Jenkins Biomedical Polymers

1. Auflage 2007
ISBN: 978-1-84569-364-0
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 236 Seiten

Reihe: Woodhead Publishing Series in Biomaterials

Given the rapid development and use of biomaterials, it is becoming increasingly important to understand the structure, processing and properties of biomedical polymers and their medical applications. With its distinguished editor and team of international contributors, Biomedical Polymers reviews the latest research on this important group of biomaterials.The book discusses natural, synthetic, biodegradable and non bio-degradable polymers and their applications. Chapters review polymeric scaffolds for tissue engineering and drug delivery systems, the use of polymers in cell encapsulation, their role as replacement materials for heart valves and arteries, and their applications in joint replacement. The book also discusses the use of polymers in biosensor applications.Biomedical polymers is an essential reference for scientists and all those concerned with the development and use of this important group of biomaterials - Reviews the latest research in this important group of biomaterials - Discusses natural, synthetic, biodegradable and non-biodegradable polymers and their applications - Examines the use of biomedical polymers in such areas as drug delivery systems and cell encapsulation

Autoren/Hrsg.

Jenkins, Mike

Leseproben

2 Introduction to polymeric drug delivery systems
K HARRISON,     GlaxoSmithKline R&D Ltd, UK Publisher Summary
This chapter discusses that polymeric delivery systems are mainly used to achieve either temporal or spatial control of drug delivery. Essentially, polymeric vehicles enable drugs to be delivered over an extended period of time and to the local site of action. They are designed to enhance drug safety and efficacy and to improve patient compliance. The use of polymers is designed to maintain therapeutic levels of the drug, to reduce the side-effect profile, to decrease the amount of drug molecule and the dosage frequency, and to facilitate the delivery of drugs with short in vivo half-lives. Polymeric drug delivery is a constantly evolving field of therapeutics and consequently, new technologies and enhanced modes of action are continuously emerging. A major advancement in the future will be the development of a continuous glucose sensor to treat diabetes. The sensor would ideally be sensitive to small changes in glucose, remain in contact with either blood or bodily fluid, and respond rapidly and reliably to any fluctuations in blood glucose levels. It could be in the form of a hydrogel that is able to respond to the local environment. It would then be regulated by a release of insulin from the hydrogel system. 2.1 Introduction: controlled drug release
Polymeric delivery systems are mainly used to achieve either temporal or spatial control of drug delivery.1 Essentially, polymeric vehicles enable drugs to be delivered over an extended period of time and to the local site of action. They are designed to enhance drug safety and efficacy, and to improve patient compliance. The use of polymers is designed to maintain therapeutic levels of the drug, to reduce the side-effect profile, to decrease the amount of drug molecule and the dosage frequency, and to facilitate the delivery of drugs with short in vivo half-lives.2 Controlled-release drug delivery systems function by enabling the drug molecule’s inherent kinetic properties to be manipulated by the property of the polymeric vehicle.3 Controlled-release devices allow potent drugs with short half-lives to be administered with minimal fluctuations over an extended period of time and with a potentially lower incidence of toxicity.4 Ultimately, sustained-action dosage forms improve therapeutic management through assuring a uniform plasma concentration of drug at a steady state. Ideally, the device should offer slow first-order or slow zero-order absorption of the drug from the gastrointestinal tract. If the blood drug level profiles of sustained-release dosage forms are compared with the administration of conventional and controlled dosage forms, the profiles in Fig 2.1 are obtained. The conventional tablet or capsule provides a single and transient burst of drug. Furthermore, a pharmacological response is only observed if the amount of drug is above the minimum effective concentration.3 Sustained-release formulations reduce the burst effect but the plasma concentrations are not maintained for as long as controlled-release systems and gradually begin to deplete. Controlled-release systems, however, reduce fluctuations in plasma drug levels by slowing down the absorption rate owing to a slower drug release rate and result in an effective pharmacological response.
2.1 Plasma drug concentration profiles for conventional tablet, sustained-release and zero-order controlled-release formulations. An understanding of the drug and polymer characteristics is essential to the success of the drug delivery device. By altering the properties of the polymer, the release rate of the drug can also be controlled. In addition, the environment in which the device is to function impacts on the choice of polymer, drug and device design. A multifaceted approach is therefore crucial for successful drug delivery from polymeric systems. 2.1.1 Conventional film coatings
