(166e) Impact of Material and Source Variability on the Performance of Roller-Compacted Formulation and Critical Drug Product Attributes

In a pharmaceutical formulation, some excipients are used for their particular functionalities, such as lubricant, superdisintegrant, surfactant, coating material etc. Although present only in small quantities in a formulation, changes in these excipients can sometimes have significant impact on the processiblity and critical quality attributes of the product. The effect can also vary with API properties such as solubility and acidity. In this study, we systematically evaluated this effect using a typical roller compaction formulation with 20% drug loading and two model compounds of different solubility and acidity (acetaminophen and aspirin). Based on risk assessment and prior knowledge on the criticality of the excipients in the formulation, the following are factors selected to be studied in this work:

1. Three different vendors of Magnesium Stearate (Mallinckrodt, Brenntag Specialties Inc, Quimdis S A) and different lubrication durations
2. Three different types of superdisintegrants (Sodium Starch Glycolate, Croscarmellose Sodium, Crospovidone)
3. Presence and absence of the surfactant Sodium Lauryl Sulfate (SLS)
4. Two different types of Opadry coatings (Hypromellose based  and Polyvinyl alcohol based)

The responses evaluated include:

1. Thickness and density of ribbons generated by the roller compactor
2. Powder properties (flow, particle size distribution and density) of milled granules
3. Compaction forces used during tablet compression
4. Dissolution and disintegration of core and coated tablets
5. Dissolution behavior of coated tablets upon stressing in accelerated conditions

Among the factors evaluated, the presence of SLS is found to have a significant impact of increasing the compactability of the blend during roller compaction hence decreasing the compactability during tablet compression. SLS also slows down the disintegration and dissolution of both compounds. Differences were observed for the effectiveness of the three superdisintegrants, which is also found to be dependent on the model API. Both types of coatings are found to slow down the dissolution of aspirin formulations, however, this effect is not as significant for acetaminophen formulations. Slow down of dissolution upon stressing in accelerated conditions was observed for aspirin tablets coated with PVA based Opadry. Details of the study and the results along with some mechanistic discussion will be covered in the presentation.