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In looking to the future buy cheap zenegra on line erectile dysfunction pills viagra, much remains to be accomplished since the requirements for peptide drugs from pharmaceutical market and the development of genomics and proteomics will continue demanding greater versatility of design and synthesis of target structures buy zenegra with a visa erectile dysfunction treatment yoga. Peptide science and scientists have a number of cases that remain unresolved order zenegra without prescription erectile dysfunction treatment chinese medicine, yet they are ready to fnd the right answers buy 100 mg zenegra fast delivery erectile dysfunction for young men. From production of peptides in milligram amounts for research to multi-tons quantities for drugs of the future. Burrill & Company (2008) Analysis for pharmaceutical research and manufacturers of America. Poly(ethylene glycols) grafted onto crosslinked polystyrenes: a new class of hydrophilic polymeric supports for peptide synthesis. Preparation and use of an aminoethyl polyethylene glycol-crosslinked polystyrene graft resin support for solid-phase peptide synthesis. A reinvestigation of the preparation, properties, and applications of aminomethyl and 4-methylbenzhydrylamine polystyrene resins. On the development of new poly(styrene-oxyethylene) graft copolymer resin supports for solid-phase organic synthesis. Solid-phase synthesis of peptide isosteres by nucle- ophilic reactions with N-terminal peptide aldehydes on a polar support tailored for solid-phase organic chemistry. Proceedings of the 25th European Peptide Symposium Budapest: Akadémiai Kiadó, 1999, p 38–39. New Polyether Based Monomers, Crosslinkers, and Highly Crosslinked Amphiphile Polyether Resins. ChemMatrix, a poly(ethylene glycol)-based support for the solid-phase synthesis of complex peptides. Polyethylene glycol-based resins as solid supports for the synthesis of diffcult or long peptides. To Rink or not to Rink amide link, that is the question to address for more economical and environmentally sound solid-phase peptide synthesis. Direct visualization of enzyme inhibitors using a portion mixing inhibitor library containing a quenched fuorogenic peptide substrate. Inhibi- tion of cruzipain visualized in a fuorescence quenched solid-phase inhibitor library assay. An effcient strategy for the preparation of one-bead-one-peptide libraries on a new biocompatible solid support. Linkers and cleavage strategies in solid-phase organic synthesis and combinatorial chemistry. Yraola F, Ventura R, Vendrell M, Colombo A, Fernandez J-C, de la Figuera N, Fernandez-Forner D, Royo M, Forns P, Albericio F. C-terminal N-alkylated peptide amides resulting from the linker decomposition of the Rink amide resin. Incorporation of the Wang linker upon cleavage from polystyrene-based resin to form O-(4-hydroxy)benzyl derivatives. Selective and very mild deprotection of allyl and allyloxycarbonyl derivatives of amino acids. Selective cleavage of the allyl and (allyloxy)carbonyl groups through palladium-catalyzed hydrostannolysis with tributyltin hydride. Application to the selective protection-deprotection of amino acid derivatives and in peptide synthesis. Occurrence and minimization of cysteine racemization during stepwise solid-phase peptide synthesis. S-2,4,6-trimethoxybenzyl (Tmob): a novel cysteine protecting group for the N- -fuorenylcarbonyl (Fmoc) strategy of peptide synthesis. Use of the S-tert-butylsulfenyl group for protection of cysteine in solid-phase peptide synthesis using Fmoc amino acids. Oxidative fold- ing of cystine-rich peptides vs regioselective cysteine pairing strategies. Formation of optically pure N -acyl-N, N′-dicyclohexylurea in N,N′ -dicyclohexylcarbodiimide-mediated peptide synthesis. Reaction of N -t-butoxycarbonylamino acid anhydrides with tertiary amines and carbodiimides. A new method for the synthesis of peptides: activation of the car- boxyl group with dicyclohexylcarbodiimide and 1-hydroxybenzotriazoles. Advantageous applications of azaben- zotriazole (triazolopyridine)-based coupling reagents to solid-phase peptide synthesis. A compara- tive study of coupling reagents for automatic multiple peptide synthesizers. Peptides 2002, Proceedings of the European peptide symposium, 27th, Sorrento, Italy, 2002 Aug 31-Sept. Contribution on the course of reaction of carbobenzoxyamino acids with dicyclohexylcarbodiimide. Increased coupling yields in solid phase peptide synthesis with a modifed carbodiimide coupling procedure (1972). For a review of the work on the use of protected amino acid chlorides see:Schröder E, Lübke K. Triphosgene as highly effcient reagent for the solid-phase coupling of N-alkylated amino acids-total synthesis of cyclosporin O. A new facile one-pot preparation of pentafuorophenyl and 3,4-dihydro-4-oxo-1,2,3-benzotriazine-3-yl esters of Fmoc amino acids. Coupling N-methylated amino acids using PyBroP and PyCloP halogenophosphonium salts: mechanism and felds