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PubMed2003

Application of artificial neural networks in the design of controlled release drug delivery systems.

Controlled release drug delivery systems offer great advantages over the conventional dosage forms. However, there are great challenges to efficiently develop controlled release drug delivery systems due to the complexity of these delivery systems. Traditional statistic response surface methodology (RSM) is one of the techniques that has been employed to develop and formulate controlled release dosage forms. However, there are some limitations to the RSM technique. Hence, another technique called artificial neural networks (ANN) has recently gained wide popularity in the development of controlled release dosage forms. In this review, the basic ANN structure, the development of the ANN model and an explanation of how to use ANN to design and develop controlled release drug delivery systems are discussed. In addition, the applications of ANN in the design and development of controlled release dosage forms are also summarized in this review.

Delayed-Action Preparations↗

PubMed1998

Importance of dissolution process on systemic availability of drugs delivered by colon delivery system.

The relationship between in vitro drug release characteristics from colon delivery systems and in vivo drug absorption was investigated using three kinds of delayed-release systems. 5-aminosalicylic acid (5-ASA), tegafur (FT) and carbamazepine (CBZ) were selected as model drugs. Pressure-controlled colon delivery capsules (PCC) for liquid preparations, time-controlled colon delivery capsules (TCC) for liquid and solid preparations and Eudragit S coated tablets for solid preparations were used in this study. At first, in vitro dissolution tests for all preparations were performed. Drug release from solid preparations was delayed compared to that from liquid preparations with all three drugs. Next, these preparations were administered to fasted beagle dogs. For 5-ASA, the mean Cmaxs (peak level) of Eudragit S coated tablets and PCC were 5.52 and 16.89 micrograms ml-1, respectively. The mean Tmaxs (time when drug reached peak level) were 3.0 and 5.3 h. AUCs were 22.57 and 48.09 micrograms.h ml-1, respectively. For FT, Cmaxs of Eudragit S coated tablet and PCC were 0.87 and 1.46 micrograms ml-1, and Tmaxs were 7.0 and 6.7 h, respectively. AUCs were 9.73 and 15.55 micrograms.h ml-1 and bioavailabilities were 43.79 and 70.84%. For CBZ, the mean Cmaxs of liquid preparations and solid preparations were 0.37 and 0.22 micrograms ml-1, respectively. The mean Tmaxs were 4.7 and 4.3 h. AUCs were 0.673 and 0.392 micrograms.h ml-1. With liquid preparations, drug was thought to contact to the colonic membrane easily because of lack of interference by stools, and to be absorbed well as compared with solid preparations. From these findings, drug release from colon delivery systems and drug dissolution in the colonic lumen are very important factors for the systemic availability of drugs from the colon delivery systems.

Animals↗

PubMed2005

Terplex Gene Delivery System.

Polymeric gene delivery systems have been developed to overcome problems caused by viral carriers. They are low cytotoxic, have no size limit, are convenient in handling, of low cost and reproducible. A Terplex gene delivery system consisting of plasmid DNA, low density lipoprotein and hydropholized poly-L-lysine was designed and characterized. The plasmid DNA, when formulated with stearyl PLL and LDL, forms a stable and hydrophobicity/charge-balanced Terplex system of optimal size for efficient cellular uptake. DNA is still intact after the Terplex formation. This information is expected to be utilized for the development of improved transfection vector for in vivo gene therapy. Terplex DNA complex showed significantly longer retention in the vascular space than naked DNA. This system was used in the augmentation of myocardial transfection at an infarction site with the VEGF gene.

Journal Article↗

PubMed2005

Terplex gene delivery system.

DNA↗

PubMed1989

Alternative delivery systems in rural areas.

Alternative delivery systems, such as HMOs, PPOs, and primary care case-management programs, have a long history in rural America despite significant impediments to their development. However, little is known about the effect of these systems on rural communities and their medical care delivery systems. Existing studies, which focus on rural HMOs, are qualitative in nature and generally are directed at identifying factors that facilitate or retard HMO development. Despite their limitations, the studies do raise a variety of issues deserving of quantitative analysis. Research is now needed that (1) investigates the effect of rural alternative delivery systems on the cost and quality of care received by rural residents, (2) assesses the effectiveness of different mechanisms used by these systems to contain costs, (3) estimates the effect of alternative delivery systems on rural providers, (4) determines the extent to which the presence or absence of alternative delivery systems influences physician decisions to locate in rural areas, (5) identifies factors that are important in consumer decisions to enroll or not enroll in a rural alternative delivery system, and (6) analyzes the diffusion patterns of these systems in rural areas.

