Formulation and evaluation of physicochemical stability of Allopurinol 20mg/mL oral suspension

V. Baillieu, P. Claraz, C. Sanchez, S. Benakouche, J. Le Liboux, V. Vasseur, T. Storme, A. Sabri
Hôpital Robert Debré, 48 Bd Sérurier, 75019 Paris, France

Introduction
Allopurinol is used in symptomatic hyperuricemia. Oral formulations currently available are not suitable for paediatrics. An oral suspension of Allopurinol 20mg/mL formulated into Ora-Blend is described in literature as being stable for 60 days at 4 and 25°C [1]. Ora-Blend is composed among other of paraben and sorbitol, two notable effects excipients, and saccharose, a cariogenic agent. Furthermore, Ora-blend’s osmolarity at 2,107 mOsm/kg can lead to digestive disorders. The aim of this project is to study physicochemical stability of Allopurinol in Inorpha, a more suitable vehicle for neonatology (fewer excipients and lower osmolarity at 170mOsm/kg).

Materials and Methods
The research for optimum formulation is undertaken and palatability is assessed (visual aspect, smell, taste, texture, aftertaste). Stability study is carried out on two oral suspension batches dosed at 1200mg/60mL and stored respectively at 5±3°C and 20±5°C. Sedimentation, pH, osmolarity and organoleptic characteristics are studied at different times. Triplicate dosages are measured at D0, 1, 2, 15, 30, 60, 90 and 120 by HPLC using a diode array detector. Analytical procedure is adjusted from European Pharmacopoeia (C18 column, mobile phase: KH2PO4 1.25g/L – Acetonitrile 95/5 (v/v)). Stability indicating method is validated according to ICH guidelines Q2 (R1) and after UV, HCl, NaOH and H2O2 forced degradation.

Results
A major sedimentation is observed in 24 hours. Addition of cellulose and xanthan gum is tested, and 0,5% of xanthan gum allows reduction of this sedimentation. Out of a total of 11 people, 72.7% find the suspension good to very good at D0 and D70. The linearity (r2 = 0.9994), accuracy (percent recovery = 99.7% ± 0.77), repeatability (coefficient of variation (CV) for 80, 100 and 120μg/mL respectively at 0.50; 0.68; 0.44%) and intermediate precision (CV = 1.56; 1.29; 1.03%) of procedure are validated. At the forced degradation, suspension is stable to the light, deteriorates in acid and basic conditions. pH remains stable at 4.78 ± 0.02 throughout all the study. Osmolarity at D60 is at 190 ± 5 mOsm/kg. The developed oral suspension is stable for 4 months both at 5±3°C and 20±5°C. Allopurinol concentration remains between 90-110% of the initial content for 120 days in both conditions.

Conclusion
Allopurinol oral suspension 20 mg/mL formulated in Inorpha with 0,5% of xanthan gum is physicochemical stable at 5±3°C and 20±5°C for 120 days.

[1] Allen LV et al. Stability of acetazolamide, allopurinol, azathioprine, clonazepam and flucytosine in extemporaneously compounded oral liquids. AJHSP 1996; 53:1944-9

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