Formulation and Evaluation of Azithromycin and Paracetamol a Combination Therapy as Suppositories Novel Drug Delivery Systems

Background: The oral administration of medication to pediatric patients, particularly during acute illness, is frequently complicated by challenges such as vomiting, poor palatability, and dysphagia. These issues can compromise the efficacy of essential treatments, including antibiotics and antipyretics, leading to uncertain dosing and potential therapeutic failure. Rectal administration offers a practical alternative, bypassing the gastrointestinal tract and providing a reliable route for drug delivery in uncooperative or ill children. Objective: This study aimed to develop and evaluate fixed-dose combination rectal suppository containing Azithromycin and Paracetamol. The primary goal was to create a physically and chemically stable formulation with appropriate quality attributes suitable for pediatric use. Methods: Elven Suppository formulations were developed using the fusion (melt molding) method. Initial with hydrophilic polyethylene glycol (PEG) bases were conducted, followed by with lipophilic Witepsol® bases. An optimized formulation (F11), composed of a Witepsol® H35/W76 blend, sodium citrate, sodium lauryl sulfate, and sodium starch glycolate, was selected for comprehensive evaluation. The final suppositories were assessed for physical properties (appearance, weight variation, disintegration time, softening time) and chemical properties (pH and drug content) using a validated High-Performance Liquid Chromatography (HPLC) method for simultaneous quantification of both APIs. Results: Formulations using PEG bases failed to meet disintegration requirements (>30 minutes). In contrast, the optimized lipophilic Witepsol®-based formulation (F11) demonstrated excellent physical characteristics. The suppositories were homogenous, torpedo-shaped, and showed acceptable weight variation. They exhibited a rapid mean disintegration time of 4 minutes and 5 seconds at 37°C and a physiologically compatible pH of 7.5. The HPLC assay was specific and linear, confirming the drug content for Azithromycin and Paracetamol was 104.87% and 108.76% of the label claim, respectively, which is within standard pharmacopeial limits. Conclusion: It was concluded that the best Formulation F11 was found to be among the all formulations of Azithromycin and Paracetamol Suppositories NDDS. This novel dosage form offers a promising solution to improve treatment adherence and clinical outcomes in pediatric infectious diseases. Formulation scientist from his experience and knowledge have to significantly in the preformulation study stage and is an important factor in the NDDS (Novel Advanced Drug Delivery Systems) product development process.