dispersions. In vitro release experiments using Franz cells showed that DIPEC systems behave as a drug reservoir that slowly releases the drug as water is placed in the receptor compartment. The release rate was raised by ionic exchange with counterions present in simulated physiological fluids placed in the receptor media. Delivery of D from DIPEC exhibited a remarkable robustness toward simulated physiological media of different pH. The DIPEC systems exhibit interesting properties to design nanoparticulate drug delivery systems for oral and/or topical routes.

  15. Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery.

    PubMed

    Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

    2013-01-01

    Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C(max) than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile.

  16. Solid Lipid Nanoparticles of Guggul Lipid as Drug Carrier for Transdermal Drug Delivery

    PubMed Central

    Gaur, Praveen Kumar; Mishra, Shikha; Purohit, Suresh

    2013-01-01

    Diclofenac sodium loaded solid lipid nanoparticles (SLNs) were formulated using guggul lipid as major lipid component and analyzed for physical parameters, permeation profile, and anti-inflammatory activity. The SLNs were prepared using melt-emulsion sonication/low temperature-solidification method and characterized for physical parameters, in vitro drug release, and accelerated stability studies, and formulated into gel. Respective gels were compared with a commercial emulgel (CEG) and plain carbopol gel containing drug (CG) for ex vivo and in vivo drug permeation and anti-inflammatory activity. The SLNs were stable with optimum physical parameters. GMS nanoparticle 1 (GMN-1) and stearic acid nanoparticle 1 (SAN-1) gave the highest in vitro drug release. Guggul lipid nanoparticle gel 3 (GLNG-3) showed 104.68 times higher drug content than CEG in receptor fluid. The enhancement ratio of GLNG-3 was 39.43 with respect to CG. GLNG-3 showed almost 8.12 times higher C max than CEG at 4 hours. The AUC value of GLNG-3 was 15.28 times higher than the AUC of CEG. GLNG-3 showed edema inhibition up to 69.47% in the first hour. Physicochemical properties of major lipid component govern the properties of SLN. SLN made up of guggul lipid showed good physical properties with acceptable stability. Furthermore, it showed a controlled drug release profile along with a promising permeation profile. PMID:24058913

  17. Pharmaceutical industry's barriers and preferences to conduct clinical drug trials in Finland: a qualitative study.

    PubMed

    Keinonen, Tuija; Keränen, Tapani; Klaukka, Timo; Saano, Veijo; Ylitalo, Pauli; Enlund, Hannes

    2003-09-01

    The objectives of our study were to explore the barriers, preferences and attitudes of the pharmaceutical industry towards conducting clinical trials in Finland. In-depth semi-structured interviews were conducted with 18 representatives of the pharmaceutical industry with different amounts of experience of clinical trials. The interviews were audiotaped, transcribed verbatim and analysed qualitatively. Overall, the respondents had a positive attitude towards conducting clinical trials in Finland. The major barriers seemed to occur at the beginning of the trial and mostly consisted of bureaucratic obstacles. The informants hoped for a more positive attitude of the public sector, more flexibility in hospitals and professionalism in practical implementation, e.g. having special research centres or site management services. The most dismotivating factors were the high costs and the constraints imposed by bureaucracy. The variety in practices of local ethics committees was considered problematic, and the need for common standard operating procedures was pointed out. The smallest barriers were encountered in subject recruitment by the investigators and their clinical work, documentation, investigational product logistics and communication with the regulatory authorities. The quality, know-how and reliability of the study personnel, the tightening of time lines in general, an investigator register/pool and collaboration with media in disseminating information about clinical trials to the general public were reported as the most appealing factors. Training in GCP, mainly incorporated in the medical education programme, and a certificate or equivalent were generally considered necessary, though a voluntary system was preferred. The barriers and preferences pointed out suggest various improvements and ways to produce high-quality, GCP-compliant clinical drug research and to ensure the availability of sufficient conditions to carry out clinical trials also in the future.

  18. pH-Responsive carriers for oral drug delivery: challenges and opportunities of current platforms.

    PubMed

    Liu, Lin; Yao, WenDong; Rao, YueFeng; Lu, XiaoYang; Gao, JianQing

    2017-11-01

    Oral administration is a desirable alternative of parenteral administration due to the convenience and increased compliance to patients, especially for chronic diseases that require frequent administration. The oral drug delivery is a dynamic research field despite the numerous challenges limiting their effective delivery, such as enzyme degradation, hydrolysis and low permeability of intestinal epithelium in the gastrointestinal (GI) tract. pH-Responsive carriers offer excellent potential as oral therapeutic systems due to enhancing the stability of drug delivery in stomach and achieving controlled release in intestines. This review provides a wide perspective on current status of pH-responsive oral drug delivery systems prepared mainly with organic polymers or inorganic materials, including the strategies used to overcome GI barriers, the challenges in their development and future prospects, with focus on technology trends to improve the bioavailability of orally delivered drugs, the mechanisms of drug release from pH-responsive oral formulations, and their application for drug delivery, such as protein and peptide therapeutics, vaccination, inflammatory bowel disease (IBD) and bacterial infections.

  19. PLGA based drug delivery systems: Promising carriers for wound healing activity.

    PubMed

    Chereddy, Kiran Kumar; Vandermeulen, Gaëlle; Préat, Véronique

    2016-03-01

    Wound treatment remains one of the most prevalent and economically burdensome healthcare issues in the world. Current treatment options are limited and require repeated administrations which led to the development of new therapeutics to satisfy the unmet clinical needs. Many potent wound healing agents were discovered but most of them are fragile and/or sensitive to in vivo conditions. Poly(lactic-co-glycolic acid) (PLGA) is a widely used biodegradable polymer approved by food and drug administration and European medicines agency as an excipient for parenteral administrations. It is a well-established drug delivery system in various medical applications. The aim of the current review is to elaborate the applications of PLGA based drug delivery systems carrying different wound healing agents and also present PLGA itself as a wound healing promoter. PLGA carriers encapsulating drugs such as antibiotics, anti-inflammatory drugs, proteins/peptides, and nucleic acids targeting various phases/signaling cycles of wound healing, are discussed with examples. The combined therapeutic effects of PLGA and a loaded drug on wound healing are also mentioned. © 2016 by the Wound Healing Society.

