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The gastric emptying time for a drug is most rapid with a fasting stomach cholesterol levels shrimp scallops purchase caduet 5mg amex, becoming slower as the food content is increased cholesterol score calculator cheap caduet online visa. Changes in gastric emptying time and/or in intestinal motility can affect drug transit time and thus the opportunity for drug dissolution and absorption cholesterol-laden definition buy generic caduet 5mg online. This can enhance the rate of absorption of drugs normally absorbed from the stomach and reduce the rate of absorption of drugs that are primarily absorbed from the small intestine cholesterol drug chart purchase caduet in india. Alternatively, drugs that enhance gastric motility, for example, laxatives, may cause some drugs to move through the gastrointestinal system and past their absorptive site at such a rate as to reduce the amount of drug absorbed. This effect has been demonstrated with digoxin, whose absorption is significantly decreased by accelerating gastrointestinal motility. In the elderly, gastric acidity, the number of absorptive cells, intestinal blood flow, the rate of gastric emptying, and intestinal motility are all decreased. However, drugs in which absorption depends on passive processes are not affected by these factors as much as those that depend on active transport mechanisms, such as calcium, iron, thiamine, and sugars. A decrease in gastric emptying time is advantageous for drugs that are absorbed from the stomach but disadvantageous for those that are prone to acid degradation, such as penicillins and erythromycin, or inactivated by stomach enzymes, such as l-dopa. The dissolution of a substance may be described by the modified Noyes-Whitney equation: dc = kS(c S - c t) dt where dc/dt is the rate of dissolution, k is the dissolution rate constant, S is the surface area of the dissolving solid, cs is the saturation concentration of drug in the diffusion layer (which may be approximated by the maximum solubility of the drug in the solvent, because the diffusion layer is considered saturated), and ct is the concentration of the drug in the dissolution medium at time t (cs - ct is the concentration gradient). The rate of dissolution is governed by the rate of diffusion of solute molecules through the diffusion layer into the body of the solution. The equation reveals that the dissolution rate of a drug may be increased by increasing the surface area (reducing the particle size) of the drug, by increasing the solubility of the drug in the diffusion layer, and by factors embodied in the dissolution rate constant, k, including the intensity of agitation of the solvent and the diffusion coefficient of the dissolving drug. For a given drug, the diffusion coefficient and usually the concentration of the drug in the diffusion layer will increase with increasing temperature. Also, increasing the rate of agitation of the dissolving medium will increase the rate of dissolution. A reduction in the viscosity of the solvent employed is another means to enhance the dissolution rate of a drug. Changes in the pH or the nature of the solvent that influence the solubility of the drug may be used to advantage in increasing dissolution rate. Effervescent, buffered aspirin tablet formulations use some of these principles to their advantage. The alkaline adjuvants in the tablet enhance the solubility of the aspirin within the diffusional layer, and the evolution of carbon dioxide agitates the solvent system, that is, gastric juices. Consequently, the rate of absorption of aspirin into the bloodstream is faster than from a conventional aspirin tablet formulation. If this dosage form is acceptable to the patient, it provides a quicker means for the patient to gain relief from a troublesome headache. Many manufacturers use a particular amorphous, crystalline, salt, or ester form of a drug that will exhibit the solubility characteristics needed to achieve the desired dissolution characteristics. As shown in the Noyes-Whitney equation, where dC = kS (Cs - C t) dT dC/dThis the rate of dissolution (concentration with respect to time); k is the dissolution rate constant; S is the surface area of the particles; Cs is the concentration of the drug in the immediate proximity of the dissolving particle, that is, the solubility of the drug; and Ct