Formulation and Evaluation of Azithromycin Dihydrate Solid Dispersion with Esther of Polyethylene Glycol-6000 and Stearic Acid Using A Co-Grinding Technique

Mardiyanto, Budi Untari, Ady Mara, Nauval Hady Prasetyo


Azithromycin is a narrow-spectrum bacterial growth inhibitory antibiotic derived from macrolides with low dissolution in water. Several methods have been carried out to increase the dissolution of medicinal substances, one of which is solid dispersion. Solid dispersions are mixtures consisting of one or more active substances in an inert carrier. The purpose of this study was to determine the effect of formatting solid dispersions with PEG 6000 polymer and stearic acid on increasing the dissolution rate of azithromycin. The method of formatting solid dispersions uses the co-grinding method. Solid dispersion of azithromycin was prepared in four formulas with variations in the amount of PEG 6000. Tests carried out on solid dispersion samples of azithromycin were XRD, FTIR, SEM, solubility tests, and dissolution tests. Test results on azithromycin solid dispersions prepared by co-grinding showed that there was an effect of the amount of PEG 6000 on decreasing the intensity of azithromycin crystals, there was no chemical interaction between azithromycin and the carrier, differences in the morphology of pure azithromycin powder and solid dispersions, and an increase in the dissolution of solid dispersions in medium SIF.


Ahuja, M., P. Verma, and M. Bhatia (2015). Preparation and Evaluation of Chitosan-itraconazole Co-precipitated Nanosuspension for Ocular Delivery. Journal of Experimental Nanoscience, 10(3); 209–221

Ainurofiq, A., A. Maharani, F. Fatonah, H. N. Halida, and T. Nurrodlotiningtyas (2021). Pre Formulation Study on The Preparation of Skin Cosmetics. Science and Technology Indonesia, 6(4); 273–284

Beynon, P. and R. Beynon (2018). Preparation of Buffer Solutions. Buffer Solutions

Blumenberg, V., M. L. Schubert, E. Zamir, S. Schmidt, R. Rohrbach, P. Waldhoff, D. Bozic, H. Pock, E. Elinav, and C. Schmidt (2020). Antibiotic Therapy and Low Gut Microbiome Diversity is Associated with Decreased Response and High Toxicity in BCP-ALL and DLBCL Patients after Treatment with CD19. CAR T-cells. Blood, 136; 33–34

Chen, Q., J. Zhang, H. Liu, T. Li, and Q. Wang (2023). Mechanism of High-moisture Extruded Protein Fibrous Structure Formation Based on the Interactions Among Pea Protein, Amylopectin, and Stearic Acid. Food Hydrocolloids, 136; 108254

Chun, N. H., I. C. Wang, M. J. Lee, Y. T. Jung, S. Lee, W. S. Kim, and G. J. Choi (2013). Characteristics of Indomethacin–saccharin (IMC–SAC) Co-crystals Prepared by an Anti-solvent Crystallization Process. European Journal of Pharmaceutics and Biopharmaceutics, 85(3); 854-861

Fitriani, L., S. Ramadhani, and E. Zaini (2016). Preparation and Characterization of Solid Dispersion Famotidine-Mannitol by Co-grinding Method. Asian Journal of Pharmaceutical and Clinical Research, 10(3); 16112

Fu, D., P. Zhang, L. Du, and J. Dai (2014). Experiment and Model for the Viscosities of MEA PEG400, DEA-PEG400 and MDEA-PEG400 Aqueous Solutions. The Journal of Chemical Thermodynamics, 78; 109–113

Guo, B., H. Liu, Y. Li, J. Zhao, D. Yang, X. Wang, and T. Zhang (2014). Application of Phospholipid Complex Technique to Improve the Dissolution and Pharmacokinetic of Probucol by Solvent evaporation and Co-grinding Methods. International journal of pharmaceutics, 474(1-2); 50–56

Gyselinck, I., W. Janssens, P. Verhamme, and R. Vos (2021). Rationale for Azithromycin in COVID 19: An Overview of Existing Evidence. BMJ Open Respiratory Research, 8(1); 806

Kalepu, S. and V. Nekkanti (2015). Insoluble Drug Delivery Strategies: Review of Recent Advances and Business Prospects. Acta Pharmaceutica Sinica B, 5(5); 442–453

Li, D., X. Wu, X. Yu, Q. Huang, and L. Tao (2015). Synergistic Effect of Non-ionic Surfactants Tween 80 and PEG6000 on Cytotoxicity of Insecticides. Environmental Toxicology and Pharmacology, 39(2); 677–682

