Objective: Develop a child-friendly Fixed Dose Combination (FDC) water-dispersible tablet for Tuberculosis (TB) treatment, with 50, 150 and 75 mg of isoniazid (INH), pyrazinamide (PZA) and rifampicin (RFP) respectively. This new formulation must contain the lowest possible number of excipients, all accepted for pediatrics, and fulfill all the pharmacopoeia requirements for this type of tablet (friability, disintegration time, fineness of dispersion and content uniformity).Significance: TB is an infectious disease which caused the death of 233,000 children in 2017. At present there is no adequate market dosage form available for children. There is, however, one in a prequalification phase by the World Health Organization but its composition contains some excipients which may not be suitable for pediatrics.Therefore, this new formulation would cover this therapeutic gap.Methods: A factorial design, based on 3 quantitative factors (compression force and concentration of AcDiSol® and Explosol®) at three levels each, was performed to elucidate their influence over disintegration time and friability. In addition, the influence of the press speed on disintegration time, friability, tensile strength, fineness of dispersion and content uniformity over the target tablet was tested. A stability test was done following ICH guideline for accelerated conditions.Results: A water-dispersible tablet was developed according to international recommendations in terms of excipients for pediatrics and meeting Ph. Eur. requirements.In addition, its production has been optimized to be elaborated at maximum eccentric press speed but maintaining quality requirements.Conclusion: A high-quality child-friendly FDC water-dispersible tablet was developed improving the treatment of TB in pediatric.
OBJECTIVES Extemporaneous or magistral formulation of active pharmaceutical ingredients using traditional compounding techniques is a common practice when no commercial form is available for pediatrics. For this vulnerable group of patients, the formulation must be prepared with the minimum quantity and lowest proportion of excipients approved for pediatrics, avoiding the use of preservatives. Often the vehicles used for these preparations are dilutions of simple syrup with water. The objective of this study is to assess the effectiveness of antimicrobial preservation in simple syrup diluted with aqua conservans (conserved water), without propylene glycol or with a reduced proportion of parabens.
METHODS The European Pharmacopoeia test of efficacy of antimicrobial preservation was applied to 5 trial vehicles prepared with simple syrup diluted with water.
RESULTS Simple syrup is stable during 14 days. Vehicles prepared with simple syrup diluted with purified water did not meet the microbiological quality criteria, but when they are diluted with water that incorporates propylene glycol and parabens (aqua conservans), then they meet the criteria. In addition, if the water is prepared with parabens and without propylene glycol, the criteria for the dilution are met. Nevertheless, if the dilution is done with water prepared with an insufficient proportion of parabens to act as preservatives, the dilution does not meet the pharmacopoeia microbiological criteria.
CONCLUSIONS Dilution of simple syrup (50:50 v/v) to prepare a vehicle for extemporaneous or magistral preparation is microbiologically safe when water with methylparaben and propylparaben is used in a proportion of 0.08% and 0.02% (w/w), respectively, avoiding the use of propylene glycol as a solvent and thus its toxic effects in pediatrics.
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