Advances in Controlled Delivery of Drugs

Melvyn Kohudic

• Publisher: Routledge
• Year: 2022
• ISBN:
  9781351468404
• Edition: 1
• Topic: Medicine
• Subtopic: Pharmacology

The development of improved methods of drug delivery has received significant attention over the last two decades. Most important is a non-toxic level of the drug at a particular body organ or body locale. To reach this goal, many variations of controlled release have been researched worldwide. This edited volume of papers from the Journal of Biomaterials Applications details many exciting technical advances in controlled release drug delivery systems. Some of the important developments described in the book include implantable delivery systems, delivery of topical drugs, and ultrasonic drug delivery.

Implantable Drug Delivery

MONICA J. NITSCH

Medical Student 4th Year
University of Nevada at Reno
School of Medicine
Reno, NV 89557

UMESH V. BANAKAR, PH.D.^*

Director of Research
Section Head: Pharmaceutical Sciences
Associate Professor of Pharmaceutics
St. Louis College of Pharmacy
4588 Parkview Place
St. Louis, MO 63110

INTRODUCTION

Conventional drug delivery utilizes routes of administration, namely, oral, rectal, intravenously, and topical, that deliver drug substances that are immediately released in bolus fashion. For a time, the drug concentration will be adequate for therapeutic effectiveness, but eventually the drug concentration falls below the minimum effective concentration and another dose of the drug is required. The increased frequency of dosing to sustain a therapeutic concentration may be several times daily, which not only results in variable drug concentrations, but also noncompliance by the patient unable to maintain this regimen. The ideal drug concentration profile would be a sustained therapeutic level without variation or the need for repeated dosing (Figure 1).

Figure 1. Conventional drug dosing and drug concentrations (from Reference [3]).

Pharmaceutical companies continue to develop new drugs with the goal of augmenting the duration of action and thus, reducing the frequency of dosing. It was not until recently that the delivery systems themselves were modified in order to facilitate controlled-release drug delivery that would also sustain the duration of action within the therapeutic range. These advancements in drug delivery have afforded many new and exciting areas of research and development aimed to optimize pharmaceutically-related therapy for many diseases. These technical advances in drug delivery are rapidly progressing to reality and it is anticipated that they will be used more frequently in clinical practice over the next decade. Major advances have already been made in the area of contraception with the development of the Norplant implantable system [1]. In addition, the insulin pump for diabetes is being perfected by several investigators and is widely reported in the literature [2].

Implantable pumps and infusion systems are two of the several innovative technologies developed in drug delivery over the past two decades. These systems employ a mechanism involving a reservoir of drug substance and an energy source to drive drug release. Each mechanism offers unique opportunities for rate and duration for controlled delivery of drug substances directly into the bloodstream either locally or systemically. Further, the control of drug delivery in this manner reduces the adverse effects of drugs and improves overall efficacy and compliance by avoiding repeated insertions of needles into peripheral vasculature.

The implantable device is surgically introduced and completely subcutaneous with nominal chance of infection. Fluids or drugs are injected into the portal chamber and flow through the catheter directly into the bloodstream. The needle may be removed or an external pump, many of which are ambulatory, may be attached for continuous infusion.

Overall, there are several advantages to these systems including the psychological benefit to the patient who experiences less pain, less anxiety and less disruption of daily routines while remaining ambulatory during treatment. In addition, implantable systems are valuable because they enable drug substances to overcome the absorption barriers encountered by oral and peripheral intravenous administration, specifically: plasma proteins, first pass hepatic effects, gastrointestinal absorption, and the blood brain barrier. Each of these biological barriers prevents a percentage of drug substance from reaching its target site and active receptor. Implantables, whether for local or systemic administration, can also protect healthy tissue by eliminating peaks and troughs resulting from periodic dosing, thus minimizing toxic side effects.

Unfortunately, there are potential problems with the use of implantable systems. These include: biocompatibility, biodegradability, the need for a minor surgical procedure for ...