Overcoming Formulation Difficulties

How does the pharmaceutical world meet the challenge of the ever-increasing pace in pharmaceutical product development? One shortcut solution for formulators is to use high-performing excipients.

nThe changing landscape of the pharmaceutical industry is increasing the commercial pressure on R&D groups to shorten time to market for new products. As a result, formulators are demanding more functionality and performance from their pharmaceutical excipients. These ingredients now play a critical role in achieving stability, reducing costs and improving manufacturing efficiencies. They must also produce a robust dosage form that is unaffected by variations in process parameters or other ingredients.

nFaced with shorter development cycles and more complex active pharmaceutical ingredients (APIs), formulators cannot afford the luxury of investigating new excipients. They need to use proven ingredients in the development of new tablets or capsules, and rely heavily on the producers of these ingredients to identify new applications.

nEnhancing drug formulation

nMulti-functional excipient products have been shown to offer unique synergies with many common ingredients. For example, combining Starch 1500 – a partially pregelatinized maize starch from Colorcon® – with microcrystalline cellulose results in very compactable formulations with excellent dissolution. This minimizes the need for super-disintegrants that can affect stability. The flow properties and friability of lactose blends can also be greatly improved. Moreover, incorporating specially designed pregelatinized starch products can reduce the amount of lubricants, which are known to cause over-blending problems, and affect dissolution and film coating quality.

nAs APIs become more sophisticated, many of them are effective at low-dose concentrations and are often micronized. But low-dose medicines can be a challenge to formulate due to problems with content uniformity and physical stability. Traditionally, these drugs have been manufactured through wet granulation to assure that each tablet contains the proper amount of active material. This process can, however, be costly and time-consuming because of the many steps involved. If water has a detrimental effect on the drug, solvents must be used — thus increasing the cost and difficulty of the process.

nPharmaceutical formulators have developed direct compression manufacturing processes for these drugs through the use of Starch 1500. Content uniformity is achieved by first preparing a pre-blend of the API and Starch 1500, followed by the addition of the remaining ingredients and tabletting. The granular morphology of this unique excipient combined with its inherent moisture content produces an ordered mix through adhesion and hydrogen bonding.

nHumidity control

nMoisture-sensitive drugs present another challenge to formulators. Potential problems associated with these APIs include reduced flow properties, as well as changes in dissolution rates, chemical stability and physical stability (in terms of color, for example). Some ways to protect moisture sensitive products involve humidity-controlled manufacturing conditions, protective packaging, moisture barrier film coating and, most importantly, selecting excipients that minimize moisture sensitivity. In this selection process, it is important to understand the difference between moisture content and water activity.

nTotal moisture content is, typically, measured by loss on drying. However, this method does not distinguish between bound moisture (unavailable for chemical interactions) and unbound moisture (available for chemical interactions). A better measure is water activity or equilibrium relative humidity, which shows only the unbound water that is free to interact with the drug.

nFor example, although the moisture content of Starch 1500 is higher than some other excipients', the water content is considerably lower. Therefore, it will equilibrate slower when exposed to moisture conditions and may, preferentially, bind the moisture, preventing interaction with the drug. Starch 1500 has been used to develop formulations with proven stability for many moisture-sensitive APIs, including aspirin and ranitidine. These robust formulations have helped lower costs by reducing the need for special manufacturing conditions and expensive packaging.

nAs formulators turn to proven excipients to meet today's challenges, multi-functional excipients such as Starch 1500 offer a long history of reliability and efficacy, and continue to provide benefits in the development of new applications.

nAbout Colorcon®

nColorcon® is a world leader in the development, supply and technical support of formulated coatings and excipients for the pharmaceutical industry. With Colorcon as their pharmaceutical product development partner, companies produce cost effective, high quality products with superior performance and appearance. To learn more, please visit http://www.colorcon.com/. n