A new method for the preparation of pure acamprosate calcium with a micron particle size

Document Type : Research Article

Authors

Department of Chemical Technologies, Iranian Research Organization for Science and Technology, Tehran, Iran

Abstract

Considering that preparing microparticle drugs enhances their solubility and bioactivity, it is the pharmaceutics’ interest to have more information about the drug’s particle size; hence, it is essential to study a drug’s particle size and morphology. So far, no work has been done on the particle size of acamprosate calcium. In this work, micronized acamprosate calcium was first prepared, then its water solubility was investigated. To this aim, acamprosate calcium was synthesized from 1,3-propane sultone through two-step reactions. The resulting powder was then micronized using Triton-X-100 using the in situ micronization method. The resulting micronized particles were found to be highly pure (99.7 %). The micronized acamprosate calcium's particle size was less than 10 µm. Kinetic solubility studies showed that micronized acamprosate calcium's water solubility had improved compared to bulk particles of acamprosate calcium.

Graphical Abstract

A new method for the preparation of pure acamprosate calcium with a micron particle size

Highlights

  • A micron-sized acamprosate calcium sample was synthesized by using Triton-X-100.
  • The product has an acceptable purity and is in accordance with international U.S. pharmacopeia.
  • The kinetic solubility of acamprosate calcium was improved by size reduction. 

