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By F. Kurt. Gallaudet University.

Transfer the paste quantitatively into a 1 litre volumetric flask and shake thoroughly generic 1000 mg carafate overnight delivery symptoms of gastritis in cats. Take a 100 ml volumetric flask buy cheap carafate 1000mg on-line gastritis diet , rinse it with a small quantity of the suspension from the 1 litre flask and finally fill it up with the suspension. Rinse out a 250 ml iodine flask containing a little dilute acetic acid and a little of the suspension from the 1-litre flask in order to oxidise any inorganic substance present in the iodine flask. From this value the percentage of chlorine present in the given sample of chlorinated lime can be calculated. Ferric Ammonium Citrate Theory : In ferric ammonium citrate it is taken for granted that the entire iron is oxidized to the Fe2+ state and practically little Fe2+ is present. Add to it slowly 1 ml of sulphuric acid and warm gently to attain a yellow colouration so as to decompose the iron and ammonium citrate complex completely. Thyroid Thyroxine and diidotyrosine are the two iodine-substituted organic compounds which essentially con- stitute the active principles present in dried thyroid gland. Therefore, the equivalent weight of the iodine present in the dried thyroid gland is 21. Add 2 ml of dilute phosphoric acid and 5 ml of potassium iodide solution and titrate immediately with 0. A blank estimation is also carried out simultaneously and necessary correction incorporated. Cognate Assays A few pharmaceutical substances can be assayed by titrating the liberated iodine from potassium iodide with sodium thiosulphate as stated in Table 7. Iodimetic titrations may be accomplished by two methods : (a) Direct titration with iodine (b) Residual titration method. How would you assay the following ‘drugs’ by iodimetric titrations : (i) Analgin (ii) Ascorbic Acid (iii) Benzylpenicillin (iv) Mechlorethamine Hydrochloride. Explain the assay of the following ‘drug substances’ by using ‘direct iodometic method’ : (i) Chlorinated line (ii) Ferric Ammonium Citrate (iii) Thyriod (iv) Mannitol. Chakrabarti, Kinetics of Decomposition of Tetrathionate, Trithionate and Thiosulphate in Alkaline Media, Enrion. Generally, it is quite difficult and tedious to locate the exact point at which further addition of reagent affords no more precipitation. There- fore, the choice and wisdom of a chemical reaction is preferably sought so as to result in either a coloured solution or a coloured precipitate at the end point. A typical instance may be cited by application of potassium chromate (K2CrO4) solution in the above case whereby any extra drop of silver nitrate, after all the chloride has been precipitated, immediately causes precipitation of red chromate showing that the end point has been duly achieved. It is, however, interesting to observe here that such reactions do offer limited usage because of the following two facts, namely : (i) Co-precipitation effects do not give a real composition of the precipitate, and (ii) Choice of appropriate indicator is very much limited. Besides, the foregoing facts another vital aspect to be taken into consideration is the solubility product that plays a major role in such titration. Hence, the equilibrium constant of the reaction giving the precipitate of AgCl may be expressed as : AgCl (s) → Ag+ (aq) + Cl– (aq) + [Ag ][Cl ] or K = [AgCl] From the above expression the solubility product constant Ksp may be designated as : Ksp = [Ag+] [Cl–] assuming the activity of solid AgCl being constant. At this juncture, the concentrations of both Ag+ and Cl– are related by the solubility-product equilibrium constant ; thus, we have : Ag+ (titrant) + Cl– (analyte) AgCl(s) Chromate ion concentration required to initiate the precipitation of Ag2CrO4 commences at the equivalence point and may be calculated with the solubility products for AgCl and Ag2CrO4 : AgCl : Ksp = 1. Therefore, normally concentrations of 5 × 10–3 M are employed in analytical procedures. However, it has been proved experimentally that even with concentrations as low as 2 × 10–3 M, the extent of error caused is negligibly small. Adsorption-coprecipitation phenomenon using fluorescein, dichlorofluorescein and tetrabromofluo- rescein (eosin) essentially impart the fluoresceinate ion that is absorbed on the AgCl particles. At the equiva- lence point, the AgCl particles change from white to pink due to the coprecipitation of silver fluoresceinate. Add 5 ml of acetic acid, 50 ml of methyl alcohol and three drops of eosin solution. Stir thoroughly on a magnetic stirrer and titrate with the silver nitrate solution till the white particles of AgCl change from white to pink. Allow the resulting mixture to stand for 2 minutes, and then titrate with N sulphuric acid, employing phenolphthalein solution as indicator till a colour change from pink to colourless is achieved. Explanation : (i) The estimation depends upon the interaction between chloral hydrate and sodium hydroxide as shown by the following equation : C. Precautions : (i) Nitric acid must be free from nitrous acid, otherwise thiocyanic acid may give an instant red colouration, and (ii) Temperature of the solution should be maintained below 25°C since at an elevated temperature the red colour of the ferric thiocyanate complex fades away rapidly. Note : Soon after the addition of ammonium thiocyanate a white precipitate of silver thiocyanate is formed first and then a reddish-brown colour appears that fades out completely upon shaking thereby leaving a white precipitate of silver thiocyanate. The end-point is indicated by the appearance of a permanent faint reddish brown colour that does not vanish upon shaking. Add to it 5 ml of sodium hydroxide solution, and boil under a reflux condenser for 15 minutes.

