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


Using absorbable sugar-based excipients for antidiabetic drugs may not be justifiable. Recently, FDA has warned healthcare professionals of the potential for life-threatening, falsely elevated glucose readings using glucose dehydrogenase pyrroloquinoline guinone-based glucose monitoring systems in patients who have received parenteral products containing maltose or galactose or oral xylose (22). Other excipients such as sodium docusate, polyethylene glycol, guar gum, methyl cellulose, polycarbophil, sodium phosphate, magnesium oxide, and magnesium carbonate, also possess laxative properties and may be used to counter the constipation side effect of some drugs. Furthermore, the magnesium mineral is an obvious powerhouse, which has the beneficial effects on many conditions, including heart attack, angina, arrhythmias, cardiomyopathy, mitral valve prolapse, intermittent claudication, low HDL, high blood pressure, diabetes, muscle cramps, kidney stones, fibromyalgia, and fatigue. In addition, magnesium may be just as important as calcium for the prevention of low bone density and osteoporosis.

Magnesium and calcium work synergistically, and both are needed for bone health, along with other cofactors of bone production, such as vitamin D and K, boron, and zinc. The calcium mineral is critical to bone strength. Calcium carbonate, dicalcium phosphate, calcium sulfate, and tricalcium phosphate can be used with a bisphosphonate drug (e.g., alendronate, risendronate, and ibandronate), a selective estrogen receptor modulator (e.g., raloxifene), or a drug with osteoporosis side effect (e.g., prednisolone) to treat and prevent osteoporosis. Long-term drug therapy for these conditions, in which the mineral can contribute significantly, is the prerequisite to consider using magnesium mineral as an excipient because mineral supplements can take as long as several weeks for results. In addition, these mineral excipients (e.g., calcium carbonate, sodium bicarbonate, and magnesium oxide can impart alkalinity to the drug microenvironment, which is another factor to be considered when using them in formulations. From the alkalinity aspect, these excipients with antacid function can be used with proton-pump inhibitors and H2 blockers to enhance the treatment additively or synergistically.

Amino acids such as glycine, lysine, isoleucine, leucine, arginine, and methionine have been used rarely in formulations as buffering agents, water-soluble lubricants, or for other functionalities. Amino acids may be used to treat certain diseases. For example, lysine is used in the treatment of cold sores and leucine may block the break down of muscle-building proteins at a lower rate. Furthermore, poly-L-lactic acid, a commonly used biodegradable polyester, is approved as an injectable implant for the restoration or correction of the sign of lipoatrophy in individuals with HIV (23). Even for a commonly used enteric polymer, preliminary data in mouse models suggest that properly formulated cellulose acetate phthalate may be an efficacious agent for preventing vaginal transmission of genital herpesvirus infections (24).

Along with the size, shape, name, and logo for drug products, formulation scientists must take the product's organoleptic attributes (i.e., visual, olfactory, and taste sensations) into consideration when formulating a drug. This organoleptic consideration is critical, especially for dosage forms designed to release the drug in the oral cavity (e.g., chewable tablets, fast disintegrating tablets, buccal tablets). First, the concept of aromatherapy, which relies on scented oils to help patients feel better physically and emotionally, may be applied to a formulation. Certain odors can have effects on mood, emotion, and behavior. For example, lavender is for relaxation and restful sleep; vanilla is for reducing anxiety; citrusy tang of lemon can be calming; rosemary is for alertness (25). Second, flavoring agents can be used for taste-masking and to produce a palatable product that can be readily consumed on a repetitive basis. Furthermore, natural spices such as cinnamon, parsley, sage, turmeric and rosemary contain many health-promoting antioxidants. This is especially true for cinnamon: the US Department of Agriculture found that half a teaspoonful a day lowered blood-sugar levels in patient with Type-2 diabetes and decreased levels of bad cholesterol (26). Third, tablet color helps in identification, branding, and reducing errors. Patients may respond better when color corresponds with the intended therapeutics of the medication, for example, calm blue for insomnia drugs, radiating yellow for depressants, and dynamic red for analgesics (27, 28). Formulation scientists rely heavily on marketing input to address product trade dress issues based on market research. The organoleptic properties of drug products can be used as a marketing strategy to ingrain a vivid product image to healthcare providers and patients.


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