Mardiyanto, B. Untari, N. F. Annuria, A. Mara, A. A. Aprianto, and G. E. Ningsih (2022). The Enhancement Solubility and Stability of Erythromycin Formatted in Solid Lipid Nanoparticles by Utilizing PVA as Stabilizer. Science and Technology Indonesia, 7(2); 195–201

Mardiyanto, M., N. A. Fithri, A. Amriani, H. Herlina, and D. P. Sari (2021). Formulation and Characterization of Glibenclamide Solid Lipid Submicroparticles Formated by Virgin Coconut Oil and Solid Matrix Surfactant. Science and Technology Indonesia, 6(2); 58–66

Martin, B., J. Seguin, M. Annereau, T. Fleury, R. Lai-Kuen, G. Neri, A. Lam, M. Bally, N. Mignet, and Y. Corvis (2020). Preparation of Parenteral Nanocrystal Suspensions of Etoposide from the Excipient Free Dry State of the Drug to Enhance in Vivo Antitumoral Properties. Scientific Reports, 10(1); 18059

Martínez, L. M., J. Cruz-Angeles, M. Vázquez-Dávila, E. Martínez, P. Cabada, C. Navarrete-Bernal, and F. Cortez (2022). Mechanical Activation by Ball Milling as a Strategy to Prepare Highly Soluble Pharmaceutical Formulations in the Form of Co-Amorphous, Co-Crystals, or Polymorphs. Pharmaceutics, 14(10); 2003

Martingano, D., S. Singh, and A. Mitrofanova (2020). Azithromycin in the Treatment of Preterm Prelabor Rupture of Membranes Demonstrates a Lower Risk of Chorioamnionitis and Postpartum Endometritis with an Equivalent Latency Period Compared with Erythromycin Antibiotic Regimens. Infectious Diseases in Obstetrics and Gynecology, 2020; 1–8

Monteyne, T., P. Adriaensens, D. Brouckaert, J.-P. Remon, C. Vervaet, and T. De Beer (2016). Stearic acid and High Molecular Weight PEO as Matrix for the Highly Water Soluble Metoprolol Tartrate in Continuous Twin-screw Melt Granulation. International Journal of Pharmaceutics, 512(1); 158–167

Pani, A., M. Lauriola, A. Romandini, and F. Scaglione (2020). Macrolides and Viral Infections: Focus on Azithromycin in COVID-19 Pathology. International Journal of Antimicrobial Agents, 56(2); 106053

Parnham, M. J., V. E. Haber, E. J. Giamarellos-Bourboulis, G. Perletti, G. M. Verleden, and R. Vos (2014). Azithromycin: Mechanisms of Action and Their Relevance for Clinical Applications. Pharmacology and Therapeutics, 143(2); 225–245

Pokhrel, S. (2015). A Review on Introduction and Applications of Starch and its Biodegradable Polymers. International Journal of Environment, 4(4); 114–125

Sabnis, S. S., S. D. Singh, and P. R. Gogate (2022). Improvements in Azithromycin Recrystallization Using Ultrasound for Size Reduction. Ultrasonics Sonochemistry, 83; 105922

Sadia Pervez, L. and S. Muhammad (2021). Solid Dispersion Preparation of a Macrolide Drug Using Natural and Synthetic Polymers to Enhance its Solubility and Bioavailability: A Pharmacokinetics Application. Latin American Journal of Pharmacy, 40(3); 76–95

Schwartz, R. A. and R. M. Suskind (2020). Azithromycin and COVID-19: Prompt Early Use at First Signs of this Infection in Adults and Children, an Approach Worthy of Consideration. Dermatologic Therapy, 33(4); e13785

Sultana, J., P. M. Cutroneo, S. Crisafulli, G. Puglisi, G. Caramori, and G. Trifirò (2020). Azithromycin in COVID-19 Patients: Pharmacological Mechanism, Clinical Evidence and Prescribing Guidelines. Drug Safety, 43; 691–698


Mardiyanto (Primary Contact)
Budi Untari
Ady Mara
Nauval Hady Prasetyo
Mardiyanto, Untari, B. ., Mara, A. ., & Prasetyo, N. H. . (2023). Formulation and Evaluation of Azithromycin Dihydrate Solid Dispersion with Esther of Polyethylene Glycol-6000 and Stearic Acid Using A Co-Grinding Technique. Science and Technology Indonesia, 8(2), 312–320.

Article Details

Most read articles by the same author(s)