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For this reason ketoconazole cream 15gm, many poorly soluble cheap ketoconazole cream 15 gm online, slowly dissolving drugs for oral drug delivery are marketed in a micronized or microcyrstalline form 15gm ketoconazole cream with visa. These include: Wetting agents Wetting agents are surfactants that lower the interfacial tension and contact angle between solid particles and liquid vehicles cheap 15gm ketoconazole cream. These agents are therefore commonly used to improve the wettability of hydrophobic compounds. Polysorbate 80 is the most widely used wetting agent because of its low toxicity and high compatibility with most formulation ingredients. For example, the common pharmaceutical wetting agent, sodium dodecyl sulfate, has been shown to increase the absorption of drugs and peptides across the human intestinal epithelium. Studies have confirmed that such agents enhance absorption via the paracellular pathway. Diluents Diluents are inert substances added to the active ingredient to bulk up the formulation, in order to make a reasonably sized tablet, or to fill a capsule. Carbohydrates are commonly used, such as lactose, dextrose, sucrose, and microcrystalline cellulose. Hydrophilic diluents promote rapid tablet disintegration and therefore liberate the drug quickly from the dosage form, which promotes absorption. Some diluents dissolve very slowly and therefore release of the drug occurs by tablet erosion, rather than tablet disintegration. However, a hydrophobic diluent impedes penetration of gastrointestinal fluids, so that dissolution of drug occurs only from the surface of the plug-shaped mass. Binders (adhesives) In tableting, binders are used to bind powders together in the wet granulation process. These agents coat the drug particles and therefore the rate of binder dissolution can determine the drug release rate. Disintegrants The purpose of a disintegrant is to cause the tablet to disintegrate rapidly, so as to generate an increased surface area which facilitates rapid drug dissolution. An alternative mechanism involves capillary action, in which liquid is drawn up through capillary pathways within the tablet and ruptures the interparticulate bonds, which serves to break the tablet apart. Obviously, disintegrants with high swelling and hydrating capacities promote rapid dissolution and thus a high bioavailability. Lubricants Lubricants act by interposing an intermediate layer between the tablet constituents and the die wall, to prevent adherence of the granules to the punch faces and dies. The most effective lubricants, such as magnesium stearate, are very hydrophobic and can also prevent wetting of powders and hence retard dissolution (Figure 6. Newer technologies may also incorporate additives such as enzyme inhibitors, to prevent premature degradation of enzymatically labile drugs. For example, the inclusion of trypsin inhibitors, such as soyabean trypsin inhibitor and aprotinin, have been shown to be effective in enhancing the effect of insulin in rats. Penetration enhancers may also be included to facilitate the uptake of poorly absorbed moieies. A brief overview of both the advantages and disadvantages of oral drug delivery is given below. Large surface area The total surface area of the small intestine in humans is approximately 200 m , which represents a large2 effective surface area for drug absorption. Rich blood supply The highly vascular surface of the gastrointestinal mucosa ensures rapid absorption and onset of action, as well as the maintenance of sink conditions. Zero-order controlled release Oral drug delivery offers the potential to achieve zero-order controlled release. Commercial advantages The cost of oral therapy is generally much lower in comparison to parenteral and other routes of delivery. In addition, a number of patient variables (gender, race, age, and disease state) can also drastically alter the absorption of orally administered drugs. As so many variables influence the availability of the drug at the target site, there is great potential amongst orally administered drugs for bioinequivalence. Adverse reactions Locally irritating or sensitizing drugs must be used with caution in this route. For example, some drugs are gastro-toxic, causing damage to the mucosal lining of the stomach. Adverse environmental effects The nature of the gastrointestinal environment also limits the types of drugs that may be administered via this route. Adverse environmental effects include: High metabolic activity The high metabolic activity creates a formidable biochemical barrier to the delivery of enzymatically labile drugs. In particular, the oral bioavailability of therapeutic peptides and proteins is very low (typically<1%). Extreme of pH Some drugs are acid-labile and are degraded by the highly acidic conditions of the stomach. Delays in gastric emptying rates can prolong the residence time of drugs in the stomach, increasing the potential for acid-mediated degradation. Intestinal motility Intestinal motility can severely constrain the contact time of a drug moiety with the absorbing surface. Mucus barrier Drug diffusion may be limited by the physical barrier of the mucus layer and the binding of drugs to mucus. P-glycoprotein efflux pump By restricting the transcellular flux of some molecules, this pump serves as further barrier to drug absorption. Impermeable epithelium 152 The organization and architecture of the gastrointestinal epithelium provides a substantial physical barrier to