Inderal
By E. Ugolf. Southern University, New Orleans.
In: Targeting of Drugs: Strategies for Stealth Therapeutic Systems (Gregoriadis purchase inderal 40 mg visa heart attack calculator, G. How can one realistically extend the blood circulation time of this particulate carrier system keeping in mind that this system should be used in patients? Both polymeric micelles and liposomes are being used as carrier systems for drugs. Human monoclonal antibodies are on the market both for therapeutic and diagnostic purposes. A hypothetical anti-leishmanial drug is strongly hydrophilic and positively charged at physiological pH. What targeting system would you recommend to develop if a fast market introduction is desirable? What is a prerequisite to use the concept of “macrophage mediated release of drugs” for therapeutic purposes? Moreover, the cost of oral therapy is generally much lower than that of parenteral therapy. Nevertheless, the oral route is not without disadvantages, particularly with respect to labile drugs such as peptide- and oligonucleotide-based pharmaceuticals. During the past two decades, numerous novel oral drug delivery systems, such as mucoadhesives, matrix systems, reservoir systems, microparticulates, and colon- specific drug delivery systems have been developed to overcome some of these limitations. It is appropriate to consider gastrointestinal structure in relation to gastrointestinal function. The function of the digestive system is to break down complex molecules, derived from ingested food, into simple ones for absorption into the blood or the lymph. This process occurs in five main phases, within defined regions of the gastrointestinal system: • ingestion (mouth); • fragmentation (mouth and stomach); • digestion (stomach and small intestine); • absorption (small and large intestine); • elimination of waste products (large intestine). There has recently been considerable interest in this site for the systemic delivery of drug moieties. The possibility of transmucosal delivery via the mucous membranes of the oral cavity is discussed in Chapter 7. The stomach The stomach is a sack that serves as a reservoir for food, where fragmentation is completed and digestion initiated. Digestion is the process by which food is progressively broken down by enzymes into molecules small enough to be absorbed; for example, ingested proteins are initially broken down into polypeptides, then further degraded into oligopeptides and finally into di- and tri-peptides and amino acids, which can be absorbed. Although the stomach does not contribute as much as the small intestine to the extent of drug 133 Figure 6. The small intestine The small intestine, comprising the duodenum, jejunum and ileum, is the principal site for the absorption of digestive products from the gastrointestinal tract. The first 25 cm of the small intestine is the duodenum, the main functions of which are to neutralize gastric acid and pepsin and to initiate further digestive processes. Digestive enzymes from the pancreas (which include trypsin, chymotrypsin, amylase and lipases) together with bile from the liver, enter the duodenum via the common bile duct at the ampulla of Vater (or hepatopancreatic ampulla). Bile contains excretory products of liver metabolism, some of which act as emulsifying agents necessary for fat digestion. The next segment of the small intestine, the jejunum, is where the major part of food absorption occurs. In addition to the great length of the small intestine, the available surface area is further enhanced by the presence of (Figure 6. The large intestine has two main functions: • to absorb water and electrolytes; • to store and eliminate fecal matter. The submucosa This is a layer of loose connective tissue that supports the epithelium and also contains blood vessels, lymphatics and nerves. The muscularis propria This consists of both an inner circular layer and an outer longitudinal layer of smooth muscle and is responsible for peristaltic contraction. The serosa This is an outer layer of connective tissue containing the major vessels and nerves. Four main types of mucosa can be identified, which can be classified according to their main function: • Protective: this is found in the oral cavity, pharynx, esophagus and anal canal. The surface epithelium is stratified squamous and may be keratinized (see Section 1. The mucosa consists of long, closely packed, tubular glands which, depending on the stomach region, secrete mucus, the hormone gastrin and the gastric juices.