Cost Control↗

PubMed2002

Complications of inhaled anesthesia delivery systems.

Inhaled anesthesia delivery systems (ADS) have evolved in the past 20 years from simple pneumatic machines to complex computer-controlled devices. For the purposes of this discussion, we will outline some of the potential complications that may result from the use of these systems. Because of the complexity of modern ADS, it is incumbent on the anesthesiologist to be cognizant of potential problems that may arise with their use. Even though it is now more difficult than ever for the practitioner to develop a comprehensive understanding of these machines, it remains essential for the safe practice of anesthesia. When the anesthesiologist understands the basic design differences between products from different manufacturers, it is more likely that the appropriate preoperative checks will be performed and that delivery of a safe anesthetic can be ensured. Although malpractice claims associated with anesthesia delivery systems are rare, when they do occur they may be severe, and they continue to occur. These complications may range in severity from mild hypercapnia to awareness and even death.

Air Pressure↗

PubMed1998

Therapeutic effect and pharmacokinetics of ketotifen transdermal delivery system.

Ketotifen transdermal delivery systems were prepared using polyisobutylene, liquid paraffin, and fatty acid. In vitro skin penetration studies were conducted in Franz diffusion cells using excised porcine skin to determine the skin permeation rates of ketotifen patches. A trend of increased skin penetration of ketotifen was observed as the amount of liquid paraffin in the patch was increased. In addition, we found that lauric acid was a suitable enhancer for percutaneous absorption of ketotifen. Challenge tests were performed in guinea pigs to determine the therapeutic effect of the delivery systems for the inhibition of anaphylactic shock using varied concentrations of chicken ovum albumin as sensitizer. Our results showed that compared with the treatment of intramuscular administration, the skin patch was more effective and produced higher survival rates. The pharmacokinetics of the ketotifen patch were determined by applying the skin patch to the dorsal skin of rabbits. The plasma levels were maintained constant (42.5-36.4 ng/ml) from 9 to 30 hr. From our study, the prepared ketotifen patch may further be developed for the treatment or prevention of allergic asthma.

Adhesives↗

PubMed1999

Intracranial delivery of recombinant nerve growth factor: release kinetics and protein distribution for three delivery systems.

PURPOSE: Three different polymeric delivery systems, composed of either poly(ethylene-co-vinyl acetate) (EVAc) or poly(lactide-co-glycolide) (PLGA), were used to administer recombinant human nerve growth factor (rhNGF) intracranially in rats. METHODS: The delivery systems were characterized with respect to release kinetics, both in the brain and in well-stirred buffer solutions. RESULTS: During incubation in buffered saline, the delivery systems released rhNGF in distinct patterns: sustained (EVAc), immediate (PLGA1) and delayed (PLGA2). One 10-mg delivery system was implanted in each rat and an ELISA technique was used to determine the amount of rhNGF in 1-mm coronal brain slices produced immediately after removal of the delivery system. High levels of rhNGF (as high as 60,000 ng in a brain slice of approximately 50 microliters) were recovered from the brain tissue at 1, 2, and 4 weeks after implantation. With all three delivery systems, the amount of rhNGF in each brain slice decreased exponentially with distance from the implant site: the distance over which concentration decreased by 10-fold was 2-3 mm for all delivery systems. When rhNGF release was moderate (10 to 200 ng rhNGF/day), the total amount of rhNGF in the brain increased linearly with release rate, suggesting an overall rate of rhNGF elimination of 0.4 hr-1 or a half-life of 1.7 hr. With higher release rates (500 to 50,000 ng rhNGF/day), total amounts of rhNGF in the brain were considerably higher than anticipated based on this rate of elimination. CONCLUSIONS: Polymeric controlled release can provide high, localized doses of rhNGF in the brain. All of the experimental data were consistent with penetration of rhNGF through the brain tissue with a diffusion coefficient approximately 8 x 10(-7) cm2/s, which is approximately 50% of the diffusion coefficient in water.