As the vaginal epithelial membrane barrier becomes thin purchase carafate no prescription gastritis diet , loose and porous cheap carafate 1000mg chronic gastritis outcome, the permeability is enhanced, particularly to hydrophilic substances. Thus even high molecular 280 weight hydrophilic drugs can be absorbed by the intercellular route during the metestrous and diestrous phases. Several examples of this phenomena are described below: Salicylic acid Vaginal absorption of salicylic acid in different pH buffers has been investigated in rats during proestrus and diestrus. For the unionized, lipophilic form of the drug, the rate of vaginal absorption is rapid and similar for both stages. The unionized, lipophilic form is absorbed via transcellular passive diffusion and thus not affected by the stage of the estrous cycle. However, for the ionized, water-soluble form, a significant difference in the degree of absorption is observed: • proestrus (tight epithelium)=29% absorbed; • diestrus (porous epithelium)=66% absorbed. The hydrophilic form is absorbed mainly through pore-like pathways such as the intercellular channels and thus is highly dependent on the stage of the cycle, with greater absorption occuring when the interceullular channels are wide and porous. The percentage of the dose of phenol red excreted in the urine increased more than an order of magnitude from the proestrous phase (2. Leuprorelin showed similar enhanced absorption during the permeable phase of the estrous cycle (Figure 11. Penicillin In humans high blood levels of penicillin, sufficient to be therapeutic, were demonstrated following insertion of a vaginal suppository near the end of the menstrual cycle and during menopause. In contrast, absorption was shown to be somewhat diminished during estrus and late pregnancy. Vidaribine The permeability coefficients of the hydrophilic antiviral compound vidaribine are 5 to 100 times higher during early diestrus or diestrus than during estrus. These results confirm that the cyclic changes in the reproductive system have profound implications for vaginal drug delivery as: • the vaginal permeability to hydrophilic substances is enhanced during the metestrous and diestrous stages of the estrous cycle, corresponding to the late luteal and early follicular phases of the menstrual cycle; • large fluctuations in absorption occur, depending on the particular stage of the menstrual cycle. Although it is well known that carrier-mediated transport systems exist for di- and tripeptides in the intestine, there is still no evidence for carrier-mediated transport of peptides across the vaginal mucosa, although prostaglandins have been demonstrated to utilize such a mechanism. Although there must be some type of endocytic transport of endogenous peptides into the epithelial cells in order to regulate proliferation, no receptor-mediated or bulk-fluid mechanisms have been reported. Hydrophilic compounds may be absorbed via the paracellular route, moving between the epithelial cells via passive diffusion whereas lipid soluble drugs are usually absorbed transcellularly, at rates which correlate with their lipid/water diffusion coefficients. However, in the vagina these factors must be considered in conjunction with the cyclical changes in the vaginal epithelium. Thus hydrophilic compounds show enhanced absorption during metestrus and diestrus, when the vaginal barrier becomes thin, loose and porous. In addition to physicochemical properties of the drug such as size, pKa, chemical stability etc. Furthermore, peptides and proteins are susceptible to self-association, aggregation or polymerization in the medium due to changes in pH, ionic strength of the medium, or concentration of the substance. It is anticipated that the monomer, oligomer, or aggregated complex may each have a characteristic diffusion and permeation coefficient. Further physicochemical factors associated with the drug which influence vaginal drug delivery include the solubility and stability of the drug in the vaginal fluids. Poorly soluble drugs may demonstrate rate- limiting dissolution in the vaginal fluids. For example, the vaginal absorption of metronidazole is limited not only by the drug permeability across the vaginal epithelium, but also by its dissolution into the small volume of fluid within the vaginal cavity. Such formulations are administered with the aid of an appropriate applicator into the vagina and have different characteristics with respect to ease of administration, drug release profile, sanitary aspects etc. Desirable attributes of all vaginal preparations include: • no adverse reactions, such as tissue irritation; • ease of application; • even distribution of the drug throughout the vagina, rather than being concentrated in one spot; • retention of the drug in the vagina, even when the patient is standing and walking; • absence of an offensive odor; • absence of staining of clothes or skin; • compatibility with other forms of medication and contraception; • minimal interference in sexual activity. Formulation factors which affect vaginal drug delivery which are common to the various types of vaginal dosage forms include: Drug release As discussed above, there is a relatively small volume of fluid within the vaginal cavity. Thus the rate- limiting step for systemic absorption of drugs from intravaginal creams, inserts and tablets is often dissolution within the vaginal fluid, particularly for poorly soluble drugs. Obviously, the type of dosage form affects the rate of dissolution; for example, a drug which is already dissolved in an aqueous vaginal gel will be more rapidly absorbed than a drug which is in solid form within a vaginal tablet preparation. The effective area of contact Although the area of the vaginal cavity is approximately 60 cm , the formulation will influence the size2 of the area over which the drug is deposited. The vehicle should facilitate even distribution of the drug throughout the vagina, rather than concentrating it in one