First buy inderal 40mg otc hypertension of the heart, viral blips or intermittent low-level viraemia (50–1000 copies/ml) can occur during effective treatment but have not been associated with an increased risk of treatment failure unless low-level viraemia is sustained (207). Most standard blood and plasma viral load platforms available and being developed have good diagnostic accuracy at this lower threshold. However, the sensitivity of dried blood spots for viral load determination at this threshold may be reduced (210,211). Programmes relying on dried blood spot technology for viral load assessment may therefore consider retaining the higher threshold (3000–5000 copies/ml) until sensitivity at lower thresholds is established (212–214). Clinical guidance across the continuum of care: Antiretroviral therapy 137 Special considerations for children These guidelines aim to harmonize monitoring approaches for children with those recommended for adults. In this context, alignment with the viral load thresholds recommended for adults is advisable. The results from a recently completed trial show that mortality and disease progression are comparable between clinical monitoring and laboratory monitoring, especially in the frst year of treatment (163). Additional implementation considerations for clinicians and health workers include the following. If viral load testing is limited, it should be phased in using a targeted approach to confrm treatment failure. Monitoring drug toxicity using a symptom-directed approach needs to be investigated further to optimize treatment. Clinical guidance across the continuum of care: Antiretroviral therapy 139 Table 7. Clinical guidance across the continuum of care: Antiretroviral therapy 141 Table 7. In addition, more data are needed to understand the frequency and clinical relevance of reduced bone mineral density in children. More accurate and affordable methods to monitor bone toxicity should be identifed for this specifc population. Clinical considerations Delaying substitutions or switches when there are severe adverse drug effects may cause harm and may affect adherence, leading to drug resistance and treatment failure. One recommended artemisinin-based combination therapy is artesunate and amodiaquine. This could subsequently cause withdrawal symptoms and increase the risk of relapse to opioid use. Increased concentrations may increase the risk of developing serious adverse events such as myopathy (including rhabdomyolysis). The available evidence is limited to studies with limited sample size or short duration. Implementing toxicity surveillance will provide the opportunity to produce evidence on specific types of toxicity, increase confidence in the use of the drugs, identify populations with risk factors and plan preventive strategies. Clinical guidance across the continuum of care: Antiretroviral therapy 147 Table 7. Those guidelines placed a high value on using simpler second-line regimens, ideally heat-stable formulations and fxed-dose combinations (once-daily formulations when possible). The use of less toxic, more convenient and more effcacious heat-stable fxed-dose combinations was also considered critical. These include the high cost and it not being available as a heat-stable fxed-dose combination. Clinical guidance across the continuum of care: Antiretroviral therapy 151 Background Recommending potent and effective second-line regimens for infants and children is especially difficult because of the current lack of experience in resource-limited settings and the limited formulations available. This highlights the importance of choosing potent and effective first-line regimens and ensuring their durability and effectiveness by optimizing adherence. The recommendations are now better informed by paediatric clinical trial data (156,158, 237) and observational data (157). The Guidelines Development Group also considered operational and programmatic issues including the availability of heat-stable formulations and fixed-dose combinations for children. Rationale and supporting evidence After reviewing data for adults and children and considering factors such as the availability of a heat-stable fixed-dose combination, optimal daily dose, regimen harmonization with adults, high cost and availability of alternatives, the main recommendations established in the 2010 guidelines were maintained.