  20. Milk derived colloid as a novel drug delivery carrier for breast cancer.

    PubMed

    Hayashi, Masamichi; Silanikove, Nissim; Chang, Xiaofei; Ravi, Rajani; Pham, Vui; Baia, Gilson; Paz, Keren; Brait, Mariana; Koch, Wayne M; Sidransky, David

    2015-01-01

    Triple negative breast cancer has an extremely poor prognosis when chemotherapy is no longer effective. To overcome drug resistance, novel drug delivery systems based on nanoparticles have had remarkable success. We produced a novel nanoparticle component 'MDC' from milk-derived colloid. In order to evaluate the anti-cancer effect of MDC, we conducted in vitro and in vivo experiments on cancer cell lines and a primary tumor derived breast xenograft. Doxorubicin (Dox) conjugated to MDC (MDC-Dox) showed higher cancer cell growth inhibition than MDC alone especially in cell lines with high EGFR expression. In a mouse melanoma model, MDC-Dox significantly suppressed tumor growth when compared with free Dox. Moreover, in a primary tumor derived breast xenograft, one of the mice treated with MDC-Dox showed partial regression, while mice treated with free Dox failed to show any suppression of tumor growth. We have shown that a novel nanoparticle compound made of simple milk-derived colloid has the capability for drug conjugation, and serves as a tumor-specific carrier of anti-cancer drugs. Further research on its safety and ability to carry various anti-cancer drugs into multiple drug-resistant primary breast models is warranted.

  1. Evaluation of the physicochemical properties of liposomes as potential carriers of anticancer drugs: spectroscopic study

    NASA Astrophysics Data System (ADS)

    Pentak, Danuta

    2016-05-01

    Vesicle size and composition are a critical parameter for determining the circulation half-life of liposomes. Size influences the degree of drug encapsulation in liposomes. The geometry, size, and properties of liposomes in an aqueous environment have to be described to enable potential applications of liposome systems as drug carriers. The characteristics of multiple thermotropic phase transitions are also an important consideration in liposomes used for analytical and bioanalytical purposes. The aim of this study was to evaluate the physicochemical properties of liposomes which accommodate hydrophilic and amphiphilic drugs used in cancer therapy. The studied liposomes were prepared with the involvement of the modified reverse-phase evaporation method (mREV). The prepared liposomes had a diameter of 70-150 nm. The analyzed compounds were 1-β- d-arabinofuranosylcytosine, cyclophosphamide, and ifosfamide. In literature, there is no information about simultaneous incorporation of cytarabine, ifosfamide, and cyclophosphamide, in spite of the fact that these drugs have been used for more than 30 years. A combination of the examined drugs is used in CODOX-M/IVAC therapy. CODOX-M/IVAC (cyclophosphamide, doxorubicin, high-dose methotrexate/ifosfamide, etoposide, and high-dose cytarabine) is one of the currently preferred intensive-dose chemotherapy regimens for Burkitt lymphoma (BL). The present research demonstrates the pioneering studies of incorporation of ifosfamide into liposome vesicles, location of and competition between the analyzed drugs and liposome vesicles. The applied methods were nuclear magnetic resonance (NMR), atomic force microscopy (AFM), differential scanning calorimetry (DSC).

  2. Structure and Dynamics of Drug Carriers and Their Interaction with Cellular Receptors: Focus on Serum Transferrin#

    PubMed Central

    Luck, Ashley N.; Mason, Anne B.

    2012-01-01

    Highly proliferative cells have a dramatically increased need for iron which results in the expression of an increased number of transferrin receptors (TFR). This insight makes the transferrin receptor on these cells an excellent candidate for targeted therapeutics. In this regard, it is critical to understand at a molecular level exactly how the TFR interacts with its ligand, hTF. Understanding of the hTF/TFR pathway could, in theory, maximize the use of this system for development of more effective small molecules or toxin-conjugates to specifically target cancer cells. Many strategies have been attempted with the objective of utilizing the hTF/TFR system to deliver drugs; these include conjugation of a toxin or drug to hTF or direct targeting of the TFR by antibodies. To date, in spite of all of the effort, there is a conspicuous absence of any successful candidate drugs reaching the clinic. We suggest that a lack of quantitative data to determine the basic biochemical properties of the drug carrier and the effects of drug-conjugation on the hTF-TFR interaction may have contributed to the failure to realize the full potential of this system. This review provides some guidelines for developing a more quantitative approach for evaluation of current and future hTF-drug conjugates. PMID:23183585

  3. Structure and dynamics of drug carriers and their interaction with cellular receptors: focus on serum transferrin.

    PubMed

    Luck, Ashley N; Mason, Anne B

    2013-07-01

    Highly proliferative cells have a dramatically increased need for iron which results in the expression of an increased number of transferrin receptors (TFR). This insight makes the transferrin receptor on these cells an excellent candidate for targeted therapeutics. In this regard, it is critical to understand at a molecular level exactly how the TFR interacts with its ligand, hTF. Understanding of the hTF/TFR pathway could, in theory, maximize the use of this system for development of more effective small molecules or toxin-conjugates to specifically target cancer cells. Many strategies have been attempted with the objective of utilizing the hTF/TFR system to deliver drugs; these include conjugation of a toxin or drug to hTF or direct targeting of the TFR by antibodies. To date, in spite of all of the effort, there is a conspicuous absence of any successful candidate drugs reaching the clinic. We suggest that a lack of quantitative data to determine the basic biochemical properties of the drug carrier and the effects of drug-conjugation on the hTF-TFR interaction may have contributed to the failure to realize the full potential of this system. This review provides some guidelines for developing a more quantitative approach for evaluation of current and future hTF-drug conjugates. Copyright © 2012 Elsevier B.V. All rights reserved.

  4. Gb3-binding lectins as potential carriers for transcellular drug delivery.

    PubMed

    Müller, Stefan K; Wilhelm, Isabel; Schubert, Thomas; Zittlau, Katharina; Imberty, Anne; Madl, Josef; Eierhoff, Thorsten; Thuenauer, Roland; Römer, Winfried

    2017-02-01

    Epithelial cell layers as well as endothelia forming the blood-brain barrier can drastically reduce the efficiency of drug targeting. Our goal was to investigate lectins recognizing the glycosphingolipid globotriaosylceramide (Gb3) for their potential as carriers for transcytotic drug delivery. We utilized an in vitro model based on Madin-Darby canine kidney cells transfected with Gb3 synthase to characterize transcytosis of the Gb3-binding lectins LecA from Pseudomonas aeruginosa and the B-subunit of Shiga toxin (StxB). Both lectins were rapidly transcytosed from the apical to the basolateral plasma membrane and vice versa. Whereas StxB proceeded on retrograde and transcytotic routes, LecA avoided retrograde transport. This differential trafficking could be explained by our observation that LecA and StxB segregated into different domains during endocytosis. Furthermore, inhibiting the small GTPase Rab11a, which organizes trafficking through apical recycling endosomes, blocked basolateral to apical transcytosis of both lectins. Gb3-binding lectins are promising candidates for transcytotic drug delivery. Our findings highlight that LecA and StxB, which both bind Gb3 but exhibit dissimilar valence and molecular structures of their carbohydrate binding sites and can take divergent intracellular trafficking routes. This opens up the possibility of developing tailor-made glycosphingolipid-binding carrier lectins, which take optimized trafficking pathways.

  5. Drug delivery by red blood cells: vascular carriers designed by Mother Nature

    PubMed Central

    Muzykantov, Vladimir R.

