Overcome moisture challenges with starch-based excipients

Excipient selection, potential interactions, desired release profile and the most appropriate film coating are just some of the many decisions involved in developing a new solid oral dosage form. It’s best to keep the strategy simple by minimising ingredients and process steps, as this is less likely to cause problems and results in the most cost-effective option.

Stability is an essential quality attribute for pharmaceutical drug products. Unstable formulations may lead to a loss of active ingredient, making the medicine ineffective. In some cases, it can also lead to the formation of toxic degradation products. Changes in colour and physical appearance on stability can also reduce patient acceptability.

Moisture is present in all solid oral dosage forms and is known to be the main cause of degradation, leading to impurities. It is absorbed to varying extents on the surface of powders and carried into the core.

To reduce the negative impact of moisture and enhance the stability of formulations, it is important to select the best excipients for the tablet core. Excipients in a drug formulation are generally assumed to be inert, which means they will have no impact on the final formulation; however, some ingredients interact with drugs or other excipients.

Core ingredients typically include the active pharmaceutical ingredient (API), filler, binder, disintegrant and other enablers or process improvers. Excipients may lose or take up moisture within the core formulation, so it is important to understand the microenvironment surrounding the API and whether the moisture is bound or free. Free water can lead to chemical or physical reactions.

Starch 1500

Although Starch 1500 has a relatively high moisture content, it has very low water activity – providing better stability for moisture-sensitive actives. The moisture scavenging properties of Starch 1500 (by hydrogen bonding inside its amorphous structure) make it an excellent excipient to enhance stability. By inhibiting water activity within the formulation and retarding interaction with the moisture sensitive API, Starch 1500 helps to reduce or eliminate the detrimental effects of other excipients.

To determine the amount of Starch 1500 that should be included in a formulation, various aspects of the dosage form need to be considered starting with the drug itself and the final dosage form, followed by flow, compressibility, disintegration and stability requirements. In most cases, drug properties are critical and determine the choice of excipient to balance these parameters. Benefits of including Starch 1500 in formulations have been observed with levels as low as 10% w/w. Starch 1500 can be used in combination with other tabletting excipients to enhance the performance of the formulation, but unlike fully pregelatinised starches, starch 1500 does not require superdisintegrant, helping to keep the total cost of the formulation low.

Starch 1500 is a partially pre-gelatinised starch

StarTab

Wet granulation involves multiple steps and the use of moisture, which can cause API degradation. Industry specialists typically use the simplest method, direct compression, which also works well at large manufacturing scale.

Colorcon’s newest excipient, StarTab is a directly compressible starch designed specifically for direct compression. It offers benefits in terms of simplifying both the formulation and processing. StarTab also provides improved flow during manufacture, because of its particle shape and size, and enhanced compactibility. The use of superdisintegrants can also be avoided by using StarTab, further simplifying the formulation.

Comparison of water activity versus loss on drying

StarCap

This starch-based excipient has an optimised particle morphology to facilitate excellent flow in capsule dosage forms. StarCap is designed and manufactured specifically for pharmaceutical and nutraceutical capsule filling and is a globally acceptable excipient.

In comparison to other capsule filling excipients, StarCap provides excellent compactability to ensure plug formation with dosator encapsulation equipment.

Conclusion

For effective drug formulation, it is crucial to consider both the interaction of excipients with the API and the interaction of excipients with moisture. Starch 1500 is a proven and trusted unique pharmaceutical excipient, manufactured exclusively for the global pharmaceutical and nutraceutical industries.

In addition to the selection of core excipients, the use of specialised film coatings such as Opadry amb II, moisture barrier film coating and primary packaging all contribute to managing moisture.

With the increasing use of multi-dose pillboxes for geriatric patients, guidance is now being provided on acceptable parameters, not only during the product shelf-life but also for the predicted in-use life of the product, reflecting how a patient is likely to remove the drug product from its primary packaging. •

PA Cuthbert – www.pacuthbert.co.za

Colorcon – www.colorcon.com