De-Risking Scale-up of a High Shear Wet Granulation Process Using Latent Variable Modeling and near Infrared Spectroscopy | AIChE

De-Risking Scale-up of a High Shear Wet Granulation Process Using Latent Variable Modeling and near Infrared Spectroscopy

Type

Conference Presentation

Conference Type

AIChE Annual Meeting

Presentation Date

October 18, 2011

Duration

30 minutes

Skill Level

Intermediate

PDHs

0.50

In the development of wet granulated drug products, two primary sources of variance (disturbance) include the operational scale of the high shear wet granulation (HSWG) process and Active Pharmaceutical Ingredient (API) lot-to-lot variability, particularly for formulations containing a high drug load. This paper presents a novel Process Analytical Technology (PAT) strategy using Latent Variable Modeling (LVM) with Near Infrared (NIR) spectroscopy to reduce risk in scale-up operations of the HSWG process while simultaneously accounting for API lot-to-lot variability, even with limited manufacturing history. The process involves building a Partial Least Square (PLS) model among the API material properties, the HSWG process parameters and the NIR end points of the HSWG process based on small scale DOE (Design of Experiment) batches. The PLS model is then used in an optimization framework to find suitable small scale mechanical process parameters (impeller/chopper speed) that approximate a previous large scale operation so as to keep the NIR end point of large scale operation constant. Prior to making additional large scale batches with a new lot of API, NIR end points of large-scale HSWG with the new API lot are predicted based on the PLS model developed from the small-scale operation. If the predicted NIR end point for the HSWG using the new API lot is not within the target region, the risks associated with the scale-up operation can then be significantly reduced by modifying other HSWG process parameters such as the total amount of water added or total granulation time to achieve the target region. A case study is presented that demonstrates the effectiveness of this methodology during development and scale-up of a drug product manufactured using a HSWG process.

Presenter(s) 

Once the content has been viewed and you have attested to it, you will be able to download and print a certificate for PDH credits. If you have already viewed this content, please click here to login.

Language 

Checkout

Checkout

Do you already own this?

Pricing

Individuals

AIChE Member Credits 0.5
AIChE Pro Members $15.00
AIChE Graduate Student Members Free
AIChE Undergraduate Student Members Free
AIChE Explorer Members $25.00
Non-Members $25.00