Review of Current Issues in Pharmaceutical Excipients - Pharmaceutical Technology

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Review of Current Issues in Pharmaceutical Excipients
Excipients facilitate formulation design and perform a wide range of functions to obtain desired properties for the finished drug product. The article reviews excipient development and functionality of these materials, including their importance in formulation design, potential processing challenges directly related to excipients, and therapeutic benefits.


Pharmaceutical Technology


Furthermore, formulation scientists should evaluate the possibility of excipient–excipient interactions and their influence on drug-product attributes. An excipient–excipient interaction sometimes can be used as a formulation strategy to achieve desired product attributes. For example, the viscosity of xanthan gum is increased in the presence of ceratonia (16), and the viscosity of non-ionic cellulose derivatives (hydroxypropyl methylcellulose and hydroxypropyl cellulose) is enhanced by the incorporation of sodium lauryl sulfate (17). These excipient–excipient interactions are used synergistically in controlled-release drug delivery systems.

Holistic formulations

Formulators must take all factors into consideration to design a holistic formulation, including physicochemical properties, stability and compatibility issues, pharmacokinetic attributes, permeation characteristics, segmental absorption behavior, drug delivery platforms, intellectual property issues, and marketing drive. Early characterization of these factors allows scientists to determine the absorption challenges and desired delivery platform for the API. Furthermore, excipients are not totally inert to the human body, and they may contribute significantly to therapeutics in ameliorating many disease symptoms, leading to a synergistic treatment with drugs or reduced side effects.

For example, oleic acid, a fatty acid found in olive oil, can help fight breast and other cancers, according to several published studies (18–20). Researchers at Northwestern University found that oleic acid inhibited expression of the breast cancer gene Her-2/neu by more than 46%. This gene is responsible for 25–30% of all breast cancers and begets a particularly aggressive form of the disease. Oleic acid also improved the efficacy of the drug Herceptin, which already is used to treat breast cancer. The accumulating evidence suggests that oleic acid may have a potential role in lowering the risk of several cancers. Both oleic acid and olive oil are used as GRAS-listed pharmaceutical excipients.

Researchers also found that the omega-6 polyunsaturated fatty acid gamma-linolenic acid has antitumor activity in vitro, and concurrent treatments of Her-2/neu overexpressing cancer cells with gamma-linoleic acid and the anti-Her-2/neu antibody trastuzumab led to synergistic increases in apoptosis and reduced growth and colony formation (20).

Several plant oils used in pharmaceuticals such as corn oil, almond oil, peanut oil, safflower oil, sesame oil, and soybean oil, contain a significant amount of linoleic acid (GRAS-listed material), which will be converted to gamma-linolenic acid by delta-6-desaturase in the body. For the other essential fatty acid family (omega-3 fatty acids), a growing body of research suggests the omega-3 fatty acids in fish oil benefit not only the cardiovascular system but also a range of psychiatric and neurological problems, inflammatory and autoimmune diseases, cancer, and bone health promotion.

Medium-chain triglycerides (e.g., glyceryl tricaprylate/caprate, glyceryl tricaprylate, glyceryl tricaprate) offer unique metabolic properties and nutritional potential for formulators to design a liquid product for a special patient population, including acquired immune deficiency disease and malabsorption disorders, to increase beneficial caloric intake. These oily liquid materials, which possess desired pharmacological or physiological effects, may be used as a liquid vehicle for other drugs.

It has been demonstrated that xylitol, a commonly used sweetener, inhibits the growth of certain bacteria and also helps prevent otitis media in a significant percentage of children (21). Xylitol is commonly used in oral pharmaceutical formulations, especially chewable tablets and syrups and is generally regarded as a nontoxic, nonallergenic, and nonirritant material. The combination of xylitol and an appropriate antibiotic in a formulation, especially liquid formulation, may provide a synergistic effect against otitis media. Other sugars such as lactulose and lactitol also are used therapeutically in the treatment of hepatic encephalopathy and as laxatives. The actions of these sugars, which are absorbed poorly after oral administration, depend on saccharolytic bacteria for breakdown in the colon to carbon dioxide, lactic acid, and small amounts of acetic acid and formic acid, which acidify the contents of the colon. This acidification of the colon area leads to retention of ammonia and removal of ammonia from the blood into the colon. The laxative action of these sugars and the metabolites then aid to expel the trapped ammonium ions from the colon. The laxative actions, ammonia-removing properties, and colonic acidification effect may help minimize the constipation side effect of certain drugs, to enhance other drugs for the treatment of hepatic encephalopathy, to create an acidic environment for improving solubility of basic drugs in the colon, or facilitate a formulation and drug delivery system.


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