the absorption of large, hydrophilic molecules such as therapeutic peptides, proteins and oligonucleotides. For example, although insulin was commercially introduced in 1923, despite intensive research efforts directed towards attaining its oral delivery, all approaches have proven unsuccessful, and an oral form of insulin is as yet not commercially available. When rapid, efficient absorption of drugs is desired, aqueous solutions represent the oral dosage form of choice. Drugs in suspension are also readily absorbed because, as described above, the large available surface area of the dispersed solid facilitates rapid dissolution and absorption. Suspensions are also suitable for young children and patients who have difficulty in swallowing tablets and capsules. Emulsions are potentially useful for improving the bioavailability of lipid-soluble drugs. Soft gelatin capsules have been shown to be efficient and reliable dosage forms, and their use has grown in recent years. Effervescent tablets are less common, but provide a convenient method for supplying sufficient amounts of a drug for relatively rapid dissolution. They are based on an acidic material in combination with a dry carbonate salt, which react in water to liberate carbon dioxide. Buccal and sublingual tablets are also available for both local and systemic drug delivery and are described in Chapter 7.

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The Magic Room Technique The trance induction itself might be initiated through the use of drugs since this would clearly convey to the prisoner that he is unable to prevent himself from responding buy ketoconazole cream 15 gm fast delivery. The second stage of "trance induction" might utilize a situation which the author has described elsewhere (53) as the "magic room buy ketoconazole cream 15gm without a prescription. An example of this would be the case of the prisoner who is given a hypnotic suggestion that his hand is growing warm ketoconazole cream 15 gm overnight delivery. Or it might be suggested to the prisoner that when he wakes up a cigarette will taste bitter 15 gm ketoconazole cream with mastercard. Here again, he could be given a cigarette prepared to have a slight, but noticeably bitter, taste. In this manner, the idea could be conveyed to the subject that he is responding to the given suggestions. It can easily be seen how, with sufficient ingenuity, a large number of "suggestions" can be made to work by means unknown to the subject. The vital issue here would be that the subject became convinced that he was responding to suggestions and, for example, that the cigarettes really do not taste bitter, but that he experiences them as such because he cannot resist the suggesion. An unresolved question is the classification of the state in which a prisoner who collaborates under these circumstances finds himself. The crucial variable is the creation of a situation where the individual is legitimately able to give tip responsibility for his actions and therefore is permitted to avoid a threatening situation. It is probable that these manipulations occasionally would elicit some form of trance phenomenon, but the crucial aspect would be the situation, not the presence of a hypnotic state. Although the hypnotic situation as a tool of interrogation might yield information, the interrogator would have no more assurance of its accuracy than with the elicitation of information by hypnosis proper. The same cautions which have been stated with regard to hypnosis remain applicable here. Furthermore, for the success of the -208- technique the interrogator would have to act, in his relationship with the captive, as though the information must be correct. Consequently, the interrogator would be denied the use of techniques of cross examination upon which much of his success in deriving accurate information ordinarily depends. In constructing a pretense that the prisoner has lost responsibility for his behavior, he is also relieved of any responsibility for giving accurate and pertinent information. On the other hand, the interrogator could utilize to advantage any information he has that the subject does not know he has. For example, the informant could be given a hypnotic drug with appropriate verbal suggestions to talk about a given topic. Eventually enough of the drug would be given to cause a short period of unconsciousness. When the subject wakens, the interrogator could then read from his "notes" of the hypnotic interview the information presumably told him. It can readily be seen how this technical maneuver fits into the general concept of the "magic room," and how it would facilitate the elicitation of information in subsequent interviews. Although there is no direct evidence that such techniques have been or will be employed by interrogators nor any evaluation of their effectiveness, they represent simple extensions of hypnosis to traditional interrogation practices as described by Biderman (10). The effectiveness of the polygraph as a lie detection device is sometimes employed, apart from the use of the machine, to create a situation where the subject feels incapable of preventing himself from revealing the truth. According to Inbau and Reid (33), many of the confessions obtained with the lie detector are obtained before the actual use of the polygraph. The hypnotic situation has been discussed in detail in order to point oat the defensive procedures which can be taken to protect personnel from this type of interrogation. Similarly in the hypnotic