The probability of particle deposition by diffusion increases as the particle size decreases generic 40mg inderal free shipping blood pressure on forearm. Brownian diffusion is also more prevalent in regions where airflow is very low or absent, e. Another method of deposition, that of interception, is of importance for fibers but is not of importance for drug delivery. As a consequence of these physical forces acting on the aerosol particle, its deposition in the lung is highly dependent on diameter. Generally: • Particles larger than 10 μm will impact in the upper airways and are rapidly removed by coughing, swallowing and mucociliary processes. An 8 μm particle inhaled at 30 L min−1 has approximately a 50% chance of impacting on the throat. If the particles are less than about 3 μm then appreciable deposition in the A region is likely to occur. The “respirable fraction” of a therapeutic aerosol is often quoted as the percentage of drug present in aerosol particles less than 5 μm in size. Each bifurcation results in an increased probability for impaction and the decrease in airway diameter is associated with a smaller displacement required for a particle to contact a surface. Thus to travel down the airways, the drug particles must pass through a successive series of branching tubes of constantly decreasing size. The aerosol particles must constantly change direction in order to remain airborne. Thus lobes of the lung which have the shortest average pathlength will show greatest peripheral deposition. For maximum effect, breath-holding for a period of 5–10 seconds post-inspiration is recommended. Under idealized conditions a 5 μm particle will settle a few mm during a 5-second breath hold. The bronchoconstriction of asthma has a greater influence on exhalation than inhalation and thus deposition by sedimentation may be greater than normal. Therefore a number of terms are used to adequately characterize an aerosol sample: • Particle size is conventionally defined as the aerodynamic diameter, which is the diameter of a spherical particle with unit density that settles at the same rate as the particle in question. Environmental fibers 50 μm in length can reach the A region because they align with the inspired airflow. Such materials then impact in the airways by a process of interception with the airway walls. Most micronized drugs for inhalation will have particle densities around 1, although materials produced by freeze-drying or spray-drying methods are likely to be significantly less dense. It should not be assumed, however, that the uptake of water vapor will always occur. If the drug is given as an aerosolized powder then the drug first needs to dissolve in the mucus layer. Although mucus has a very high water content, varying between approximately 90–95%, its viscosity may result in a slow dissolution of drugs. Thus dissolution may be a rate determining step, especially for poorly soluble drugs, such as some of the corticosteroids which are delivered as dry powder aerosols. Improvement of drug penetration into mucus has been attempted using mucolytic drugs such as N- acetylcysteine, which act to reduce mucus viscosity. Highly water-soluble drugs, given as dry powder 256 aerosols, may dissolve at the very high relative humidity (>99%) present in the airways air and impact as solution droplets. Once in solution, the drug will diffuse through the mucus layer and enter the aqueous environment of the epithelial lining fluid. The rate of diffusion through the mucus will be dependent upon such factors as: • the thickness of the mucus layer; • mucus viscosity—although it should be appreciated that it is the viscosity of the mucus gel intersticies (i. Mucus secretion may be stimulated as a response to “assault” by what the lung perceives as foreign bodies such as microorganisms and dusts or irritants such as cigarette smoke. Airways disease states such as bronchitis, cystic fibrosis and asthma are often associated with a hypersecretion of mucus. Clearly this presents a far greater barrier than is seen in the normal healthy lung.
The polymer coacervate adsorbs on to the drug particle surface buy cheap inderal 80 mg on line heart attack 6 minutes, resulting in the encapsulation of the drug by the precipitated polymer. It was noted that the o/w emul- sion template produced smaller particle size and higher entrapment efficiency for the hydrophobic drug than the nonaqueous o/o template used for the same drug. On the other hand, the entrapment of a highly water-soluble agent, a Bowman-Birk inhibitor, was significantly increased by using the nonaqueous o/o template (73). Large-Scale Pilot Production of Drug-Loaded Nanoparticles Spray Drying Some of the challenges faced by this technique include the production of small-sized nanoparticles and the need for innovative methods to increase the drug-entrapment efficiency. However, when compared