Excipients Used in Vaccines 333

Manmohan Singh and Derek O'Hagan Introduction 333 Adjuvants 333 Preservatives 335 Additives 336 Salts 337 Residuals from the Manufacturing Process 337 Excipients Used to Improve Stability of Vaccines 337 Excipients Used in Vaccine Formulations Currently in Clinical Trials 337 Analytical Assays and Quality Control of Excipients for Vaccine Formulations 338 Selection of Excipients for Next Generation Vaccines 339 Summary 339 References . . . . 339

Excipients In New Drugs

Most OTC monograph drugs are ones with long histories of use. They are generally unsophisticated, and contain relatively simple and well-characterized excipients. Aside from some issues discussed above that arose during the OTC monograph process, there are relatively few regulatory issues regarding these ingredients. Problems that do occur generally have to do with the quality and purity of the excipient rather than use of novel excipients. Most novel excipient issues are related to use of the...

Indication For Which The Chemical Entity Is Administered

The indication for which a chemical entity is administered may also differentiate its designation as a drug or an excipient. For example, tyloxapol is an oligomer of octoxynol 9 (Triton X-100) that is used as an active agent in respiratory distress Table 1 Summary of Emerging Excipients increasing protein Tocophersolan PEG succinate, PEG Radioisotope delivery to tumor cells, MRI contrast agents Increases antibiotic activity Antioxidant, solubility enhancer hydroxystearate Fluorocarbon-filled,...

Introduction

Vaccines available on the market contain various types of antigens, adjuvants, and additives, which in combination provide maximum protection against several infectious diseases. These vaccines might contain live or killed viruses, purified viral proteins, inactivated bacterial toxins, and polysaccharides or purified subunit recombinant proteins. The diverse nature of these antigens requires different excipients to be used to stabilize them for use within their designated shelf life. Because...

Joint Food and Agriculture Organization World Health Organization Expert Committee on Food Additives

The JECFA is a scientific committee administered by the FAO of the United Nations and the WHO. JECFA is a very important supranational organization responsible for the evaluation and assessment of the safety, specifications, and intake analysis of food additives and contaminants. Procedures for the preparation of a toxicological monograph, an intake assessment, and the specifications for the FAO and WHO are discussed in the FAO and WHO procedural guidelines (3,4) and on their Web sites (5,6)....

Nebulizers and Aqueous Based Systems

Nebulizer systems are universally aqueous in nature and can be either solution or suspension based. Excipients that have been used in nebulizer formulations relate to typical aqueous formulations and the formulation issues common to this type of preparation (i.e., stability and sterility issues). Table 3 provides several examples of nebulizer formulations that are commonly marketed along with the excipients Table 3 Examples of Commonly Marketed Nebulizer Products and Their Excipients Inhaled...

References

Parenteral drug administration routes, precautions, problems, complications, and drug delivery systems. Chapter 2. In Avis KE, Lieberman HA, Lachman L, eds. Pharmaceutical Dosage Forms Parenteral Medications. 1. New York Marcel Dekker, Inc., 1992. 2. Prescott B, Kauffman G, James WG. Further studies on effect of glycerine on toxicity of isoniazid-streptomycin mixtures in mice. Antibiot Chemother 1958 8 225. 3. Cohen LS, Rosenthal JE, Horner DW, et al. Plasma...

Edta

Similarly to the solubility of active drugs, the solubility of surfactants that were used in CFC systems has significantly changed. Surfactant solubility in HFA 134a ranges from 0.005 to 0.02 w v, much lower than the concentration required to stabilize suspensions 0.1-2.0 w v 24,42 . The surfactants can be solubilized with the addition of cosolvents such as ethanol. However, it is most likely that cosolvents will be incompatible with suspension formulations because drug solubility will also be...

Physicochemical Properties of Excipients in Dry Powder Inhalers

To generate a dry powder aerosol, the powder in its static state must be fluidized, deaggregated into individual particles, and entrained into the patient's inspiratory airflow. The powder is subject to numerous cohesive and adhesive forces, which must be overcome if it is to be successfully aerosolized in this schema 59 . Therefore, fluidi-zation and entrainment requires the input of energy to the static powder bed. The required energy input depends on the physicochemical nature of the powder...

Importance Of Excipient Selection In The Process Of Oral Liquid Formulation Development

When developing an oral liquid dosage formulation, consideration is first given to the characteristics of the active drug. The major challenges in developing oral liquid dosage forms are i the stability of a drug in solution, ii the solubility of a drug at the required level, and iii an acceptable taste. It is the effective use of excipients, which allows for-mulators overcome these challenges. Additionally, an excipient's compatibility with a drug in the solid state cannot infer the same...

Suppositories

Suppositories are pharmaceutical dosage forms intended for administration of medicine via the rectum, vagina, or urethra that melt, soften, or dissolve in the body cavity. Rectal and vaginal suppositories are most common but urethral suppositories are sometimes used. Suppositories are indicated for administering drugs to infants and small children, severely debilitated patients, those who cannot take medications orally, and those for whom the parenteral route might be unsuitable. Suppositories...

Excipients For Overthecounter Drugs

In contrast to the requirement that excipients in new drugs be approved as a component of that new drug, for OTC drugs that are regulated under the FDA's OTC monograph system, there is no required approval for excipients. FDA's monograph system is a series of regulations that define what active ingredients and claims are permitted for a variety of OTC drugs. These regulations do not define specific formulations, but rather set forth dose ranges for acceptable active ingredients. For inactives,...

Food and Drug Administration Perspective on Regulation of Pharmaceutical Excipients

Division of Drug Information HFD-240 , Center for Drug Evaluation and Research CDER , United States Food and Drug Administration, Rockville, Maryland, U.S.A. The Food and Drug Administration FDA is generally recognized as one of the, if not the, premier therapeutic agent gatekeepers among nations. Consequently, the pharmaceutical and medical library stacks are laden with journals and manuals devoted to drug development and instructions on how to run the FDA gauntlet to reach the jackpot of drug...

Excipient Compatibility Studies

Excipient compatibility studies are an important part of any preformulation screen for a new API. However, it is important to remember that an excipient compatibility screen can only indicate the excipients to be avoided because of an obvious chemical incompatibility. The results from excipient compatibility studies are not always easy to interpret, particularly if a physical interaction is found. As stated above, physical interactions can be detected using some form of calorimetry in...

General Considerations For Excipient Selection For Pulmonary Dosage Forms Excipient Use Determined Via Principles Of

The preceding section discussed the wide range of principles by which therapeutic aerosols may be generated and delivered to the patient. The excipients used in these formulations are largely determined via mechanisms by which particles and droplets can be successfully aerosolized for efficient targeting of the airways. Due to the variety of mechanisms of operation of pulmonary drug delivery systems, selection of excipients will follow distinct pathways according to the device used. Excipient...

Contributors

Meagan Anderson Aptuit, Kansas City, Missouri, U.S.A. Gopal Anyarambhatla Research and Development, Akorn, Inc., Decatur, Illinois, U.S.A. Shireesh P. Apte Chemologic LLC, Mansfield, Texas, U.S.A. Jane P. F. Bai ZyxBio, Cleveland, Ohio, U.S.A. Paul Baldrick Scientific and Regulatory Consulting, Covance Laboratories Ltd., Harrogate, North Yorkshire, U.K. Arvind K. Bansal Department of Pharmaceutical Technology Formulations , National Institute of Pharmaceutical Education and Research NIPER ,...