of application. Cyclization of all-L-pentapeptides by means of 1-hydroxy-7-azabenzotriazole-derived uronium and phosphonium reagents. Use of uronium and phosphonium salt coupling reagents in peptide synthesis in solu- tion. Occurrence and minimization of cysteine racemization during stepwise solid-phase peptide synthesis. New and highly effcient immonium-type peptide coupling reagents: syn- thesis, mechanism, and application. O-Benzotriazolyl-N,N-tetramethyluronium hex- afuorophosphate: a new and effective reagent for peptide coupling. O-Benzotriazolyl-N,N, N’,N’-tetramethyluronium hexafuorophosphate as coupling reagent for the synthesis of peptides of biological interest. Effciency in peptide coupling: 1-hydroxy-7-azabenzotriazole vs 3,4-dihydro-3-hydroxy-4-oxo-1,2,3-benzotriazine. Novel proton acceptor immonium-type coupling reagents: application in solution and solid-phase peptide synthesis. Morpholine-based immonium and halogenoamidinium salts as coupling reagents in peptide synthesis. Application of diphenyl phosphorazidate to the synthesis of peptides containing various functions.
Thus at the pH of the small intestine cheapest generic zenegra uk erectile dysfunction is often associated with quizlet, the drug is much less ionized than in the stomach and is therefore more readily absorbed generic zenegra 100 mg fast delivery erectile dysfunction statistics india. The amount3 of steroid passing from the reservoir through the membrane in 4 hours is 40 µg generic 100 mg zenegra overnight delivery youth erectile dysfunction treatment. Provided that the drug release rate be constant order zenegra in india erectile dysfunction treatment chicago, calculate the flux (F) that is defined as the amount of a solute flowing through a membrane per unit time. The effective surface area, permeability coefficient, thickness, and osmotic reflection coefficient of the semi-permeable membrane used for the pump are 3. Initially, the pump has a reservoir compartment with a drug4 2 having Cd of 100mg/ml, and the observed ∆π is 100 atm. Now, consider that we have changed the reservoir medium and osmotic agent to increase Cd of the drug from 100 to 300mg/ml and to increase ∆π from 100 to 300 atm, by how much will the release rate of the drug be increased? Solution As dV/dt is proportional to ∆π increasing both Cd and ∆π by 3 fold will result in an overall 9 fold increase in release rate of the drug. This book or any part thereof must not be reproduced in any form without the written permission of the publisher, except for any purpose of the United States Government. Bower, director of the Bureau, generously gave his time and talents to this project. The work of the editors was greatly facilitated by representatives of the Air Force, particularly Major Leo N. Dies mag vielen wehe, manchen wol getan haben, beides nicht meine Schuld und nicht mein Verdienst. Sigmund Freud in a letter to Romain Rolland, May 13 1926 * Introduction — manipulations of human behavior In recent years, concern has been expressed, in both scholarly and popular literature, about the dangers of scientific developments that could be used to control and manipulate human behavior. The fear is frequently voiced that techniques have been developed to an extent which threatens fundamental values of Western civilization. Anxious alarms and dramatic speculations have overshadowed reports of sober efforts to determine which dangers are real and which imagined. This book represents a critical examination of some of the conjectures about the application of scientific knowledge to the manipulation of human behavior. The problem is explored within a particular frame of reference: the interrogation of an unwilling subject. A number of scientific areas have figured prominently in speculations regardirig the application of science to the manipulation of behavior in interrogation (69). For this work, scientists who had done research in each of these areas were asked to review the state of relevant knowledge in their fields, to consider whether and how it might be applied by interrogators, and to evaluate the recourse available to highly motivated persons for resisting the attempted influence. Attention has been focused on interrogation because of the central position this topic has had in recent public discussions of prisoner-of-war behavior — issues that made scientific methods of manipulating behavior a major public concern. Air Force because of their interest in the problems which face the prisoner of war. Such aspects of prisoner exploitation as ideological conversion and the elicitation of false con- *E. Nonetheless, the editors believe that there are some major advantages to approaching the broader topic of the manipulation of human behavior by limiting attention initially to the latter type of situation. The background of recent concern with these problems may illuminate some of the considerations leading to the particular emphasis of this work. Background The notoriety that Communist exploitation of