with other methods, it provides a relatively rapid and convenient production technique that is easy to scale up, involves mild processing conditions, and has relatively less dependence on the solubility char- acteristics of the drug and the polymer. In this method, a solution or dispersion (w/o) of a drug in an organic solvent containing the polymer is sprayed from the sonicating nozzle of a spray dryer and subsequently dried to yield nanoparticles. The process parameters that can be varied include the inlet and outlet air temper- atures, spray flow, and compressed spray air flow (represented as the volume of the air input). In a novel, low-temperature, freeze–spray-drying method (74), the solution or dispersion of the drug in an organic solvent containing the dissolved polymer is sprayed or atomized through an ultrasonic nozzle into a vessel contain- ing liquid nitrogen overlaying frozen ethanol and frozen at −80◦C and lyophilized. The liquid nitrogen is evaporated, whereupon the melting liquefied ethanol extracts the organic solvent from the frozen droplets causing the particles to harden. A schematic diagram for pro- duction of nanoparticles by spray-drying is presented in Figure 4. Higher encapsulation efficiency for hydrophilic drugs can be achieved with the spray-drying method using aqueous solutions. With an aim to avoid signifi- cant product loss due to nanoparticulate adhesion on to the interior wall of the spray dryer, as well as to prevent the aggregation of the nanoparticles, a double- nozzle spray-drying method has been developed together with the use of manni- tol as an antiadherent (75). In this process, the surface of the spray-dried nanoparticles gets coated with mannitol and the degree of agglom- eration is reduced. Supercritical Fluid Spraying This technology is advantageous in that the use of an organic solvent/surfactant can be avoided or minimized, thus producing nanoparticles that are free from toxic impurities. The rates of two-way mass transfer are much faster than those for conventional organic antisolvents. This causes the solvent concentration to be significantly lowered, resulting in the precipitation of the drug inside the poly- mer matrix. A major challenge of this process is the need to filter the precipitate from the organic solvent solution without particle growth and aggregation. Various parameters that affect the resulting particle size and morphology are the pre- and postexpansion temperature and pressure, noz- zle geometry, and solution concentration (77,82). The disadvantages of this method include the use of higher temperatures to form homogenous precipitates (thus degrading thermally labile drugs) and the limited solubility of the polymers and drugs that result in low drug loading (83). In general, they possess several poten- tial advantages, such as better oral bioavailability for poorly water-soluble drugs, formulating intravenous injections, and targeting of drugs to specific tissues, thus reducing general toxicity. The nanoparticulate mode of drug delivery using biodegradable polymers is viewed as one of the most promising approaches for (i) improving the bioavailability of the drug with the possibility of reduction of the effective dose, thus reducing the chance of potential toxicity and the adverse effects of the drug, (ii) passive drug targeting to specific tissues, and (iii) effective stabi- lization of the drug in the polymer matrix, protecting from enzymes and other nor- mal defense mechanisms of the body. Besides nanoparticles, other colloidal carriers such as emulsions for the administration of drugs and parenteral nutrition offer the advantage of reduction of adverse effects such as pain and inflammation at the injec- tion site. Successful commercial products include Diazemuls r , Diazepam-Lipuro r , Etomidate-Lipuro r , and Diprivan r. However, a major disadvantage of this sys- tem is the critical, physical instability caused by the incorporated drug, which leads to a decrease in the zeta-potential and thus promotes agglomeration, drug expul- sion, and, finally, breaking of the emulsion (85). The expensive toxicity studies associated with the search for new oils with improved solubility properties present a challenge to the further development of this delivery system (86). Another particulate carrier system, lipo- somes, have been introduced to reduce the toxic adverse effects of the highly potent drugs and thereby enhance the efficacy of the system. However, low physical stability, drug leakage, nonspecific tumor targeting, nonspecific phagocytosis, problems in up- scaling and their high cost limit the total number of products in the market (87,88). The polymeric nanoparticulate carrier system consisting of either biodegradable or nonbiodegradable polymers are thus advantageous in terms of site-specific target- ing and controlled release of the encapsulated drug molecules (89).
