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The porous osmotic pump based drug delivery system for excellent controlled release of drug for 24 hrs. The porous osmotic pump contains pore forming water soluble additives in the coating membrane, which after coming in contact with water, dissolve, resulting in an in situ formation of a microporous structure. The porous osmotic pump delivery from this system is not influenced by the different physiological factors. The present review is concerned with the patent study of drug release through controlled porous osmotic pump. This patent review is useful in knowledge of controlled porous osmotic pump for its application.

In this paper formulation of porosity osmotic tablet containing isradipine (model drug) as a low and pH dependent solubility was optimized based on the simultaneous optimization technique in which an artificial neural network (ANN) was incorporated. Nonlinear relationships between the causal factors and the response variables were represented well with the response surface predicted by ANN. Three causal factors, i.e., drug, osmotic pressure promoting agent rate (Lactose: Fructose), PEG400 content in coating solution and coating weight, were evaluated based on their effects on drug release rate. In vitro dissolution profile time profiles at four different sampling times (1, 12, 20 and 24h) were chosen as output variables. Commercially available STATISTICA 7 (Stat soft, USA) was used throughout the study. The optimize values for the factors X1-X3 were 1.25:0.75, 22% and 2.5% respectively. Calculated difference (f1 = 11.19) and similarity (f2 = 70.07) factors indicate that there is no difference between predicted and experimental observed drug release profile. Artificial neural network technique can be particularly suitable in the pharmaceutical technology of controlled release dosage forms where systems are complex and nonlinear relationships between independent and dependent variables often exist.

Conventional drug delivery systems have little control over their drug release and almost no control over the effective concentration at the target site. This kind of dosing pattern may result in constantly changing, unpredictable plasma concentrations. Drugs can be delivered in a controlled pattern over a long period of time by the process of osmosis. Osmotic devices are the most promising strategy based systems for controlled drug delivery. They are the most reliable controlled drug delivery systems and could be employed as oral drug delivery systems. The present review is concerned with the study of drug release through asymmetric membrane capsule systems. When these systems are exposed to water, low levels of water soluble additive are leached from polymeric material i.e. the semipermeable membrane and the drug releases in a controlled manner over an extended period of time. Drug delivery from this system is not influenced by the different physiological factors within the gut lumen and the release characteristics can be predicted easily from the known properties of the drug and the dosage form. This patent review is useful in the knowledge of asymmetric membrane capsule osmotic pump for its application.

Allosteric proteins bind an effector molecule at one site resulting in a functional change at a second site. We hypothesize that networks of contacts altered, formed, or broken are a significant contributor to allosteric communication in proteins. In this work, we identify which interactions change significantly between the residue-residue contact networks of two allosteric structures and then organize these changes into graphs. We perform the analysis on 15 pairs of allosteric structures with effector and substrate each present in at least one of the two structures. Most proteins exhibit large, dense regions of contact rearrangement, and the graphs form connected paths between allosteric effector and substrate sites in five of these proteins. In the remaining ten proteins, large-scale conformational changes such as rigid-body motions are likely required in addition to contact rearrangement networks to account for substrate-effector communication. On average, clusters which contain at least one substrate or effector molecule comprise 20% of the protein. These allosteric graphs are small worlds; that is, they typically have mean shortest path lengths comparable to those of corresponding random graphs and average clustering coefficients enhanced relative to those of random graphs. The networks capture 60 to 80% of known allostery-perturbing mutants in three proteins, and the metrics degree and closeness are statistically good discriminators of mutant residues from non-mutant residues within the networks in two of these three proteins. For two proteins, coevolving clusters of residues which have been hypothesized to be allosterically important differ from the regions with the most contact rearrangement. Residues and contacts which modulate normal mode fluctuations also often participate in the contact rearrangement networks. In summary, residue-residue contact rearrangement networks provide useful representations of the portions of allosteric pathways resulting from coupled local motions.

In this study, we evaluated immunocytochemical staining for milk proteins (α-lactalbumin and β-lactoglobulin) in tracheal aspirates of mechanically ventilated infants, and assessed whether this staining technique supported a clinical diagnosis of aspiration in infants receiving orogastric feedings. All newborns requiring mechanical ventilation in the neonatal intensive care unit of a major tertiary care hospital were potential subjects for this study. Tracheal aspirates were obtained prior to the introduction of enteral feeding and at various time points thereafter in newborns requiring mechanical ventilation. Cells were obtained and processed for immunocytochemical staining of α-lactalbumin and β-lactoglobulin. In total, 88 specimens recovered from 34 infants were adequate for staining. Alveolar macrophages recovered from most of the infants who were never fed (true negative controls) did not display immunoreactivity for milk proteins: 4/34 or 12% of infants' aspirates demonstrated presence of milk proteins before enteral feeding was commenced. Tracheal aspirates obtained from 12 infants after introduction of enteral feedings appeared to support clinical and radiological findings suggestive of aspiration events, with positive immunostaining on several occasions. These observations support our work in a murine model and demonstrate that immunocytochemical staining of tracheal aspirates for milk proteins may enhance the ability to diagnose pulmonary aspiration. Further studies are needed to define the clinical significance of our findings and the effects of single and repeated aspiration events on respiratory status. Pediatr Pulmonol. 2002; 34:369–374. © 2002 Wiley-Liss, Inc.