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...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-02-01
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| Series: | Pharmaceutics |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4923/15/2/594 |
| _version_ | 1797618667435851776 |
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| author | Brandon G. Gerberich Grace A. Okoh James C. DiNunzio Michael B. Lowinger |
| author_facet | Brandon G. Gerberich Grace A. Okoh James C. DiNunzio Michael B. Lowinger |
| author_sort | Brandon G. Gerberich |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-11T08:16:49Z |
| format | Article |
| id | doaj.art-5bebb8bac66a4b92baa7e3f95d5c3f3f |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-11T08:16:49Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-5bebb8bac66a4b92baa7e3f95d5c3f3f2023-11-16T22:42:02ZengMDPI AGPharmaceutics1999-49232023-02-0115259410.3390/pharmaceutics15020594Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill ErrorsBrandon G. Gerberich0Grace A. Okoh1James C. DiNunzio2Michael B. Lowinger3Oral Formulation Sciences, Merck & Co., Inc., Kenilworth, NJ 07065, USAOral Formulation Sciences, Merck & Co., Inc., Kenilworth, NJ 07065, USAOral Formulation Sciences, Merck & Co., Inc., Kenilworth, NJ 07065, USAOral Formulation Sciences, Merck & Co., Inc., Kenilworth, NJ 07065, USACompressed 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.https://www.mdpi.com/1999-4923/15/2/594mini-tabletcontent uniformityfill countsachetfill errorsdose uniformity |
| spellingShingle | Brandon G. Gerberich Grace A. Okoh James C. DiNunzio Michael B. Lowinger Pediatric Mini-Tablets: Predicting the Hidden Risk of Fill Errors Pharmaceutics mini-tablet content uniformity fill count sachet fill errors dose uniformity |
| 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 | mini-tablet content uniformity fill count sachet fill errors dose uniformity |
| url | https://www.mdpi.com/1999-4923/15/2/594 |
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