As the metrological parameter of validation we also calculated the expanded uncertainty of the measurement under conditions of convergence order inderal 80 mg amex blood pressure normal variation, reproducibility and accuracy of the technique. Expanded uncertainty showed that the values of gamma-glutamyltransferase, alkaline phosphatase and direct bilirubin can be considered as accurate and reliable results. It was also proved that measurements made using these equipments are comparable and the results can be correlated in medical research. Alcohol abnormality in the structure of other forms of substance dependence is the dominant. Alcohol-related polyneuropathy is a neurological disorder in which multiple peripheral nerves throughout the body malfunction simultaneously. Alcohol-related polyneuropathy is a chronic and potentially debilitating disease that can be associated with sensory, motor, and autonomic nerve dysfunctions. Alcohol-related polyneuropathy is caused primarily by chronic alcoholism; however, vitamin deficiencies are also known to contribute to its development. The most constant and frequent damage to the nervous system when alcohol abuse is polyneuropathy. Polyneuropathy occurs in people who abuse alcohol, or as a result of the toxic effects of alcohol. It is believed that alcohol impairs the protective barrier of the peripheral nervous system, on the one hand, and can be a risk factor for development of chronic hyperglycemia, breaking the utilization of B vitamins. Timely correction of vitamin metabolism disorders, along with other therapeutic measures, can prevent the development of polyneuropathy or to facilitate its flow. Aim: to study aspects of pharmacotherapy of alcoholic polyneuropathy drug Neyromultivit®. All the patients underwent a thorough clinical and neurological examination with the study of anamnestic data. Polyneuropathy results confirmed data electroneuromyographic, was observed in 62 (71%) patients with alcohol dependence who were randomized into 2 groups: the main group (n = 30) received Neyromultivit® 1 tablet 3 times a day for 21 days, and a control group (n = 32) that received the standard vitamin therapy (B1, B6, B12) drugs administered parenterally. In the course of the study in both groups noted a decrease in the severity of pain (clinically and scales). No significant differences in efficacy and safety between the two groups of patients receiving Neyromultivit®, and a group of patients treated with vitamins parenterally received. The study showed the effectiveness of treatment of alcoholic polyneuropathy by Neyromultivit® when dosing regimen of 1 tablet 3 times daily for 21 days as an equivalent replacement of B vitamins for intramuscular injection. According to epidemiological studies worldwide nonallergic rhinitis affects about 450 million people. Nonallergic rhinitis is not-IgE-mediated disease with chronic nasal symptoms such as nasal congestion, rhinorrhea, sneezing. The study of modern pharmacotherapy nonallergic rhinitis according to current standards of care for patients with nonallergic rhinitis. The analysis of contemporary foreign literature on aspects of pharmacotherapy nonallergic rhinitis, standards of care for patients with rhinitis. For pharmacotherapy nonallergic rhinitis group of drugs used are nasal anticholinergics, nasal steroids, nasal sympathomimetics and systemic antihistamines. Among nasal corticosteroids are widely used beclomethasone dipropionate, budesonide, fluticasone propionate, mometasone, fluticasone furoate. Among the nasal anticholinergic agents according to foreign sources recommend nasal ipratropium bromide. Among the designated nasal sympathomimetic is oxymetazoline, xilometazoline, nafazoline, tramazoline, tetryzoline. Systemic antihistamines such as loratadine, dezloratadine, cetirizine, levocetirizine are used. For vasomotor rhinitis, drugs of choice are nasal anticholinergic and sympathomimetic drugs. For pharmacotherapy nonallergic rhinitis with eosinophilic syndrome, nasal corticosteroids and nasal sympathomimetic are recommend. The nasal corticosteroids, antihistamines, nasal anticholinergic and sympathomimetic drugs prescribed hormonal rhinitis. For the treatment of rhinitis occupational shows nasal corticosteroids and nasal antihistamines.
