Abstract
Epidermolysis bullosa is a genetically heterogenous skin fragility disorder with multiorgan involvement appearing already in newborn children. Severe progressive fibrosis follows skin blistering, mucosa lesions, and wound healing, favouring development of highly aggressive squamous cell carcinomas. Losartan potassium (LP) has been described to show positive effects; therefore, it was of clinical interest to develop 2 mm mini-tablets with LP for treatment of the affected children. Several challenges emerged during development: limited flowability and sticking to punches were observed in the first tableting experiments due to a high drug load, and a bitter taste of the LP was reported. Sticking to punches was reduced by using SMCC 50 and a combination of different lubricants; however, direct compression trials on a Korsch XM 12 rotary press were not successful due to compaction phenomena in the hopper. Thus, an intermediate dry granulation was successfully introduced. Two final formulations of the mini-tablets complied with the requirements of the European Pharmacopoeia regarding disintegration times (<15 min) and friability (<1.0%); mean tensile strengths amounted to about 1 MPa as a compromise between manufacturability and sufficient mechanical strength for further coating studies. The subsequent coating step succeeded delaying the initial drug release for more than 2 min. An acceptance value ≤15 was matched for the coated mini-tablets, and stability studies showed a promising shelf life.
Highlights
The development of mini-tablets is becoming increasingly important in the field of paediatric formulations
The mean Hausner ratio of Losartan potassium (LP) amounted to 1.50 ± 0.01[39–41]
(2.5 mg per mini-tablet) after intermediate dry granulation; this is of clinical insium (2.5 mg per mini-tablet) after intermediate dry granulation; this is of clinical interest terest with regard to the treatment of the rare disease epidermolysis bullosa
Summary
The development of mini-tablets is becoming increasingly important in the field of paediatric formulations. The Paediatric Regulation 1901/2006 was established in 2007 with the aim to promote the development of medicine for children. Further goals are appropriate authorization and more information on the application of medicines for paediatric patients, while not delaying authorization of medicinal products for adults [1,2]. In the Report of the Informal Expert Meeting on Dosage Forms of Medicines for Children published by the World. Health Organization (WHO) in 2008, the use of oral solid dosage forms over liquids was suggested for children, and was further supported by scientific experts [3–5]. The main focus was to develop an oral solid dosage form to address the rare disease epidermolysis bullosa (EB) [6], which can appear already in newborn children. EB is an inherited skin fragility disorder characterised by genetic heterogeneity
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