situation, knowledge seems to be the most effective defense. Even one or two lectures on hypnosis might be highly effective in conveying the information that an individual cannot be hypnotized against his will, but that a situation can be devised where he could be tricked into believing that he has been hypnotized. Furthermore, demon- -209- strating that the individual is able to lie under hypnosis and cannot be compelled to speak the truth, or to follow suggestions really contrary to his beliefs, would probably be extremely effective. A method of "trance induction," similar to what we have called the "magic room," could be employed to produce a hypnotic situation. The use of the hypnotic situation, as opposed to hypnosis, would make this interrogation technique applicable to a greater percentage of potential informants. Defensive measures to protect personnel from those techniques depend upon the knowledge and confidence of the subject. Summary and Conclusions This report has attempted to evaluate the utility of hypnosis in interrogation procedures. Because of the dearth of evidence bearing directly on the question of the use of hypnosis in interrogation, the problem was broken down into a series of component questions, with each considered separately. A review of the available literature bearing on the question of whether trance can be induced in resistant subjects led us to conclude that such a possibility is extremely doubtful. Assuming that a trance may be induced in a potential informant, what degree of behavioral control does hypnosis allow? This question generally focuses on the possibility of inducing a subject to violate social prohibitions. Although many laboratory experiments have -210- been directed at this question, they suffer from the criticism that they are only, after all, "contrived" situations and the subject, in all probability, perceives them as such at some level. There are three documented cases of "real, nonlaboratory" situations involving the use of hypnosis for compelling criminal behavior. However, close scrutiny of these instances reveals that in each case an intense emotional relationship existed between hypnotist and subject. One need not invoke hypnosis to explain behavior on the part of one individual to please another, be it criminal or not, when an intense emotional relationship exists between the individuals involved. The question of the accuracy of information obtained during a hypnotic trance has been considered. It seems clear from the evidence that such information need not be veridical; the subject remains fully capable of distortions, despite hypnotic suggestions to the contrary. These various proposals lo utilize hypnosis as a defense against interrogation have been discussed: (a) to give hypnotic suggestions designed to prevent further trance induction, (b) to increase resistance to pain and psychic stress by appropriate posthypnotic suggestion, and (c) to induce amnesia posthypnotically for sensitive information in the event of capture. They function as artificially induced repressive mechanisms and suffer from the same drawbacks commonly seen in repression: a loss of ego control and a consequent lessened degree of flexibility in dealing with reality. Captured personnel are already threatened by loss of ego control, and we feel that proposals which would further impoverish the ego are extremely hazardous and would make the individual more vulnerable than he already is. We have suggested alternative defensive measures which would not sacrifice ego control, namely, appropriate instructions and the technique of autogenous training. The distinction has been drawn between the use of hypnosis per se and the hypnotic situation. The hypnotic situation could be used quite effectively for interrogation purposes. The common belief that -211- an individual in hypnosis is not responsible for his actions, although probably incorrect, could be exploited.

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The sampling protocol should be submitted Stability testing for long-term studies generally should in the drug application 15gm ketoconazole cream with mastercard. If the individual units example order 15gm ketoconazole cream amex, certain radiopharmaceuticals discount 15gm ketoconazole cream otc, the intervals entered the container randomly cheap 15 gm ketoconazole cream with mastercard, then samples may be taken between sampling times should be shortened. However, testing for accelerated studies generally should be per- because dosage units near the caps of large containers may formed at a minimum of four time points, including the have different stability properties than do dosage units in initial sampling time. For dosage units sampled of scheduling analysis is not an acceptable practice in this fashion, the location within the container from because it may cause delay in finding and responding to which the samples were taken should be documented and out-of-specification test results or may adversely affect the this information included with the test results. Unless the product is being tested for homogeneity, The degradation curve is estimated most precisely, in composites may be assayed, rather than individual units. If composites are used, increased number of replicates at the later sampling Stability Testing of Drug Substances and Drug Products 43 times—particularly the latest sampling time—is encour- 2. Expiration Dating Period aged because this will increase the average sampling time for an Individual Batch toward the desired