Abstract
Access to medicines, including their availability and affordability, is a major public health challenge worldwide. This research aimed to characterise rectal formulations containing amoxicillin for the treatment of pneumonia in children under five, as an accessible alternative to existing formulations. Lipophilic Suppocire (S-NA15) and hydrophilic polyethylene glycol (PEG; 80% PEG 1500 and 20% PEG 4000, w/w) suppositories containing 250 mg amoxicillin were prepared. Hardness, apparent viscosity, uniformity of mass, uniformity of content, disintegration and dissolution time were determined. Irritation potential was screened using a slug mucosal assay and antibacterial efficacy against Staphylococcus aureus determined by isothermal microcalorimetry. Both lipophilic and hydrophilic formulations met the European Pharmacopoeia standards for suppositories when tested in vitro. They disintegrated within 30 min with rapid amoxicillin release profiles (98.6 ± 0.9%, 94.9 ± 1.2% over 30 min, respectively). Over-encapsulation of S-NA15 suppositories with hydroxypropyl methylcellulose shells slowed drug release and improved stability over 2 months. S-NA15 suppositories were classified as non-irritant and PEG suppositories only mildly irritant. Antibacterial efficacy of formulations was equivalent to amoxicillin alone. Both PEG and over-encapsulated S-NA15 rectal formulations developed in the present work have shown promise based on pre-clinical screening, and further development is justified to develop a product with commercial potential.
Highlights
Pneumonia is one of the leading causes of mortality globally in children under 5 years old [1], with an estimated 880,000 children dying of pneumonia in 2016 [2]
The Differential scanning calorimetry (DSC) thermograms of pure Amoxicillin trihydrate (amoxTH) samples showed an endothermic peak at a temperature range between 64.6 and 88.8 °C, corresponding to dehydration of amoxTH to its anhydrous form
Fatty base S-NA15 started melting at a temperature range between 33 and 35 °C, whereas the hydrophilic physical mixture of 80% w/w polyethylene glycol (PEG) 1500 and 20% w/w PEG 4000 resulted in two peaks at 48.5 °C and 57.3 °C, corresponding to PEG 1500 and PEG 4000, respectively
Summary
Pneumonia is one of the leading causes of mortality globally in children under 5 years old [1], with an estimated 880,000 children dying of pneumonia in 2016 [2]. Pneumonia is caused by a variety of pathogens including bacteria, fungi and viruses—Streptococcus pneumoniae and Haemophilus influenzae type B are vaccine-preventable pathogens that are responsible for 18% and 7% of severe pneumonia episodes worldwide, respectively. Amoxicillin is considered a “priority essential” medicine and is recommended by the World Health Organization (WHO) as first-line treatment for outpatient paediatric pneumonia [4,5,6]. Child friendly dosage forms are not available in many countries, and adult formulations are often manipulated to achieve appropriate dosages, which can compromise efficacy, adherence and medicine stability [6].
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