    2010-01-01

    Importance of the field Vascular delivery of several classes of therapeutic agents may benefit from carriage by red blood cells (RBC), for example, drugs that require delivery into phagocytic cells and those that must act within the vascular lumen. The fact that several protocols of infusion of RBC-encapsulated drugs are been currently explored in patients illustrates a high biomedical importance for the field. Areas covered by this review Two strategies for RBC drug delivery are discussed: encapsulation into isolated RBC ex vivo followed by infusion in compatible recipients and coupling therapeutics to surface of RBC. Studies of pharmacokinetics and effects in animal models and in human studies of diverse therapeutic enzymes, antibiotics and other drugs encapsulated in RBC are described and critically analyzed. Coupling to RBC surface of compounds regulating immune response and complement, affinity ligands, polyethylene glycol alleviating immune response to donor RBC and fibrinolytic plasminogen activators is d escribed. Also described is a novel, translation-prone approach for RBC drug delivery by injecting of therapeutics conjugated with fragments of antibodies providing safe anchoring of cargoes to circulating RBC, without need for ex vivo modification and infusion of RBC. What the reader will gain The readers will gain historical perspective, current status, challenges and perspectives of medical applications of RBC for drug delivery. Take home message RBC represent naturally designed carriers for intravascular drug delivery, characterized by unique longevity in the bloodstream, biocompatibility and safe physiological mechanisms for metabolism. Novel approaches for encapsulating drugs into RBC and coupling to RBC surface provide promising avenues for safe and widely useful improvement of drug delivery in the vascular system. PMID:20192900

  6. Drug carrier interaction with blood: a critical aspect for high-efficient vascular-targeted drug delivery systems

    PubMed Central

    Sobczynski, Daniel J; Fish, Margaret B; Fromen, Catherine A; Carasco-Teja, Mariana; Coleman, Rhima M; Eniola-Adefeso, Omolola

    2015-01-01

    Vascular wall endothelial cells control several physiological processes and are implicated in many diseases, making them an attractive candidate for drug targeting. Vascular-targeted drug carriers (VTCs) offer potential for reduced side effects and improved therapeutic efficacy, however, only limited therapeutic success has been achieved to date. This is perhaps due to complex interactions of VTCs with blood components, which dictate VTC transport and adhesion to endothelial cells. This review focuses on VTC interaction with blood as well as novel ‘bio-inspired’ designs to mimic and exploit features of blood in VTC development. Advanced approaches for enhancing VTCs are discussed along with applications in regenerative medicine, an area of massive potential growth and expansion of VTC utility in the near future. PMID:26272334

  7. Assessment of the Biological Effects of a Multifunctional Nano-Drug-Carrier and Its Encapsulated Drugs.

    PubMed

    Song, Yipeng; Zhao, Ruifang; Hu, Yili; Hao, Fuhua; Li, Ning; Nie, Guangjun; Tang, Huiru; Wang, Yulan

    2015-12-04

    Polymer-nanoparticle-encapsulated doxorubicin (DOX) and paclitaxel (TAX) have the potential for novel therapeutic use against cancer in the clinic. However, the systemic biological effect of the nanoparticle material, namely, methoxypoly(ethylene glycol)-poly(lactide-co-glycolide) (mPEG-PLGA), and its encapsulated drugs have not been fully studied. We have applied NMR-based metabonomics methodology to characterize and analyze the systemic metabolic changes in mice after being exposed to mPEG-PLGA, mPEG-PLGA-encapsulated DOX and TAX (NP-D/T), and their free forms. The study revealed that mPEG-PLGA exposure only induces temporary and slight metabolic alternations and that there are detoxification effects of nanoparticle packed with D/T drugs on the heart when comparing with free-form D/T drugs. Both NP-D/T and their free forms induce a shift in energy metabolism, stimulate antioxidation pathways, and disturb the gut microbial activity of the host. However, mPEG-PLGA packaging can relieve the energy metabolism inhibition and decrease the activation of antioxidation pathways caused by D/T exposure. These findings provide a holistic insight into the biological effect of polymer nanoparticle and nanoparticle-encapsulated drugs. This study also furthers our understanding of the molecular mechanisms involved in the amelioration effects of mPEG-PLGA packaging on the toxicity of the incorporated drugs.

  8. Antihypertensive drugs: a perspective on pharmaceutical price erosion and its impact on cost-effectiveness.

    PubMed

    Refoios Camejo, Rodrigo; McGrath, Clare; Herings, Ron; Meerding, Willem-Jan; Rutten, Frans

    2012-01-01

    When comparators' prices decrease due to market competition and loss of exclusivity, the incremental clinical effectiveness required for a new technology to be cost-effective is expected to increase; and/or the minimum price at which it will be funded will tend to decrease. This may be, however, either unattainable physiologically or financially unviable for drug development. The objective of this study is to provide an empirical basis for this discussion by estimating the potential for price decreases to impact on the cost-effectiveness of new therapies in hypertension. Cost-effectiveness at launch was estimated for all antihypertensive drugs launched between 1998 and 2008 in the United Kingdom using hypothetical degrees of incremental clinical effectiveness within the methodologic framework applied by the UK National Institute for Health and Clinical Excellence. Incremental cost-effectiveness ratios were computed and compared with funding thresholds. In addition, the levels of incremental clinical effectiveness required to achieve specific cost-effectiveness thresholds at given prices were estimated. Significant price decreases were observed for existing drugs. This was shown to markedly affect cost-effectiveness of technologies entering the market. The required incremental clinical effectiveness was in many cases greater than physiologically possible so, as a consequence, a number of products might not be available today if current methods of economic appraisal had been applied. We conclude that the definition of cost-effectiveness thresholds is fundamental in promoting efficient innovation. Our findings demonstrate that comparator price attrition has the potential to put pressure in the pharmaceutical research model and presents a challenge to new therapies being accepted for funding. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

  9. Antitumor and Antimetastasis Activities of Heparin-based Micelle Served As Both Carrier and Drug.

    PubMed

    Mei, Ling; Liu, Yayuan; Zhang, HuaJin; Zhang, Zhirong; Gao, Huile; He, Qin

    2016-04-20

    Effective treatments for tumors are not easy to achieve due to the existence of metastases, which are responsible for most tumor death. Hence, a new drug delivery system is a pressing need, which should be biocompatible, stimuli-responsive, and multifunctional, including antitumor, antimetastasis, and antiangiogenesis effects. However, it is challenging to achieve all of these properties in one drug delivery system. Here, we developed a system of drug DOX and heparin into one self-assemble nanoparticle via pH-sensitive hydrazone bond and hydrophobic groups, deoxycholate. In the process, heparin itself was not only as the hydrophilic segments of the carrier, but also processed multiple biological functions such as antiangiogenesis and antimetastasis effect. The micelle nanoparticle HD-DOX processed good stability and acidic pH-triggered drug release property. After systemic administration, heparin-based micelle nanoparticle showed longer half-time and enhanced accumulation of DOX in tumors through the enhanced permeability and retention effect, leading to more efficient antitumor effects. In addition, heparin could hinder platelet-induced tumor cells epithelial-mesenchymal transition (EMT) and partially affect cell actin cytoskeletal arrangement, resulting in the disorganization of the actin cytoskeleton. Therefore, HD-DOX exhibited significant inhibitory effect on the metastasis in melanoma animal model in C57BL/6 mouse. Meanwhile, benefited from the antiangiogenesis effect of heparin, tube formations in endothelial cells were effectively inhibited and tumor vascular density was decreased by HD-DOX. Taken together, our study developed a self-assembly nanoplatform that both the drug and carrier had therapeutic effects with ideal antitumor efficacy.

