Effects of the abrupt switch from solution to modified-release granule formulation of valproate

Verrotti, Alberto; Nanni, Giuseppe; Agostinelli, Sergio; Alleva, E. T.; Aloisi, Paolo; Franzoni, Emilio; Spalice, Alberto; Chiarelli, Francesco; Coppola, Giangennaro

doi:10.1111/j.1600-0404.2011.01568.x

Cited by 18 publications

(21 citation statements)

References 15 publications

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“…Five sources of strong evidence were identified (Table S1) all of which concluded that sprinkle/granule formulations were well‐accepted by children from 3 months of age . The studies also showed a preference for multiparticulates over oral liquids.…”

Section: Resultsmentioning

confidence: 99%

Evidence of acceptability of oral paediatric medicines: a review

Mistry

Batchelor

2017

Journal of Pharmacy and Pharmacology

125

109

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Objectives The aim of this review was to map the currently available evidence on acceptability of oral paediatric medicines to aid in the selection of suitable platform formulations for the development of new acceptable paediatric products. Methods This process used a defined search strategy of indexed publications and included methods to assess the quality of the evidence retrieved. Key findings Taste/palatability was the most extensively studied area of paediatric medicine acceptability yet standard methods or criteria that define what is classed as acceptable to children is still to be defined. There have been many reports on the acceptability of medicines to paediatric populations yet major gaps in the acceptability knowledge base exist including the shape and dimensions of tablets, minitablets and capsules swallowed whole in infants and children; size and overall volume of multiparticulates; volume of liquids completely swallowed in infants and children; duration of retention within the oral cavity, size and taste of orodispersible tablets, lozenges and chewable tablets and the number of solid units dosed at each time point. Conclusions The review highlights where further information is required to support knowledge around acceptability of age-appropriate medicines. An algorithm to aid in selection of a formulation that is likely to be acceptable based on the age range to be treated by the medicine is presented as a result of this review. IntroductionThere is much evidence to support the need for age-appropriate medicines to treat paediatric patients. Pharmaceutical products for the paediatric population have a number of considerations that may not apply to adult products. In particular, the acceptability of a product needs to be clearly defined for paediatric populations and this is currently an area of great interest.The importance and incentive to study the acceptability, including palatability, of paediatric formulations was discussed in the reflection paper [1] and endorsed in the latest European Paediatric guideline on pharmaceutical development of formulations for paediatric use.[2] Before this regulatory change, there was no requirement for medicines to be demonstrated to be acceptable to children. Guidance issued by the European Medicines Agency (EMA) in 2013 states that patient acceptability must be an integral part of paediatric formulation development and described in the paediatric investigation plan (PIP).[3] Acceptability has previously been defined as 'an overall ability of the patient and caregiver (defined as "user") to use a medicinal product as intended (or authorised)'.[4] The palatability of paediatric medicines is one of the most important formulation factors in the acceptability of liquid medicines with potential to influence adherence to therapeutic regimens and outcomes.[5] Palatability has been defined as, 'the overall appreciation of a (often oral) medicine by organoleptic properties such as vision (appearance), smell, taste, aftertaste and mouth feel (e.g. texture, cooli...

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Section: Resultsmentioning

confidence: 99%

Evidence of acceptability of oral paediatric medicines: a review

Mistry

Batchelor

2017

Journal of Pharmacy and Pharmacology

125

109

View full text Add to dashboard Cite

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“…Furthermore, the validity of the ASQ has been investigated in Norwegian samples. Decreased scores found in premature children have been regarded as supporting the construct validity of the Norwegian version of the scales [51]. Further studies are needed to assess the validity of the specific language and attention items included in the MoBa questionnaires, namely with regards to concurrent validity in relation to standardized assessments.…”

Section: Discussionmentioning

confidence: 99%

“…Nevertheless, a more accurate way of framing our results would be to interpret them as pertaining to relations between attention problems and presence/absence of language delay. In fact, the ASQ high negative predictive value has supported its use as a screening tool in premature children [51]. …”

