Vitthal S. Kulkarni

Considerations for the Development of Nasal Dosage Forms

The anatomy and physiology of the nasal cavity provide unique advantages for accessing targets for local, systemic, and potentially central nervous system drug delivery. This chapter discusses these advantages and the challenges that must be overcome to reach these targets. The chapter then comprehensively reviews nasal dosage forms, analytical testing, and regulatory requirements in the context of existing nasal spray products. Since nasal sprays are moving towards being preservative-free, the chapter covers specialized methods of achieving a sterile product, namely, formulation strategies, manufacturing strategies, and the device landscape that support this upcoming platform. Finally, the chapter reviews various pathways for regulatory approval around the world, for brand and generic, with particular emphasis on the growing acceptance of in vitro data for locally acting nasal spray products.

Use of Polymers and Thickeners in Semisolid and Liquid Formulations

Abstract Polymers are extremely versatile ingredients in semisolid formulations, being used to create a range of different effects, from thickening to preservation and conditioning. Polymers are macromolecules consisting of a long-chain backbone of smaller repeating units (monomers) and side groups. Polymers that contain only a single type of repeat unit are known as homopolymers, whereas polymers containing a mixture of repeat units are known as copolymers. Depending on the type of polymer, the backbone can be either linear or branched. The side groups influence the functional properties of the polymer, such as how well it thickens, conditions, and forms films.

Surfactants, Lipids, and Surface Chemistry

This chapter provides an overview of surfactants and surface properties that play important roles in pharmaceutical formulations. Examples of ionic, nonionic, and zwitterionic surfactants are provided. Structures of different lipids and their applications as excipients or actives are discussed. A brief introduction to the HLB system is provided. Examples of drug products in the marketplace that use various surfactants and lipids are listed indicating the importance of surfactants and lipids in pharmaceutical formulations. Surface and interfacial tension measurement, and the significance of the role of surface tension and contact angle in designing the pharmaceutical formulations has been discussed.

Drug Delivery Vehicles

Current trends are to use newer, targeted drug-delivery approaches to effectively deliver smaller dosages to target sites—thereby reducing toxicity and possible unwanted side effects. Different drug-delivery systems including emulsions, liposomes, and nanodrug delivery systems are reviewed and discussed. Methods of producing liposomes, and some existing drug products based on liposomes, are presented.

Miscellaneous Physical, Chemical, and Microbiological Test Methods

This chapter covers test methods typically used to evaluate and characterize semisolid formulations. The methods have been subdivided into physical, chemical, and microbiological, as well as separating them into tests that might typically be performed on all semisolid formulations, and those that are specific to a type of product. When they are performed during the product lifetime, and what information they can provide, is also described.

Aerosols and Nasal Sprays

Many types of aerosol products exist—such as deodorants, antiperspirants, hair sprays, insecticides, oils, polishes, and paints. The pressurized metered-dose inhaler is one type of aerosol product that is used to deliver drugs as a mist or spray via the pulmonary system. The common formulation types used for aerosol and nasal spray products are solutions, suspensions, and emulsions. This chapter looks at the manufacturing processes for aerosol and nasal spray products, the types of excipients that are used in aerosol and nasal spray formulations, and the effect that the excipients can have on the physical characteristics of the expelled product.

Preparation and Stability Testing

Liquid and semisolid formulations contain many different functional ingredients depending on their physical form and intended use—for example, pH buffers, antioxidants, microbial preservatives, chelators, osmolality agents, penetration enhancers, thickeners, emulsifiers, solvent systems, humectants, pharmaceutically active ingredients, moisturizers, fragrances, flavorings, and colorants. When and how these ingredients are added to the formulation will determine whether the finished formulation is successful—aesthetically, functionally, and stable. This chapter looks at how formulations are typically put together, gives examples of different mixing systems, shows how Quality by Design can be applied to formulation development, and how to evaluate the stability of a formulation.

Formulating Creams, Gels, Lotions, and Suspensions

Different semisolid dosage forms and various excipients used in pharmaceutical formulations are discussed. The current approach of the US Food Drug Administration for the classification of semisolid dosages is presented. The formation and formulation of emulsions are discussed in detail. The formulation of liposomes, one of the major drug-delivery systems used in pharmaceutical dosages, is also discussed.

Particle Size Analysis: An Overview of Commonly Applied Methods for Drug Materials and Products

An understanding of the particle size of semisolids, suspended liquids, or dry powder formulations is one of the critical control parameters used in product development and stability studies for pharmaceutical products. In the pharmaceutical field, the most commonly used techniques are laser diffraction (static and dynamic laser-light scattering) and optical microscopy for both size distribution and morphology of particles. Details of method development and validation for particle-size methods by laser diffraction are discussed along with advantages and concerns of the laser diffraction technique.

An Overview of Regulatory Aspects for Pharmaceutical Semisolid Dosages

Although the regulatory landscape for pharmaceutical semisolid products is well established, the regulations are under constant review to improve the quality, safety, and efficacy of products both under development and in the marketplace. This chapter highlights some of the development/quality guidance in place at the time of writing and, more importantly, provides references to where the most up-to-date compliance information can be obtained.