The accuracy, precision and sustainability of different techniques for tablet subdivision: Breaking by hand and the use of tablet splitters or a kitchen knife

Riet‐Nales, Diana A. van; Doeve, Myrthe E.; Nicia, Agnes E.; Teerenstra, Steven; Notenboom, Kim; Bemt, Bart J F van den

doi:10.1016/j.ijpharm.2014.02.031

Cited by 76 publications

(59 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Evidence providing a scientific basis for such dosage form modifications is frequently lacking, though concerns about safety and efficacy are not unfounded. Potential and proven risks include calculation and practical errors ), inaccuracy of dosing (Quinzler et al, 2006, van Riet-Nales et al, 2014a) and harm to the individual who alters the medicine (Akram and 395 Mullen, 2012). Altered bioavailability and palatability issues can also be of significant consequence (Best et al, 2011, Ferrarini et al, 2013.…”

Section: Practicesmentioning

confidence: 99%

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Ranmal¹,

Cram

Tuleu³

2016

International Journal of Pharmaceutics

View full text Add to dashboard Cite

A lack of evidence to guide the design of age-appropriate and acceptable dosage forms has been a longstanding knowledge gap in paediatric formulation development. The Children's Acceptability of Oral Formulations (CALF) study captured end-user perceptions and practices with a focus on solid oral dosage forms, namely tablets, capsules, chewables, orodispersibles, multiparticulates (administered with food) and mini-tablets (administered directly into the mouth). A rigorous development and testing phase produced age-adapted questionnaires as measurement tools with strong evidence of validity and reliability. Overall, 590 school children and adolescents, and 428 adult caregivers were surveyed across hospitals and various community settings. Attitudes towards dosage forms primarily differed based on age and prior use. Positive attitudes to tablets and capsules increased with age until around 14 years. Preference was seen for chewable and orodispersible preparations across ages, while multiparticulates were seemingly less favourable. Overall, 59.6% of school children reported willingness to take 10mm diameter tablets, although only 32.1% of caregivers perceived this size to be suitable. While not to be taken as prescriptive guidance, the results of this study provide some evidence towards rational dosage form design, as well as methodological approaches to help design tools for further evaluation of acceptability within paediatric studies.

show abstract

Section: Practicesmentioning

confidence: 99%

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Ranmal¹,

Cram

Tuleu³

2016

International Journal of Pharmaceutics

View full text Add to dashboard Cite

show abstract

“…It is estimated that 3000 compounding pharmacies fill more than 30 million prescriptions per year in the United States in an attempt to customize drugs for individual patients (6). Tablet division is achieved mainly using hands, knives or tablet splitters, which introduce dose variations due to uneven weight distribution after splitting (7)(8)(9)(10)(11)(12). Splitting solid dosage forms could also impact on release kinetics, especially for controlled or extended release formulations (13,14).…”

Section: Introductionmentioning

confidence: 99%

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

et al. 2016

View full text Add to dashboard Cite

The recent introduction of the first FDA approved 3D-printed drug has fuelled interest in 3D printing technology, which is set to revolutionize healthcare. Since its initial use, this rapid prototyping (RP) technology has evolved to such as extent that it is currently being used in a wide range of applications including in tissue engineering, dentistry, construction, automotive and aerospace. However, in the pharmaceutical industry this technology is still in its infancy and its potential yet to be fully explored. This paper presents various 3D printing technologies such as stereolithographic, powder based, selective laser sintering, fused deposition modelling and semi-solid extrusion 3D printing. It also provides a comprehensive review of previous attempts at using 3D printing technologies on the manufacturing dosage forms with a particular focus on oral tablets. Their advantages particularly with adaptability in the pharmaceutical field have been highlighted, including design flexibility and control and manufacture which enables the preparation of dosage forms with complex designs and geometries, multiple actives and tailored release profiles. An insight into the technical challenges facing the different 3D printing technologies such as the formulation and processing parameters is provided. Light is also shed on the different regulatory challenges that need to be overcome for 3D printing to fulfil its real potential in the pharmaceutical industry.

show abstract

“…In Europe, break marks may be present to provide fractions of the full tablet dose or to ease swallowing (84). The EMA paediatric guideline clearly indicates that the function of the break mark should be stated in the product information, i.e.…”

Section: Breakingmentioning

confidence: 99%

“…test on the Buniformity of mass of subdivided tablets.^Acknowledging that scientific evidence had indicated that breaking may not be accurate in clinical practice, the guideline also indicates that break marks for paediatric dosing may not be accepted in case of potent active substances with a narrow therapeutic window. The guideline does not address the use of tablet splitters which have generally proven to be less accurate than breaking tablets by hand but rather states that justification of the suitability of the break mark includes the ease of breaking (33,84).…”

Section: Breakingmentioning

confidence: 99%

Paediatric Drug Development and Formulation Design—a European Perspective

Riet‐Nales

Kozarewicz²,

Aylward

et al. 2016

AAPS PharmSciTech

Self Cite

View full text Add to dashboard Cite

Abstract.The availability of licensed paediatric drugs is lagging behind those for adults, and there is a lack of safe formulations in suitable doses that children are able and willing to take. As a consequence, children are commonly treated with off-label or unlicensed drugs. As off-label and unlicensed drug use are associated with a greater risk for harm than on-label drug use, a range of global initiatives have been developed to realize Bbetter^medicines for children. This review describes the challenges and achievements of the European Union to realize this goal, with a focus on paediatric drug development and formulation design. In 2007, a European Paediatric Regulation was installed enforcing companies to consider children in the early development of drugs with a new drug substance, for a new indication or with a new route of administration. The Regulation, e.g. requires companies to develop a paediatric investigation plan discussing the proposed clinical trials in children of different ages and the formulations for future marketing. Since 2013, the pharmaceutical design of any newly marketed paediatric drug should comply with the BGuideline on the Pharmaceutical Development of Medicines for Paediatric Use.^Companies should, e.g. justify the route of administration, dosage form, formulation characteristics, safety of excipients, dosing frequency, container closure system, administration device, patient acceptability and user information. In this review, the guideline's key aspects are discussed with a focus on novel formulations such as mini-tablets and orodispersible films, excipients with a potential risk for harm such as azo dyes and adequate user instructions.

show abstract

The accuracy, precision and sustainability of different techniques for tablet subdivision: Breaking by hand and the use of tablet splitters or a kitchen knife

Abstract: Health care professionals should realize that tablet splitting may result in inaccurate dosing. Authorities should undertake appropriate measures to assure good function of tablet splitters and, where feasible, to reduce the need for their use.

Cited by 76 publications

References 15 publications

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Age-appropriate and acceptable paediatric dosage forms: Insights into end-user perceptions, preferences and practices from the Children’s Acceptability of Oral Formulations (CALF) Study

Emergence of 3D Printed Dosage Forms: Opportunities and Challenges

Paediatric Drug Development and Formulation Design—a European Perspective

Contact Info

Product

Resources

About