Where appropriate discount inderal 40 mg mastercard blood pressure medication protocol, attention should be drug substance or shelf life for a drug product beyond paid to reviewing the adequacy of the mass balance. The Although the parent guideline (see Chapter 4) states that degree of variability of individual batches affects the regression analysis is an acceptable approach to analyzing confidence that a future production batch will remain quantitative stability data for retest period or shelf-life within acceptance criteria throughout its retest period estimation and recommends that a statistical test for batch or shelf life. In addition, the parent guide- approaches are not intended to imply that use of statistical line does not cover situations in which multiple factors evaluation is preferred when it can be justified as being are involved in a full or reduced-design study. However, statistical analysis can be useful in the extrapolation of retest periods or shelf lives in certain situations and may be called for to verify the retest periods B. This guideline, an annex to the parent guideline (Chapter 4), The basic concepts of stability data evaluation are the is intended to provide a clear explanation of expectations same for single- vs. Data evaluation from the formal conditions based on the evaluation of stability data for stability studies and, as appropriate, supporting data both quantitative and qualitative test attributes. This guide- should be used to determine the critical quality attributes line outlines recommendations for establishing a retest likely to influence the quality and performance of the drug period or shelf life based on stability data from single or substance or product. Q6A and Q6B provide guidance on the setting and justi- The retest period or shelf life proposed should not exceed fication of acceptance criteria. The purpose of a stability study is to establish, based In general, certain quantitative chemical attributes on testing a minimum of three batches of the drug sub- (e. Qualitative attributes are not presentation and evaluation of the stability information, amenable to statistical analysis and microbiological which should include, as appropriate, results from the attributes, and certain quantitative attributes (e. The circumstances are delineated under which extrapolation of retest period or Data for all attributes should be presented in an appropri- shelf life beyond the observed length of long-term data ate format (e. No Significant Change at Accelerated and the assumptions underlying the model should be stated and justified. A tabulated summary of the outcome Condition of statistical analysis or graphical presentation of the long- Where no significant change occurs at the accelerated con- term data should be included. Long-Term and Accelerated Data Showing Limited extrapolation to extend the retest period or shelf Little or No Change over Time and Little or No life beyond the observed range of available long-term data Variability can be proposed in the application, particularly if no sig- Where the long-term data and accelerated data for an attribute nificant change is observed at the accelerated condition. An extrap- circumstances, it is normally considered unnecessary to go olation of stability data assumes that the same change through a statistical analysis, but justification for the omission pattern will continue to apply beyond the observed range should be provided. Hence, the use of extrapola- the mechanisms of degradation or lack of degradation, rele- tion should be justified in terms of, for example, what is vance of the accelerated data, mass balance, or other support- known about the mechanisms of degradation, the good- ing data as defined in the parent guideline. A The correctness of the assumed change pattern is cru- proposed retest period or shelf life up to twice the length cial if extrapolation beyond the available long-term data of available long-term data can be proposed, but it should is contemplated. For example, when estimating a regres- not exceed the length of available long-term data by more sion line or curve within the available data, the data them- than 12 months. Long-Term or Accelerated Data Showing test the goodness of fit of the data to the assumed line or Change over Time and Variability curve. No such internal check is available beyond the If the long-term or accelerated data for an attribute show length of observed data. Thus, a retest period or shelf life change over time or variability within a factor or among granted on the basis of extrapolation should always be factors, statistical analysis of the long-term data can be verified by additional long-term stability data as soon as useful in establishing a retest period or shelf life. Care should be taken to there are considerable differences in stability observed include in the protocol for commitment batches a time among batches or other factors (e. Extrapolation beyond the length In general, stability data for each attribute should be of available long-term data can be proposed; however, the Guidelines for Evaluation of Stability Data in Retest Periods 71 extent of extrapolation would depend on whether long- would depend on whether long-term data for the attribute term data for the attribute are amenable to statistical are amenable to statistical analysis. Data Not Amenable to Statistical Analysis (for Based on an attribute that is not amenable to statistical Qualitative Attributes or Certain Quantitative analysis, a retest period or shelf life can be proposed when Attributes) relevant supporting data are provided, but the proposed When relevant supporting data are provided, a retest retest period or shelf life should not exceed the length of period or shelf life up to one and one-half times the length available long-term data by more than 3 months. Data Amenable to Statistical Analysis not exceed the length of available long-term data by more If the long-term data for an attribute are amenable to than 6 months. Relevant supporting data include satisfac- statistical analysis but such an analysis is not performed, tory long-term data from development batches that are the extent of extrapolation would be the same as above. Data Amenable to Statistical Analysis term data when supported by the statistical analysis and If a statistical analysis is not performed, the extent of extrap- relevant supporting data, but not exceeding the length of olation should be the same as above (i. Significant Change at Intermediate Condition to one and one-half times the length of available long-term Where significant change occurs at the intermediate con- data can be proposed, but it should not exceed the length of available long-term data by more than 6 months). How- dition, the proposed retest period or shelf life should not ever, if a statistical analysis is performed, it can be appro- exceed the extent of available long-term data. If priate to propose a retest period or shelf life of up to twice the length of available long-term data when supported by the long-term data show variability, verification of the the statistical analysis and supporting data, although this retest period or shelf life by statistical analysis can be proposed retest period or shelf life should not exceed the appropriate.
