Chapter 7 - Formulations

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7.1 Hydrofluoroalkane Propellant Driven Metered-Dose Inhaler Formulations by Hugh Smyth, PhD, Daniel Moraga-Espinoza, BPharm, Tania Bahamondez-Canas, BPharm, Matthew Herpin, BS, Andy Maloney, PhD, Ashkan Yazdi, PharmD, Ping Du, PhD, and Ju Du, PhD

The unique properties and characteristics of pressurized metered-dose inhaler (pMDI) formulations stem from the physicochemical properties of the hydrofluoroalkane (HFA) propellants. The limited number of excipients used in marketed pMDIs products adds to the complexity of development. In addition to the challenges for formulators, these systems require specialized analytical chemists, regulatory scientists, and pMDI manufacturing expertise. These challenges highlight the importance of understanding HFA formulations across multiple disciplines. Thus, influence of formulation variables must be appreciated for both formulation design and understanding product performance.

7.2 Developing Dry Powder Inhaler Formulations by David A.V. Morton, PhD and David Barling, PhD

This section aims to provide a concise and contemporary technical perspective and reference resource covering dry powder inhaler (DPI) formulations. While DPI products are currently the leading inhaled products in terms of sales value, a number of confounding perspectives are presented to illustrate why they are considered surprisingly, and often frustratingly, poorly understood on a fundamental scientific level, and most challenging to design from first principles. At the core of this issue is the immense complexity of fine cohesive powder systems. This review emphasizes that the difficulty of successful DPI product development should not be underestimated and is best achieved with a well-coordinated team who respect the challenges and who work in parallel on device and formulation and with an appreciation of the handling environment faced by the patient. The general different DPI formulation types, which have evolved to address the challenges of aerosolizing fine cohesive drug-containing particles to create consistent and effective DPI products, are described. This section reviews the range of particle engineering processes that may produce micron-sized drug-containing particles and their subsequent assembly as either carrier-based or carrier-free compositions. The creation of such formulations is then discussed in the context of the material, bulk, interfacial and ultimately drug-delivery properties that are considered to affect formulation performance. A brief conclusion then considers the future DPI product choices, notably the issue of technology vs. affordability in the evolving inhaler market.

7.3 Liposomes for Inhalation by Hui Xin Ong, PhD, Daniela Traini, PhD, and Paul M. Young, PhD

Inhalation of liposomes formulated with phospholipids similar to endogenous lung surfactants and lipids offers biocompatibility and versatility within the pulmonary medicine field to treat a range of diseases such as lung cancer, cystic fibrosis and lung infections. Manipulation of the physicochemical properties of liposomes enables innovative design of the carrier to meet specific delivery, release and targeting requirements. This delivery system offers several benefits: improved pharmacokinetics with reduced toxicity, enhanced therapeutic efficacy, increased delivery of poorly soluble drugs, taste masking, biopharmaceutics degradation protection and targeted cellular therapy. This section provides an overview of liposomal formulation and delivery, together with their applications for different disease states in the lung.