Excipient Selection

Intravenous aqueous injections provide an excellent means of achieving a rapid therapeutic response. Parenteral product design, eg, vehicle and other excipient selection, as well as choice of route of adrninistration, can prolong therapeutic activity and increase onset times. Thus, oily solutions, suspensions, or emulsions can be adrninistered by subcutaneous or intramuscular routes to create prolonged effect, ie, depot injection (28). 

Finally, knowledge of excipient mechanical and physical properties is essential to creating a robust formulation that manufactures tablets that meet specifications in a time- and material-efficient manner. Excipient selection must also take into consideration API stability and biopharmaceutical performance of the dosage form. Uneducated selection of excipients will likely lead to numerous formulating iterations that require much time and material, which are luxuries that product development scientists do not have in the competitive pharmaceutical environment. 

IMPORTANCE OF EXCIPIENT SELECTION IN THE PROCESS OF ORAL LIQUID FORMULATION DEVELOPMENT... 

Intimately related to these factors is the design of the device, formulation, and the interface with the patient. Much of the discussion below will focus on the implications of excipients on formulation challenges for inhaled aerosol products. This chapter summarizes excipients for pulmonary formulations from several perspectives (i) excipient selection based on principles of delivery, (ii) physicochemical requirements for excipients, and (iii) specific challenges for formulations faced with aerosol drug delivery systems, including (a) biological aspects, (b) microbiological aspects, (c) analytical issues, and (d) future prospects. 

GENERAL CONSIDERATIONS FOR EXCIPIENT SELECTION FOR PULMONARY DOSAGE FORMS EXCIPIENT USE DETERMINED VIA PRINCIPLES OF DELIVERY... 

Excipient Selection and Criteria for Injectable Dosage Forms... 

The primary objective of the early efLcacy studies is to validate the pharmacology model with a compound that is known to interact with the desired receptor and develop the Pharmacokinetics-Pharmacodynamics (PK-PD) relationship for further screening during lead optimization (Neervan-nan, 2006). It is essential that the excipients selected forthe vehicle do not interfere with the measured end points especially, for a disease-relevant animal model that has no clinically effective drugs to validate an animal model. In this situation, vehicles should be used as negative controls in the studies. 

Gad and Cassidy (2006) summarized the comprehensive information of maximum tolerabilities for 65 single component vehicles used in 368 studies across multiple species (e.g., dog, primate, rat, mouse, rabbit, guinea pig, minipig, chick embryo, and cat) by multiple routes. The paper serves as a good reference for excipient selection in the toxicology formulation development. 

Therefore, the excipient selection will not only be performed based on the preformulation results, but also based on a careful consideration of physical parameters such as particle size and surface characteristics. 

Airaksinen S, Kaijalainen M, Kivikero N, Westrmarck S, Shevchenko A, Rantanen J, Yliruusi J. 2005. Excipient selection can significantly affect solid-state phase transformation in formulation during wet granulation. AAPS PharmSciTech. 6(2) Article 41. 

This chapter discusses key considerations in excipient selection formulation and process design and control and blending and content uniformity during development of a low-dose direct compression formulation. 

One of the critical factors in excipient selection and concentration is the effect on preferential hydration of the biopharmaceutical product [53, 54], Preferential hydration refers to the hydration layers on the outer surface of the protein and can be utilized to thermodynamically explain both stability enhancement and denatur-ation. Typical excipients used in protein formulations include albumin, amino acids, carbohydrates, chelating and reducing agents, cyclodextrins, polyhydric alcohols, polyethylene glycol, salts, and surfactants. Several of these excipients increase the preferential hydration of the protein and thus enhance its stability. Cosolvents need to be added in a concentration that will ensure their exclusion from the protein surface and enhance stability [54], A more comprehensive review of excipients utilized for biopharmaceutical drug products is available elsewhere [48],... 

An inert substance is frequently added to increase the bulk of a tablet for processing and handling. The lower weight limit for formulation of a tablet is usually 50 mg. Ideally, diluents should be chemically inert, nonhygroscopic, and hydrophilic. Having an acceptable taste is important for oral formulations, and cost is always a significant factor in excipient selection. 

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