Effectiveness of Antimicrobial Preservation of Extemporaneous Diluted Simple Syrup Vehicles for Pediatrics

Abstract

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.

Extemporaneous Compounding: Selective Pharmacists with Separate Skill

“…Efforts to mask flavors using sweetening agents, coatings, agglomeration, or microencapsulation often result in poorly-controlled, heterogeneous particle size distributions that result in a gritty or granular mouth feel and can provide ineffective taste masking, characteristics that may also compromise patient acceptance. The design of an ideal paediatric formulation needs to consider the following factors: (i) producing minimal impact on the lifestyle of the child, manifesting as the lowest dosage frequency and a palatable product, (ii) provision of individualized dosing or dose banding appropriate for effective therapy, (iii) sufficient bioavailability, (iv) non-toxic excipients in the formulation, (v) convenient and reliable administration and (vi) robust production process at minimal cost [ 20 ], [ 36 – 39 ].…”

Stability of extemporaneous sulfadiazine oral suspensions from commercially available tablets for treatment of congenital toxoplasmosis

“…Extemporaneous formulation using traditional compounding techniques is a common practice when no commercial form is available for paediatrics. The use of preservatives must be avoided for this vulnerable group of patients and microbiological stability in the absence of preservatives must be verified to ensure patient safety . In this study, the suitability of microbiological counting method was proven through microbial recovery of more than 70% of the microorganisms, demonstrating the effectiveness and absence of toxicity of the neutraliser.…”

“…However, USP recommends a shelf life of only 14 days when the liquid formulation does not contain preservatives. In addition, according to Santoveña‐Estévez et al, the simple 85% syrup can be guaranteed to preserve the antimicrobial of the formulation for 14 days .…”

“…However, USP recommends a shelf life of only 14 days when the liquid formulation does not contain preservatives. In addition, according to Santoveña-Est evez et al, the simple 85% syrup can be guaranteed to preserve the antimicrobial of the formulation for 14 days [43]. Although USP considers 14 days a default BUD in the absence of documentation, there are many studies which reveal drug instability before this time, and also physical instability when stored in a refrigerator [20,44,45].…”

Extemporaneous compounding: Selective pharmacists with separate skill

“…The design of an ideal paediatric formulation needs to consider the following factors: (i) producing minimal impact on the lifestyle of the child, manifesting as the lowest dosage frequency and a palatable product, (ii) provision of individualized dosing or dose banding appropriate for effective therapy, (iii) sufficient bioavailability, (iv) non-toxic excipients in the formulation, (v) convenient and reliable administration and (vi) robust production process at minimal cost. 20,[36][37][38][39] Health and Safety Risks: When handling hazardous products, units should be equipped with suitable containment devices and systems should be put in place to eliminate the risk of cross-contamination. Therapeutic Risks and Clinical Consequences: Any inaccuracy of dosing associated with medicines that have a narrow therapeutic index can lead to significant morbidity, whether due to under-dosing leading to treatment failure or overdosing leading to toxicity.…”