(183c) Impact of API Properties and Excipient Source on the Process and Performance of a Typical High Shear Wet Granulation Formulation

In a pharmaceutical formulation, some excipients, such as binder and disintegrant are used for their particular functionalities. While present only in small quantities, changes in these excipients can sometimes have significant impact on the processiblity and performance of a drug product. When a formulation contains high drug loading, properties of the API can also interplay with the process parameters to impact the properties of drug intermediate and drug product. In this study, we evaluated the effect of differences in binder, disintegrant, as well as API properties on the process and performance of a typical high drug loading high shear wet granulation formulation. The factors evaluated include:

1. Types of disintegrant (Sodium Starch Glycolate vs. Croscarmellose Sodium)
2. Source of the binder Hydroxylpropyl cellulose (Ashland Klucel vs Nisso)
3. API solubility and wettability
4. API particle size and surface area

The responses evaluated include:

1. Amount of granulation water needed for desirable granule properties
2. Granule growth ratio
3. Granule compactability
4. Tablet disintegration

Salicylic acid, aspirin, citric acid as well as some BMS compounds were used in this study, which covers a broad range of solubility and contact angle (0.002-590 mg/ml, 0-146º). It was found that the amount of granulation water needed for optimal granule properties is highly sensitive to the solubility and contact angle of the API. For highly soluble API, water amount needed for granulation is significantly reduced. Granule growth ratio has a significant dependence on the particle size/surface area of the API. Using the same granulation parameters, smaller API particle size results in higher granule growth ratio. For the low solubility API that was selected for the disintegrant type and binder source study, no significant difference was observed in the processibililty and disintegration of the drug product.