5.2.1. Project Target Profile for the development of clarithromycin pellets for administration with the SIP ® technology

• Three different doses strengths of 125 mg, 187.5 and 250 mg of clarithromycin in a single dose dosage unit to treat children between 2 years and 12 years of age
• Correct dosing of the prescribed dose of clarithromycin for each age group and for each administration throughout the complete treatment interval (twice daily over 7 – 10 days)
• Solid dosage form with palatably tasting pellets with high drug load; low filling volume per drinking straw allows for fast sipping of the dose and easy ingestion
• Extremely bitter taste of drug substance (clarithromycin) needs to be masked during ingestion – this may take up to several minutes for small children, especially when they initially reject to take the medication
• Taste masking needs to be capable under the conditions cited in the instruction leaflet for the administration of the drug product, i.e. sipping of the medication with a clear beverage at room temperature, listing Coca Cola, apple juice, mineral water and other carbonated beverages
• Compound is poorly soluble at the prescribed dose but needs to show fast dissolution in the gastrointestinal tract to be quickly absorbed and bioequivalent to the competitor’s product
• Multiparticulate dosage form with small particles (200 - 500 μm) to promote ease of ingestion and to prevent biting on pellets during ingestion which would damage the taste masking coat
• Suitable for filling into Dose Sipping ® Technology with established manufacturing processes and for administration of the complete dose by this system
• Complying with all regulatory and quality requirements for marketing authorisation approval
• (COGS not exceeding the current costs for granules for oral suspension in multi-dose containers)

Figure 8: ClaroSip ® a novel dosage form to improve compliance of the antibacterial treatment of infections in children⁶²

Based on the defined project target profile (≅ QTPP) and the expert knowledge in the team the requirements were translated into attributes that can be measured to confirm that the product will have the desired quality providing the relevant performance attributes. These attributes (≅ CQAs) were continuously monitored and logged in product score cards from the start of development.

⁶² Source: Ziegler I.; Dose Sipping Technology; 2007; slide 2