By V. Hector. Clearwater Christian College.
For example generic nootropil 800mg online, the addition of /β-cyclodextrin to dihydroergotamine can enable the drug concentration to be increased from 4 mg mL−1 to 10 mg mL−1 cheap nootropil 800mg online. Cyclodextrins are also capable of dissociating insulin hexamers into smaller aggregates which may provide an additional mechanism for absorption promotion. However, it should not be overlooked that a direct relationship has been reported between the extent of absorption enhancement by cyclodextrins and damage to the nasal membrane. Penetration enhancers may also promote delivery by increasing drug stability, due to the enhancer decreasing the activity of enzymes which may degrade the drug. Since drugs may be cleared from the nasal cavity by mucociliary clearance, swallowing and/or by metabolism, the inhibition or avoidance of these clearance mechanisms should result in increased absorption. Thus drug deposited in the anterior region of the nasal cavity may be expected to clear less rapidly and have a greater opportunity to be absorbed. As already described, this explains why nasal sprays, which deposit anteriorly in the nasal cavity, offer improved bioavailability compared to nasal drops, which deposit throughout the nose. Increasing the viscosity of solutions administered to the nasal cavity with, for example, methylcellulose, hyaluronan etc. It is thought that, up to an optimum viscosity, higher viscosity solutions give a more localized deposition in the anterior portion of the nose (i. As viscosity can affect droplet size by altering the surface tension of the solution, the more localized deposition in the anterior of the nose may be due to viscosity-related changes in the particle size of the delivered droplets. The volume of drug solution delivered to the nose also seems to have an effect on the bioavailability of the drug. For example, the bioavailability of desmopressin was doubled when it was delivered as two 50 μ1 actuations from a metered nasal spray in comparison to the delivery of one 100 μ1 actuation. This may be attributed to prolonged retention of the dose at the administration site. Bioadhesives are proposed to influence drug bioavailability by: • decreasing the rate of clearance from the absorption site thereby increasing the time available for absorption; • increasing the local drug concentration at the site of adhesion/absorption; • protecting the drug from dilution and possible degradation by nasal secretions. A number of different bioadhesive formulations are possible: Bioadhesive solutions/suspensions Many viscosity enhancers are also considered to be bioadhesive and putative bioadhesive polymer gels, including methylcellulose, sodium carboxymethylcellulose, chitosan, Carbopol 934P (one of the carbomers) 241 and Pluronic F127, have been shown to decrease the rate of mucociliary clearance in the rat by 7–57%. By reducing or abolishing ciliary motility, the rate of clearance of the drug from the nasal cavity is reduced. In addition, chitosan has been shown to enhance the nasal absorption of insulin (molecular weight 5. Some bioadhesives, such as carbomers, have also been shown to complex with mucus, increasing the viscoelasticity of the latter and reducing its clearance. In aqueous solution above a certain concentration, such systems are liquid at room temperature and below, but at physiological temperatures (32–37 °C), the viscosity of the solutions increases. Once in the nasal cavity, the viscosity of these solutions will increase, due to the increased temperature, and the contact time between the drug and the absorbing membrane should be extended compared to that of a simple solution. Such systems have also been investigated to enhance vaginal and ocular drug delivery (see Sections 11. Dry powder bioadhesives A slightly different approach is to deliver the active drug in a dry powder carrier system, for example microcrystalline cellulose, hydroxyethyl starch, cross-linked dextran, microcrystalline chitosan, carbomer, pectin, or alginic acid. The polymer absorbs water upon contact with the nasal mucosa and swells to become a viscous gel, often demonstrating bioadhesive properties. For example, the bioavailability in rats of the somatostatin analogue, octreotide, was shown to be enhanced by the co-administration of alginic acid and cross-linked dextran as dry powders. Certain carriers prolong the time during which therapeutic plasma concentrations of drug are maintained, effectively providing sustained release. This is believed to occur due to the rate and extent of water uptake being modified by the formulation, as well as to the type of gel formed by the excipients. As the polymers hydrate by withdrawing water from the secretions of the nasal epithelium, localized changes in mucociliary clearance occur, due to the presence of a hydrating polymer and potentially due to induced alterations in the viscoelasticity of the mucus gel. Colloidal bioadhesives Bioadhesive microspheres composed from a variety of materials such as starch, carbomer, hyaluronan esters, dextrans have been used to prolong the retention time of the drug within the nasal cavity. The clearance half-life of microspheres can be in the order of 3–4 hours, in comparison with 15 minutes for a simple solution. Improved bioavailabilities have been seen for gentamicin, insulin and desmopressin. A temporary widening of the tight junctions of cultured cells, which coincided with an increase in the rate of absorption of the applied drug, insulin, has been observed in the presence of starch microspheres. It is likely that the dry starch microspheres took up water from the cells causing them to dehydrate and “shrink” resulting in a separation of the intercellular junctions. Should this be the case, it provides evidence for the paracellular absorption of insulin.
