Hydrophilic Polymer Coatings for Medical Devices PDF

PREFACE

Scientific research, in its purest form, is the critical inquiry and examination of events or of the environment whose goal is that of discovering and interpreting new information. Engineering involves understanding the varied interpretations of acquired knowledge and applying them to control events or the environment. These disciplines are symbiotic and each proliferates the scope of the other: the acquisition of knowledge leads to the development of technology, which makes possible the acquisition of further knowledge. In highly technical industries, research is most often performed with the intent that any results could have commercial application; however, the research is normally conducted in the laboratory setting. For the engineers who design products and manufacturing processes based on this research, there are different objectives and motivations.

The current state of the literature specifically related to hydrophilic (water-soluble) polymers for biomedical and pharmaceutical applications is replete with articles and texts written mostly by research scientists. This is understandable, because initial research on hydrophilic systems pertinent to these applications did not begin in earnest until the early 1940s. Evaluation of hydrophilic systems continued through the 1950s, but it was not until 1960 that Wichterle and Lim, of the Czechoslovakian Academy of Sciences, reported the viability of poly(2-hydroxyethyl methacrylate) (PHEMA) as a material for contact lenses. Granted, hydrophilic materials are extremely unique, dynamic polymers that demand intensive research to characterize accurately their properties and behavior. It is also true that many more years of research will be necessary to exploit their potential for biomedical applications to the fullest. However, there is at present a burgeoning industry that is exploiting what little is already known about this family of materials. Relative to this last point is the main intent of writing the following text.

Providing a practical perspective for the product design engineer, the process engineer, or the manufacturing engineer, on current information pertaining to these unique polymers is the primary objective of this discourse. Hydrophilic polymers are presently incorporated into the design of a rich variety of biomedical and pharmaceutical products. Contact lenses, ocular implants, a surfeit of drug delivery systems, lubricious coatings for less invasive devices, biological adhesives, antithrombogenic coatings, soft tissue replacement, and permanent implants are a few of the current commercial applications that incorporate hydrophilic polymers. Issues related to product feasibility, ease of manufacture, and product-process constraints, as well as environmental and regulatory concerns all have a direct bearing on the agenda of the engineer.

To this end I have attempted to present an overview of the current literature in a usable form for the engineer. Mathematical models for predicting behavior have been limited to those that are conveniently applied in a commercial processing environment. Overviews of manufacturing techniques, evaluation techniques, and current applications have been provided based on existing technologies, and in consideration of the many guidelines and restrictions imposed by regulatory bodies (e.g., FDA, OSHA, ERA, ISO, et al.) on medical device manufacturers. Because of the limited exchange of information among companies in the biomedical industry, which results from the proprietary constraints placed on the work being done from company to company, an engineer working on an ocular implant may not discover certain useful techniques developed by an engineer working on drug delivery systems. The information presented here will hopefully bridge the gap between seemingly unrelated applications and foster a better overall understanding of hydrophilic polymers for the medical device industry.

As a result of the proliferation in the use of computers in industry, access to information and the acquisition thereof have been dramatically enhanced. In fact, the use of computers and their ability to scan the established databases made the writing of this text possible. A list of key terms and phrases related to the subject matter was provided to NERAC, a literature search company. These key terms and phrases were used to scan the following: chemical abstracts, rubber and plastics research abstracts, biomedical industry business publications, engineering indexes, citations from pharmaceutical abstracts, citations from life science collections, the Medline database, and the United States patent bibliographic database. From these, a list of current published abstracts, articles, texts, and patents that deal specifically with hydrophilic materials in biomedical and pharmaceutical applications was generated.

The study can be divided into two themes, more or less. The first deals with theoretical concepts and information that are more scientific in nature than pragmatic. The topics of wettability and hydrophilicity are treated first, because of their importance to coating operations in which the substrates are usually polymeric and the formulations include hydrophilic polymers as primary substituents. The general molecular structure of hydrophilic polymers, relative to their physical and chemical behavior, as well as pertinent evaluation techniques are treated next. This is followed by an overview of many synthetic and naturally occurring hydrophilic materials, which is intended to facilitate the choice of material for particular applications or formulation designs. It was thought that, with a more complete understanding of hydrophilic materials, more sensible development and manufacturing plans can be generated.

The discussion then turns to the more practical matters of particular importance to the manufacturing engineer. Hydrophilic coatings are first compared with conventional coatings (e.g., paints and other protective coatings) to provide some perspective on necessary process requirements. Considerations for process and product design, as well as major facility requirements are furnished to give some structure to the decision-making process. Major technical areas related to coating processes are then treated in chronological order to provide direction in developing and coordinating an appropriate process. Because of the critical nature of medical devices, the engineer has an opportunity to exploit technologies not commonly used in more industrial type settings. Methods for surface preparation using plasma treatments and irradiation, as well as coating and surface modification techniques, ranging from conventional methods to more advanced plasma and grafting systems, are discussed. Analytical techniques and testing methods are covered, because characterizing substrates and evaluating applied coatings are essential in optimizing the final process. Because the medical device industry is so highly regulated, a section on regulatory and safety considerations is presented. Finally, current product applications for hydrophilic coatings are cited, demonstrating how the general concepts discussed throughout the study are put to use.

The information is organized in such a way that the requirements and considerations associated with such an undertaking form the basis for the major topics discussed. The decision to present these particular topics in the order in which they appear is based on personal experience. Presented in this manner, it is hoped that the information will serve as a reference through all stages of formulation design, product development, pilot operations, process scale-up, and actual manufacture of the product.

Author: Richard J. LaPorte