United Nations prisoners of war has received in the United States gave impetus to professional and lay concern with problems of the manipulation of behavior. Various writers have associated the compliance effected by Communist captors with phenomena observed in the laboratory; e. The most radical expressions of concern have alleged that techniques for manipulating behavior are now capable, or are at least on the threshold of being capable, of eliminating the determination of the subject as a barrier to successful influence (21, 32, 33, 34, 35, 36, 37, 38, 39, 44, 52, 60). These claims have been challenged: other investigators have been impressed by the strength, stability, and resilience of long-established values and social controls, and by rational regard for self-interest, either as limiting the compliance of those subjected to coercive and persuasive influence attempts, or as enabling the subject to resist completely (2, 4, 7, 11, 15, 18, 50, 53, 54, 55, 65, 66, 68). Certain other commentators have viewed the successful exploitation of captives in Korea and similar incidents as less indicative of increasing perfection in the arts of influence and coercion. They have attributed the successes of the captor to individual defects of background and stamina in the prisoners who collaborated, or to a general deterioration of the vitality of social values and controls in contemporary society (16, 25, 31, 61, 62, 63). Scientific examination of the manipulation of behavior has been made difficult by the intensity of the recent controversy over national -2- prisoner-of-war policy. There has been dispute regarding the extent to which individual repatriated prisoners of war are legally or morally responsible for deviations from ideal standards of military conduct, especially in the matter of yielding information or making "confessions" to the captor (9, 25, 31, 39, 41, 47, 49, 54, 64). A central question of fact has stood out in this controversy, quite apart from the moral and philosophical issues raised: whether all individuals, regardless of how strongly motivated to resist, could be made to comply with demands for information, "confessions," or other collaboration by methods employed by the Communists, provided that the intensity, duration, and quality of the pressures were sufficiently great. Critics of the policy evolved after the Korean War — "The Code of Conduct" — argued that the failure of the policy makers to consider imminent developments in scientific methods of human manipulation has been a more serious error than a lack of understanding of the practices actually encountered by prisoners in Korea. Air Force through their sponsorship has sought an authoritative examination of publicized speculations regarding the possible use of scientific developments in the manipulation of behavior against future prisoners of war. Aside from treatments of its more sensational aspects, -3- very little information on the topic appears in open-source literature. The dearth of sober information on interrogation has had the unfortunate consequence of facilitating the exploitation of United States prisoners of war by Communist captors (64). Our purpose here has been to bring together in one book authoritative information on methods of behavioral control that have been the subject of considerable speculation in discussions of interrogation. Scientists representing a variety of fields have examined a number of hypothetical means that might occur to an interrogator for eliciting information against the will of his subject. Their attention has been more on what could be done than on what actually may have been done. All the questions that are frequently raised about these methods cannot be answered by such an approach, however, since many of them are not translatable into scientific terms. Origin of Nonrational Concern Many scholars have observed that science replaces magic and witchcraft as societies secularize. The problems of living in the present age remain much as they have always been, however. The aspirations and anxieties that not so long ago were projected onto conceptions of the wizard and witch are now directed to the scientist. These opposites are incongruously exaggerated in paranoid thinking, one of the most prevalent mental symptoms of Western man. They doubtless exist in the fantasy of most persons, to extents that differ from paranoia in intensity and pervasiveness. The profound fascination of the topic under consideration may stem from the primitive, unconscious, and extreme responses to these problems, which gain expression in myth, dreams, drama, and literature. On the one hand, there is the dream- wish for omnipotence; on the other, the wish and fear of the loss of self through its capture by another. The current interest in problems of manipulation of behavior involves basic ambivalences over omnipotence and dependency, which, if projected, find a ready target in the "omniscient" scientist (30). With the perfection of mass-destruction weapons and the elaboration of totalitarian efforts to control human behavior, the myth has begun to converge with aspects of reality. Regarding weapons of physical destruction, responsible scientific evidence is offered along with uninformed and ill-informed surmises, both in support of forecasts of doom and in rebuttal. In the case of the threats science poses to human autonomy, however, sensationally speculative expressions, like those of the Brave New World that Aldous Huxley (21) recently revisited, have enjoyed a near monopoly.