expiration dating period. Annual Stability Batches within specifications depends not only on the rate of phys- ical, chemical, or microbiological changes but also on the After the expiration dating period has been verified with initial average value for the batch. Thus, information on three production batches, a testing program for an the initial value for the batch is relevant to the determina- approved drug product should be implemented to confirm tion of the allowable expiration dating period and should ongoing stability. For every approved application, at least be included in the stability study report. Percentage of one batch of every strength in every approved container label claim, not percentage of initial average value, is the and closure system, such as bottles or blisters, should be variable of interest. If the manufacturing interval is greater than 1 year, is based on the observed pattern of change in the quan- the next batch of drug product released should be added titative attributes (e. Bracketing and matrixing can be under study and the precision by which change is used to optimize testing efficiency. The recommendations in this section do not apply to An acceptable approach for analyzing an attribute that compressed medical gases, blood, or blood products. Data Analysis and Interpretation mated curve intersects the acceptable lower specification limit. Where the estimated curve is assumed to be linear for Long-term Studies based on 24 months of real-time data and the lower spec- A stability protocol should describe not only how the ification limit is assumed to be 90% of label claim, an stability study is to be designed and carried out but also expiration dating period of 24 months could be granted. When analyzing an attribute that is expected to increase This section describes an acceptable statistical approach with time, the 95% one-sided upper confidence limit for to the analysis of stability data and the specific features the mean is recommended. In When analyzing an attribute with both an upper and general, an expiration dating or retest period should be a lower specification limit, special cases may lead to appli- determined on the basis of statistical analysis of observed cation of a two-sided 95% confidence limit. Limited extrapolation of the real-time data although chemical degradation of the active ingredient in beyond the observed range to extend the expiration dating a solution product would cause a decrease in the assayed or retest period at approval time may be considered if it concentration, evaporation of the solvent in the product is supported by the statistical analysis of real-time data, (through the container and closure) would result in an satisfactory accelerated data, and other nonprimary stabil- increase in the concentration. If both mechanisms were acting, establish with a high degree of confidence an expiration the concentration might decrease initially and then dating period during which average drug product attributes increase. In this case, the degradation pattern would not such as assay and degradation products of the batch will be linear, and more complicated statistical approaches remain within specifications. If the approach presented in this should be applicable to all future batches produced by the section is used, average parameters such as assay and same manufacturing process for the drug product. In this setting, testing of individual units, sects the appropriate specification limit. The a priori correctness of the assumed described above, such as the assumption that the variability pattern of change as a function of time is crucial in the case of the individual units from the batch average remains con- of extrapolation beyond the observed range. When estimat- stant over the several sampling times, are well known and ing a line or curve of change within the observed range of have been discussed in numerous statistical texts. The above data, the data themselves provide a check on the correctness procedures will remain valid even when these assumptions of the assumed relationship, and statistical methods may are violated to some degree. If severe violation of the be applied to test the goodness of fit of the data to the line assumptions in the data is noted, an alternate approach may or curve. No such internal check is available beyond the be necessary to accomplish the objective of determining an range of observed data. For example, if it has been assumed expiration dating period with a high degree of confidence. Expiration Dating Period for All Batches range of the observed data, the true curve is close enough to a straight line that no serious error is made by approxi- If batch-to-batch variability is small, that is, the relation- mating the relationship as a straight line. However, beyond ship between the parameter of interest such as assay or the observed data points, the true curve may diverge from degradation products and time is essentially the same from a straight line enough to have a significant effect on the batch to batch, stability data should be combined into one estimated expiration dating period. Combining the data should be supported For extrapolation beyond the observed range to be by preliminary testing of batch similarity. The similarity valid, the assumed change must continue to apply through of the estimated curves among the batches tested should the estimated expiration dating period. Thus, an expiration be assessed by applying statistical tests of the equality of dating period granted on the basis