Animals↗

PubMedDate not supplied

Implementing the Hospital Emergency Incident Command System: an integrated delivery system's experience.

INTRODUCTION: Hospital disaster manuals and response plans often lack formal command structure; instead, they rely on the presence of key individuals who are familiar with hospital operations, or who are in leadership positions during routine, day-to-day operations. Although this structure occasionally may prove to be successful, it is unreliable, as this leadership may be unavailable at the time of the crisis, and may not be sustainable during a prolonged event. The Hospital Emergency Incident Command System (HEICS) provides a command structure that does not rely on specific individuals, is flexible and expandable, and is ubiquitous in the fire service, emergency medical services, military, and police agencies, thus allowing for ease of communication during event management. METHODS: A descriptive report of the implementation of the HEICS throughout a large healthcare network is reviewed. RESULTS AND CONCLUSIONS: Implementation of the HEICS provides a consistent command structure for hospitals that enables consistency and commonality with other hospitals and disaster response entities.

Delivery of Health Care, Integrated↗

PubMed2002

Preparation of theophylline hydrogels of atactic poly(vinyl alcohol)/NaCl/H2O system for drug delivery system.

Theophylline (TH) was loaded in an a-PVA/NaCl/H2O hydrogels system by one cycle gelation only at -20 degrees C. However, it developed some unwanted crystal-like structure surrounding the hydrogels while kept at room temperature. The physical, chemical and thermal analyses of this crystal-like structure indicated TH embedded with thin hydrogels of a-PVA/NaCl. Later during dissolving of feed-mixture at least 3 h heat treatment with proper mixing at high temperature contributed hydrogels of almost no crystal-like structure. 3% of TH was successfully loaded by this way. This type of hydrogels showed Fickian type drug release (Higuchi Model) and it showed a more sustained effect than that of traditional cyclic FT. Comparatively lower release rate, diffusion coefficient and kinetic constant values of this system prevail over other systems studied here. A DSC thermogram revealed that apparently homogeneous microgel junctions might play the key role behind the above properties. Moreover the a-PVA/TH/NaCl/H2O system depresses the freezing point at -30 degrees C instead of above this temperature. The hydrogels of this system were also prepared by freezing at -30 degrees C for 16 h as one cycle. Three cycles were done in cyclic FT (freezing at -30 degrees C for 16 h and thawing at room temperature for 8 h). Drug release was studied for a total of 750 min. Up to the asymptotic value, 10.5 h TH release from the hydrogel matrices of the a-PVA/NaCl/H2O system (gelation at -20 degrees C) and 6.5 h from those of a-PVA/NaCl/H2O (freezing at -30 degrees C) and a-PVA/H2O systems (cyclic FT) were found.

Calorimetry, Differential Scanning↗

PubMed2006

Rationale for the selection of an aerosol delivery system for gene delivery.

Genetic therapeutics show great promise toward the treatment of illnesses associated with the lungs; however, current methods of delivery such as jet and ultrasonic nebulization decrease the activity and effectiveness of these treatments. Extremely low transfection rates exhibited by non-complexed plasmid DNA in these nebulizers have been primarily attributed to poor translocation and loss of molecular integrity as a consequence of shear-induced degradation. Current research focusing on methods to increase transfection rates via the pulmonary delivery route has largely concentrated on the incorporation of carbon dioxide in the air stream to increase breath depth as well as the addition of cationic agents that condense DNA into compact, ordered complexes. The purpose of this study was to examine the impact of several classic as well as the latest atomization devices on the structure of non-complexed DNA. Various sizes of plasmid and cosmid DNA were processed through an electrostatic spray, ultrasonic nebulizer, vibrating mesh nebulizer, and jet nebulizer. Results varied dramatically based upon atomization device as well as DNA size. This may explain the inefficiency experienced by genetic therapeutics during pulmonary delivery. More importantly, this suggests that the selection of an atomization device should consider DNA size in order to achieve optimal gene delivery to the lungs.

Administration, Inhalation↗

PubMed1994