Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

Parrish, Richard H.; Ashworth, Lisa D.; Löbenberg, Raimar; Benavides, Sandra; Cies, Jeffrey J.; MacArthur, Robert B.

doi:10.20944/preprints202203.0117.v1

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…Indeed, before specific products can be considered for inclusion in the EMLc or enter the GAP-f prioritization and acceleration process, these results need to be analysed in conjunction with the ongoing work of others involved in the upcoming revision of the EMLc, namely, an expert review of the products already available in the EMLc and a detailed analysis of the global market of paediatric medicines. As previously reported, efforts to develop oral formulations for vulnerable populations, such as paediatric patients, should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised and therapeutic benefits are optimised (Singer and Zaïr, 2016;Parrish et al, 2022).…”

Section: Discussionmentioning

confidence: 99%

“…Oral liquid formulations have major disadvantages such as chemical, physical or microbial instability, taste issues, need for refrigerated storage conditions and lack of controlled release properties. WHO now recommends that, where available, dispersible tablets should be chosen above suspensions due to advantages in dosing, stability, storage, cost and transportation, especially in LMICs (Angwa et al, 2020;Vallet et al, 2021;Parrish et al, 2022;WHO, 2023a).…”

Section: Discussionmentioning

confidence: 99%

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Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project

et al. 2023

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The WHO Model List of Essential Medicines for Children (EMLc) has not been systematically revised in the last few years. We conducted a survey addressed to healthcare professionals prescribing, preparing, or administering medicines to children and a narrative review to identify problematic paediatric formulations or missing medicines in all therapeutic fields to inform the review of the EMLc in 2023. A total of 285 physicians (63%), 28 nurses (6%) and 142 pharmacists (31%), mostly working in the hospital setting, reported at least one problematic medicine. 290 medicines were reported as missing (completely or the child-appropriate formulation). The top three most mentioned were ciprofloxacin together with phenobarbital and omeprazole. 387 medicines were reported as problematic (34% were oral liquid formulations, 34% tablets, 18% parenteral preparations. Mostly of the products were antibacterials (27%), cardiovascular medicines (11%) and antivirals (11%). The obtained responses show the perspective of healthcare workers working around the world, particularly in the European region (25%), in the African region (24%), and in the Region of the Americas (19%), with limited representation from Northern Africa and the Middle East. Our results need to be analysed with the outputs of other ongoing works before specific products can enter the WHO-hosted Global Accelerator for Paediatric formulations network prioritisation process. Efforts to develop appropriate formulations for children should be accelerated so that the uncertainties associated with off-label drug preparation and use are minimised, and therapeutic benefits are optimised.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project

et al. 2023

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How Compounding Pharmacies Fill Critical Gaps in Pediatric Drug Development Processes: Suggested Regulatory Changes to Meet Future Challenges

MacArthur

Ashworth²,

Zhan

et al. 2022

Children

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Drugs administered to children in the United States fall into two broad categories: (1) those that have followed the US Food and Drug Administration (US-FDA) pediatric drug approval process and are marketed as finished dosage forms with pediatric labeling; and (2) all others, many of which are used “off-label”. The use of most drug products in pediatrics is still off label, often requiring special preparation, packaging, and, in some cases, compounding into preparations. The latter category includes compounded preparations that incorporate either a US-FDA approved finished dosage form (e.g., a sterile solution, sterile powder, nonsterile capsules, oral solution, crushed tablets, etc.), or rely on bulk active pharmaceutical ingredients (APIs). Compounded preparations are prepared for individual patients in 503A pharmacies, or on a larger scale and not just for specific patients, in licensed 503B establishments. Critical gaps in the current drug approval process for finished dosage forms have created a proverbial “Gordian knot” that needs to be untangled thoughtfully to facilitate increased production and approval of vitally needed medications for pediatric patients. This opinion will describe current regulatory processes pertaining to pediatrics-only drug approval in the United States. Additionally, discussed are steps required for a product to acquire pediatric labeling. Gaps in regulatory approval pathways for both manufactured and compounded pediatric drugs will be identified, especially those that complicate and slow development and availability to patients. Finally, suggestions for regulatory modifications that may enhance pediatric product development strategies for both manufacturers and compounders are suggested.

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Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability

et al. 2023

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Pantoprazole is a model substance that requires dosage form adjustments to meet the needs of all patients. Pediatric pantoprazole formulations in Serbia are mostly compounded as capsules (divided powders), while in Western Europe liquid formulations are more common. The aim of this work was to examine and compare the characteristics of compounded liquid and solid dosage forms of pantoprazole. Three syrup bases were used: a sugar-free vehicle for oral solution (according to USP43-NF38), a vehicle with glucose and hydroxypropyl cellulose (according to the DAC/NRF2018) and a commercially available SyrSpend Alka base. Lactose monohydrate, microcrystalline cellulose and a commercially available capsule filler (excipient II, composition: pregelatinized corn starch, magnesium stearate, micronized silicon dioxide, micronized talc) were used as diluents in the capsule formulations. Pantoprazole concentration was determined by the usage of the HPLC method. Pharmaceutical technological procedures and microbiological stability measurements were performed according to the recommendations of the EP10. Although dose appropriate compounding with pantoprazole is suitable using both liquid vehicles as well as solid formulations, chemical stability is enhanced in solid formulation. Nevertheless, according to our results, if liquid formulation is a pH adjusted syrup, it could be safely kept in a refrigerator for up to 4 weeks. Additionally, liquid formulations could be readily applied, while solid formulation should be mixed with appropriate vehicles with higher pH values.

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Compounded Nonsterile Preparations and FDA-Approved Commercially Available Liquid Products for Children: A North American Update

Cited by 3 publications

References 54 publications

Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project

Paediatric medicine issues and gaps from healthcare workers point of view: survey results and a narrative review from the global accelerator for paediatric formulations project

How Compounding Pharmacies Fill Critical Gaps in Pediatric Drug Development Processes: Suggested Regulatory Changes to Meet Future Challenges

Compounding of Liquid and Solid Dose Adjustable Formulations with Pantoprazole: Comparison of Stability, Applicability and Suitability

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