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Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors

Compressed mini-tablets in sachets or capsules are an increasingly prevalent oral solid dosage form for pediatric products. While resembling adult tablets, additional care is required to control weight and potency (blend uniformity) variation due to their small size (≤2.5 mm average diameter). Addit...

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Detalles Bibliográficos
Autores principales: Gerberich, Brandon G., Okoh, Grace A., DiNunzio, James C., Lowinger, Michael B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961976/
https://www.ncbi.nlm.nih.gov/pubmed/36839916
http://dx.doi.org/10.3390/pharmaceutics15020594
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author Gerberich, Brandon G.
Okoh, Grace A.
DiNunzio, James C.
Lowinger, Michael B.
author_facet Gerberich, Brandon G.
Okoh, Grace A.
DiNunzio, James C.
Lowinger, Michael B.
author_sort Gerberich, Brandon G.
collection PubMed
description Compressed mini-tablets in sachets or capsules are an increasingly prevalent oral solid dosage form for pediatric products. While resembling adult tablets, additional care is required to control weight and potency (blend uniformity) variation due to their small size (≤2.5 mm average diameter). Additionally, sachet fill count errors complicate dose accuracy as they are difficult to resolve with weight-checking equipment. This study quantified the probability of failing content uniformity (CU) specifications (which results in the inability to release a batch) defined in USP <905> using a Monte Carlo computational model. Failure risk was modeled as a function of sachet fill count, mini-tablet weight, potency distribution, and fill error frequency. The model allows product developers to (1) determine appropriate fill counts based on anticipated product weight and potency relative standard deviation (RSD), (2) set fill error probability tolerances for sachet filling processes, (3) identify CU improvement opportunities, and (4) quantify the probability of CU failure informing risk management activities and risk disclosure for regulatory agencies. A representative product with weight and potency RSD no greater than 5%, fill count of 1–4 mini-tablets per sachet, and fill error probability per mini-tablet filled of 0.1% may experience CU batch failure probabilities as high as 8.23%, but only 0.283% if the fill count is increased to 5–10 mini-tablets per sachet. Generally, fill counts of less than five mini-tablets per sachet should be avoided where possible.
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spelling pubmed-99619762023-02-26 Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors Gerberich, Brandon G. Okoh, Grace A. DiNunzio, James C. Lowinger, Michael B. Pharmaceutics Article Compressed mini-tablets in sachets or capsules are an increasingly prevalent oral solid dosage form for pediatric products. While resembling adult tablets, additional care is required to control weight and potency (blend uniformity) variation due to their small size (≤2.5 mm average diameter). Additionally, sachet fill count errors complicate dose accuracy as they are difficult to resolve with weight-checking equipment. This study quantified the probability of failing content uniformity (CU) specifications (which results in the inability to release a batch) defined in USP <905> using a Monte Carlo computational model. Failure risk was modeled as a function of sachet fill count, mini-tablet weight, potency distribution, and fill error frequency. The model allows product developers to (1) determine appropriate fill counts based on anticipated product weight and potency relative standard deviation (RSD), (2) set fill error probability tolerances for sachet filling processes, (3) identify CU improvement opportunities, and (4) quantify the probability of CU failure informing risk management activities and risk disclosure for regulatory agencies. A representative product with weight and potency RSD no greater than 5%, fill count of 1–4 mini-tablets per sachet, and fill error probability per mini-tablet filled of 0.1% may experience CU batch failure probabilities as high as 8.23%, but only 0.283% if the fill count is increased to 5–10 mini-tablets per sachet. Generally, fill counts of less than five mini-tablets per sachet should be avoided where possible. MDPI 2023-02-10 /pmc/articles/PMC9961976/ /pubmed/36839916 http://dx.doi.org/10.3390/pharmaceutics15020594 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gerberich, Brandon G.
Okoh, Grace A.
DiNunzio, James C.
Lowinger, Michael B.
Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors
title Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors
title_full Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors
title_fullStr Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors
title_full_unstemmed Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors
title_short Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors
title_sort pediatric mini-tablets: predicting the hidden risk of fill errors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9961976/
https://www.ncbi.nlm.nih.gov/pubmed/36839916
http://dx.doi.org/10.3390/pharmaceutics15020594
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