Finally purchase zenegra 100 mg without prescription erectile dysfunction 19 years old, the use of the “multiple-antigenic-peptide” approach where many molecules are attached to a carrier with multiple attachment points can produce molecules that zenegra 100 mg discount erectile dysfunction doctors northern va, due to their size cheap 100mg zenegra with amex psychological erectile dysfunction wiki, are not recognized by proteases purchase 100mg zenegra with visa doctor's guide to erectile dysfunction. This chapter emphasizes the role of creative synthetic chemistry is the modifcation of peptides to achieve stability and bioavailability. The book concludes with Chapter 8, provided by Jeffrey-Tri Nguyen Yoshiaki Kiso, that discusses the important area of peptide delivery. While progress in the past 50 years has permitted peptide chemists to make almost any sequence of amino acids that is desired in high yield and purity, getting those molecules into humans and into the specifc area in the body where they can exert a therapeutic effect is a problem that has not progressed as rapidly. Thus, this chapter is very important for future advances in drug discovery based on peptides. Many of the readers may already be familiar with the Lipinski’s Rule of Five that includes recommendations for the size of a molecule, the number of hydrogen bonding atoms, and the lipophilicity. These rules are discussed in this chapter, but much more information is provided regarding solubility, membrane transport, and metabolic stability. In conclusion, this book provides a primer for anyone in the feld of drug discovery and specifcally in the area of the use of peptides as molecules for both the discovery phase and, in favorable cases, the fnal phase of the creation of new molecular entities that can be moved into further studies to evaluate their potential as therapeutic drugs. I want to thank the authors of the chapters for their friendship, for many discussions, and for their excellent writing for this book. Craik, Institute for Molecular Bioscience, The University of Queens- land, Brisbane, Queensland, Australia Ayman El-Faham, Department of Chemistry, Alexandria University, Alexandria, Egypt; Department of Chemistry, King Saud University, Riyadh, Kingdom of Saudi Arabia Gregg B. During that period a number of great peptide drugs such as Sandostatin, Lupron, Copaxone, and Zoladex were developed with great therapeutic beneft. It was not until the last decade that we have seen a signifcant surge in the number of peptide therapeutics on the market (Figure 1. While 10 peptides were approved between 2001 and 2010, the current decade has thus far witnessed the approval of six new peptide therapeutics – a remarkable yearly increase [1, 2]. The number of peptides in development is also steadily growing roughly doubling every decade (Figures 1. This is due to the advances made in our understanding of peptide stability, peptide syn- thesis, and formulation over the last three decades. Although the market share of peptide drugs is still relatively small (about 2% of the global market for all drugs), the approval rate for peptide drugs is twice as fast as the rate for small molecules, and the market is growing similarly at a rate that is twice the global drug market [3, 4]. With the exception of a few peptides, the approved drugs so far tar- get the extracellular compartment, and thus have to compete with biologics. We have seen a great advance in extending the circulating half-life of the peptides through the use of unnatural amino acids and formulation technologies, but have not yet reached the half-life achieved by antibodies. To dramatically heighten their impact, peptides need to access the intracellular space to target protein–protein interactions. These interactions represent a vast source of potential targets with signifcant biological impact (there are estimated 300,000 such interactions in the cell), and will not in the majority of cases be modulated by small molecules. Peptides and biologics, given their relative size and ability to bind to extended surface areas, are the perfect candidates to inhibit protein–protein interac- tions. The duration of action of peptides needs to be extended, and while peptides are inherently selective against their targets, they need to more selectively distribute to the desired tissue. Finally, the route of administration needs to be expanded to include oral delivery. Many of the techno- logical advances are already