药物鼻黏膜递送的影响因素

鼻腔给药以其吸收快、使用方便、可避免药物胃肠道降解和肝脏首过效应、生物利用度高、实现脑靶向等特点，日益受到人们的重视，成为制剂学领域的研究热点之一。现综述影响药物在鼻腔内吸收的各种因素，包括生理因素、药物的理化性质、剂型和辅料的性质，以及给药装置的影响，为鼻腔给药系统的研究提供参考。     

Drug release kinetics and physicochemical characteristics of floating drug delivery systems

Introduction: Absorption of drugs through the gastrointestinal tract poses a variety of limitations, making the in vivo performance of drug delivery systems uncertain. Following on from recent advances, in a time of increased consideration of floating drug delivery systems, it is as important as ever to continue the progress by studying different aspects of these systems. Moreover, it seems imperative to gain a deeper insight into drug release mechanisms, in order to design a more systematic and intellectual floating system.

Areas covered: This paper summarizes current approaches in the research and development of ideal floating drug delivery systems, from recent literature. Also, in order to have predictability and reproducibility in designing an efficient floating dosage form, some kinetic studies are mentioned, and the drug release mechanism from floating drug delivery systems is discussed.

Expert opinion: Developing an efficient floating dosage form is reliant on a better understanding of the relation between formulation variables and performance of the floating systems. Generally, the combination of two buoyancy mechanisms and gas-generating systems with swellable polymers would be beneficial for obtaining an appropriate floating lag time and duration of buoyancy, which in turn guarantees optimum efficiency of the pharmaceutical dosage form.     

Drug release kinetics and physicochemical characteristics of floating drug delivery systems

INTRODUCTION: Absorption of drugs through the gastrointestinal tract poses a variety of limitations, making the in vivo performance of drug delivery systems uncertain. Following on from recent advances, in a time of increased consideration of floating drug delivery systems, it is as important as ever to continue the progress by studying different aspects of these systems. Moreover, it seems imperative to gain a deeper insight into drug release mechanisms, in order to design a more systematic and intellectual floating system. AREAS COVERED: This paper summarizes current approaches in the research and development of ideal floating drug delivery systems, from recent literature. Also, in order to have predictability and reproducibility in designing an efficient floating dosage form, some kinetic studies are mentioned, and the drug release mechanism from floating drug delivery systems is discussed. EXPERT OPINION: Developing an efficient floating dosage form is reliant on a better understanding of the relation between formulation variables and performance of the floating systems. Generally, the combination of two buoyancy mechanisms and gas-generating systems with swellable polymers would be beneficial for obtaining an appropriate floating lag time and duration of buoyancy, which in turn guarantees optimum efficiency of the pharmaceutical dosage form.     

Sustained drug delivery systems II: Factors affecting release rates from poly(epsilon-caprolactone) and related biodegradable polyesters

The release rates of several steroids from films and capsules of homopolymers and copolymer of epsilon-caprolactone, DL-lactic acid, and glycolic acid were measured in vitro and in vivo for up to 200 days. Relatively constant release rates from capsules (reservoir devices) were observed only under certain conditions. Factors that influence the drug release kinetics were evaluated. Release from poly(epsilon-caprolactone) and poly(epsilon-caprolactone-co-DL-lactic acid) was diffusion controlled. Release from poly(DL-lactic acid-co-glycolic acid) was associated with polymer degradation. Release from poly(DL-lactic acid) was very slow when diffusion controlled.     

Development of controlled release oral drug delivery system by membrane-coating method-I

In order to develop a controlled-release oral drug delivery system (DDS) which sustains the plasma acetaminophen (AAP) concentration for a certain period of time, microporous membrane-coated tablets were prepared and evaluatedin vitro. Firstly, highly water-soluble core tablets of AAP were prepared with various formulations by wet granulation and compression technique. Then the core tablets were coated with polyvinylchloride (PVC) in which micronized sucrose particles were dispersed. Effect of formula compositions of core tablets and coating suspensions on the pharmaceutical characteristics such as drug release kinetics and membrane stability of the coated tablets was investigatedin vitro. AAP was released from the coated tablets at a zero-order rate in a pH-independent manner. This independency of AAP release to pH change from 1.2 to 7.2 is favorable for the controlled oral drug delivery, since it will produce a constant drug release in the stomach and intestine regardless of the pH change in the GI tract. Drug release could be extended upto 10 h according to the coating condition. The release rate could be controlled by changing the formula compositions of the core tablets and coating suspensions, coat weight per each tablet, and especially PVC/sucrose ratio and particle size of the sucrose in the coating suspension. The coated tablets prepared in this study had a fairly good pharmaceutical characteristicsin vitro, however, overall evaluation of the coated tablets should awaitin vivo absorption study in man.     