Asking residents about adverse events in a computer dialogue: how accurate are they? Utilizing information technology on patient care rounds to enhance pharmacist effectiveness 800mg nootropil visa. Diffusion of pharmacist interventions within the framework of clinical pharmacy activity in the clinical ward purchase 800mg nootropil with mastercard. Drug supply chain safety in hospitals: current data and experience of the Grenoble university hospital. A computerized system for identifying and informing physicians about problematic drug use in nursing homes. Individualised aminoglycoside dosage based on pharmacokinetic analysis is superior to dosage based on physician intuition at achieving target plasma drug concentrations. Use of hospital prescribing data to monitor the implementation of clinical guidelines. A conceptual framework for evaluating outpatient electronic prescribing systems based on their functional capabilities. Management of patients with diabetes through information technology: tools for monitoring and control of the patients’ metabolic behavior. Reducing medication errors and increasing patient safety: case studies in clinical pharmacology. A computerised prescribing decision support system to improve patient adherence with prescribing. Computerised reminders and feedback in medication management: a systematic review of randomised controlled trials. Evaluation of the quality of drug therapy among elderly patients in nursing homes. Evaluation of a newly implemented once-daily aminoglycoside dosing and monitoring program. Use of antibiotics at hospitals in Stockholm: A benchmarking project using internet. A novel point-of-care information system reduces anaesthesiologists’ errors while managing case scenarios. Economical impact of an automated dispensing system in the emergency ward of a general hospital. Opinion survey about the correct use of an automated dispensing machine in the emergency ward of a general hospital. Analysis of failures detected during the medication-dispensing process and their contributing factors. Implementation of an integrated instrument control and data management system for point of care blood gas testing. Data quality in the outpatient setting: impact on clinical decision support systems. Journal of Pharmaceutical Finance, Economics and Policy 2007;15(3): Database: Embase Sept 22-09. Use of telepharmacy technology offers potential for improved financial management. What do patients want to know: An empirical approach to explanation generation and validation. Prevention of adverse drug reactions in intensive care patients by personal intervention based on an electronic clinical decision support system. Cognitive analysis of physicians and nurses cooperation in the medication ordering and administration process. Drug-related problems and adverse drug events: negligence, litigation and prevention. Physicians’ resistance toward healthcare information technology: A theoretical model and empirical test. Establishing user requirements for a patient held electronic record system in the United Kingdom. The impact of the electronic health record on patient safety: an Alberta perspective. Conversion of conventional human insulin vials to analog insulin pens in a community hospital. Proceedings - the Annual Symposium on Computer Applications in Medical Care 1995;17-21. Patient safety in emergency situations: A Web-based pediatric arrest medication calculator. Journal for Healthcare Quality: Promoting Excellence in Healthcare 2006;28(2):27-31. Implementation and evaluation of a pharmacy- based computer-assisted antimicrobial surveillance service.