  10. Behavior of silica particles introduced into an isolated rat heart as potential drug carriers.

    PubMed

    Borak, B; Arkowski, J; Skrzypiec, M; Ziółkowski, P; Krajewska, B; Wawrzyńska, M; Grotthus, B; Gliniak, H; Szelag, A; Mazurek, W; Biały, D; Maruszewski, K

    2007-12-01

    Silica powders consisting of small spherical particles (50-200 nm) have been obtained by the sol-gel method. A suspension of such particles in the Krebs-Hanseleit solution has been introduced into the coronary circulation of a beating perfused rat heart. The influence of the suspension on the heart muscle and the coronary vessels in the rat body has been histopathologically examined. The particles have not left the lumen of the vessels and have not caused any side effects. These observations suggest the possibility of using such silica particles as a carrier for selected drugs.

  11. Cyclodextrin-gated mesoporous silica nanoparticles as drug carriers for red light-induced drug release

    NASA Astrophysics Data System (ADS)

    Chai, Shiqiang; Guo, Yu; Zhang, Zhenyu; Chai, Zhen; Ma, Yurong; Qi, Limin

    2017-04-01

    Long wavelength light-responsive drug delivery systems based on mesoporous silica nanoparticles (MSNs) have attracted much attention in the last few years. In this paper, a red light (660 nm)-responsive drug delivery system based on low-cost cyclodextrin (CD)-gated MSNs containing a photodynamic therapy (PDT) photosensitizer (Chlorin e6, Ce6) was developed for the first time. The drug release experiment in water demonstrated that with the irradiation of red light, Ce6 can be excited to generate singlet oxygen, which can further cleave the singlet oxygen sensitive linker to trigger the departure of CD and the release of cargo. Further in vitro release experiments confirmed that cargo can be released from MSNs with the irradiation of red light and spread into the entire cell. The relative low power density (0.5 W cm‑2) of excitation light together with the short irradiation time (one–three min) result in a low light dose (30–90 J cm‑2) for the drug delivery, contributing to their potential clinical applications.

  12. Cyclodextrin-gated mesoporous silica nanoparticles as drug carriers for red light-induced drug release.

    PubMed

    Chai, Shiqiang; Guo, Yu; Zhang, Zhenyu; Chai, Zhen; Ma, Yurong; Qi, Limin

    2017-04-07

    Long wavelength light-responsive drug delivery systems based on mesoporous silica nanoparticles (MSNs) have attracted much attention in the last few years. In this paper, a red light (660 nm)-responsive drug delivery system based on low-cost cyclodextrin (CD)-gated MSNs containing a photodynamic therapy (PDT) photosensitizer (Chlorin e6, Ce6) was developed for the first time. The drug release experiment in water demonstrated that with the irradiation of red light, Ce6 can be excited to generate singlet oxygen, which can further cleave the singlet oxygen sensitive linker to trigger the departure of CD and the release of cargo. Further in vitro release experiments confirmed that cargo can be released from MSNs with the irradiation of red light and spread into the entire cell. The relative low power density (0.5 W cm(-2)) of excitation light together with the short irradiation time (one-three min) result in a low light dose (30-90 J cm(-2)) for the drug delivery, contributing to their potential clinical applications.

  13. Retrovirus budding may constitute a port of entry for drug carriers.

    PubMed

    Ropert, C; Mishal, Z; Rodrigues, J M; Malvy, C; Couvreur, P

    1996-01-10

    This paper investigates the relation between viral infection and cell uptake of liposomes and nanoparticles. A defective virus was used to infect two types of cells: cells allowing virus budding (psi2neo cells) and cells bereft of a virus exit process (NIH 3T3 cells). This study has revealed that cell uptake of pH-sensitive-liposomes is highly dependent on the virus exit process, since it ensued only when virus budding occurred. This preferential uptake of pH-sensitive liposomes by infected cells was not carrier-specific because similar uptake was observed with non-biodegradable fluorescent nanoparticles using confocal microscopy. Also, inhibition of neo gene expression by oligonucleotide pH-sensitive-liposomes was only observed in the cell system (psi2neo) endowed with a virus exit process. Finally, increased membrane fluidity was noted in the infected cells, possibly reflecting membrane perturbation due to virus budding. We suggest that this membrane perturbation may be the key to the uptake of the different colloidal carriers. Infected cells could, thus, constitute a natural target for particulate drug carriers.

  14. Walnut kernel-like mesoporous silica nanoparticles as effective drug carrier for cancer therapy in vitro

    NASA Astrophysics Data System (ADS)

    Ge, Kun; Ren, Huihui; Sun, Wentong; Zhao, Qi; Jia, Guang; Zang, Aimin; Zhang, Cuimiao; Zhang, Jinchao

    2016-03-01

    In drug delivery systems, nanocarriers could reduce the degradation and renal clearance of drugs, increase the half-life in the bloodstream and payload of drugs, control the release patterns, and improve the solubility of some insoluble drugs. In particular, mesoporous silica nanoparticles (MSNs) are considered to be attractive nanocarriers for application of delivery systems because of their large surface areas, large pore volume, tunable pore sizes, good biocompatibility, and the ease of surface functionalization. However, the large-scale synthesis of monodisperse MSNs that are smaller than 200 nm remains a challenge. In this study, monodisperse walnut kernel-like MSNs with diameters of approximately 100 nm were synthesized by a sol-gel route on a large scale. The morphology and structure of MSNs were characterized by scanning electron microscope, and transmission electron microscopy, N2 adsorption-desorption isotherms, Zeta potentials, and dynamic light scattering. Drug loading and release profile, cellular uptake, subcellular localization, and anticancer effect in vitro were further investigated. The results indicated that the loading efficiency of doxorubicinhydrochloride (DOX) into the MSNs was 57 %. The MSNs-DOX delivery system exhibited a drug-pronounced initial burst release within 12 h, followed by the slow sustained release of DOX molecules; moreover, MSNs could improve DOX release efficiency in acidic medium. Most free DOX was localized in the cytoplasm, whereas the MSNs-DOX was primarily distributed in lysosome. MSNs-DOX exhibited a potential anticancer effect against MCF-7, HeLa, and A549 cells in dose- and time-dependent manners. In summary, the as-synthesized MSNs may have well function as a promising drug carrier in drug delivery fields.