Drug release kinetics from stent device-based delivery systems

In an effort to overcome the limitations of balloon-expandible intravascular metal stent-induced neointimal formation, drug-coated stent devices have been developed. The stent platform allows the local delivery of drugs to an injury site, thereby reducing the amount of drug exposure to the systemic circulation and other organs. The drug carrier matrix allows the release of the drug in a diffusion-controlled manner over an extended time period after the stent implant. The drugs are chosen such that the complex cascade of events that occurs after stent implantation that leads to smooth muscle cell proliferation and migration towards the intima are inhibited. The success of an antirestenotic drug therapy from a drug-coated stent is dependent, at least partially, on the extent of drug elution from the stent, the duration and rate of release, and accumulation of drug in the arterial wall in such a way that it covers the initiation and progression of vessel wall remodeling. The local vascular drug concentrations achieved are directly correlated with the biological effects and local vascular toxicity, and there is therefore a challenge in finding an optimum dose of drug to be delivered to tissues (ie, one that has the desired therapeutic effect without local adverse effects). There is increased focus on optimization of various factors that affect drug release from the stent system, including the physicochemical properties of the drugs, carrier vehicle formulation, and profile of elution kinetics. This review highlights the various factors involved in drug release kinetics, local vascular toxicity, carrier vehicle matrix, tissue deposition, and distribution through the arterial wall from stent-based drug delivery systems.     

Hydrogels: from controlled release to pH-responsive drug delivery

Hydrogels are one of the upcoming classes of polymer-based controlled-release drug delivery systems. Besides exhibiting swelling-controlled drug release, hydrogels also show stimuli-responsive changes in their structural network and hence, the drug release. Because of large variations in physiological pH at various body sites in normal as well as pathological conditions, pH-responsive polymeric networks have been extensively studied. This review highlights the use of hydrogels (a class of polymeric systems) in controlled drug delivery, and their application in stimuli-responsive, especially pH-responsive, drug release.     

Factors affecting drug delivery from a syringe-pump infusion set

In vitro testing of drug delivery via dual-lumen, small-volume i.v. extension tubing designed for use with a syringe pump was conducted. From a dual-lumen extension set with intraluminal diameters of 0.020 inch, effluent samples were collected at 5, 10, and 20 minutes after injection of a 1-mL volume of drug solution intended for delivery over 20 minutes by a syringe infusion pump. Variables were flow rate (5 or 25 mL/hr) of the primary infusion, tubing position (vertical or horizontal), and density of the drug solution (penicillin G potassium 250,000 units/mL and aminophylline 25 mg/mL represented high and low specific gravities, respectively). Each drug solution was labeled with radioactive carbon and the drug content of the effluent was analyzed by liquid scintillation. For each set of variables, samples were also tested after the tubing was flushed with 5% dextrose injection 0.2-0.6 mL. Similar procedures were followed to determine delivery of the labeled penicillin G potassium solution via a dual-lumen extension set with intraluminal diameters of 0.020 inch (for drug) and 0.060 inch (for the primary infusion); a 13-mm-diameter, 0.2 micron filter was attached to the smaller-lumen tubing. A primary infusion flow rate of 5 mL/hr and flush volumes of 0.3 and 0.6 mL were used in this study. To determine the influence of intraluminal diameter on the flush volume required for delivery of a dose of aminophylline (1-mL volume), single-lumen extension tubings with different diameters were tested. The final percentage of the drug dose delivered via the dual-lumen extension set with 0.020-inch lumens was affected only by flush volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Intrinsic release rate from matrix-type drug delivery systems

A simple method was presented for evaluation of the intrinsic release rate from a matrix-type drug delivery system. The effect of the hydrodynamic diffusion boundary layer on the rate of drug release was corrected to obtain the release profile without any diffusion boundary layer effect. The experimental release data was logically explained in terms of the intrinsic rate of release evaluated from the present method.     

Pulsed release of nitroglycerin from transdermal drug delivery systems

Non-ionic surfactant vesicles (niosomes) formed by a hexadecyl diglycerol ether (C16G2) and a series of polyoxyethylene alkyl ethers exhibit a variety of shapes dependent on their membrane composition. These surfactants form with an equimolar amount of cholesterol a mixture of largely spherical and tubular niosomes. In the absence of cholesterol, they form faceted polyhedral structures. The physicochemical and biological differences between polyhedral and spherical/tubular niosomes were studied. Polyhedral niosomes undergo a reversible shape transformation into spherical structures on heating above their phase transition temperature (Tm). The viscosity of polyhedral niosomes at room temperature is higher than their spherical counterparts due to their faceted and relatively rigid shape, and is more dependent on temperature due to shape transformation. At room temperature, polyhedral niosomes possess more rigid gel phase membranes and are less osmotically sensitive; however, they are more permeable because of a lack of or low levels of cholesterol in their membranes. Polyhedral niosomes loaded with luteinising hormone releasing hormone (LHRH), nonetheless, slow the release of drug compared to solution, albeit to a small extent.     

