Excipients

Drug dosage forms can be rather complex systems containing many components in addition to active pharmaceutical ingredients (APIs). Formulators apply practical understanding of pharmaceutical excipients to develop optimal, robust formulations and the appropriate manufacturing processes. Technical information about these excipients is readily available (1–2). The authors review some of the important issues regarding pharmaceutical excipients, current industry trends in using pharmaceutical additives, and basic principles of formulation design.

View Full Article

SELLING PHARMACEUTICALS in a managed care environment presents unique challenges, because two distinct entities exert enormous influence on a patient's decision to purchase and use a pharmaceutical product. The first and most obvious influence is the physician. The second influence is the organization or individual that pays for the prescription.

To maximize sales in a managed care environment, pharmaceutical representatives must have a solid understanding of three concepts:

Who is ultimately paying for pharmaceuticals.
How these payers exert influence over the sale of a pharmaceutical product.
How to leverage the payers' influence to maximize a product's sales.

Tablets and capsules are preferred drug delivery vehicles because they can be precisely dosed, easily manufactured and packaged on a large scale, and can contribute to good patient compliance. Over the years, significant advances in the manufacturing processes of oral solid dosage forms have occurred, including the transition from tablet preparation by wet granulation to direct compression. The development of various added functionality excipients (AFEs), which are used to achieve formulations with desired end-effects, is equally important. The majority of excipients used in the manufacture of solid oral dosage forms have existed for the past two to three decades, many of them continue to be used today for large-scale tablet and capsule manufacturing.

View Full Article

Excipient functionality” is one of the latest buzz phrases, but it is frequently used by those who have little understanding of the particular nature of excipients. Excipients are not active pharmaceutical ingredients (APIs) and they do not treat medical conditions. But without them, the therapeutic revolution of the past 50–60 years could not have occurred. The watchwords for APIs and finished products are—and rightly so—safety and efficacy. Although the emphasis on APIs and analytical chemistry has resulted in many very good methods for assay development and the determination of purity (including impurities), it is clear that we still lack the understanding and the means to determine why some materials behave in certain ways when included in a formulation (i.e., their functionality).

View Full Article

Tablets and capsules are the most preferred dosage forms of pharmaceutical scientists and clinicians because they can be accurately dosed and provide good patient compliance,

Recently, we reported that light accelerates the rate of moisture gain by a hygroscopic drug, ethambutol (1). This physical phenomenon was observed when ethambutol and its combinations with other antituberculosis drugs were subjected to stability studies in chambers set at 40
C and 75% relative humidity (RH) in the absence and the presence of light. The study was later extended to packed and unpacked marketed antituberculosis products to determine whether those formulations also exhibited different behavior in the absence and the presence of light. The same phenomenon was found to occur in the case of even unpacked and blisterpacked products (2). In the meantime, a study was also undertaken to determine whether this phenomenon was applicable, in general, to other drug substances and excipients. For the study, 54 pure drug substances and excipients were exposed to accelerated conditions of 40
C and 75% RH in the absence and the presence of light.

One of the major changes brought about by the introduction of the International Conference on Harmonization (ICH) guidelines for stability testing of pharmaceutical products has been to standardize temperature and humidity testing conditions (1). Although the environment typically consists of temperature, humidity, and light, the ICH still preferred to develop a separate photostability testing guideline because products in ICH member countries are sold in secondary packages, which eliminates the necessity for light testing along with temperature and humidity (2). Although light isn’t considered a main testing factor in several ICH member regions (e.g.,United States, Europe, and Japan), it is an important factor with respect to the sale of products in several countries outside the ICH’s influence.Many tropical countries have adverse environmental conditions, including high temperature, humidity, and intense light.

The International Pharmaceutical Excipients Council defines excipients as “substances, other than the active drug substance of finished dosage form, which have been appropriately evaluated for safety and are included in a drug delivery system to either aid the processing of the drug delivery system during its manufacture; protect; support; enhance stability, bioavailability, or patient acceptability; assist in product identification; or enhance any other attributes of the overall safety and effectiveness of the drug delivery system during storage or use” (1).

View Full Article

Many methods have been used to investigate the compression behavior of pharmaceutical excipients. For example, the Heckel plot, which describes the relationship between the porosity of the formulation and the compression pressure, is the most popular technique (1,2). It has also been used to investigate the decompression phase, that is, elastic recovery (3).

View Full Article

Currently the only drug master file (DMF) systems that exist to handle the submission of confidential excipient information to support drug applications are in the United States and Canada. The European Union and Japan do not have such systems for excipients. The International Pharmaceutical Excipients Council (IPEC) is developing a global master file guide to meet the industry’s need to submit confidential excipient information. The format for the guide will be coordinated and harmonized with the electronic International Committee on Harmonization (ICH) common technical document (CTD) for presenting chemistry, manufacturing, and controls and safety information (1,2). This system will accelerate the process for submitting information globally because a confidentiality agreement between a DMF holder and a drug application sponsor will not be needed.