Authors: Ms. Snehal Kadbhane, Mr. Ritesh Khandagale, Dr. Vijaykumar Kale, Dr. Mahesh Thakare, Vaibhav Narwade
Abstract: Background: The near-universal reliance on high-sucrose vehicles in paracetamol oral syrups creates an increasingly untenable clinical tension for vulnerable patient populations—diabetic individuals experiencing glycemic excursions, children at heightened risk of dental caries, and obese or metabolically compromised patients. With global diabetes prevalence now exceeding 537 million adults and dental caries ranking as the world's most prevalent non-communicable condition, the pharmacoeconomic and public health argument for sugar-free alternatives has become irrefutable. Methods: Five trial formulations (F1–F5) of a sugar-free paracetamol oral syrup at 120 mg/5 mL were developed using a Quality by Design (QbD) framework. Sorbitol (20–30% w/v), hydroxypropyl methylcellulose K4M (0.25–0.75% w/v), and sucralose (30–70 mg/100 mL) were systematically varied while all other excipients were held constant. Formulations were evaluated for organoleptic acceptability, pH, viscosity, drug content, density, surface tension, sedimentation ratio, and antimicrobial preservative effectiveness per USP <51> Category 2. The optimized formulation (F3) underwent 90-day accelerated stability testing per ICH Q1A(R2) at 40°C ± 2°C/75% ± 5% RH and was benchmarked against a commercially marketed sugar-free reference product. Results: F3, containing sorbitol 25% w/v, HPMC K4M 0.50% w/v, and sucralose 50 mg/100 mL, emerged as the optimized formulation. It exhibited a pH of 5.82 ± 0.02, viscosity of 92 ± 2.5 cps, drug content of 99.4 ± 0.5% of label claim, and a palatability score of 4.5/5.0—superior to both lower-concentration variants and the marketed comparator (4.2/5.0). Accelerated stability studies confirmed drug content above 98.6% and p-aminophenol below 0.08% at day 90, well within pharmacopoeial limits. All five challenge organisms met USP <51> Category 2 acceptance criteria. Conclusion: The optimized sugar-free paracetamol syrup demonstrates pharmacopoeial compliance, chemical and microbiological stability supportive of a 24-month shelf life, and patient acceptability equivalent or superior to a marketed reference. The formulation strategy—combining a polyol bulk sweetener with a high-intensity non-caloric sweetener and a cellulose-ether viscosity modifier—provides a scientifically validated, clinically advantageous platform for analgesic-antipyretic therapy in patient populations for whom conventional sucrose-based preparations are contraindicated or undesirable.