Encapsulated hydrophilic polymer beads containing indomethacin as controlled release drug delivery systems

Encapsulated hydrophilic polymer beads containing indomethacin were prepared by a combined technique of bead polymerization and phase separation. The drug delivery system consisted of the copolymer of 2-hydroxyethyl methacrylate and acrylamide as the core matrix and ethyl cellulose as the barrier membrane. The drug was incorporated into the polymer matrix during the formation of the beads. The system was found to be useful as a sustained release dosage form. Release of drug from the coated beads followed a zero-order rate up to 40% of the drug released. A linear relationship exists between the rate of release and the reciprocal amount of ethyl cellulose used for coating, indicating that the drug release was controlled by the coating thickness. Addition of polyvinyl pyrrolidone in the formulation significantly increased the amount of drug released. Blood level studies showed that drug absorption from the encapsulated beads was lower than that of indomethacin powder. It appeared that indomethacin was completely absorbed from the encapsulated beads.     

微凝胶的制备及其在药物缓控释系统中的应用

微凝胶是一种具有分子内交联网状结构,粒径在0.1~100 μm之间的功能性聚合物,具有粒径小、载药量高、环境响应性灵敏、生物相容性好等特点,在药物缓控释系统中的应用具有独特优势。笔者在查阅近年国内外文献的基础上综述了微凝胶的基本特性、制备方法、制备材料及在药物缓控释系统中的应用。     

Thermo-responsive systems for controlled drug delivery

Controlled drug delivery systems represent advanced systems that can be tightly modulated by stimuli in order to treat diseases in which sustained drug release is undesirable. Among the many different stimuli-sensitive delivery systems, temperature-sensitive drug delivery systems offer great potential over their counterparts due to their versatility in design, tunability of phase transition temperatures, passive targeting ability and in situ phase transitions. Thus, thermosensitive drug delivery systems can overcome many of the hurdles of conventional drug delivery systems in order to increase drug efficacies, drug targeting and decrease drug toxicities. In an effort to further control existing temperature-responsive systems, current innovative applications have combined temperature with other stimuli such as pH and light. The result has been the development of highly sophisticated systems, which demonstrate exquisite control over drug release and represent huge advances in biomedical research.     

Thermo-responsive systems for controlled drug delivery

Controlled drug delivery systems represent advanced systems that can be tightly modulated by stimuli in order to treat diseases in which sustained drug release is undesirable. Among the many different stimuli-sensitive delivery systems, temperature-sensitive drug delivery systems offer great potential over their counterparts due to their versatility in design, tunability of phase transition temperatures, passive targeting ability and in situ phase transitions. Thus, thermosensitive drug delivery systems can overcome many of the hurdles of conventional drug delivery systems in order to increase drug efficacies, drug targeting and decrease drug toxicities. In an effort to further control existing temperature-responsive systems, current innovative applications have combined temperature with other stimuli such as pH and light. The result has been the development of highly sophisticated systems, which demonstrate exquisite control over drug release and represent huge advances in biomedical research.     

Modified release intra-articular drug delivery systems

Beside the many advantages of intraarticular formulations (e.g., the systemic side effects are kept away), there is a big drawback. During the injections, there is the risk for infection therefore the number of injections in a year should be reduced. Also a long-term drug exposure should be achieved with an injection, and if it is possible, a combination of active ingredients should be used. At present there are only formulations with hyaluronic acid or glucocorticoid on the market. One of these formulations, a liposomal preparation, is of sustained drug release. Many different active ingredients could have a long-term drug exposure with carrier systems like micro- and nanoparticles, liposomes, hydrogels and physically activated delivery systems (thermoresponsive or magnetically modulated). The present paper gives an overview about these carrier systems, the novel scientific results and the aim of the future researches, as well.     

Mechanistic analysis of drug release from tablets with membrane controlled drug delivery.

The objective of this study was to receive detailed information on the mechanism of drug release from polyvinyl acetate (PVAc)/polyvinyl alcohol-polyethylene glycol graft copolymer (PVA-PEG) coated Propranolol HCl and Theophylline tablets. For this purpose the coating composition (PVAc/PVA-PEG: 90/10 and 80/20) and the amount of the coating layer have been varied. Due to its better solubility Propranolol HCl showed higher release rates than Theophylline. As expected, a higher percentage of the water soluble polymer accelerated drug release. Increased coating thickness led to amplified lag times of drug release. The water uptake of the tablets was quantified by gravimetric analysis. Furthermore, the microenvironment of the tablet core was monitored by EPR spectroscopy. For this purpose a hydrophilic EPR spin probe was incorporated into tablets. Surprisingly, despite a lag phase at the beginning and a controlled drug release over 24 h, the results of the EPR studies indicated an immediate water penetration through the coating layer into the tablet core. The water is able to solubilise the majority of water soluble compounds within minutes. The results obtained in this study demonstrate, that EPR is a powerful method to monitor the first steps of diffusion processes and the physicochemical state of coated dosage forms.