title: Dissolution of Intact, Divided and Crushed Circadin Tablets: Prolonged vs. Immediate Release of Melatonin.
abstract: Circadin 2 mg prolonged-release tablet is the only licensed melatonin product available in the UK. Circadin is indicated for patients with primary insomnia aged 55 and over, but is more widely used "off-label" to treat sleep disorders especially in the paediatric population. Children and older people often have difficulty swallowing tablets and dividing the tablet is sometimes required to ease administration. The aim of this study was to measure the release profile of melatonin from Circadin tablets when divided or crushed, and compare this with release from intact tablets. Dissolution testing was also performed for unlicensed melatonin products for comparison. Dissolution tests were performed using the pharmacopoeial paddle apparatus, with melatonin release analyzed by high performance liquid chromatography. Melatonin content, hardness, friability, and disintegration of the products were also evaluated. The prolonged release of melatonin from Circadin tablets was unlike that of any other product tested. When divided into halves, Circadin preserved most of the prolonged-release characteristic (f2 = 58), whereas quarter-cut and crushed tablet had a more immediate melatonin release profile. Circadin is significantly less expensive and should be preferred to unlicensed medicines which are not pharmaceutically equivalent and offer less quality assurance.
authors.affiliation: Institute of Pharmaceutical Science, King's College London, King's Health Partners, London SE1 9NH, UK. chua81@gmail.com.
authors.forename: Hui Ming
authors.initials: HM
authors.lastname: Chua
authors.affiliation: Institute of Pharmaceutical Science, King's College London, King's Health Partners, London SE1 9NH, UK. nataloldigo@gmail.com.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Hauet Richer
authors.affiliation: Institute of Pharmaceutical Science, King's College London, King's Health Partners, London SE1 9NH, UK. magda.swedrowska@kcl.ac.uk.
authors.forename: Magda
authors.initials: M
authors.lastname: Swedrowska
authors.affiliation: Institute of Pharmaceutical Science, King's College London, King's Health Partners, London SE1 9NH, UK. steve.ingham@kcl.ac.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Ingham
authors.affiliation: Pharmacy Department, Evelina London Children's Hospital, Guy's &amp; St. Thomas' NHS Foundation Trust, King's Health Partners, London, UK. Stephen.tomlin@gstt.nhs.uk.
authors.forename: Stephen
authors.initials: S
authors.lastname: Tomlin
authors.affiliation: Institute of Pharmaceutical Science, King's College London, King's Health Partners, London SE1 9NH, UK. ben.forbes@kcl.ac.uk.
authors.forename: Ben
authors.initials: B
authors.lastname: Forbes
keywords: ADHD; autism; controlled release; insomnia; paediatric; pharmacoenconomics; quality assurance; quality control; sleep