Basic Fundamentals of Drug Delivery

• Publisher: Academic Press
• Year: 2018
• ISBN:
  9780128179109
• Topic: Negocios y empresa
• Subtopic: Industria farmacéutica, biotecnológica y sanitaria

Basic Fundamentals of Drug Delivery covers the fundamental principles, advanced methodologies and technologies employed by pharmaceutical scientists, researchers and pharmaceutical industries to transform a drug candidate or new chemical entity into a final administrable drug delivery system. The book also covers various approaches involved in optimizing the therapeutic performance of a biomolecule while designing its appropriate advanced formulation.

• Provides up-to-date information on translating the physicochemical properties of drugs into drug delivery systems
• Explores how drugs are administered via various routes, such as orally, parenterally, transdermally or through inhalation
• Contains extensive references and further reading for course and self-study

Chapter 1

Scientific Rationale for Designing Controlled Drug Delivery Systems

Anu Hardenia¹, Neha Maheshwari², Shiv Shankar Hardenia³, Sunil Kumar Dwivedi¹, Rahul Maheshwari^4,5 and Rakesh K. Tekade⁴, ¹Sri Aurobindo Institute of Pharmacy, Indore, India, ²School of Pharmacy, Devi Ahilya Vishwavidyalaya, Indore, India, ³College of Pharmacy, IPS Academy, Indore, India, ⁴National Institute of Pharmaceutical Education and Research (NIPER)-Ahmedabad, Gandhinagar, Gujarat, India, ⁵Department of Pharmaceutics, BM College of Pharmaceutical Education and Research, Indore, India

Abstract

The past few decades have seen giant investigations and observations in novel and controlled drug delivery systems. There are diverse operations that necessitate the generation of such systems that can control the release rate or delivery of drugs systemically thereby reducing the frequent dosing, improving the fluctuations in plasma levels, which in turn can lower the risk of unwanted side effects. In addition, they show better targeting. The ideal drug delivery system may deliver at a constant rate and can give a required therapeutic response. This chapter aims to describe the rationale involved in the fabrication of a controlled drug delivery system with emphasis on different approaches (physical, chemical, and biological) and properties of drug candidates.

Keywords

Controlled drug delivery systems; novel drug delivery system; therapeutic response; scientific rationale; medical rationale; biological rationale

Outline

• 1.1 Conventional Drug Delivery Systems and Limitations 2
• 1.2 Controlled Release Drug Delivery System 4
  • 1.2.1 Historical Perspective 4
  • 1.2.2 Concept and Understanding 5
  • 1.2.3 Advantages of CRDDS Over Conventional Delivery Systems 6
  • 1.2.4 Compounds That Are Unsuitable for CRDDS 6
• 1.3 Design of CRDDS: Understanding of Factors 7
  • 1.3.1 Physicochemical Properties of Drug and Design Considerations 8
  • 1.3.2 Pharmacokinetic/Dynamic Considerations 8
  • 1.3.3 Polymers for CRDDS 9
• 1.4 Approaches for the Design of CRDDS 15
  • 1.4.1 Chemical Approach 15
  • 1.4.2 Biological Approach 17
  • 1.4.3 Pharmaceutical Approach 17
• 1.5 Medical Rationale of CRDDS 17
  • 1.5.1 Reduction in Dosing Frequency 19
  • 1.5.2 Lesser Drug Exposure to the Biological Environment 19
  • 1.5.3 Minimization of Plasma Concentration Fluctuations 19
  • 1.5.4 Better Patient Compliance 20
  • 1.5.5 Lower Adverse/Side Effects 20
  • 1.5.6 Augmented Efficacy 20
• 1.6 The Biological Rationale for CRDDS 21
  • 1.6.1 Absorption 21
  • 1.6.2 Drug–Protein Binding 21
  • 1.6.3 Distribution 21
  • 1.6.4 Elimination 22
  • 1.6.5 Dose-Dependent Bioavailability 22
  • 1.6.6 Duration of Drug Residence Within the Therapeutic Window 23
  • 1.6.7 Better Safety Margin 23
  • 1.6.8 Individualization in a Diseased Condition 23
• 1.7 Conclusion 24
• Acknowledgment 24
• Abbreviations 24
• References 25

1.1 Conventional Drug Delivery Systems and Limitations

In addition to the acceptable patient compliance, the purpose of drug delivery systems is to maximize the therapeutic efficacy of the incorporated drug(s) by the means of bioavailability enhancement or minimization of adverse effects. The conventional delivery systems, for example, tablets, capsules, solutions, etc. are yet successful for feeble therapeutic agents, where slight fluctuations in plasma profile do not affect the therapeutic efficacy.

But in the case of potent substances, the role of delivery systems extend from just the release of the drug at the site of absorption to the management of the drug release to maintain the plasma profile within the therapeutic window for the duration of therapy (Kreuter, 2014). A similar role of drug delivery systems is also desired in case of critical pathological conditions, for example, cancer, central nervous system (CNS) related diseases, and bacterial infections where the excess release of potent therapeutic agents may cause prominent adverse effects (Singh et al., 2017).

For the achievement of therapeutic goals with any drug therapy, the delivery system or dosage regimen must be capable to attain the therapeutic plasma levels immediately and further maintenance of these levels for the duration of therapy. To accomplish these targets, conventional delivery systems were designed by incorporating the suitable dose of the active drug(s) for administration at a particular frequency according to the pharmacokinetic properties of the incorporated agent(s). When considering the convenient dosing frequency for optimum therapeutic efficacy one has to take insightful account of biological half-life and therapeutic index of the compound under consideration (Mitragotri et al., 2014). In case of conventional delivery systems, dosing frequency is generally significantly shorter than the biological half-life of the incorporated drug(s), which poses several limitations in terms of the following:

• • Poor patient compliance as the complete dosage regimen needs more than twice or thrice a day administration, which multiplies the chances of missing a dose, especially in the case of geriatric and pediatric patients.
• • Due to the frequent dosing with fluctuating drug concentration-time intervals between the doses, the plasma drug concentration profile encompasses a combination of alternate peaks and valleys, which poses a prominent hindrance for the attainment of the desired steady-state profile.
• • Due to the immeasurable fluctuations in plasma drug concentration profile, there may be chances of under or overmedication, that is, at certain points during the therapy the plasma drug concentration may fall below the minimum effective concentration or may rise above the maximum safe concentration (Tiwari et al., 2012).

A diagrammatic view of the limitations of conventional delivery is also shown in Fig. 1.1.

Figure 1.1 Limitations of conventional drug delivery systems.

The above consequences related to plasma drug concentration fluctuation seek more emphasis in case of drugs with narrow therapeutic window; otherwise they may lead to the eruption of dose associated adverse effects (Naahidi et al., 2013). Within the view of patient-convenient drug delivery systems, the developers are focused on the overhauling of limitations associated with conventional drug delivery systems. Consequently, much effort is directed for the development of modified release drug delivery systems, which will be able to provide reproducible and effective drug plasma concent...