Specification Setting and Manufacturing Process Control for Solid Oral Drug Products

Chen, Wei; Stithit, Suchinda; Zheng, Jack; Hwang, Richard

doi:10.1016/b978-0-444-53242-8.00026-6

Cited by 1 publication

(1 citation statement)

References 9 publications

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“…), with the exception of dry granulation (roller compaction (5)) usually involve the addition of water in an early step and therefore the removal of the water, often via an evaporative drying unit operation, in a later step (6). The "drying endpoint", defined as the acceptable range of water content for material exiting the dryer, is generally chosen to yield acceptable processability (e.g., tablet compactibility) (6) of the granules and/or stability of the final drug product (7). The drying endpoint is generally not considered a potential quality attribute for drug product assay (8).…”

Section: Introductionmentioning

confidence: 99%

Using a Mass Balance to Determine the Potency Loss during the Production of a Pharmaceutical Blend

Mackaplow

2010

AAPS PharmSciTech

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The manufacture of a blend containing the active pharmaceutical ingredient (API) and inert excipients is a precursor for the production of most pharmaceutical capsules and tablets. However, if there is a net water gain or preferential loss of API during production, the potency of the final drug product may be less than the target value. We use a mass balance to predict the mean potency loss during the production of a blend via wet granulation and fluidized bed drying. The result is an explicit analytical equation for the change in blend potency a function of net water gain, solids losses (both regular and high-potency), and the fraction of excipients added extragranularly. This model predicts that each 1% gain in moisture content (as determined by a loss on drying test) will decrease the API concentration of the final blend at least 1% LC. The effect of pre-blend solid losses increases with their degree of superpotency. This work supports Quality by Design by providing a rational method to set the process design space to minimize blend potency losses. When an overage is necessary, the model can help justify it by providing a quantitative, first-principles understanding of the sources of potency loss. The analysis is applicable to other manufacturing processes where the primary sources of potency loss are net water gain and/or mass losses.

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Section: Introductionmentioning

confidence: 99%

Using a Mass Balance to Determine the Potency Loss during the Production of a Pharmaceutical Blend

Mackaplow

2010

AAPS PharmSciTech

View full text Add to dashboard Cite

show abstract

Specification Setting and Manufacturing Process Control for Solid Oral Drug Products

Cited by 1 publication

References 9 publications

Using a Mass Balance to Determine the Potency Loss during the Production of a Pharmaceutical Blend

Using a Mass Balance to Determine the Potency Loss during the Production of a Pharmaceutical Blend

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