RT Journal Article
SR Electronic
T1 Content uniformity of quartered hydrocortisone tablets in comparison with mini-tablets for paediatric dosing
JF BMJ Paediatrics Open
FD BMJ Publishing Group Ltd
SP e000198
DO 10.1136/bmjpo-2017-000198
VO 2
IS 1
A1 Jude Madathilethu
A1 Matthew Roberts
A1 Matthew Peak
A1 Joanne Blair
A1 Rebecca Prescott
A1 James L Ford
YR 2018
UL http://bmjpaedsopen.bmj.com/content/2/1/e000198.abstract
AB Objectives Children requiring cortisol replacement therapy are often prescribed hydrocortisone doses of 2.5 mg, but as this is commercially unavailable 10 mg tablets, with functional break lines, are split commonly in an attempt to deliver the correct dose. This study aimed to determine the dose variation obtained from quartered hydrocortisone tablets when different operators performed the splitting procedure and to ascertain whether better uniformity could be attained from mini-tablets as an alternative formulation.Methods Hydrocortisone 10 mg tablets were quartered by four different operators using a standard pill splitter. Hydrocortisone 2.5 mg mini-tablets (3 mm diameter) were formulated using a wet granulation method and manufactured using a high-speed rotary press simulator. The weight and content uniformity of the quartered tablets and mini-tablets were assessed according to pharmacopoeial standards. The physical strength and dissolution profiles of the mini-tablets were also determined.Results More than half of all quartered 10 mg tablets were outside of the ±10% of the stated US Pharmacopoeia hydrocortisone content (mean 2.34 mg, SD 0.36, coefficient of variation (CV) 15.18%) and more than 40% of the quartered tablets were outside the European Pharmacopoeia weight variation. Robust mini-tablets (tensile strengths of >4 MPa) were produced successfully. The mini-tablets passed the pharmacopoeial weight and content uniformity requirements (mean 2.54 mg, SD 0.04, CV 1.72%) and drug release criteria during in vitro dissolution testing.Conclusion This study confirmed that quartering 10 mg hydrocortisone tablets produces unacceptable dose variations and that it is feasible to produce 3 mm mini-tablets containing more accurate doses for paediatric patients.