However buy generic nootropil 800mg, it is important to note that the system does not actually facilitate oral transmucosal delivery per se purchase nootropil 800mg with amex, rather it allows rapid release of the drug in the mouth. The drug is then washed down with the saliva for subsequent absorption in the gastrointestinal tract. The convenience and acceptability of a Zydis formulation make it particularly suitable for patients who find it difficult or inconvenient to swallow solid dosage forms. In trials, up to 90% of patients expressed a preference for taking the Zydis formulation compared with a conventional tablet. Important features for drug delivery associated with these novel buccal patches include: 7. Multi-directional release The type of patch allows release of the drug moiety to the underlying mucosa (and thus the systemic circulation) and also to the saliva bathing the oral cavity (Figure 7. Drug released into the saliva may also be absorbed systemically through the mucus membranes of the oral cavity and/or remain locally. However, disadvantages associated with this approach include: • the drug becomes substantially diluted in the saliva; • substantial loss of the drug may occur when the saliva is swallowed; 182 Figure 7. Unidirectional release In this type of system, drug loss to the saliva can be decreased by using an impermeable backing layer (Figure 7. An additional advantage of these systems is that the effect of additives can be restricted to the site of application. However, this approach also means that the drug moiety is confined to the site of application, thus the available absorption area is quite small. Furthermore, presence of a backing layer can also decrease the flexibility of the dosage form leading to increased patient discomfort and reduced patient compliance. Drug release rate can be controlled by the use of: Matrix or drug-in-adhesive systems The drug is distributed throughout a polymer matrix. Such a system can be relatively easy to manufacture, the simplest case being when the drug is dispersed directly in a blend composed of, for example, a mixture of poly(acrylic acid) and elastomeric compounds such as poly(isobutylene) and poly(isoprene). Reservoir systems The reservoir patch has a similar bioadhesive component but pharmaceutical formulations containing certain excipients, such as penetration enhancers and enzyme inhibitors, can be placed in the center of the design. Matrix and reservoir systems, and their drug release profiles (firstorder, and square-root time order, respectively), have been discussed in detail in Chapters 3 and 4. However, patch size must always be considered with respect to patient comfort and acceptability and must not be too large so that these factors are compromised. Thus the size of adhesive patches is generally in the range 2–5 cm, with 10–15 cm being2 2 the upper limit. The principal mechanism for bioadhesion of oral patches appears to be physical entanglement of the adhesive polymer of the patch in the mucus glycoprotein chains, with secondary (electrostatic, hydrogen, hydrophobic) chemical bonding playing a minor role. Adhesive polymers used in oral patches include poly(hydroxyethylcellulose), poly (hydroxypropylcellulose), poly(sodium carboxymethylcellulose), poly(acrylic acid), poly(methacrylic acid), poly(vinylpyrrolidone) and poly (vinyl alcohol). The binding properties of a given polymer are affected by physicochemical properties such as its molecular weight, configuration, cross-linking density, charge and concentration. As well as initial tack properties, another important consideration is the duration of bioadhesion. The influence of viscosity on adhesion time depends on the type of polymer, for example poly(vinylpyrrolidone) affords an adhesion time which increases exponentially with viscosity grade. Poly(hydroxyethylcellulose) and poly(vinyl alcohol) also show increased adhesion times with increasing viscosity; however, the reverse is true for hydroxypropylcellulose. Regardless of the viscosity, increasing the amounts of polymer in the patch increases the adhesion time. Patches with backing layers that are permeable to water generally show shorter adhesion times than those with impermeable backing layers. This is due to the slower erosion of the hydrocolloid when one side of the patch is protected against water uptake. The limited surface area available for absorption often means that a2 penetration enhancer is necessary to ensure: • an effective dose can be delivered from a patch of reasonable size; • the range of transmucosal drug delivery candidates can be extended, for example, to include poorly absorbed moieties such as therapeutic peptides and proteins. Penetration enhancers are discussed extensively for the transdermal nasal route in Sections 8. Comparatively few penetration enhancers have been tested for buccal absorption enhancement; those which have been investigated include bile salts. In addition, the buccal delivery of insulin in rabbits has been shown to be increased from approximately 3–5% by co-administration of edetate (least effective), sodium dextransulfate, sodium methoxysalicylate, sodium deoxycholate, sodium lauryl sulfate, sodium taurocholate and Brij 35 (most effective); with Brij 35 increasing the bioavailability of insulin to 12% by this route. A smooth surface and good flexibility are prerequisites to prevent mechanical irritation or local discomfort. Adequate evaluation of patient acceptability and compliance of buccal patches should include a clinical examination to observe local tolerance, and the incidence and degree of irritation. Trials should also involve the use of questionnaires, in order to determine a subject assessment of such factors as: • overall comfort; • sensation (taste, movement, swelling); • pain (during wear, on removal); • whether the patch interferes with normal activities (talking, eating, drinking, sleeping). The pill-sized patch uses a new bioadhesive which sticks to the gum, the cheek or the lip without causing irritation and is designed to deliver drugs for short and extended periods (up to 24 h). Cydot technology accommodates both uni-directional and multidirectional release, and both reservoir- and matrix-type systems are possible.
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