Oil-in-Water Nanosized Emulsions for Drug Delivery and Targeting. Tamilvanan Shunmugaperumal

to systematically optimize the emulsion formula matching with ICH guidelines Q8(R2), Q9, and Q10, to characterize the emulsions and perform safety assessment, to monitor the biofate of nanosized emulsions, etc. All these abovesaid issues are detailed in this book with few case studies wherever possible.

      Chapter 1 starts with terminology confusion prevailing about emulsion in medical and pharmaceutical fields. The purpose of this section is to clarify the terminology needed to indicate authentically this drug delivery/targeting system and finally gives reasons for judicious selection of the term “nanosized emulsion.” It will also provide generations of oil‐in‐water nanosized emulsions so far developed with short justification followed by a brief description regarding the purpose and contents of the book.

      Chapter 2 introduces the quality‐by‐design (QbD) approach applied onto the emulsion optimization during the preformulation studies. The effect of amount of NCE or lipophilic drug, quantity of excipients (oils, emulsifiers, and other excipients) onto the drug incorporation patterns, final particle size distribution of dispersed oil droplets of the emulsion, stability of final emulsion over different temperature conditions, etc., are the subject of interest discussed in this chapter.

Chapter 3 provides an overview of how nanosized emulsions are serially or systematically characterized to meet the requirements against physical, chemical, biological, and safety points of view. Safety evaluations using animal or human volunteers and cell‐culture models are separately discussed in terms of the requirements needed by the regulatory agencies for allowing the emulsions to undergo clinical trials and then, commercial usage.

      Chapter 4 shows how changes in terms of formulation excipients were being constantly made on the nanosized emulsions over the last few decades. To understand better this changeover process, the o/w nanosized emulsions are classified based on the generations with decade‐wise gap.

      Chapter 5 arranges the various issues relevant to the o/w nanosized emulsions to implicate in parenteral and ocular drug delivering systems. Understanding the mechanisms of interactions between emulsion droplets and plasma protein components helps the formulation developers to design long‐circulating stealth emulsions for parenteral drug delivery and drug targeting purposes. Similar attention is also being given to the consequences of nanosized emulsions following ocular topical instillation or intraocular injection. The published reports in conjunction with these points are covered thoroughly in this chapter.

      Chapter 6 starts with a narrative on how the emulsion surfaces can possibly be decorated with different functional molecules for the purpose of extracting a multifunctional activity in a single drug delivery and drug targeting system. Various medical applications of emulsions achieved/obtained through different administration routes are discussed in detail in this chapter.

      Chapter 7 intends to provide an overview of some selected and miscellaneous uses of nanosized emulsions to interface with the recent application.

      Chapter 8 describes the various steps ranging from laboratory level manufacturing together with safety aspects evaluation in animal and human eyes to industrial scaleup and then successful commercialization of cyclosporin A‐loaded nanosized emulsions. Other case study included in this chapter is fish oil‐based emulsions.

      With these collective information, this book serves as a guide for emulsion formulation developers working in academic environment and at the industrial level.

      Tamilvanan Shunmugaperumal

CHAPTER 1 INTRODUCTION: AN OVERVIEW OF NANOSIZED EMULSIONS

      TAMILVANAN SHUNMUGAPERUMAL

      Department of Pharmaceutics, National Institute of Pharmaceutical Education and Research (NIPER), Guwahati, Assam, India

      1  1.1. Introduction 1.1.1. Nanotechnology: Definition 1.1.2. Nanosized emulsions

      2  1.2. Conclusion References

EXPANSION OF ABBREVIATIONS

      APIactive pharmaceutical ingredientsBCSbiopharmaceutics classification systemDCSdevelopability classification systemGSEgeneral solubility equationLSWLifshitz and Slezov and Wagner theoryMSmetastableNPsnanoparticlesO/Woil‐in‐waterTmmelting pointUSFDAUnited States Food and Drug AdministrationW/Owater‐in‐oil

1.1. INTRODUCTION

Inadequacy is the term that influences in every corner of modern scientific world. Starting from clothes, food, water, and shelter for covering the basic needs of living to affordable medicines for managing any ailments, the inadequacy plays major roles to judge the standard living of every country in the world. In the present scenario of democratic countries like India, USA, etc., the political party which acquires the adequate number of parliamentary members either elected by highest number of people votes in the constituency or after election shuffling with opposite party, is able to form the government for ruling the country another 3 or 5 years. Here too the adequacy means a lot to form the government and the inadequacy leads the party to sit opposite to ruling party. Coming to the affordable medicines, the presence of adequate amount of active pharmaceutical ingredient (API) in a dosage form becomes the prime importance to elicit the desired and often required pharmacological activity following administration of the same into human body. But achieving the adequate amount of API in the particular dosage form requires a lot of formulation knowledge input. How to manufacture the dosage form with adequate amount of API? The answer to this query primarily depends on solubility of API followed by its permeability, molecular size, therapeutic index, etc. If the water solubility of API is low, then, the enhancement of API’s solubility becomes a major concern in pharmaceutical industries for converting the inadequate API aqueous solubility amount into adequate category. This type of converting the API amount from inadequate to adequate category needs the tremendous supports from formulation scientist who has the experience to solve this concern. The lucrative way adapted routinely in the pharmaceutical industry for deleting the word inadequate from the API aqueous solubility is just to combine the API with a suitable nanosized API delivery system or just to pulverize or micronize the API into nano‐level size ranges. This book accentuates the use of one of the nanosized API delivery system to erase the inadequate aqueous solubility from API. Before proceeding with the nanosized API delivery system, a brief history of nanotechnology is being described below.

1.1.1. Nanotechnology: Definition

      Pulverized API having nanometer size ranged particles and intact API‐loaded nanoparticles (either preformed or forming in situ) are considered one of the most‐prevalent improvement methods which have been used to overcome the problem of API's poor solubility and, thus, bioavailability, as well as to achieve targeted API delivery. Having said the importance of pulverized API as nanoparticles (NPs) or API‐entrapped nanoparticulate system, there is no single definition of what a NP is. This might be because of the highly multidisciplinary nature of nanotechnology. The term “nanotechnology” was first used by Norio Taniguchi in 1974, at the University of Tokyo, Japan, for any material in the nanometer size range (Taniguchi 1974) and the materials somehow handled by human beings in their everyday life. According to the United States Food and Drug Administration (USFDA), materials are classified as being in the nanoscale range if they have at least one dimension at the size range of approximately 1–100 nm. However, the characteristic properties of nanoscale such as solubility, light scattering and surface effects are predictable and even these properties are indeed continuous characteristics