Bruschi Strategies to Modify the Drug Release from Pharmaceutical Systems

1. Auflage 2015
ISBN: 978-0-08-100112-7
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: Adobe DRM (»Systemvoraussetzungen)

E-Book, Englisch, 208 Seiten

Since the earliest dosage forms to modern drug delivery systems, came a great development and growth of knowledge with respect to drug delivery. Strategies to Modify the Drug Release from Pharmaceutical Systems will address principles, systems, applications and advances in the field.It will be principally a textbook and a reference source of strategies to modify the drug release. Moreover, the characterization, mathematical and physicochemical models, applications and the systems will be discussed. - Addresses the principles, systems, applications and advances in the field of drug delivery - Highlights the mathematical and physicochemical principles related to strategies   - Discusses drug release and its possible modifications

Marcos Luciano Bruschi, Ph.D., is Professor of Pharmaceutics andPharmaceutical Technology in the Department of Pharmacy at the State University of Maringá (UEM), Paraná, Brazil. He gained a BSc in Pharmacy (1996 - UEM, Brazil), a MD in Pharmaceutical Sciences (2002 - State University of São Paulo - UNESP - Brazil) and a PhD in Pharmaceutical Sciences (2006 - University of São Paulo - USP - Brazil and School of Pharmacy, Queen's University of Belfast, Northern Ireland, UK). In 2013-2014, he is accomplishing a Post-Doctoral Degree in Pharmaceutics in the School of Pharmacy, Queen's University of Belfast (QUB - Northern Ireland, UK). He is registered with the Brazilian Pharmaceutical Society and, in 1998, took up a lectureship in Pharmaceutics in the School of Pharmacy, UEM, Brazil. In 1999, he was appointed as a senior lectureship and to a personal Chair in Pharmaceutics and Pharmaceutical Technology in 2006. His research concerns the development and characterization of pharmaceutical dosage forms and drug delivery systems, using natural or synthetic sources. Dr. Bruschi's work has involved the development of novel drug delivery systems, with particular emphasis on micro/nanoparticles, semisolids, bio/mucoadhesives, thermoresponsive systems, liquid crystaline phases, and natural products. He is the author of three Brazilian patent requests and over 150 research papers/communications.

Autoren/Hrsg.