  15. Magnetic graphene oxide as a carrier for targeted delivery of chemotherapy drugs in cancer therapy

    NASA Astrophysics Data System (ADS)

    Huang, Ya-Shu; Lu, Yu-Jen; Chen, Jyh-Ping

    2017-04-01

    A magnetic targeted functionalized graphene oxide (GO) complex is constituted as a nanocarrier for targeted delivery and pH-responsive controlled release of chemotherapy drugs to cancer cells. Magnetic graphene oxide (mGO) was prepared by chemical co-precipitation of Fe3O4 magnetic nanoparticles on GO nano-platelets. The mGO was successively modified by chitosan and mPEG-NHS through covalent bindings to synthesize mGOC-PEG. The polyethylene glycol (PEG) moiety is expected to prolong the circulation time of mGO by reducing the reticuloendothelial system clearance. Irinotecan (CPT-11) or doxorubicin (DOX) was loaded to mGOC-PEG through π-π stacking interactions for magnetic targeted delivery of the cancer chemotherapy drug. The best values of loading efficiency and loading content of CPT-11 were 54% and 2.7% respectively; whereas for DOX, they were 65% and 393% The pH-dependent drug release profile was further experimented at different pHs, in which 60% of DOX was released at pH 5.4 and 10% was released at pH 7.4. In contrast, 90% CPT-11 was released at pH 5.4 and 70% at pH 7.4. Based on the drug loading and release characteristics, mGOC-PEG/DOX was further chosen for in vitro cytotoxicity tests against U87 human glioblastoma cell line. The IC50 value of mGOC-PEG/DOX was found to be similar to that of free DOX but was reduced dramatically when subject to magnetic targeting. It is concluded that with the high drug loading and pH-dependent drug release properties, mGOC-PEG will be a promising drug carrier for targeted delivery of chemotherapy drugs in cancer therapy.

  16. Pharmaceutical companies' variation of drug prices within and among countries can improve long-term social well-being.

    PubMed

    Lichtenberg, Frank R

    2011-08-01

    Drug prices vary considerably across and within countries. On average, pharmaceutical companies charge lower prices in low-income countries than in industrialized nations. Manufacturers' ability to price products differently for different markets--a practice known as price discrimination--increases their profits overall. But it is also likely to result in greater investment in research and development, and therefore in more new drugs on the market. Although reducing price discrimination in order to cut costs might benefit consumers in the short run, it would harm them in the long run by reducing the number of new drugs developed.

  17. How do pharmaceutical companies handle consumer adverse drug reaction reports? An overview based on a survey of French drug safety managers and officers.

    PubMed

    Fleuranceau-Morel, P

    2002-01-01

    It is surprising to see how consumer Adverse Drug Reaction (ADR) reports have been continuously increasing for the last few years in Europe. This probably results from the influence of United States (US) market where the patients feels justified in telephoning the pharmaceutical companies directly with queries regarding their treatment. The growing number of alternative sources of information (e.g. health and popular magazines, spots on radio and TV etc.) to which a consumer is exposed has added to this growth too. The changing relationship between patients and doctors may also contribute to this phenomenon. It is then interesting to evaluate the way pharmaceutical companies currently deal with consumer ADR reports. The management of consumer ADR reporting was investigated by means of a questionnaire sent to 46 French drug safety managers and drug safety officers (DSOs) of multinational pharmaceutical companies. The analysis of the survey stressed the fact that pharmaceutical companies should be prepared to face up to an increase in the number of consumer ADR reports. It clearly appears that the consumers who telephone to register side-effects should be forwarded to a trained DSO with medical or pharmaceutical background and the communication skills acquired through specific training. This person should also be able to release adequate product information validated by his/her own company. The influence of the US market seems to be changing the way pharmaceutical companies deal with consumer ADR reports. Nowadays, these reports are entered into a drug safety database by most of the companies without previously having contacted the patient's general practitioner (GP) or specialist for medical confirmation. Lastly, the drug safety managers and DSOs consulted have divided opinions about the usefulness of call centres and e-mails as tools for ADR reporting. But both tools are globally rejected by the pharmaceutical companies as a reliable means of reporting. As stated

  18. Functionalized graphene oxide as a drug carrier for loading pirfenidone in treatment of subarachnoid hemorrhage.

    PubMed

    Yang, Lijun; Wang, Feng; Han, Haie; Yang, Liang; Zhang, Gengshen; Fan, Zhenzeng

    2015-05-01

    Subarachnoid hemorrhage (SAH) is a life-threatening disease that causes high morbidity and mortality. Pirfenidone is a SAH drug that prevents secondary bleeding and cerebral infarction. To improve its therapeutic efficacy, this study aimed to employ a functionalized graphene oxide nanosheet (FGO) as a drug carrier loading pirfenidone to treat SAH. The graphene oxide nanosheet was introduced with transcription activator peptide (Tat), followed by functionalization with methoxy polyethylene glycol (mPEG) and loading with pirfenidone. The pirfenidone-loaded FGO (pirfenidone-FGO) exhibits better treatment efficacy than the single pirfenidone due to more effective loading and controlled release of the drug in tissue. The introduction of Tat and mPEG onto GO nanosheet contributes to the ability to cross the blood-brain barrier and the stability in blood circulation of the drug. At lower pH values, the highly efficient release of the drug from the pirfenidone-FGO exerts effective treatment to acidic inflammatory lesion after severe SAH. Besides its treatment function, FGO is also shown as a strong near infrared absorbing material which can be applied in photoacoustic imaging, allowing rapid real-time monitoring with deep resolution of brain tissues after SAH. The treatment efficacy of pirfenidone-FGO for central nervous system injuries is further demonstrated by hematoxylin and eosin staining of coronal brain slices, as well as measurements of brain water content and blood-brain barrier permeability. Our study supports the potential of FGO in clinical application in treatment of SAH.

  19. Vitamin B12-loaded solid lipid nanoparticles as a drug carrier in cancer therapy.

    PubMed

    Genç, Lütfi; Kutlu, H Mehtap; Güney, Gamze

    2015-05-01

    Nanostructure-mediated drug delivery, a key technology for the realization of nanomedicine, has the potential to improve drug bioavailability, ameliorate release deviation of drug molecules and enable precision drug targeting. Due to their multifunctional properties, solid lipid nanoparticles (SLNs) have received great attention of scientists to find a solution to cancer. Vitamin supplements may contribute to a reduction in the risk of cancer. Vitamin B12 has several characteristics that make it an attractive entity for cancer treatment and possible therapeutic applications. The aim of this study was to produce B12-loaded SLNs (B12-SLNs) and determine the cytotoxic effects of B12-SLNs on H-Ras 5RP7 and NIH/3T3 control cell line. Results obtained by MTT assay, transmission electron and confocal microscopy showed that B12-loaded SLNs are more effective than free vitamin B12 on cancer cells. In addition, characterization studies indicate that while the average diameter of the B12 was about 650 nm, B12-SLNs were about 200 nm and the drug release efficiency of vit. B12 by means of SLNs increased up to 3 h. These observations point to the fact that B12-SLNs could be used as carrier systems due to the therapeutic effects on cancer.