proving that it is possible to make peptides permeable to cells, target tissues, have longer half-lives, and be orally bioavailable. The discovery that certain peptides can penetrate cells and can, therefore, be an effective therapeutic on their own or alternatively bring other drugs into cells allowed for the frst time to imagine targeting the intracellular compartment (Figures 1. It is hard to compete with the screening of the mil- lions of small molecule compounds in various pharmaceutical companies and more recently in many academic centers. Indeed, over the last decade, there has been an explosion of very elegant tech- nologies that now allow the generation of large to extremely large libraries of linear and macrocyclic peptides with unnatural amino acids and unnatural linkers. For the frst time, it is possible to engineer stability, cell permeability, and possibly oral bioavailability at once and screen for the desired properties very rapidly. These major advancements have resulted in the generation of a number of companies that are pushing the limits of these technologies to rapidly screen and identify novel peptide therapeutics against protein–protein interaction targets (Figure 1. Through medicinal chemistry optimization, they have now identifed picomolar inhibitors with good properties . These peptides contain a com- bination of natural, unnatural, and N-methyl amino acids and exhibit good physico- chemical properties and membrane permeability . They recently presented on their discovery of potent antagonists of mcl-1 and Ras with good cell permeability . David Craik and colleagues at Cyclotide are systematically exchanging the various loops present on cyclotides with sequences that have important biological function . Moreover, novel technologies developed for the rapid generation and screening of extremely large libraries of knottins and cyclotides will undoubtedly have a major impact on this class of peptide therapeutics. Of note is the Intein-based technology from Julio Camarero capable of introducing unnatural amino acids to facilitate screening . Sutro and MitiBio also have very sophisticated and effcient biosynthetic methods to generate very large libraries. Finally, Verdine and Wollensky and colleagues [22, 23] as well as the investiga- tors at Aileron Therapeutics have developed a novel stapling technology that imparts stability and membrane permeability to alpha helical structure. This is due to the fact that once the peptide enters the cell, the major elimination pathway is through enzymatic catabolism. Not only can stability be tuned for circulating half-life, it can also be tuned to withstand cellular catabolism to lengthen the desired effcacy. This could offer a signifcant advantage over (small) molecules that passively diffuse through the cell membrane. Main reasons for diminished safety are selectivity against the target and tissue/cell specifcity. If one could direct a therapeutic to only the site of pathology, then the therapeutic window of the agent increases and correspondingly decreases the side effects. Peptides, due to their specifcity against receptors, are perfect candidates to be able to home into one type of cell/tissue versus another. There has been a tremen- dous amount of progress in identifying homing peptides (cell-penetrating as well as nonpenetrating) that can then be conjugated to a cargo to deliver it to a specifc organ . In vivo phage display by Pasqualini and colleagues marked the discovery of the frst homing peptide that was able to selectively target the blood vessel of brain and kidney . Since then a number of peptides have been identifed that target many other tissues . Arrowhead Research is currently in Phase I proof of targeting with a peptide drug conjugate utilizing this homing peptide. The majority of advances in this area have been the result of very interesting formulation strategies. They employ a combination of stabilizers, absorption enhancers, and carriers to achieve this. While signifcant, cyclosporin remains the only marketed peptide drug that is administered orally and absorbed into the systemic environment. Learning from nature and systematic studies on macrocyclic peptides will have a tremendous impact in discovering peptide drugs with inherent oral bioavailability that could then be enhanced through formulation to achieve bioavailabilities, which would compete with small molecules. As mentioned earlier, PeptiDream and Ra Pharmaceuticals are generating large libraries of macrocyclic peptides mimicking the core structure of cyclosporin.