Bruschi, Marcos Luciano

Leseproben

2 Modification of drug release
Abstract
Drug delivery refers to the technology utilized to present the drug to the desired body site for drug release and absorption, or the subsequent transport of the active ingredients across the biological membranes to the site of action. A drug delivery system is a formulation or a device that enables the introduction of a therapeutic substance in the body and improves its efficacy and safety by controlling the rate, time and place of release of drugs in the body. The increasing interest in sustained release originated the concept of controlled release systems, displaying various advantages and disadvantages. Drug delivery history can be divided into three distinct periods. Nowadays, personalized medicines are the aim of the drug delivery scientist, looking for biologically precise and accurate controlled delivery systems with more biological and fewer materials-oriented characteristics. Keywords Drug delivery Drug delivery systems Drug delivery technology Controlled release Therapeutic systems Administration History Drug targeting Advantages Disadvantages. 2.1 Objectives
The administration of an active agent has the main objective of enabling the action for which it is intended. Many times, the conventional therapeutic regimens are characterized to use a high amount of a drug, with a high fraction excreted without exert activity. According to the definition, modified drug release means that the release of the active agent is different from traditional release. Therefore, modified release dosage forms are those whose drug release characteristics of time course and/or location are chosen to accomplish therapeutic or convenience objectives not offered by conventional forms (USP, 2014). The term drug delivery covers a very broad range of techniques used to get therapeutic agents into the human (or animal) body. It refers to the technology utilized to present the drug to the desired body site for drug release and absorption, or the subsequent transport of the active ingredients across the biological membranes to the site of action. A drug delivery system (DDS) is defined as a formulation or a device that enables the introduction of a therapeutic substance into the body and improves its efficacy and safety by controlling the rate, time, and place of release of drugs in the body. The therapeutic agent can also be an agent such as gene therapy, which will induce in vivo production of the active therapeutic agent. Despite the fact that gene therapy has its own special regulatory control, gene vectors may need to be introduced into the human body by novel delivery methods (Jain, 2008). In this context, time and spatial control of drug release constitutes the main aim of controlled drug delivery from the systems and has evolved as a multidisciplinary science, with the contribution of engineering technologies and polymer science. This field is not recent, considering the publication of the Noyes–Whitney equation in 1897 (Noyes & Whitney, 1897), the investigations about drug dissolution and particle size in the 1950s, the mathematical studies about diffusion (Philibert, 2005) and drug release of Takeru Higuchi and his team in the 1960s (Higuchi, 1961, 1962, 1963) and the more precise appreciation of the underpinning technologies and biologies. The controlled drug delivery technology is complex and has originated a terminology that is sometimes ambiguous and controversial. It has been common to use many terms to describe the sustained and controlled release dosage forms. These terms are used to identify specific products and their performance characteristics. They have obscured the capabilities of the products to the point where practitioners are often unclear about their advantages and limitations. Therefore, it is helpful to distinguish some terms and definitions. In immediate release systems, the rate of appearance of a drug in the body is controlled by the biological absorption process; whereas in sustained release systems, this is controlled by the dosage form. In this sense, suspensions, emulsions, capsules and tablets can be sustained by DDSs. However, the purpose of the DDS is to decrease the dosing frequency by at least a factor of 2, and in most cases an attempt is being made for all routes of administration to prepare at least once-daily products (Longer, Middleton, & Robinson, 1988). In this context, to achieve a therapeutic drug concentration promptly in the body, and then to maintain that concentration for a given period of time, it is necessary that the total active agent in the formulation consist of two portions: one to provide the initial loading dose (burst) and another to provide the maintenance or sustained dose. The initial dose provides a rapid onset of the desired therapeutic response, while the maintenance portion remaining in the dosage form is released at a slow but defined rate (according to zero-order kinetics). It is very important to consider that the kinetics of absorption of the maintenance dose will be characterized by the same zero-order release rate constant. Moreover, the rate at which the maintenance dose is released from the dosage form, and hence the input of the drug into the body, must be equal to the rate of drug output from the body when the concentration of the drug in the body is at the required therapeutic value. Therefore, considering rate and time, the difficulty of developing an ideal modified or controlled DDS is evident. The physiological conditions associated with the site of administration and the elimination rate constant of a given drug vary from patient to patient and conduce to imprecise controlled rates. Therefore, many modified-release products are not ideal controlled-release dosage forms. However, such products provide modified release in which the initial priming dose of the active agent is released immediately and the maintenance dose is then released slowly, thereby resulting in a therapeutic drug/tissue concentration that is prolonged but not kept constant (Collett & Moreton, 2001). With the increased interest in sustained release drug delivery originated the concept of controlled release systems, carrying a superior performance concept where predictive control over the release pattern and subsequent tissue or blood levels can be achieved. Based on a simple one-compartment model, the system should be equivalent to an intravenous infusion of the drug (zero-order input). This analysis assumes that pharmacokinetics mimics pharmacodynamics; this assumption is invalid for a great number of drugs, particularly peptides and proteins. Moreover, it assumes that the biological noise is small enough that zero-order delivery can be distinguished from other kinetic input functions. The optimal rate of the drug input may not be zero order for all active agents and disease states. For example, it is known that circadian rhythm influences enzyme induction and inhibition, and that down regulation of receptors may modify drug response or metabolism (Longer et al., 1988). Therefore, the tendency is for the authors to try to define, each in their own way, just how the release occurs or should occur. Thus, there is a great variety of terms used to describe these systems (Collett & Moreton, 2001): (1) Delayed release (This indicates that the drug is not being released immediately following administration, but at a later time (e.g., enteric coated tablets, pulsatile-release capsules).) (2) Repeat action (This indicates that an individual dose is released fairly soon after administration, and second or third doses are subsequently released at intermittent intervals.) (3) Prolonged action/release (This indicates that the drug is provided for absorption over a longer period of time than for a conventional dosage form. However, there is an implication that onset is delayed because of an overall slower release rate from the dosage form.) (4) Sustained action/release (This indicates an initial release of drug sufficient to provide a therapeutic dose soon after administration, and then a gradual release over an extended period.) (5) Extended release (The dosage forms release the drug slowly, so that plasma concentrations are maintained at a therapeutic level for a prolonged period of time, usually between 8 and 12 h.) (6) Controlled release (The dosage forms release the drug at a constant rate and provide plasma concentrations that remain invariant with time.) Other terms are also utilized and include “programmed release,” “slow release,” “timed release,” “double release,” “gradual release,” “delayed action,” “long acting,” and “retard.” The term “controlled release” is general and encompasses all the others without specifying the type of control that occurs and how it is reached. Actually, this term has more fidelity, considering that the controlled DDS needs to provide the release of an active agent with control according to the objective and independent of environmental conditions. Thus, the development of highly controllable DDS that allow the release of an...