of extrapolation should slopes and of zero time intercepts. The level of signifi- always be verified by actual stability data as soon as these cance of the tests, expressed in the P value, should be data become available. Computation of Expiration Date equality of intercepts do not result in rejection at a level of significance of. The data generated in If the preliminary statistical test rejects the hypothesis support of the assigned expiration dating period should be of batch similarity because of unequal initial intercept val- from long-term studies under the storage conditions rec- ues, it may still be possible to establish that the lines are ommended in the labeling. If so, the data may only a month and year, the product should meet specifi- be combined for the purpose of estimating the common cations through the last day of the month. E, the initial values and the common slope using appropriate should support at least a 1-year expiration dating period. If data from several batches are Exceptions do exist, for example, with short half-life combined, as many batches as feasible should be combined radioactive drug products. Extension of Expiration Dating Period expiration dating period will depend on the minimum time An extension of the expiration dating period based on full a batch may be expected to remain within acceptable limits. The expiration dating period may be extended The statistical methods for determining an expiration dating in an annual report only if the criteria set forth in the period beyond the observed range of time points are the approved stability protocol are met in obtaining and ana- same as for determining an expiration dating period within lyzing data, including statistical analysis if appropriate. To approval, it is feasible to extend the tentative expiration extend the retest period, full long-term data from a formal dating period based on full long-term data obtained from stability study on three production batches using a proto- these batches in accordance with the approved protocol, col approved in an application or found acceptable in a including statistical analysis if appropriate, through a Prior drug master file should be provided. However, the expiration dating Similar to the extension of an expiration dating period period thus derived remains tentative until confirmed with for a drug product, a retest period for a drug substance full long-term data from at least three production batches. This can be achieved through an annual a Prior Approval Supplement before the change is made, report based on full long-term stability data (i. If the data are obtained under a a drug substance, it may be inappropriate to use a retest new or revised stability protocol, a Prior Approval Sup- date. Shortening of Expiration Dating Period When warranted, a previously approved expiration dating period may be shortened via a Changes Being Effected 3. The Intermediates supplemental application should provide pertinent infor- Intermediates such as blends, triturates, cores, extended- mation and the data that led to the shortening of the expi- release beads, or pellets may be held for up to 30 days ration dating period. The expiration dating period should from their date of production without being retested before be shortened to the nearest available real-time long-term use.

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Vladimir Dobrokhotov Department of Physics and Astronomy buy ketoconazole cream 15 gm on-line, Western Kentucky University discount ketoconazole cream 15gm otc, Bowling Green discount 15gm ketoconazole cream, Kentucky safe ketoconazole cream 15 gm, U. Herrera Department of Civil and Environmental Engineering, University of Western Ontario, London, Ontario, Canada Zach Hilt Department of Chemical and Materials Engineering, University of Kentucky, Lexington, Kentucky, U. Holloway Department of Materials Science and Engineering, University of Florida, Gainesville, Florida, U. Kaushik Department of Biology & Microbiology/Veterinary Science, South Dakota State University, Brookings, South Dakota, U. Kwangmeyung Kim Biomedical Research Center, Korea Institute of Science and Technology, Seoul, South Korea Ajoy Koomer Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy, Louisville, Kentucky, U. Ick Chan Kwon Biomedical Research Center, Korea Institute of Science and Technology, Seoul, South Korea Robert P. University of Baroda, Vadodara, India Yashwant Pathak Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy, Louisville, Kentucky, U. Perumal Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, U. Podaralla Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, U. Lei Qian Department of Materials Science and Engineering, University of Florida, Gainesville, Florida, U. Sergei Rouvimov Laboratory for Structural Fingerprinting and Electron Crystallography, Department of Physics, Portland State University, Portland, Oregon, U. Venkata Vamsi Venuganti Department of Pharmaceutical Sciences, South Dakota State University, Brookings, South Dakota, U. Jinsong Wu Department of Materials Science and Engineering, Northwestern University, Evanston, Illinois, U. A Gian Paolo Zara Department of Anatomy, Pharmacology and Forensic Medicine, University of Turin, Turin, Italy Zhiguo Zhou Luna a nanoWorks (A Division of Luna Innovations, Inc. Recent Developments in Nanoparticulate Drug Delivery Systems Yashwant Pathak Department of Pharmaceutical Sciences, Sullivan University College of Pharmacy, Louisville, Kentucky, U. The biotechnology has also