Formulation Improvement of Paracetamol Syrup at Maharat Nakhon Ratchasima Hospital

Abstract

Introduction: The problem in production of paracetamol syrup at Maharat Nakhon Ratchasima Hospital had been that paracetamol had very low solubility. The former formulation of the syrup then contained alcohol and propylene glycol that were used to increase the drug's solubility. However, the two agents were reported to be harmful to children. Moreover, paracetamol was easily oxidized when exposed to light, heavy metals, and oxygen. In addition, the syrup had not a pleasant taste and its pH was not optimal.

Objectives: To develop paracetamol syrup that contains no alcohol and propylene glycol, and to improve the syrup stability (chemically and physically), and taste.

Materials and methods: We studied 9 formulas of co-solvents that might increase paracetamol solubility. We also tried improving syrup stability by adding anti-oxidant, acid-base buffer, and preservative. Developed of paracetamol syrup were produced and kept at room temperature for analysis of active ingredient, pH, and microoganism contamination at certain intervals.

Result: The most appropriate co-solvents which could solubilize paracetamol completely were 7.5% polyethylene glycol (PEG) 1500 + 15% glycerine + 40% syrup + water. The syrup was more stabilized by adding disodium edetate, a chelating agent that could prevent oxidation reaction. The optimal pH for the syrup was 5-6. This condition could be maintained by adding citrate buffer. Preservative were methyl paraben and propyl paraben. Flavoring agents included syrup 70%, sorbitol solution, and sodium chloride.

Conclusion: Developed paracetamol syrup was well stable for 24 months at room temperature. Amount of paracetamol and pH were appropriate according to US Pharmacopoeia (USP XXII) and British Pharmacopoeia (BP 1988). No microorganism contamination was found. The syrup had pleasant taste and has been produced for use within Maharat Nakhon Ratchasima Hospital. It has been included in the National Drug List in 1999.