Comparison of sprinkle versus syrup formulations of valproate for bioavailability, tolerance, and preference

https://doi.org/10.1016/S0022-3476(05)82496-5Get rights and content

We compared a new coated-particle formulation of valproate (Depakote Sprinkle) capsules with valproic acid (Depakene) syrup for bioavailability, side effects, and patient and parent preference. Twelve children with epilepsy, aged 5 to 16 years, participated in this randomized, two-period, crossover study. They were assigned to a 7-day regimen with one formulation and then crossed over to the other; the drug was given every 12 hours. On day 7, blood samples collected during a 12-hour period were analyzed for the presence of valproate. At the study's end, parents and children were asked structured questions regarding formulation preference and adverse events. The extent of absorption from sprinkle equaled that from syrup (relative bioavailability=1.02), but absorption was slower (time to maximum concentration=4.2 vs 0.9 hour; p<0.01). Fluctuations in serum concentrations were less with sprinkle (34.8% vs 62.3%; p<0.01). Sprinkle was preferred by 9 of the 12 parents because of ease of administration, and by nine of the children because of improved palatability. We conclude that sprinkle may be substituted for syrup without changing the daily dose. Furthermore, sprinkle, because of its prolonged absorption, may be given every 12 hours to children receiving monotherapy. Compliance may be enhanced because of the more convenient dosing schedules and the high degree of patient and parent acceptance.

References (13)

  • HenriksenO et al.

    Clinical and pharmacokinetic observations on sodium valproate: a five-year follow-up study of 100 children with epilepsy

    Acta Neurol Scand

    (1982)
  • WilderBJ et al.

    Gastrointestinal tolerance of divalproex sodium

    Neurology

    (1983)
  • FischerJH et al.

    Effect of food on the serum concentration profile of enteric-coated valproid acid

    Neurology

    (1988)
  • AcardiJ

    Epilepsy in children

  • GibaldiM et al.

    Pharmacokinetics

  • Eeg-OlofssonO et al.

    Diurnal variation of carbamazepine and carbamazepine-10, 11-epoxide in plasma and saliva in children with epilepsy: a comparison between conventional and slow-release formulations

    J Child Neurol

    (1990)
There are more references available in the full text version of this article.

Cited by (48)

  • Determination of healthcare resource and cost implications of using alternative sodium valproate formulations in the treatment of epilepsy in children in England: A retrospective database review

    2021, European Journal of Pharmaceutics and Biopharmaceutics
    Citation Excerpt :

    Previous research compared a sprinkle formulation (Depakote) to valproic acid syrup (Depakene) in twelve children with epilepsy aged from 5 to 16 years; the sprinkle was preferred by parents and children due to ease of administration and palatability, respectively. Furthermore there were fewer fluctuations in serum concentrations with the sprinkle compared to the syrup [7]. Another study compared the acceptance of a sodium valproate prolonged release microgranule to a liquid product in 199 children; the results showed that refusal to take the medicine decreased upon switching to the microgranule (Micropakine®LP; MPK) as did the frequency that parents were using rewards [8].

  • Sprinkle formulations—A review of commercially available products

    2020, Asian Journal of Pharmaceutical Sciences
    Citation Excerpt :

    Sprinkle formulations can improve compliance of patients with dysphagia. Indeed, more than 75% and 93% of children preferred sprinkle dosage form to syrup and oral drops, respectively [26,27]. This preference spurred the growth of sprinkle products since the early 1990s as can be seen in Fig. 1.

  • The effect of administration media on palatability and ease of swallowing of multiparticulate formulations

    2018, International Journal of Pharmaceutics
    Citation Excerpt :

    A range of studies showed acceptance of iron supplement sprinkles and preference for these compared to oral drops in children with anaemia (Adu-Afarwuah et al., 2008; Geltman et al., 2009; Zlotkin et al., 2003). Likewise, studies involving children suffering from epilepsy consistently showed preference for sprinkle formulations over syrup (Cloyd et al., 1992; Motte et al., 2005; Verrotti et al., 2012). In a recent study, children showed preference for sprinkles over syrup after 12-week antiretroviral therapy; 72% of children below 12 months and 64% of children between 1 and 4 years preferred the multiparticulate dosage form.

View all citing articles on Scopus

Supported in part by a grant from Abbott Laboratories.

Presented in part at the annual meeting of the American Epilepsy Society, Baltimore, Md., Dec. 7, 1987.

View full text