spot. Factors such as the hydrophilicity and viscosity of the vehicle will determine how well it spreads through the vagina. Contact time The formulation will also influence the extent of the contact time the drug has with the absorbing surface of the vaginal epithelium. Typical delivery systems such as foams, gels and tablets are removed in a relatively short period of time by the self- cleansing action of the vaginal tract. New bioadhesive gel delivery systems are being developed to prolong contact time with the absorbing surface and are described below. Concentration The rate of absorption via passive diffusion processes (transcellular and paracellular) can be increased by increasing the drug concentration in solution at the absorbing surface (see Section 1. For systems intended for prolonged administration, a highly saturated formulation will also ensure that sufficient drug is present to ensure sustained drug delivery throughout the intended time of application.

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This may cause an overloading of the ciliary transport process cheap carafate 1000mg mastercard gastritis diet , resulting in 257 a debilitated mucociliary clearance and the build-up of mucus as a thick order cheapest carafate and carafate gastritis diet , highly viscous layer. Thus while the mucociliary clearance of particles takes hours under normal circumstances, induced coughing may result in rapid removal of mucus and any associated drug within minutes. It should be remembered, however, that aerosolized drug deposition is likely to occur over a large surface area in the healthy and mild to moderate airways diseased lung. Coughing will remove mucus from a few localized areas where build-up has occurred and thus the fraction of the deposited dose removed by coughing is likely to be small. In cases of severe lung disease, drug deposition is likely to be highly localized and the situation may be different. For example, in cystic fibrosis patients, high levels of gentamicin, representing significant proportions of the deposited dose, were found in the sputum, when the aerosolized drug was deposited in the central airways. The main route is via the mucociliary escalator, although transport from the A region to the start of the mucociliary escalator is a very slow process and may involve transport through interstitium and lymphatic tissues in addition to a transfer by random movement by macrophages. Macrophages may also be transported via lymphatic systems to lymph nodes and the bloodstream. The uptake of particles by macrophages is a fairly rapid process but the subsequent clearance of particle-laden macrophages only occurs over days or weeks. Absorption is clearly important for systemically-acting drugs since it is one element of the events leading to delivery of drug to its site of action. Absorption is equally important for locally-acting drugs since for these compounds it represents removal of drug from its site of action. Metabolism of drugs is also an important consideration since it may lead to drug inactivation or the production of active or toxic metabolites. These same features also offer great potential for the delivery of systemically-acting compounds. The surface area of the airways is approximately 140 m , slightly larger than that of the small intestine. More importantly, however, a well-2 designed aerosol system can rapidly deliver drug to a high proportion of this surface area, whereas an orally delivered drug will have its access to the small intestine delayed by gastric emptying. In some parts of the alveolar region the airways to blood pathlength is less than 0. This property facilitates very rapid transfer of gases, vapors and other small molecules. Drug absorption from this region is usually more rapid than from any other epithelial route of delivery. This rich blood supply which promotes rapid gaseous exchange is also beneficial for systemic drug delivery. Drugs absorbed from the lung pass directly to the heart avoiding first-pass metabolism in the liver, although some drugs will be subject to first-pass metabolism during absorption in the lung. These regional differences play an important role in the absorption of drugs into the systemic circulation, which is likely to occur more efficiently from the A region. Thus delivery systems designed for systemically-acting drugs should target the A region. Bronchodilator drugs act upon the smooth muscle of conducting airways and we might expect that a more central deposition of these drugs would give a greater pharmacodynamic response. Targeting locally-acting anti-inflammatory drugs is complex since there is dispute as to whether inflammation in the central airways is less or more important than that in peripheral airways. The situation is further complicated by possible redistribution of drugs within the lung, which seems likely to occur after deposition. The epithelial permeability towards hydrophilic solutes is at least 10-fold lower than that of the endothelium. The epithelium of the lung is much more permeable than that of other mucosal routes. For example, less than 3% of an oral dose of sodium cromoglycate reaches the circulation whereas more than 70% is absorbed from the lung into the bloodstream after inhalation. In the A region the tight junction gap between type-I alveolar cells is reported as 1 nm. Consequently the permeability of the paracellular route is much greater than seen with other membranes. Large molecules up to 150 kDa are reported to be absorbed to a small extent into the bloodstream after pulmonary administration. Permeability then decreases during the first few weeks of life and then shows no further age-related changes. An increase in permeability of the alveolar membrane is seen in a number of pulmonary disease states including adult respiratory distress syndrome and fibrosis. Increased permeability will be seen in association with inflammatory reactions, where there is an influx of polymorphs and other cells into the airways.