Section: Discussionmentioning

confidence: 99%

Attention problems and language development in preterm low-birth-weight children: Cross-lagged relations from 18 to 36 months

et al. 2011

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BackgroundResearch has highlighted a series of persistent deficits in cognitive ability in preterm low-birth-weight children. Language and attention problems are among these deficits, although the nature of the relation between attention and language in early development is not well known. This study represents a preliminary attempt to shed light on the relations between attention problems and language development in preterm low-birth-weight children.MethodsThe aim of this study was to analyse reciprocal influences between language and attention problems from 18 to 36 months. We used maternal reports on attention problems and language ability referring to a sample of 1288 premature low-birth-weight infants, collected as part of the Norwegian Mother and Child Cohort Study (MoBa). A sample of children born full-term was used as the control group (N = 37010). Cross-lagged panel analyses were carried out to study reciprocal influences between attention problems and language.ResultsLanguage ability at 18 months did not significantly predict attention problems at 36 months, adjusting for attention problems at 18 months. Attention problems at 18 months significantly predicted changes in language ability from 18 to 36 months, pointing to a precursor role of attention in relation to language in children born preterm. Gender, age corrected for prematurity, and mother's education emerged as important covariates.ConclusionsPreliminary evidence was found for a precursor role of early attention problems in relation to language in prematurity. This finding can contribute to a better understanding of the developmental pathways of attention and language and lead to better management of unfavourable outcomes associated with co-morbid attention and language difficulties.

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“…Some other medicines have a narrow therapeutic index and need exact dosing, necessitating higher demands on the dosing flexibility of the formulation. The formulations based on solid platform technology can, in contrast to liquid formulations, be manufactured also in slow-release form, which allows less frequent dosing as for example with valproate modified-release granules [8].…”

Section: Ceylon Medical Journalmentioning

confidence: 99%

Time to change the paradigm of children’s medicines from liquid formulations to flexible solid oral dosage forms

Hoppu

2016

Ceylon Med. J.

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Time to change the paradigm of children's medicines from liquid formulations to flexible solid oral dosage formsWorldwide, people prefer a liquid formulation when paediatric medicines have to be given orally. The syrups and suspensions can be dosed flexibly by increasing the volume with age and weight of the child. We believe that young children can swallow liquids better than solids and prefer to take a sweet tasting liquid medicine. Simply liquid medicines are what children choose if they are given the chance -or at least that is what we adults think. When new innovative medicines are developed for use in children, the global pharmaceutical industry usually develops a liquid formulation for children if the medicine is to be given orally. In rich countries liquid formulations for oral medicines continue to be the rule.In resource limited settings (RLS) age appropriate paediatric formulations for children are not commonly available [1,2]. If what the pharmaceutical industry develops for children are liquid formulations, then one could think that the lack of paediatric medicines in RLS could be just a consequence of the general lack of availability of children's medicines in those settings. But what if the domination of liquid oral formulations as the perceived first choice for children is in fact also a cause and not only a consequence of the problem of poor availability of age appropriate paediatric medicines in RLS? Indeed, liquid oral formulations possess problematic characteristics particularly relevant in RLS [1]. Logistics of liquid oral formulations are complicated by increased bulk and commonly need cold-chain, problems for both the professional of bulk transport, and for the family who has to carry the child's medicines home. From a pharmaceutical development and manufacturing point of view, liquid medicines are problematic in many ways. Taste-masking is challenging, liquid formulations require more excipients than solid ones, and some excipients may not be suitable for children. Importantly, liquid formulations are more expensive to produce than solid dosage forms. The higher costs of production and logistics make liquid medicines more expensive than medicines in solid formulations. A switch to solid oral paediatric formulations would be a way to improve availability of paediatric medicines, if only the children would accept them and be able to swallow them.May be we should ask the children! That is exactly what we did in Helsinki in 1999 when we interviewed 150 children who were 3-7 years old andThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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Effects of the abrupt switch from solution to modified-release granule formulation of valproate

Abstract: Modified-release granule formulation of VPA may be a reliable alternative to solution for its convenience of use.

Cited by 18 publications

References 15 publications

Evidence of acceptability of oral paediatric medicines: a review

Evidence of acceptability of oral paediatric medicines: a review

Attention problems and language development in preterm low-birth-weight children: Cross-lagged relations from 18 to 36 months

Time to change the paradigm of children’s medicines from liquid formulations to flexible solid oral dosage forms

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