Whether that means because of the way we do things in this ibility and facility throughput is high discount zenegra 100mg mastercard impotence with diabetes. As long as in multiproduct facilities that switch prod- will be more along the lines of using a unit people can think about how they can use ucts frequently purchase 100 mg zenegra otc erectile dysfunction drugs in canada, especially at small scale safe zenegra 100mg young living oils erectile dysfunction, for for a campaign purchase line zenegra vodka causes erectile dysfunction, then once the campaign the product as a disposable or semidis- example, in process development, produc- is done you get rid of it. So you still get the posable step and it makes sense to them, tion for clinical trials, or contract manufac- benefits of disposablility but leverage some then they can easily see it fit within the turing. Manufactur- rier is the availability of systems, includ- guidance, and it’s an easy step to make. This is what will take us down the path from leachables, poor documentation, and Greater capability and system choice will to truly game-changing technology in the increased risk of operator error. The job of In other words, outsourcing involves After the outsourced service provider an operations manager for a modern contracting a whole function, rather has been selected, the client and service pharmaceutical facility includes operat- than a specific task. Greater savings provider should agree on a well-defined ing and maintaining outlying building and efficiencies are found in outsourc- scope and clear objectives, which should services and the utilities required to cre- ing, rather than out-tasking. Using a risk-based approach, the capabilities, energy management, and Greater savings scope and responsibility of the service essential non-manufacturing services, provider can be built up over time, such as cleaning, building maintenance, and efficiencies which will ensure client satisfaction, spe- catering, and other ancillary services. In out-tasking, pharmaceutical tech- Identifying a key subject matter ex- nology and manufacturing companies Outsourcing energy services pert to serve as a liaison between the utilize third-party vendors to carry out Implementing highly reliable energy solu- service provider and client will ensure various maintenance tasks on specialized tions at research and manufacturing facil- compliance to quality and regulatory equipment, such as water-for-injection ities is a significant challenge for pharma- systems. The traditional model sign escalation and process flows for while leaving the responsibility for the has been to run a facility with the com- change controls and equipment devia- quality and scope of the work and the in- pany owning, operating, and maintaining tion, which pose the most risk to the ternal documentation in the hands of the all equipment itself, thus assuming expo- pharmaceutical manufacturer. For the sure to risk on issues such as equipment service provider, customer satisfaction durability, fuel volatility, and maintaining and adherence to quality systems in this the expertise required to keep the system highly regulated industry are essential. Pharmaceu- The client and service provider can tical facilities, however, are increasingly develop a performance scorecard that is embracing the outsourcing model. Each Mel Palmer is business development director • On-site generation and cogenera- line item can be linked to a performance for Veolia energy North america, marketing@ tion assets metric, and each metric can be weighted veoliaenergy. David Lyons is client operations manager at • Steam, hot-water, and chilled-water with agreed-upon scoring criteria that Dalkia ireland’s Pharmaceutical & healthcare division. Our added informatics capabilities continue to redeﬁne and Business Intelligence revolutionize the role of a services provider. Expect more and discover the Instrument Repair most comprehensive set of tools to help empower your science and drive Laboratory Relocation your business. Utility power outages the score to contract payments, by with- separate heat and power production. This multi-fuel core-business company headcount and, generated during the power production ability increases energy security as the pharmaceutical company becomes process can be captured, recycled, and and can also mitigate volatility in the customer of the service provider, to used for process applications without fuel commodity prices. Pharmaceutical research and Another key advantage of outsourcing other 12% are used by commercial and manufacturing processes are costly to energy management is that full-service institutional entities such as hospitals, operate, so outsourcing the facility’s en- outside providers possess the expertise municipal and state governments, col- ergy plant operations and management to evaluate, design, build, and then op- leges, and universities. Burning less fuel References ergy, which is used for heating, cooling, generates cost savings. For over 30 years Cangene bioPharma has successfully entered into cooperative arrangements to produce over 17 commercial and 175 clinical products for customers in more than 43 countries. It is possible, in some cases, to improve bioavailability to adequate levels while preserving the stability of a crystalline form. Cocrystal formation is a favored ap- proach for increasing apparent aqueous solubility for poorly water-soluble