  20. Propolis as lipid bioactive nano-carrier for topical nasal drug delivery.

    PubMed

    Rassu, Giovanna; Cossu, Massimo; Langasco, Rita; Carta, Antonio; Cavalli, Roberta; Giunchedi, Paolo; Gavini, Elisabetta

    2015-12-01

    Propolis shows therapeutic properties ascribed to the presence of some flavonoids, phenolic acids, and their esters; it is a natural multifunctional material, solid at room temperature, and composed mainly of resin and waxes. We therefore used propolis as a lipid material to prepare solid lipid nanoparticles (SLNs); SLNs are proposed bioactive medications for topical intranasal therapy. Suitable formulation parameters were studied and the SLNs obtained by the high shear homogenization method were characterized; a selected formulation was viscosized to increase the residence time. Dimensional, morphological, and solid-state characterizations of the formulated SLNs were performed. In vitro and ex vivo permeation tests of diclofenac sodium, the model drug, and polyphenols were carried out. The propolis amount and surfactant concentration represent the key parameters that affect nanoparticle properties in terms of size, drug and polyphenol content, and physical stability. Size dispersions of about 600 nm and 0.4 PI were obtained, which do not change by increasing the viscosity. Drug is encapsulated in SLNs, as demonstrated by FTIR and DSC analyses. In vitro and ex vivo studies prove that drug and polyphenols do not cross the membranes; therefore, propolis-based SLNs could be used as delivery systems of diclofenac and flavonoids for the local treatment of nasal cavity diseases. Due to propolis composition, the proposed formulation could be used as a bioactive medication in which the carrier can exert a complementary effect with the loaded drug. Copyright © 2015 Elsevier B.V. All rights reserved.

  1. The global diversion of pharmaceutical drugs: opiate treatment and the diversion of pharmaceutical opiates: a clinician's perspective.

    PubMed

    Bell, James

    2010-09-01

    To provide a clinician's perspective on the problem of diversion of prescribed pharmaceuticals. The paper provides a personal account of working in a treatment context where diversion from opioid substitution treatment (OST) became a political issue potentially compromising the continued delivery of OST. It summarizes evidence on the impact of diversion, and measures to contain it, from the United Kingdom 1986-2006, Australia 1996-2008 and the United States and France from the mid-1990s. Opioid diversion to the black market occurs in proportion to the amount of opioids prescribed to be taken without supervision, and in inverse proportion to the availability of heroin. Diversion for OST programmes using supervision of dosing is less than diversion of opioids prescribed for pain, which is now a growing public health problem. Adverse consequences of diversion include opioid overdose fatalities, an increased incidence of addiction (particularly in jurisdictions where heroin is scarce) and compromising the public acceptance of long-term opioid prescribing. All long-term opioid prescribing requires monitoring of risk and appropriate dispensing arrangements--including dilution of methadone take-aways, supervision of administration for high-risk patients and random urine testing. Clinical guidelines influence practice, although prescribing often deviates from guidelines. Clinical guidelines and clinical audit to enhance compliance with guidelines are helpful in maintaining the quality and integrity of the treatment system, and can contribute to keeping diversion within acceptable levels.

  2. Effects of liposomes with polyisoprenoids, potential drug carriers, on the cardiovascular and excretory system in rats.

    PubMed

    Gawrys, Olga; Polkowska, Marta; Roszkowska-Chojecka, Malwina; Gawarecka, Katarzyna; Chojnacki, Tadeusz; Swiezewska, Ewa; Masnyk, Marek; Chmielewski, Marek; Rafałowska, Janina; Kompanowska-Jezierska, Elżbieta

    2014-04-01

    The unpredictable side effects of a majority currently used drugs are the substantial issue, in which patients and physicians are forced to deal with. Augmenting the therapeutic efficacy of drugs may prove more fruitful than searching for the new ones. Since recent studies show that new cationic derivatives of polyisoprenoid alcohols (APrens) might exhibit augmenting properties, we intend to use them as a component of liposomal drug carriers. In this study we investigate if these compounds do not per se cause untoward effects on the living organism. Male Sprague-Dawley rats received for four weeks daily injections (0.5 ml sc) of liposomes built of dioleoyl phosphatidylethanolamine (DOPE), liposomes built of DOPE and APren-7 (ratio 10:1) or water solvent. Weekly, rats were observed in metabolic cages (24h); blood and urine were sampled for analysis; body weight (BW) and systolic blood pressure (SBP) were determined. After chronic experiment, kidneys and heart were harvested for histological and morphometric analysis. The 4-week BW increments were in the range of 97 ± 4 to 102 ± 4%, intergroup differences were not significant. Microalbuminuria was the lowest in the group receiving liposomes with APren-7 (0.22 ± 0.03 mg/day). Water and food intake, plasma and urine parameters were similar in all groups. Newly designed liposomes containing APren-7 did not affect functions of the excretory and cardiovascular systems, and renal morphology; therefore we find them suitable as a component of liposomal drug carriers. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. CaCO3/Tetraethylenepentamine-Graphene Hollow Microspheres as Biocompatible Bone Drug Carriers for Controlled Release.

    PubMed

    Li, Jie; Jiang, Hongkun; Ouyang, Xiao; Han, Shihui; Wang, Jun; Xie, Rui; Zhu, Wenting; Ma, Ning; Wei, Hao; Jiang, Zhongyi

    2016-11-09

    CaCO3 is one kind of important biological mineral, which widely exists in coral, shell, and other organisms. Since it is similar to bone tissue elements and has good biocompatibility, it was very suitable as a candidates for bone drug carriers. In this work, we used tetraethylenepentamine-graphene (rGO-TEPA) sheet matrices induction of CaCO3 mineralization and successfully constructed CaCO3/rGO-TEPA drug carriers with a hollow structure and rough surface. As potential drug carriers, doxorubicin (DOX) loading and release measurements were carried out. It showed that load efficiency was 94.7% and the release efficiencies were 13.8% and 91.7% at values of pH 7.4 and 5.0. The as-prepared drug carriers showed some appealing advantages, such as the pH-sensitive release characteristics and mild storage-release behaviors. The excellent biocompatibility and nontoxicity of CaCO3/rGO-TEPA hybrid microspheres were tested by the cell viability of mouse preosteoblast cells (MC3T3-E1). And cytotoxicity with human osteosarcoma cells (MG-63) was carried out to demonstrate the drug release effect in the cells system. Therefore, the CaCO3/rGO-TEPA hybrid microspheres would be a competitive alternative in bone drug carriers.