is the concentration of the drug in the bulk fluid. It is evident that Cs cannot be significantly changed, Ct is often under sink conditions (an amount of the drug is used that is less than 20% of its solubility), and k comprises many factors, such as agitation and temperature. This leaves the S, surface area, as a factor that can affect the rate of dissolution. An increase in the surface area of a drug will, within reason, increase the dissolution rate. Circumstances in which it may decrease the rate include a decrease in the effective surface area, that is, a condition in which the dissolving fluid cannot wet the particles. However, even though the surface area has been increased, the dissolution fluid-water-because of surface tension and so on cannot necessarily penetrate the new holes and displace the air. Adsorbed air and other factors can decrease the effective surface area of a dosage form, including powders. This is the reason that particle size reduction does not always raise the dissolution rate. One can also visualize a powder that has been comminuted to a very fine state of subdivision; when it is placed in a beaker of water, the powder floats because of the entrapped and adsorbed air. The effective surface area is not the same as the actual surface area of the powder. The chemical and physical characteristics of a drug substance that can affect safety, efficacy, and stability must be carefully defined by appropriate standards in an application for U. For drug substances that are poorly or slowly soluble, this generally results in an increase in the rate of dissolution. Increased therapeutic response to orally administered drugs due to smaller particle size has been reported for a number of drugs, among them theophylline, a xanthine derivative used to treat bronchial asthma; griseofulvin, an antibiotic with antifungal activity; sulfisoxazole, an anti-infective sulfonamide; and nitrofurantoin, a urinary anti-infective drug. Although not officially defined, micronized powders generally consist of drug particles reduced in size to about 5 mm and smaller. In the molten state and if the drug dissolves in the carrier, a molecular dispersion of the drug in the carrier results. Solidification produces a solid dispersion that can be pulverized and formed into tablets or capsules. When this powder is placed in water, the water-soluble carrier rapidly dissolves, leaving the poorly soluble drug molecules enveloped in water, thus forming a solution. For example, ophthalmic and topical ointments use micronized drugs for their preferred release characteristics and nonirritating quality after application. Because of the different rates and degrees of absorption obtainable from drugs of various particle sizes, products of the same drug substance prepared by two or more reliable pharmaceutical manufacturers may result in different degrees of therapeutic response in the same individual. A classic example of this occurs with phenytoin sodium capsules, which have two distinct forms. The former has a dissolution rate of not less than 85% in 30 minutes and is recommended for use three to four times per day.

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It provides low radiation dosimetry and highly efficient detection of photons by planar scintigraphy cholesterol chart hdl order caduet paypal. Unfortunately cholesterol lowering through diet order cheapest caduet, widespread use of this radionuclide in immunoscintigraphy has been hindered by the lack of a simple cholesterol level chart pdf buy discount caduet 5 mg line, efficient low cholesterol foods.com buy discount caduet 5 mg online, and stable method for attaching the 99m Tc to the antibody molecule. In addition, it has also been used for other diagnosing purposes, for example, imaging of lymphatic vessels and nodes draining a particular organ or disease site. The uptake of 89Sr by bone occurs preferentially in sites of osteogenesis imperfecta, a condition characterized by the formation of brittle bones prone to fractures. Thus, as mentioned, it finds utility with primary bone tumors and metastatic bone lesions. Prior to administration of 89Sr, a risk-tobenefit ratio must be determined because of its bone marrow toxicity. It should be used with caution in patients with platelet counts below 60,000 and white cell counts below 2,400. Because the average hematologic recovery time is 