mol- ecules that have no ionizable groups, and for which salt formation is not possible, or for where the physical properties of the salts formed are not desirable. In many ways, a cocrystal can be thought of as a solvate, but one whose components in Solid-State Chemistry are solid at room temperature. The co- crystal will form if the resulting crystal is Patricia Van Arnum thermodynamically more stable than the components. To increase the probability cocrystals, particle-size reduction, and amorphous of success, we [Hovione] recommend that at early-development stages to test other solid dispersions, help to optimize delivery of a drug. What are the mechanisms for gies can be applied in various ways: crys- Crystallization controlling crystallization? Pharmaceutical further discussion and counter propos- crystal form, typically a polymorph that als from the industry. On the other hand, crys- Patricia Van Arnum crystalline materials containing two or tallization may also be a purification is executive editor of more molecules in the same crystal lat- stage, whereby the impurities remain Pharmaceutical technology, 485 Route One South, tice is limited but can serve as a start- mostly dissolved in the mother liquors. The degree of supersaturation, 60 Pharmaceutical Technology OctOber 2012 PharmTech. Sensient is a global leader in the development and manufacture of innovative coatings and colors for the pharmaceutical and nutraceutical industries. To use these meth- Particle-size reduction ods, however, the compound needs PharmTech: What factors determine Amorphous solid dispersions to be soluble in the polymer/matrix particle size? What are the differences PharmTech: What factors determine and physically stable complexes need in particle size achieved through jet- which method (i. The mecha- Minchom: Amorphous solid disper- established within the pharmaceutical nism of generating the material of the sions represent a tremendous oppor- industry, although spray-drying is a prescribed particle size has a profound tunity for solubility enhancement of step ahead in terms of maturity. Jet-milling method, is the most versatile technique the development of a stable amorphous and wet polishing may generate mate- to obtain solid dispersions due to its solid dispersion. Spray-congealing can rials with equivalent median particle gentle process conditions and much uses a number of lipophilic excipients, sizes; however, the resulting span from wider formulation options. Spray-dry- which are useful in formulating poorly jet-milled material is likely to be wider ing is a technology that works well in water-soluble compounds that will form than the wet-polished material. The research facilitates the process for evaluating the technology for licensing for commercial development with placing drugs from solution into an amorphous state. The researchers applied an acoustic levitator that uses two small Chris Benmore, an X-ray physicist at Argonne National Laboratory, speakers to generate sound waves at frequencies slightly above the led the study and teamed with various scientists for adapting the audible range at approximately 22 kilohertz (1). These scientists include Professors alignment of the top and bottom speakers, the speakers create two sets Stephen Byrn and Lynne Taylor in the Department of Industrial and of sound waves that produce a standing wave. At certain points along the Physical Pharmacy in the College of Pharmacy at Purdue University standing wave, there is no net transfer of energy. A video showing the technology may be found at are now working on identifying drugs most suited to applications with the laboratory’s website (www. The technology now can produce only small quantities in an amorphous Source state, but it is considered a useful tool in elucidating the conditions that 1. Sagoff, “Real-world Levitation to Inspire Better Pharmaceuticals” (Ar- optimize producing amorphous material. We are committed to providing quality services • Monograph Testing to our clients in support of their product development needs. We are committed to developing long • Container Closure Assessment term strategic alliances with our clients. Producing a well-ordered crystal, particularly part of understanding the protein’s biological properties and potential for proteins, which can be studied through crystallography, however, utility as a drug. Recent research involves examining the effects of can be subtle given the complexity of proteins and the noncovalent microgravity on protein crystallization and a computational model for interactions that govern crystallization (1). The research will examine the theoretical physical chemistry at the University of Pennsylvania, in a effect on protein crystallization using microgravity. Protein crystals are attractive as a nano-scale advancing protein crystallization using microgravity. The final agreement with Merck is dependent on containing a sequence of 26 amino acid positions.
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