Density cheap inderal 40mg arrhythmia getting worse, solubility, refec- tance spectra, refractive indices, and optical rotation are examples of bulk properties (Brown et al. The malaria drug artesunate, for example, has some distinctive physical properties: It yields characteristic crystals when precipitated from water, and its extract acidifes water (Deisingh, 2005; Newton et al. These properties can be used to distinguish some authentic and fake antimalarials. The refractive index, the measure of how light passes through a sub- stance relative to the speed at which light passes through a vacuum, is a similarly useful bulk property. The refractive index can be used to measure the purity of pure liquids and can detect materials separated by liquid chro- matography. Field inspectors can use handheld refractometers to measure the refractive index and use it as a quantitative test for some active ingre- dients (Kaur et al. Green and colleagues explored the practical use of refractive index to measure the amount of active ingredients selectively dissolved in certain solvents (Green et al. They found that while the refractive index can measure the amount of an unknown active ingredient, colorimetry can be used to help confrm its presence (Green et al. It relies on chemicals that undergo color changes when reacted with certain compounds to provide qualitative data about a drug’s identity. In addition to verifying the presence of an active ingredient, colorimetry can serve as a semi-quantitative technique to provide information about tablet potency; a more drastic color change or deeper color generally indicates a larger amount of ingredient. More precise colorimetric testing is possible with a handheld photometer, a spectroscopic device that measures absorbance of light through a substance (Newton et al. Colorimetry gives limited information and destroys the sample under investigation, but it is invaluable to feld inspectors because it is an inexpensive technique that requires very little training. Disintegration and dissolution testing may identify common formula- tion problems. Dissolution tests require more training than colorim- etry and disintegration testing but may help predict the bioavailability of drugs, an important aspect of their effcacy. If a drug has poor dissolution, then the target dose of active ingredient may not be available to the patient. Incorrect excipient formulation, poor-quality manufacturing, and improper storage conditions can all lead to poor dissolution (Kaur et al. Even if the drug contains the correct dose of active ingredient, disintegration and dissolution tests may be able to identify an illegitimate drug (Deisingh, 2005). Disintegration tests are fairly simple and can be done in the feld, but dissolution tests require sophisticated equipment (Kaur et al. Chromatography Chromatography separates mixtures into their constituent parts based on a variety of chemical and physical properties. It can be used to separate drug ingredients for further testing and, when used with appropriate detec- tors, provides both qualitative and quantitative information about active ingredients and impurities (Kaale et al. Chromatography is there- fore the most common analytical method used in drug evaluations (Martino et al. The distance the sample travels is associated with its identity; the intensity of the spot correlates with the amount of the drug present. The plates are only used once, preventing contamination and limiting maintenance requirements (Kaale et al. The systems also require reliable electrical power, which can be an obstacle in develop- ing countries. Although the drugs are chemically similar (see Figure 6-3b), mefoquine is signif- cantly more expensive, and the cheaper drugs are sometimes sold labeled as mefoquine (Gaudiano et al. Gas chromatography, the most powerful chromatographic technol- ogy, provides similar information as the other chromatography systems. However, it may only be used for separation of volatile materials, such as residual solvents, undeclared ingredients, and any volatile impurities. This technique can only be used when the compounds of interest are gaseous in the analytical temperature range and do not degrade at or before the assay’s minimum temperature.