produced sev- eral potent drugs, but many of these drugs encounter problems delivering them in biological systems. Their therapeutic efficacy is significantly marred owing to their incompatibilities and specific chemical structure. The input of today’s nanotech- nology is that it allows real progress to achieve temporal and spatial site-specific delivery. The market of nanotechnology and drug delivery systems based on this technology will be widely felt by the pharmaceutical industry. In recent years, the number of patents and products in this field is increasing significantly. The most straightforward application is in cancer treatment, with several products (Table 1) in market such as Caelyx r , Doxil r , Transdrug r , Abraxane r , etc. In 1904, Paul Ehrlich (1854–1915), one of the great architects of medical sci- ence, published three articles in the Boston Medical and Surgical Journal, the imme- diate predecessor of the New England Journal of Medicine. These articles, which concerned Ehrlich’s work in immunology, were summaries of the Herter lectures he had given at Johns Hopkins University. They dealt with immunochemistry, the mechanism of immune hemolysis in vitro, and the side-chain theory of antibody formation. At the time of the Herter lectures, Ehrlich was at the peak of his intellec- tual powers and scientific influence. He was not only the father of hematology but also one of the founders of immunology. He made key contributions in the field of infectious diseases and, with his idea of the “magic bullet,” initiated a new era of chemotherapy (4). The concept of Paul’s magic bullet has turned out to be a reality with the approval of several forms of drug-targeting systems for the treatment of certain cancer and infectious diseases. In most cases, either polymers or lipids are used as carriers for the drug, and the delivery systems have particle size distribution from few nanometers to few hundred nanometers (Table 2). New and newer polymers have been tried to develop nanoparticles for their application as drug carriers. Various parameters such as particle size distribution, dimensional analysis, and zeta-potential were used to characterize these systems. These nanosystems were evaluated for cell compatibility, and their ability to escape phagocytosis was also characterized. Protein-based nanoparticulate drug delivery systems are defined as pro- teins being biodegradable, biocompatible, very versatile molecules, and can be used as drug carriers (28). A protein-based nanoparticulate drug delivery system is already in the market (paclitaxel-loaded albumin nanoparticles, Abraxane r ). Protein macromolecules offer many advantages over their synthetic counterparts (synthetic polymers that are commonly used as drug carriers). Terminologies used (nm) References Polymeric systems 1 Dendrimers 1–10 1,5 2 Polymer micelles 10–100 1 3 Niosomes 10–150 1 4 Nanoparticles 50–500 1,6–10 5 Nanocapsules 100–300 1,11,12 6 Nanogels 200–800 1 7 Polymer–drug nanoconjugates 1–15 13–16 8 Chitosan polymers 100–800 17,18 9 Methacrylate polymers 100–800 19 Lipid systems 1 Solid lipid nanoparticles 50–400 20 2 Lipid nanostructured systems 200–800 21 3 Cubosomes 50–700 1 4 Liposomes 10–1000 22 5 Polymerosomes 100–300 13 6 Immunoliposomes 100–150 13 Protein/peptide nanotubes 1 Peptide nanotubes 1–100 23 2 Fusion proteins and immunotoxins 3–15 13 Metal nanostructures 1 Metal colloids 1–50 1,9 2 Carbon nanotubes 1–10 (diameter) 1 and 1–1000 (length) 3 Fullerene 1–10 1 4 Gold nanoparticles 100–200 13,24 5 Gold nanoshells 10–130 13 6 Silicone nanoparticles 25 7 Magnetic colloids 100–600 26 when used as drug carriers. Owing to this property, these can be used for deliv- ering different drug molecules. As these protein molecules are biocompatible and biodegradable, this is a distinct advantage over their synthetic counterparts. Some of the natural organic and protein molecules are also described as carriers for drug. These are fabricated as nanoparticles or nanofibers for delivering the drugs (29–31). Gregory Gregoriadis in 1974 (32) lead to several breakthrough discoveries by using nanoparticles as drug carriers resulting from cutting-edge researches based on multidisciplinary approaches, many more applications have developed. We have 4 Pathak discussed in detail about the nanoparticulate drug delivery systems in our first vol- ume in chapters 1 and 13, which covered most of the development and technologies and applications till 2005. Several research reports have been published on the applications of nanoparticulate drug delivery systems using various drug entities and polymers and different forms of drug delivery systems. The employment of poly(butyl cyanoacrylate) nanoparticles showed high efficacy of nanoparticle-bound doxoru- bicin in intracranial glioblastoma in rats. An interest- ing review on the application of nanotechnology in breast cancer therapy is covered by Tanaka et al. More than 150 clinical trials are being conducted worldwide for the treat- ment of breast cancer by using nanotechnology-based products. This review covers different generations of nanotechnology tools used for drug delivery, especially in breast cancer. Injectable drug delivery nanovectors are used for cancer therapy, especially when multiple-drug therapy is used. These vectors need to be large enough to evade the body defense but should be sufficiently small to avoid blockages in even the capillaries. As these vectors are smaller than the diameters of the capillaries, the blockages can be effectively prevented (13).