Excipient ingredients

The selection of excipient ingredients is important. These must be both chemically and physically compatible with the dmg moiety and cannot negatively affect product stabihty or therapeutic performance, ie, bio avadabihty. A comprehensive hst of various types of excipient ingredients, with comment upon usage, is available (16). 

Bioavailability, Bioequivalence, and Pharmacokinetics. Bioavailabihty can be defined as the amount and rate of absorption of a dmg into the body from an adrninistered dmg product. It is affected by the excipient ingredients in the product, the manufacturing technologies employed, and physical and chemical properties of the dmg itself, eg, particle size and polymorphic form. Two dmg products of the same type, eg, compressed tablets, that contain the same amount of the same dmg are pharmaceutical equivalents, but may have different degrees of bioavailabihty. These are chemical equivalents but are not necessarily bioequivalents. For two pharmaceutically equivalent dmg products to be bioequivalent, they must achieve the same plasma concentration in the same amount of time, ie, have equivalent bioavadabihties. 

Single-dose preparations intended for use in eye surgery do not contain excipient ingredients, in order to avoid tissue irritation. However, multiple-dose containers may require antioxidants (qv), antimicrobial preservatives, or buffers to maintain stabiHty and stefiHty. Such solutions are packaged in polyethylene flexible dropper units called droptainers or in glass dropper botdes. 

The inactive ingredient is used at a level no higher than reasonably required to achieve its physical or technical function. For example, an antimicrobial excipient ingredient could only be used at a level consistent with preservation of the finished product (not at therapeutic levels), and a sunscreen ingredient could only be used at levels that protected the product from breaking down if the top of the jar was left open, not for protecting the user. 

The existing structure for review of excipient ingredients has several structural defects that result in significant disincentives in the development of novel excipients. Currently, only excipients that have been approved in an NDA are subject to a USP/NF monograph, or excipients that have an FDA- or a JECFA-sanctioned food... 

Recently, IPEC has taken the initiative in evaluating different models for evaluation of novel excipient ingredients in an attempt to obtain some acceptance of new... 

This chapter will deal with the objective of manufacturing excipient ingredients to appropriate good manufacturing practices (GMP) requirements, as stipulated by the United States Pharmacopeia (USP) (1) and the International Pharmaceutical Excipients Council excipient GMP guide (2). It is beyond the scope to address the many quality techniques for minimizing variation in excipient quality. However this chapter will address the issues concerning assurance that all excipient material within each batch meets compendial or manufacturer s specification. 

This chapter will focus on those additional GMP requirements for the manufacture of excipient ingredients under an ISO 9001 compliant quality system. While certification to ISO 9001 is unnecessary for compliance to excipient GMPs, many of the manufacturing-related requirements as noted above are essential for adequate GMP conformance. With the numerous ISO 9001 compliance resources available, this chapter will assume the reader has the knowledge to implement those relevant general ISO 9001 requirements. 

Excipients Ingredients added intentionally to the drug substance which should not have pharmacological properties in the quantity used. 

One tricyclic antidepressant, doxepin, inhibits both Hi and H2 receptors, and it has been used for treating adults with AD in doses of 10 to 75 mg at night and up to 75 mg twice daily. This may be beneficial in those atopic patients who have some depression as well. ° Topical antihistamines, such as 5% doxepin cream or diphenhydramine cream, also have demonstrated neutral results, but are generally not recommended because of high cutaneous sensitization from excipient ingredients in the formulation. ... 

Excipients—Ingredients that are intentionally added to therapeutic products but that do not directly exert pharmacologic effects at the intended dosage Indirect Photoeffects—Effects of an agent, vehicle, or product on the optical, structural, molecular, or physiologic properties of the skin, such that the interaction of light and skin or effects of drug in skin are altered IR—Infrared radiation 0.76-1000 pm MED—Minimal erythema dose 8-MOP—8-methoxypsoralen... 

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