6 months of treatment, at least 90 days is required prior to retreatment. A small percentage of patients receiving 89Sr report a transient increase in bone pain 36 to 72 hours after injection. Pain relief from the administration of 89Sr typically manifests 7 to 20 days postinjection, and a key benefit of its use is a decreased dependence on opioids. Yttrium-90 (90Y) Yttrium-90 (90Y), a trivalent radioactive metal, is a pure beta-emitting radionuclide. TheraSphere is a therapeutic device approved for use in patients with liver cancer. It is being used for patients with biopsy-proven unresectable hepatocellular carcinoma. It is administered to a conscious patient via a catheter inserted into the femoral artery and is delivered directly into the hepatic artery in an interventional vascular radiology suite to go to the left or right lobe of the liver. This beta emission is very harmful to skeletal tissue, and thus, its clinical use is reserved for bone pain palliation associated with primary bone tumors and metastatic involvement (blastic lesions). An advantage of 89Sr is that it is retained and accumulated in metastatic bone lesions much longer and in significantly greater concentration than in normal bone. Following intravenous administration, strontium compounds demonstrate similar characteristics to calcium analogs. When administered to a clinically stable patient following the onset of myocardial infarct symptoms, it helps to assess the site and size of the perfusion defect. Identified ischemia on 201 Tl scanning has been demonstrated to be a strong predictor of long-term mortality in Figure 18. After injection, the product produces radiation to tissue with an average range of 2. These lodge in end arterioles and capillaries in tumors, which minimizes or prevents delivery of the injected radionuclide to other body organs and tissues. The sterile, pyrogen-free glass spheres are preformed by incorporating 89Y oxide into the glass matrix. Because the 90Y is embedded in the spheres, it is not leached from the glass or metabolized. However, longterm survival after major vascular surgery is improved significantly if patients with moderate to severe ischemia on preoperative 201Tl scanning undergo selective coronary revascularization (16). When used in conjunction with exercise stress testing to help differentiate between ischemic and infarcted tissue, 201Tl should be administered at the inception of a period of maximum stress sustained for 30 seconds after injection of the agent. Imaging commences within 10 minutes after administration to obtain maximum target-to-background ratios. If the patient is unable to undergo a treadmill stress exercise because of physical limitation, pharmaceutical agents Because of decreased blood flow, the uptake and washout of 201Tl are not quick in ischemic cardiac tissue. Chemically, this drug behaves similarly to ferric ion (Fe+ 3) and demonstrates a half-life of 78 hours. Investigational studies demonstrate that perhaps 67Ga accumulates in lysosomes and is bound to a soluble intracellular protein. The optimal target-to-background concentration ratios are often obtained 48 hours postinjection, and delayed imaging is necessary to allow for the ideal target-to-background ratio. However, considerable biologic variation can occur in individuals, and acceptable imaging may be performed 6 to 120 hours after injection. This could be problematic for those patients who demonstrate hypersensitivity to this preservative. The advantage of using 111In for immunoscintigraphy is its long half-life, which allows multiple images to be taken up to 10 to 14 days after administration. In addition, its dual photon peaks provide superior planar and tomographic images. ProstaScint images can aid management by helping identify when the cancer has metastasized from the prostate bed to regional lymph nodes or to distant soft tissues. During the infusion, the patient should be monitored for any hypersensitivity reaction and the infusion stopped if hypersensitivity occurs. If hypersensitivity does occur and is treated, the infusion is resumed at half the previous rate when symptoms improve. After rituximab infusion has been administered, within 4 hours, the diagnostic biodistribution dose of 5 mCi of 111In-labeled ibritumomab tiuxetan is injected over 10 minutes with use of a syringe shield to reduce exposure during administration.

