Releasing systems, development

A prolonged action/controlled release system developed to deUver levonorgestrel for contraceptive therapy involves implantation of a set of flexible closed capsules made of demethylsiloxane—methylvinyl—sdoxane copolymer (see Contraceptives). Each capsule measures 2.4 mm in diameter and 34 mm in length. A set of six such capsules is surgically implanted beneath the skin of the upper arm. These capsules are intended to be removed by the end of the fifth year after implantation. 

This is the case of the avalanche release system developed by the firm Technologie Alpine de Securite (Alpine Safety Technology = TAS), which designed a preventive avalanche release system involving the explosion of a mixture of oxygen/hydrogen. What is at stake is the ability to control risks related with the e q)losion, which moreover constitutes the normal framework of operation of the system. 

Other above-ground continuous flow systems have been designed and operated for SCWO processes. A system developed by ModeU Development Corp. (Modec) uses a tubular reactor and can be operated at temperatures above 500°C. It employs a pressure letdown system in which soHd, Hquids, and gases are separated prior to pressure release. This simplifies valve design and material selection on the Hquid leg. 

Bovine growth hormone, a difficult protein for which to develop controlled release systems due to its propensity toward self-aggregation and inactivation, has successfully been incorporated into polyanhydride matrices (18). The growth hormone was colyophilized with sucrose, dry-mixed with finely powdered polyanhydride, and then compression molded into 1.4-cm-diaraeter wafers, 1 mm thick. As is shown in Fig. 15, release of bovine growth hormone was well controlled over a prolonged period of time. The assay for bovine... 

Historically, the oral route of administration has been used the most for both conventional and novel drug-delivery systems. There are many obvious reasons for this, not the least of which would include acceptance by the patient and ease of administration. The types of sustained- and controlled-release systems employed for oral administration include virtually every currently known theoretical mechanism for such application. This is because there is more flexibility in dosage design, since constraints, such as sterility and potential damage at the site of administration, axe minimized. Because of this, it is convenient to discuss the different types of dosage forms by using those developed for oral administration as initial examples. 

This system is the only osmotic system developed commercially at this time that is suitable for the oral administration of insoluble drugs to humans. It has been utilized in the development of several other drugs including isradipine, doxazosin, diltiazem, contraceptive steroids, glipizide, and verapamil [48-53], The system has also been utilized to codeliver the free bases of compounds normally administered as water-soluble salts such as pseudoephedrine and bromo-pheniramine [54], The latter system includes both a loading dose and a controlled release dose and is intended for applications in the over-the-counter market. 

Various aspects of in vitro gas production test have been reviewed by Getachew et al. [33], and these authors reported that gas measurement were centered on investigations of rumen microbial activities using manometric measurements and concluded that these methods do not have wide acceptability in routine feed evaluation since there was no provision for the mechanical stirring of the sample during incubation. Another in vitro automated pressure transducer method for gas production measurement was developed by Wilkins [34], and the method was validated by Blummel and Orskov [35] and Makkar et al. [36]. There are several other gas-measuring techniques such as (i) Flohenheim gas method or Menke s method [37] (ii) liquid displacement system [38] (iii) manometric method [39] (iv) pressure transducer systems manual [40], computerized [41], and combination of pressure transducer and gas release system [42]. 

The development of new polyanhydrides has sparked researchers to developed new device fabrication and characterization techniques, instrumentation, and experimental and mathematical models that can be extended to the study of other systems. The growing interest in developing new chemistries and drug release systems based on polyanhydrides promises a rich harvest of new applications and drug release technologies, as well as new characterization techniques that can be extended to other materials. Future endeavors will likely focus on multicomponent polyanhydride systems, combining new chemical functionalities to tailor polyanhydrides for specific applications. 

Controlled drug delivery, membrane technology in, 15 847-848 Controlled drug release formulations (CDRFs), 9 51, 55 polymers in, 9 71-73 Controlled drug release systems, 9 50-51 design, 9 51-52 development, 9 55-57 intelligent, 9 56-57 in market, 9 83—85... 

Controlled expansion alloys, 13 520-522 Controlled flavor release systems, 11 528, 543-553, 554-555 characteristics of, ll 544t demand for, 11 555 developments in, 11 558 elements of, 11 555-557 extrusion encapsulation for, 11 550 key aspects of, 11 556t morphologies of, 11 545 Controlled free-radical polymerization, block copolymers, 7 646 Controlled humidity drying, ceramics processing, 5 655-656 Controlled indexing, 18 241 Controlled initiation, 14 268-269 Controlled laboratory studies, in... 

McCormick, C.L. and K.E. Savage, "Development of Controlled Release Systems Containing Pendant Metribuzin," Proceedings of the 1977 Controlled Release Symposium, pp. 28-40, Corvallis, Oregon (1977). 

To develop an HPLC stability-indicating method for Type I or II dissolution, the linearity must be wide enough, in combination with good sensitivity and minimal interference, to accommodate concentrations from low (possibly LOQ) to very high end, as the samples drawn represent the cumulative drug amount dissolved over time. As for an FiPLC method that is designed for Type VII dissolution, the linearity should accommodate the lower concentrations since it is a drug measurement of a controlled-release system. 

Another model, used in the USA, is the OASYS Pollution Prevention Optional Analysis System, developed by the Toxic Use Reduction Institute. Technologies are assessed on a variety of hazard criteria, including acute and chronic human toxicity, physical properties, aquatic impacts, persistence/bioaccumulation, atmospheric releases, disposal, chemical properties, energy/resource use, product hazard and exposure potential. Alternatives are rated to... 

Polyelectrolytes have recently found application in the development of pH sensitive liposomal controlled release systems. This application arises from the fact that polyelectrolytes may be used both to stabilize liposomes, and to disrupt liposomes in a pH dependent manner. Although the use of liposomes in oral pharmaceutical compositions has been discussed [424], liposomes generally suffer from poor stability and are therefore prone to leakage of the entrapped active agents. To overcome this problem, several authors have stabilized the liposomes using polyelectrolytes. For example, Tirrell and coworkers have employed ionene [425], and polyethylene imine) [426] to stabilize liposomes. Similarly, Sato and coworkers have studied maleic acid copolymers [427], and Sumamoto and coworkers have studied liposomes [428] coated with polysaccharides. In related work, Kondo and coworkers have emphasized the use of carboxymethyl chitin to produce artificial red blood cells [429-435]. 

Control System Development Model-based design space development offers an ideal segue between process and control development. Quite literally, a model-based design space would provide the template for development of feedforward process control models. Moreover, development of a process design space using a model-based framework would facilitate control system validation and identification of science-based, in-process, and release specifications. 

In other indications such as hypertension, the OROS technology (oral osmotic system developed by ALZA) has already proven its value, and therefore it seemed appropriate to use this technology with its typical, virtually constant, release rate (zero-order kinetics) for once-daily opioid tablets. Such a morphine tablet is already available, but is not yet on the market, and a hydromorphone OROS is currently being clinically developed by Knoll. 

The finding that intragranular polymer networks can undergo phase transition, and that product release in secretion might operate in a way similar to the newly developed drug release systems based on intelligent polymers, opens a... 

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