Conventional dosage forms are typically drug dispersed through soluble excipients. The drug is rapidly liberated from its dosage form and quickly builds up to a high concentration.5 The concentration falls exponentially until the next dose is administered. Consequently, there is an undulating concentration pattern of the drug in the plasma and tissue and the optimal therapeutic level is only present briefly. Conventional dosage forms, unlike controlled-release systems, do not control the rate of drug release.6 A conventional film coating is utilised to improve product appearance, to improve handling and to prevent dusting.7 In addition, a film coating is used to mask unpleasant taste and odour and to improve product stability.8 However, film coats are not typically applied to modify the drug-release characteristics. This can often cause conventional dosage forms to exhibit fluctuating drug levels, insufficient influence on the mechanism of the disease and inconvenient dosing regimens.5 Typically, cellulose derivatives are chosen to act as film coats, with the most common polymer being hydroxypropyl methylcellulose (HPMC). HPMC provides aqueously soluble films which can also be coloured by the use of pigments. It also affords easy processing because of its non-tacky nature. However, HPMC has a very high tensile strength and a very low elongation value.8 Consequently, a large force can be applied to the film before it breaks, but the film lengthens only a small amount before the break occurs. This can present problems if the film is required to coat difficult tablet cores such as vitamins and monogrammed tablets. In order to modify the characteristics of the polymer, plasticisers are added to improve flexibility.8 HPMC can also be blended with hydroxypropylcellulose, which has a lower tensile strength and much higher elongation value. A blend of the two grades can eliminate the bridging observed in monogrammed tablets, improve film adherence to tablet substrates and also reduce the incidence of cracking at tablet edges.8 A conventional coat, however, will not control the rate of drug release from the core. 2.1.2 Functional polymers
Functional polymers are designed to modify the pharmaceutical function of the dosage form and to control the release of the active ingredient.7 The majority of controlled-release dosage forms can be categorised as matrix, reservoir or osmotic systems.9 In matrix systems, the drug is embedded in the polymer matrix and release takes place by partitioning of the drug into the matrix and the release medium.10 It may be characterised as a mass transport phenomenon. In contrast, reservoir systems have a drug core surrounded by a rate-controlling membrane such as enterically coated products and implants. Factors such as pH and presence of food affect the drug release rate from reservoir devices. An increase in hydrostatic pressure drives osmotic devices, forcing the drug solution or suspension out of the device through a small delivery port.11 Drug release is independent of pH and it is possible to modulate the release characteristics by optimising the properties of the drug and polymer coat. 2.2 Mechanisms of action for controlled drug release
The most important attribute of a controlled-release device is the ability to maintain a constant rate of drug delivery. The duration must also be compatible with the physiological constraints and the route of administration.12 As such, numerous devices have been developed, which function via various mechanisms of action to achieve the desired rate of drug release. Three common mechanisms of action, namely diffusion, osmotic effects and erosion, are outlined below. 2.2.1 Diffusion
Polymer films that use a diffusion mechanism permit the entry of aqueous fluids from the gastrointestinal (GI) tract into the tablet core. Dissolution of the drug ensues, which is followed by diffusion of the drug solution through the polymeric membrane into the body.12 The rate of drug diffusion can be determined by the physicochemical properties of the drug and the membrane itself.7 The properties of the polymer membrane can be altered by the choice of polymer, the molecular weight of the polymer and the inclusion of plasticisers. All these factors can alter the structure of the film and the drug can diffuse through a network of pores and channels within the membrane, thus facilitating the release process. If the chosen polymer membrane is hydrophilic, the rate of absorption of liquid is very high and the dosage swells. Consequently, as the dosage form swells, there is an associated increase in diffusivity, which enhances the rate of drug release.5 Conversely, if the polymer is hydrophobic and swelling is negligible, the diffusion of the drug out of the polymer matrix is much slower. Diffusion-controlled devices tend to be divided into two main types: monolithic devices and reservoir devices.3 Monolithic devices consist of the active pharmaceutical ingredient...