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Ointments cholesterol in shrimp tempura generic caduet 5 mg visa, creams cholesterol test hdl ldl ratio 5mg caduet with amex, and suppositories acquire their characteristic features from their pharmaceutical bases cholesterol food free buy caduet paypal. Thus cholesterol mortality chart cheap caduet 5 mg with visa, for each dosage form, the pharmaceutical ingredients establish the primary features of the product and contribute to the physical form, texture, stability, taste, and overall appearance. Additional discussion of many ingredients may be found in the chapters where they are most relevant; for example, pharmaceutical materials used in tablet and capsule formulations are discussed in Chapters 7 and 8, and those used in modified-release solid oral dosage forms and drug delivery systems in Chapter 9. All drug products should be labeled to state the identity of all added substances (excipients). Such listing should be in alphabetical order by name and be distinguished from the identification statement of the active ingredient(s). If not listed in the above, then the reference works should be identified by the common or usual name or, if no common or usual name is available, by its chemical or other technical name. In such use, they are also called sequestering agents Used to impart color to liquid and solid Cosolvents, such as water and alcohol (hydroalcoholic) and water and glycerin, may be used when needed. May be used alone or with a colorant Used to impart an attractive sheen to coated tablets Used to render solution similar in osmotic-dextrose characteristics to physiologic fluids, for example, in ophthalmic, parenteral, and irrigation fluids Carrying agent used in formulating a variety of liquids for oral and parenteral administration Generally, oral liquids are aqueous Solutions for intravenous use are aqueous, whereas intramuscular injections may be aqueous or oleaginous Vehicle Flavored, sweetened Acacia syrup Aromatic syrup Aromatic elixir Cherry syrup Cocoa syrup Orange syrup Syrup Corn oil Mineral oil Peanut oil Sesame oil Bacteriostatic sodium chloride injection Used to render preparations more resistant to flow. Used in suspensions to deter sedimentation, in ophthalmic solutions to enhance contact time Alginic acid Bentonite Carbomer Carboxymethylcellulose Sodium Methylcellulose Povidone Sodium alginate Tragacanth Oleaginous Sterile Viscosityincreasing agent may or may not be present, it should be qualified by words such as "or" or "may also contain. Each monograph includes such information as nonproprietary, chemical, and commercial names; empirical and chemical formulas and molecular weight; pharmaceutical specifications and chemical and physical properties; incompatibilities and interactions with other excipients and drug substances; regulatory status; safety, stability, and handling information; and applications in pharmaceutical formulation or technology. These qualities, which are the rule rather than the exception, have virtually eliminated the natural reluctance of many patients to take medications because of disagreeable odor or taste. There is some psychologic basis to drug therapy, and the odor, taste, and color of a pharmaceutical preparation can play a part. An appropriate drug has its most beneficial effect when it is accepted and taken properly by the patient. The proper combination of flavor, fragrance, and color in a pharmaceutical product contributes to its acceptance. An "electronic tongue" is used to aid in providing a global "taste fingerprint" during formulation development. It provides information on bitterness levels and the stability of flavors in terms of taste (Figure 4. The 10,000 taste buds on the tongue, roof of the mouth, cheeks, and throat have 60 to 100 receptor cells each (13). These receptor cells interact with molecules dissolved in the saliva and produce a positive or negative taste sensation. Medication in liquid form comes into immediate and direct contact with these taste buds. The addition of flavoring agents to liquid medication can mask the disagreeable taste. Drugs placed in capsules or prepared as coated tablets may be easily swallowed with no contact between the drug and the taste buds. Tablets containing drugs that are not especially distasteful may remain uncoated and unflavored. Swallowing them with water usually is sufficient to avoid undesirable taste sensations. However, chewable tablets, such as certain antacid and vitamin products, usually are sweetened and flavored to improve acceptance. The flavor sensation of a food or pharmaceutical is actually a complex blend of taste and smell, with lesser influences of texture, temperature, and even sight. In flavorformulating a pharmaceutical product, the pharmacist must give consideration to the color, odor, texture, and taste of the preparation. It would be incongruous, for example, to color a liquid pharmaceutical red and give it a banana taste and a mint odor. The color of a pharmaceutical must have a psychogenic balance with the taste, and the odor must also enhance that taste. Although there are no rules for unerringly predicting the taste sensation of a drug based on its chemical constitution, experience permits the presentation of several observations. For instance, although we recognize and assume the salty taste of sodium chloride, the formulation pharmacist knows that not all salts are salty but that their taste is a function of both cation and anion. Whereas salty tastes are evoked by chlorides of sodium, potassium, and ammonium and by sodium bromide, bromides of potassium and ammonium elicit bitter and salty sensations, and potassium iodide and magnesium sulfate (epsom salt) are predominantly bitter. In general, low molecular weight salts are salty, and high molecular weight salts are bitter. Sucrose, which has eight hydroxyl groups, is sweeter than glycerin, another pharmaceutical sweetener, which has three hydroxyl groups. In general, the organic esters, alcohols, and aldehydes are pleasant to the taste, and since many of them are volatile, they also contribute to the odor and thus the flavor of preparations in which they are used.