Keywords

Main Subjects


[1] Charalabidis, A., Sfouni, M., Bergström, C., & Macheras, P. (2019). The Biopharmaceutics Classification System (BCS) and the Biopharmaceutics Drug Disposition Classification System (BDDCS): Beyond Guidelines. Int. J. Pharm. 566, 264-281.
[2] Tran, P., & Park, J.S. (2021). Recent Trends of Self-Emulsifying Drug Delivery System for Enhancing the Oral Bioavailability of Poorly Water-Soluble Drugs. J. Pharm. Investig. 51, 439-463.
[3] Khan, K.U., Minhas, M.U., Badshah, S.F.,  Suhail, M., Ahmad, A. & Ijaz, S. (2022). Overview of Nanoparticulate Strategies for Solubility Enhancement of Poorly Soluble Drugs. Life Sci. 291, 120301.
[4] Kesisoglou, F., & Wu, Y. (2008). Understanding the Effect of API Properties on Bioavailability Through Absorption Modeling, AAPS J. 10(4) 516-525.
[5] Arnold, S.L.M. & Isoherranen, N. (2022). Role of Pharmacokinetics and Pharmacokinetic Modeling in Drug Development. in T. kenakin (Ed.), Comprehensive Pharmacology (pp. 743-768). Elsevier.
[6] Kim, D.H., Kim, Y.W., Tin, Y.Y., Soe, M.T.P., Ko, B.H., Park, S.J., & Lee, J.W. (2021). Recent Technologies for Amorphization of Poorly Water-Soluble Drugs. Pharmaceutics, 13(8) 1318.
[7] Tran, P., Pyo, Y.C., Kim, D.H., Lee, S.E., Kim, J.K., & Park, J.S. (2019). Overview of the Manufacturing Methods of Solid Dispersion Technology for Improving the Solubility of Poorly Water-Soluble Drugs and Application to Anticancer Drugs. Pharmaceutics, 11(3) 132.
[8] Loh, Z.H., Samanta, A.K., Heng, P.W.S. (2015). Overview of Milling Techniques for Improving the Solubility of Poorly Water-Soluble Drugs. Asian J. Pharm. Sci. 10(4) 255-274.
[9] Williams, H.D., Trevaskis, N.L., Charman, S.A., Shanker, R.M., Charman, W.N., Pouton, C.W., & Porter, C.J.H. (2013). Strategies to Address Low Drug Solubility in Discovery and Development. Pharmacol. Rev. 65(1) 315-499.
[10] Savjani, K.T., Gajjar, A.K., & Savjani, J.K.  (2012). Drug Solubility: Importance and Enhancement Techniques. ISRN Pharm. 2012, 195727.
[11] Abuzar, S.M., Hyun, S.M., Kim, J.H., Park, H.J., Kim, M.S., Park, J.S., & Hwang, S.J. (2018). Enhancing the Solubility and Bioavailability of Poorly Water-Soluble Drugs Using Supercritical Antisolvent (SAS) Process. Int. J. Pharm. 538, 1-13.
[12] Kim, S., Bilgili, E., & Davé, R.N. (2021). Impact of Altered Hydrophobicity and Reduced Agglomeration on Dissolution of Micronized Poorly Water-Soluble Drug Powders After Dry Coating. Int. J. Pharm. 606, 120853.
[13] Yadav, K., Sachan, A.K., Kumar, S., & Dubey, A. (2022). Techniques for Increasing Solubility: A Review of Conventional and New Strategies. Asian J. Pharm. Res. Dev. 10(2) 144-153.
[14] Cun, D., Zhang, C., Bera, H., & Yang, M. (2021). Particle Engineering Principles and Technologies for Pharmaceutical Biologics. Adv. Drug Deliver. Rev. 174, 140-167.
[15] Hanafy, A., Spahn-Langguth, H., Vergnault, G., Grenier, P., Tubic Grozdanis, M., Lenhardt, T., & Langguth, P. (2007). Pharmacokinetic Evaluation of Oral Fenofibrate Nanosuspensions and SLN in Comparison to Conventional Suspensions of Micronized Drug. Adv. Drug Deliver. Rev. 59(6) 419-426.
[16] Kim, J.S., Park, H., Kang, K.T., Ha, E.S., Kim, M.S., & Hwang, S.J. (2022). Micronization of a Poorly Water-Soluble Drug, Fenofibrate, via Supercritical-Fluid-Assisted Spray-Drying. J. Pharm. Investig. 52, 353-366.
[17] Arms, L., Smith, D.W., Flynn, J., Palmer, W., Martin, A., Woldu, A., & Hua, S. (2018). Advantages and Limitations of Current Techniques for Analyzing the Biodistribution of Nanoparticles. Front. Pharmacol. 9, 802.
[18] Heng, D., Ogawa, K., Cutler, D.J., Chan, H.K. Raper, J.A., Ye, L., & Yun, J. (2010). Pure Drug Nanoparticles in Tablets: What Are the Dissolution Limitations?. J. Nanopart. Res. 12, 1743-1754.
[19] De Jong, W.H., & Borm, P.J.A. (2008). Drug Delivery and Nanoparticles: Applications and Hazards. Int. J. Nanomed. 3(2) 133-149.
[20] Brunaugh, A., Smyth, H.D.C. (2017). Process Optimization and Particle Engineering of Micronized Drug Powders via Milling. Drug Deliv. Transl. Re. 8(6) 1740-1750.
[21] Rasenack, N., & Müller, B.W. (2004). Micron‐Size Drug Particles: Common and Novel Micronization Techniques. Pharm. Dev. Technol. 9(1) 1-13.
[22] Vandana, K.R., Prasanna Raju, Y., Harini Chowdary, V., Sushma, M., & Vijay Kumar, N. (2014). An Overview on in Situ Micronization Technique - An Emerging Novel Concept in Advanced Drug Delivery. Saudi Pharm. J. 22(4) 283-289.
[23] Janiszewska-Turak, E. (2017). Carotenoids Microencapsulation by Spray Drying Method and Supercritical Micronization. Food Res. Int. 99 (part 2) 891-901.