  4. Carbonyl-reducing enzymes as targets of a drug-immobilised affinity carrier.

    PubMed

    Andrýs, Rudolf; Zemanová, Lucie; Lenčo, Juraj; Bílková, Zuzana; Wsól, Vladimír

    2015-06-05

    Proteins, peptides and nucleic acids are commonly isolated and purified in almost all bioscience laboratories. Methods based on molecular recognition are currently the most powerful tool in separation processes due to their selectivity and recovery. The aim of this study was to prove the versatility and the ability of an affinity carrier containing the immobilised ligand oracin (previously developed by our workgroup) to selectively bind carbonyl-reducing enzymes. These enzymes play an important role in metabolic pathways of various endogenic compounds and xenobiotics. Many important drugs, such as doxorubicin, daunorubicin, haloperidol and the model anticancer drug oracin, are metabolised by carbonyl-reducing enzymes. The functionality of the presented carrier was demonstrated with pure recombinant enzymes (AKR1A1, AKR1B1, AKR1B10, AKR1C1, AKR1C2, AKR1C3, AKR1C4, CBR1 and CBR3) as well as with two model biological samples (cell extract from genetically modified Escherichia coli and pre-purified human liver cytosol). Enzymes that show an affinity toward oracin were efficiently captured, gently eluted using 150 mM ammonium hydroxide and subsequently identified by MS. The method is highly selective and robust and may be applied to the purification and identification of various carbonyl-reducing enzymes from any biological sample. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  5. Tamoxifen-loaded nanostructured lipid carrier as a drug delivery system: characterization, stability assessment and cytotoxicity.

    PubMed

    How, Chee Wun; Rasedee, Abdullah; Manickam, Sivakumar; Rosli, Rozita

    2013-12-01

    Cancer nanotherapeutics is beginning to overwhelm the global research and viewed to be the revolutionary treatment regime in the medical field. This investigation describes the development of a stable nanostructured lipid carrier (NLC) system as carrier for Tamoxifen (TAM). The TAM-loaded NLC (TAM-NLC) developed with 200mg of TAM showed a spherical particle with the size of 46.6nm, polydispersity index of 0.267, entrapment efficiency of 99.74% and with the zeta potential of -23.78mV. Besides, the equivalent cytotoxicity of TAM and TAM-NLC to human (MCF-7) and mice (4T1) mammary breast cancer cell lines were observed. Incubating the formulation at the physiological pH resulted into reduced Ostwald ripening rate but without any significant change in the absorptivity. When coupled with the measurements of zeta potential and Ostwald ripening rate, the absorbance assay may be used to predict the long-term stability of drug-loaded nanoparticle formulations. The results of the study also suggest that TAM-NLC is a promising drug delivery system for breast cancer therapy. This is the first encouraging report on the in vitro effect of TAM-NLC against human and mouse mammary adenocarcinoma cell lines. Copyright © 2013 Elsevier B.V. All rights reserved.

  6. Self-assembled vesicles prepared from amphiphilic cyclodextrins as drug carriers.

    PubMed

    Sun, Tao; Guo, Qie; Zhang, Cai; Hao, Jingcheng; Xing, Pengyao; Su, Jie; Li, Shangyang; Hao, Aiyou; Liu, Guangcun

    2012-06-12

    Controlled self-assembly of amphiphilic cyclodextrin is always a challenging topic in the field of supramolecular chemistry, since it provides the spontaneous generation of well-defined aggregation with functional host sites with great potential applications in drug-carrier systems. β-Cyclodextrin modified with an anthraquinone moiety (1) was successfully synthesized. In the aqueous solution, 1 was found able to self-assemble into vesicles, which was characterized in detail by TEM, SEM, EFM, and DLS. The formation mechanism of the vesicles was suggested based on the 2D ROESY and UV-vis results, and further verified by the MD simulation. Subsequently, the stimuli response property of the vesicles, including to Cu(2+) and H(+), was also studied. The vesicles can efficiently load Paclitaxel inside the membrane with functional macrocyclic cavities available, which can further carry small molecules, such as ferrocene. The vesicles loading with Paclitaxel have remarkable anticancer effects. This work will provide new strategy in drug-carrier systems and tumor treatment methods.

  7. The international pharmaceutical market as a source of low-cost prescription drugs for U.S. patients.

    PubMed

    Kesselheim, Aaron S; Choudhry, Niteesh K

    2008-04-15

    In response to increasing prescription drug costs, more U.S. patients and policymakers are importing less-expensive pharmaceutical products from other countries. Large-scale prescription drug importation is currently illegal, but the U.S. Food and Drug Administration permits individuals to bring in 90-day supplies of drugs for personal use. As patient use of foreign-bought drugs has increased, federal legislators have continued to debate the full legalization of importation. Three factors help guide whether U.S. patients and policymakers can rely on other countries as sources of imported prescription drugs: whether the safety of the product can be ensured, how the import price compares with domestic prices, and how importation might affect the exporting country's pharmaceutical market. In wealthier countries with active regulatory systems, drug safety can be adequately ensured, and brand-name products are usually less expensive than in the United States (although generic drugs may be more expensive). However, implementing large-scale importation can negatively impact the originating country's market and can diminish the long-term cost savings for U.S. consumers. In low- and middle-income countries, prices may be reduced for both brand-name and generic drugs, but the prevalence of unauthorized products on the market makes ensuring drug safety more difficult. It may be reasonable for individual U.S. consumers to purchase essential medicines from certain international markets, but the most effective way to decrease drug costs overall is the appropriate use of domestic generic drugs, which are available for almost every major therapeutic class.

  8. [Pharmaceutical assistance in the basic units of health: from the national drug policy to the basic attention to health].

    PubMed

    de Oliveira, Luciane Cristina Feltrin; Assis, Marluce Maria Araújo; Barboni, André René

    2010-11-01

    This study of theoretical revision discuss the Pharmaceutical Assistance in the Basic Units of Health, rescuing briefly the history of the National Drug Policy, the mechanisms of financing in the process of health decentralization and Pharmaceutical Assistance on the Basic Attention to Health. The expansion of the population access to the health system has demanded changes on drug distribution in order to increase the coverage and at the same time to reduce costs. It was identified advances in legal and institutional structures: the management decentralization of actions on pharmaceutical assistance; the expansion of the population access to essential medicines; and the establishment of the pharmaceutical assistance in some cities. However, it still persists priority actions in relation to the financing and population coverage, in detriment of quality processes. The conclusion is that, many Brazilian cities has low availability and discontinuity of essential medicine offer; dispensation by workers without qualification; inadequate conditions of storage that compromise the quality of medicines; medicine prescription that does not belong to the National Reference of Essential Medicines; and problems related to the access of users to the pharmacotherapy.

  9. High-throughput NIR-chemometric methods for determination of drug content and pharmaceutical properties of indapamide tablets.