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The term "isolation" is one which seems to be relevant to the social dimension rather than to the sensory and perceptual aspects of the various experimental conditions employed discount 1000 mg carafate with visa symptoms of gastritis in babies. At this stage of -56- our knowledge carafate 1000 mg lowest price gastritis diet , it is unclear as to whether there are different behavioral consequences of sensory as opposed to perceptual deprivation, in the sense used above. It is possible to conceive of this range of stimulus conditions as a complex continuum. In view of the unique complexities presented by research in this area, it is clear that somewhat arbitrary choices of procedure have been made. These choices must be evaluated in terms of the limitations they impose on the results obtained. Thus the observation of cognitive and perceptual functioning and the descriptions of emotional and affective changes makes simultaneous verbal reports of experience in the experimental situation most desirable. Retrospective reports raise difficult questions about their accuracy and make it impossible to study the concurrence of physiological events and verbal behavior. On the other hand, verbal reports of experiences by the subject during the experiment provide a complex feedback situation. The testing of perceptual and cognitive functions during the experiment constitutes a definite modification of procedure. This is accomplished by restraining the subject, limiting the space available to him or by instructions to remain still. It is difficult to know whether the results obtained are a function of the additional sense of confinement or restriction which goes beyond reduction in sensory stimulation. Most studies in this field have striven for absolute isolation of the subject from other human contact by avoiding all communication between subject and experimenter. Although social isolation contributes to reduced sensory input, whether this reduction is primarily effective in terms of loss of social contact per se, loss of patterned stimulation from speech, absolute reduction of sensory stimulation, or some combination of these is still to be determined. Furthermore, the social isolation in these experimental settings is artificial and limited in that the subject knows there is an observer who is interested in his performance. He usually has good reason to suspect that this observer has strong motivation to prevent the occurrence of any long lasting or profoundly debilitating effects. These implicit aspects of the subject-experimenter contract may be major factors in the presumed social isolation seen in experimental studies. These limitations to isolation do not apply to situations such as those of the prisoner or shipwrecked sailor. The "escape at will" clause present in laboratory studies constitutes a major difference from the motivational conditions of real life isolation situations. These factors, along with the use of volunteers in experimental studies, constitute serious limitations to the laboratory testing of hypotheses regarding responses to real life isolation and sensory deprivation. We are unable to assess the effects of coercion or the ultimate consequences of prolonged confinement in a deprived environment. These conditions undoubtedly have a profound effect on the motivational aspects of the situation and thus influence response. The inability to replicate these conditions in the laboratory must limit our generalizations from the experimental data. The first experimental work which focused on the response of man exposed to reduced environmental stimulation per se was begun in 1951 in the laboratory of D. Although earlier studies had dealt with more limited aspects of this problem, they grew out of an essentially different experimental interest. The McGill studies initially arose out of a concern with the contribution of perceptual isolation to the mechanism of brainwashing and the effects of monotony upon a person with a long sustained watchkeeping task. Previously Mackworth (52) had shown that in a vigilance task requiring prolonged observation, subjects increasingly and strikingly failed to respond to an appropriate stimulus. From this point of departure, the framework of these and other studies was expanded to focus on a wide variety of other variables. Our approach in reviewing these studies has been influenced by the consideration that in the early stages of acquiring systematic knowledge about a problem, it may be useful to underemphasize considerations of experimental rigor and elegance in favor of developing a richer background of hypotheses and conceptual formulations, even if only at a suggestive level. Because of their exploratory nature, these investigations have often been designed to look for a wide range of possible relationships, rather than to test specific, focused hypotheses. For these reasons this review will not dwell upon limitations of experimental method and procedure. In general, the studies are uneven in quality, and range from carefully designed and -58- executed procedures to vaguely formulated, poorly controlled observations with small samples. Similarly, measurement in these studies has varied from precise psychophysical calibration to loosely defined clinical judgments unchecked for reliability. The effort has been to provide a comprehensive review of all pertinent studies for whatever light they shed on the problem or support they lend other studies.

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