[24] Dobrowolski, A, Strob, R, Dräger-Gillessen, J.F., Pieloth, D., Schaldach, G., Wiggers, H., & Thommes, M. (2019). Preparation of Submicron Drug Particles via Spray Drying from Oganic Solvents. Int. J. Pharm. 567, 118501.
[25] Aguiar-Ricardo, A. (2017). Building Dry Powder Formulations Using Supercritical CO2 Spray Drying. Curr. Opin. Green Sust. Chem. 5, 12-16.
[26] Knez, Ž., Pantić, M., Cör, D., Novak, Z., & Hrnčič, M.K. (2019). Are Supercritical Fluids Solvents for the Future?. Chem. Eng. Process. 141, 107532.
[27] Soh, S.H., & Lee, L.Y. (2019). Microencapsulation and Nanoencapsulation Using Supercritical Fluid (SCF) Techniques. Pharmaceutics, 11(1) 21.
[28] Zhou, X., Zhu, X., Wang, B., Li, J., Liu, Q., Gao, X., Sirkar, K.K., & Chen, D., Continuous Production of Drug Nanocrystals by Porous Hollow Fiber-Based Anti-Solvent Crystallization. J. Membrane Sci. 564, 682-690.
[29] Maghsoodi, M., Montazam, S.H., Rezvantalab, H., & Jelvehgari, M. (2020). Response Surface Methodology for Optimization of Process Variables of Atorvastatin Suspension Preparation by Microprecipitation Method Using Desirability Function. Pharm. Sci. 26(1) 61-74.
[30] Enteshari, S. & Varshosaz, J. (2018). Solubility Enhancement of Domperidone by Solvent Change in Situ Micronization Technique. Adv. Biomed. Res. 7, 109.
[31] Rasenack, N., & Müller, B.W. (2002). Dissolution Rate Enhancement by in Situ Micronization of Poorly Water-Soluble Drugs. Pharm. Res. 19(12) 1894-1900.
[32] Bahr, M.N., Angamuthu, M., Leonhardt, S., Campbell, G., & Neau, S.H. (2021). Rapid Screening Approaches for Solubility Enhancement, Precipitation Inhibition and Dissociation of a Co-Crystal Drug Substance Using High Throughput Experimentation. J. Drug Deliv. Sci. Tech. 61, 102196.
[33] Ala’A, D.N., & Al-Khedairy, E.B.H. (2019). Formulation and Evaluation of Silymarin Microcrystals by in Situ Micronization Technique. Iraqi J. Pharm. Sci. 28(1) 1-16.
[34] Boonkanokwong, V., Khinast, J.G., & Glasser,  B.J. (2021). Scale-up and Flow Behavior of Cohesive Granular Material in a Four-Bladed Mixer: Effect of System and Particle Size. Adv. Powder Technol. 32(12) 4481-4495.
[35] Csiszar, E., Szabo, Z., Balogh, O., Fekete, E., & Koczka, K. (2021). The Role of the Particle Size Reduction and Morphological Changes of Solid Substrate in the Ultrasound-Aded Enzymatic Hydrolysis of Cellulose. Ultrason. Sonochem. 78, 105711.
[36] Hussain, Z., & Sahudin, S. (2016). Preparation, Characterisation and Colloidal Stability of Chitosan - Tripolyphosphate Nanoparticles: Optimisation of Formulation and Process Parameters. Int. J. Pharm. Pharm. Sci. 8(3) 297-308. 
[37] Sigwadi, R., Dhlamini, S.,  Mokrani, T. , & Nonjola, P. (2017). Effect of Synthesis Temperature on Particles Size and Morphology of Zirconium Oxide Nanoparticle. J. Nano Res. 50, 18-31.
[38] Hassanzadeh, B. & Mohanazadeh, F. (2017). A New Method for the Preparation of Pure Topiramate with a Micron Particle Size. J. Particle Sci. Technol. 3(3) 169-174.
[39] Rasenack, N., Steckel, H., & Müller, B.W. (2004). Preparation of Microcrystals by in Situ Micronization. Powder Technol. 143-144, 291-296.
[40] Acamprosate calcium, retrieved June 24, 2022 from https://www.chemicalbook.com/ChemicalProductProperty_EN_CB4310705.htm.
[41] Acamprosate calcium, retrieved June 24, 2022 from https://go.drugbank.com/salts/DBSALT000002.
[42] Mason, B., Heyser, C. (2010). Acamprosate: A Prototypic Neuromodulator in the Treatment of Alcohol Dependence. CNS Neurol. Disord. - Dr. 9(1) 23-32.
[43] Plosker, G.L. (2015). Acamprosate: A Review of Its Use in Alcohol Dependence. Drugs, 75(11) 1255-1268.
[44] FDA Approves New Drug for Treatment of Alcoholism, FDA Talk Paper, Food and Drug Administration. 2004-07-29. Archived from the original on 2008-01-17. Retrieved August 15, 2009 from https://www.accessdata.fda.gov/drugsatfda_docs/nda/2004/21-431_Campral.cfm.
[45] Chuacharoen, T., Prasongsuk, S., & Sabliov, C.M. (2019). Effect of Surfactant Concentrations on Physicochemical Properties and Functionality of Curcumin Nanoemulsions Under Conditions Relevant to Commercial Utilization. Molecules, 24(15) 2744.
[46] Wang, C., Cui, B., Guo, L., Wang, A., Zhao, X., Wang, Y., Sun, C., Zeng, Z., Zhi, H., Chen, H., Liu, G, & Cui, H. (2019). Fabrication and Evaluation of Lambda-Cyhalothrin Nanosuspension by One-Step Melt Emulsification Technique. Nanomaterials-Basel, 9(2) 145.
[47] Kirankumar, A., Mamatha, B., Sasikala, M., Monika, S., Ranganayakulu, D. (2013). Validated UV Spectrophotometric Method Development AndStability Studies of Acamprosate Calcium in Bulk and Tablet Dosage Form, Int. J. PharmTech Res. 5(3) 1241-1246.