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Among the materials used in the manufacture of the various valve parts are plastic anti cholesterol medication side effects caduet 5mg otc, rubber cholesterol definition nutrition order caduet 5mg otc, aluminum cholesterol test ratio results generic caduet 5mg fast delivery, and stainless steel cholesterol jumped 50 points buy caduet 5mg line. Actuator: the button the user presses to activate the valve assembly for emission of the product. The design of the inner chamber and size of the emission orifice of the actuator contribute to the physical form (mist, coarse spray, solid stream, or foam) in which the product is discharged. The type and quantity of propellant used and the actuator design and dimensions control the particle size of the emitted product. Larger orifices (and less propellant) are used for products to be emitted as foams and solid streams than for those intended to be sprays or mists. Stem: supports the actuator and delivers the formulation in the proper form to the chamber of the actuator 3. Gasket: placed snugly with the stem and prevents leakage of the formulation when the valve is closed 4. Spring: holds the gasket in place and is the mechanism by which the actuator retracts when pressure is released, returning the valve to the closed position 5. Mounting cup: attached to the aerosol can or container and holds the valve in place. Because the underside of the mounting cup is exposed to the formulation, it must receive the same consideration as the inner part of the container with respect to meeting criteria of compatibility. Housing: Directly below the mounting cup, the housing links the dip tube and the stem and actuator. With the stem, its orifice helps to determine the delivery rate and the form in which the product is emitted. Dip tube: extends from the housing down into the product; brings the formulation from the container to the valve. The actuator, stem, housing, and dip tube are generally made of plastic, the mounting cup and spring of metal, and the gasket of rubber or plastic resistant to the formulation. Metered-Dose inhalers Metering valves are employed when the formulation is a potent medication, as in inhalation therapy. In these metered valve systems, the amount of material discharged is regulated by an auxiliary valve chamber by virtue of its capacity or dimensions. A single depression of the actuator causes evacuation of this chamber and delivery of its contents. However, in this position, the chamber is permitted to fill with the contents of the container, to which it is open. Depression of the actuator causes a simultaneous reversal of positions; the chamber becomes open to the atmosphere, releasing its contents, at the same time becoming sealed from the contents of the container. As noted previously, the effectiveness of delivering medication to the lower reaches of the lungs for local or systemic effects depends in part on the particle size of the inhaled drug. Breathing patterns and the depth of respiration also play important roles in the deposition of inhaled aerosols to the lungs. The product contains 200 doses of nitroglycerin in a propellant mixture of dichlorodifluoromethane and dichlorotetrafluoroethane. Filling operations As explained earlier, fluorinated hydrocarbon gases may be liquefied by cooling below their boiling point or by compressing the gas at room temperature. The cooling system may be a mixture of dry ice and acetone or a more elaborate refrigeration system. After the chilled product concentrate has been quantitatively metered into an equally cold aerosol container, the liquefied gas is added. The heavy vapors of the cold liquid propellant generally displace the air in the container. When sufficient propellant has been added, the valve assembly is inserted and crimped into place. Because of the low temperatures required, aqueous systems cannot be filled by this process, because the water turns to ice. For nonaqueous systems, some moisture usually appears in the final product due to the condensation of atmospheric moisture within the cold containers. The desired amount of propellant is allowed to enter the container under its own vapor pressure. When the pressure in the container equals that in the burette, the propellant stops flowing. The trapped air in the package may be ignored if it does not interfere with the quality or stability of the product, or it may be evacuated with a special apparatus. After the container is filled with sufficient propellant, the valve actuator is tested for proper function. This spray testing also rids the dip tube of pure propellant prior to consumer use. It has two advantages over cold filling: There is less danger of moisture contamination of the product, and less propellant is lost in the process. When compressed gases are employed as the propellant in aerosol systems, the gas is transferred from large steel cylinders into the aerosol containers. Prior to filling, the product concentrate is placed in the container, the valve assembly is crimped into place, and the air is evacuated from the container by a vacuum pump.

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