    PubMed

    Tomuta, Ioan; Rus, Lucia; Iovanov, Rares; Rus, Luca Liviu

    2013-10-01

    This paper describes the development, validation and application of NIR-chemometric methods for API content and pharmaceutical characterization (disintegration time and crushing strength) of indapamide intact tablets. Development of the method for chemical characterization was performed on samples corresponding to 80, 90, 100, 110 and 120% of indapamide content and for pharmaceutical characterization on samples prepared at nine different compression forces (covering the interval 7-45 kN). NIR spectra of prepared tablets were recorded in transmission mode, and partial least-squares followed by leave-one-out cross-validation were used to develop models for the prediction of the drug content and the pharmaceutical properties of tablets. All developed models were validated in terms of trueness, precision and accuracy. No statistical differences were found between results predicted by NIR-chemometric methods and the ones determined by reference methods. Therefore, the developed NIR-chemometric methods meet the requirements of a high-throughput method for the determination of drug content, pharmaceutical properties of indapamide tablets.

  10. Inductively coupled plasma mass spectrometry in the analysis of biological samples and pharmaceutical drugs

    NASA Astrophysics Data System (ADS)

    Ossipov, K.; Seregina, I. F.; Bolshov, M. A.

    2016-04-01

    Inductively coupled plasma mass spectrometry (ICP-MS) is widely used in the analysis of biological samples (whole blood, serum, blood plasma, urine, tissues, etc.) and pharmaceutical drugs. The shortcomings of this method related to spectral and non-spectral interferences are manifested in full measure in determination of the target analytes in these complex samples strongly differing in composition. The spectral interferences are caused by similarity of masses of the target component and sample matrix components. Non-spectral interferences are related to the influence of sample matrix components on the physicochemical processes taking place during formation and transportation of liquid sample aerosols into the plasma, on the value and spatial distribution of plasma temperature and on the transmission of the ion beam from the interface to mass spectrometer detector. The review is devoted to analysis of different mechanisms of appearance of non-spectral interferences and to ways for their minimization or elimination. Special attention is paid to the techniques of biological sample preparation, which largely determine the mechanisms of the influence of sample composition on the results of element determination. The ways of lowering non-spectral interferences by instrumental parameter tuning and application of internal standards are considered. The bibliography includes 189 references.

  11. Animals on drugs: understanding the role of pharmaceutical companies in the animal-industrial complex.

    PubMed

    Twine, Richard

    2013-12-01

    In this paper I revisit previous critiques that I have made of much, though by no means all, bioethical discourse. These pertain to faithfulness to dualistic ontology, a taken-for-granted normative anthropocentrism, and the exclusion of a consideration of how political economy shapes the conditions for bioethical discourse (Twine Medicine, Health Care and Philosophy 8(3):285-295, 2005; International Journal of Sociology of Agriculture and Food 16(3):1-18, 2007, 2010). Part of my argument around bioethical dualist ontology is to critique the assumption of a division between the "medical" (human) and "agricultural" (nonhuman) and to show various ways in which they are interrelated. I deepen this analysis with a focus on transnational pharmaceutical companies, with specific attention to their role in enhancing agricultural production through animal drug administration. I employ the topical case of antibiotics in order to speak to current debates in not only the interdisciplinary field of bioethics but also that of animal studies. More generally, the animal-industrial complex (Twine Journal for Critical Animal Studies 10(1):12-39, 2012) is underlined as a highly relevant bioethical object that deserves more conceptual and empirical attention.

  12. Determination of aromatic hydrotropic drugs in pharmaceutical preparations by the surfactant-binding degree method.

    PubMed

    Pedraza, Ana; Sicilia, María Dolores; Rubio, Soledad; Pérez-Bendito, Dolores

    2005-07-01

    An aggregation parameter-based analytical approach, the surfactant-dye binding degree (SDBD) method, was used, for the first time, to determine aromatic hydrotropic compounds. The anionic dye Coomassie Brilliant Blue G (CBBG) was used as inductor of didodecyldimethylammonium bromide (DDABr) aggregates, whose formation was monitored from changes in the spectral features of the dye. Interactions between hydrotrope and DDABr molecules resulted in a decrease of the degree of binding of the cationic surfactant to CBBG, which was proportional to the concentration of hydrotrope in the aqueous solution. The CBBG-DDABr-hydrotrope chemical system was found to fit to the mathematical expression previously derived for the determination of amphiphilic compounds. The hydrotrope-surfactant bond strength determined the sensitivity achieved for the determination of hydrotropic compounds, which was highly dependent on the molecular structure of the analyte. The high precision (the relative standard deviation for 7 mg l(-1) of salicylic acid was 0.8%), rapidity (measurements were performed in a few minutes) and low cost (in both instrumentation and reactants) of the proposed method, made it especially suitable for quality control. The practical analytical applicability of the SDBD method for the control of hydrotropic drugs in pharmaceutical preparations was demonstrated by quantifying salicylic acid and acetyl salicylic acid in liquid (solutions) and solid (tablets, granulates, unguents, gels and creams) samples, which were directly analyzed after dissolution of the samples.

  13. Oxidative effects of the pharmaceutical drug paracetamol on the edible clam Ruditapes philippinarum under different salinities.

    PubMed

    Correia, Bárbara; Freitas, Rosa; Figueira, Etelvina; Soares, Amadeu M V M; Nunes, Bruno

    2016-01-01

    Paracetamol, a drug with analgesic and antipyretic properties, is one of the most used substances in human therapeutics, being also frequently detected in aquatic environments. Recent studies report its toxicity towards aquatic species, but the overall amount of data concerning its effects is still scarce. Global changes, likely alterations in abiotic conditions, including salinity, can modulate the interactions of contaminants with biota, conditioning the toxicological responses elicited also by pharmaceuticals. The present article describes the oxidative toxic effects posed by paracetamol on the clam species Ruditapes philippinarum under different salinity conditions. The results demonstrated the establishment of an oxidative-based effect, with significant alteration of several parameters, such as superoxide dismutase (SOD) and the ratio of reduced/oxidized glutathione (GSH/GSSG). Water salinity influenced the response of clams exposed to different paracetamol concentrations, showing the importance of studying physiological traits under realistic test conditions, which are likely to vary in great extent as a result of climate change. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. An overview of recent applications of inductively coupled plasma-mass spectrometry (ICP-MS) in determination of inorganic impurities in drugs and pharmaceuticals.

    PubMed

    Nageswara Rao, R; Talluri, M V N Kumar

    2007-01-04

    The recent applications of inductively coupled plasma-mass spectrometry (ICP-MS) in determination of trace level inorganic impurities in drugs and pharmaceuticals have been reviewed. ICP-MS coupled with LC, GC and CE was used for speciation of heavy metals in pharmaceutical products. The review covers the period from 1995 to 2005 during which the technique was applied not only for determination of metallic impurities but also the assay of various trace elements in pharmaceuticals.

  15. UV-curable gel formulations: Potential drug carriers for the topical treatment of nail diseases.

    PubMed

    Kerai, Laxmi Valji; Hilton, Stephen; Murdan, Sudaxshina

    2015-08-15

    Nail diseases are common, cause significant distress and treatments are far from successful. Our aim was to