Process Factors Affecting the Preparation and Characterization of Dutasteride Nanosuspension

Authors

  • Shaimaa N. Abd-Alhammid Department of Pharmaceutics, College of Pharmacy, University of Baghdad, Baghdad, Iraq.
  • Rusul Wahhab Kadhum Department of Pharmaceutics, College of Pharmacy, University of Babylon, Babylon, Iraq.

DOI:

https://doi.org/10.31351/vol34iss1pp35-48

Abstract

Dutasteride, a synthetic compound belonging to the 4-azasteroid class, functions as a selective and competitive inhibitor of both type 1 and type 2 5-alpha-reductase enzymes. It has been approved for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men. It is Categorized within BCS class II due to its limited aqueous solubility. Dutasteride is available only as a soft gelatin capsule, and the oral bioavailability of this dosage form is approximately 60%. This study's main objective was to create and characterize dutasteride nanoparticles that would enhance their solubility and release rate. The approach utilized in the study consisted of generating a nanosuspension through the solvent/antisolvent precipitation method employing different stabilizers at different concentrations. The research investigated how various process factors affected the particle size and PDI of selected dutasteride nanosuspension formulas. The assessment parameters included particle size, polydispersity index, entrapment efficiency (EE), and in-vitro dissolution patterns. These parameters collectively aided in determining the optimized dutasteride nanosuspension formula. The resulting optimized formula, consisting of 0.5% w/v soluplus as a stabilizer and a solvent/antisolvent volume ratio of 1:10, yielded a particle size of 73.24 nm, and a polydispersity index of 0.184. In vitro dissolution studies revealed that the optimized formulation enhanced the dissolution rate of dutasteride significantly compared to pure drug, it displayed complete release of the drug within 15. The most favorable formulation underwent compatibility testing using FTIR, an investigation of surface morphology with a Field Emission Scanning Electron Microscope (FESEM), and an examination of its crystalline structure via XRPD analysis. The outcome demonstrates that the utilization of the solvent anti-solvent method in the production of dutasteride nanoparticles demonstrates its effectiveness in improving the dissolution rate of dutasteride.

How to Cite

1.
Shaimaa N. Abd-Alhammid, Rusul Wahhab Kadhum. Process Factors Affecting the Preparation and Characterization of Dutasteride Nanosuspension. Iraqi Journal of Pharmaceutical Sciences [Internet]. 2025 Mar. 29 [cited 2025 Apr. 1];34(1):35-48. Available from: https://bijps.uobaghdad.edu.iq/index.php/bijps/article/view/3007

Publication Dates

Received

2023-09-25

Revised

2023-10-12

Accepted

2023-11-29

Published Online First

2025-03-29

References

Madersbacher S, Sampson N, Culig Z. Pathophysiology of Benign Prostatic Hyperplasia and Benign Prostatic Enlargement. Karger Journal. 2019; 65: 458-464. DOI: 10.1159/00049628.

Sakhri S, Gooren LJ. Safety aspects of androgen treatment with 5α-dihydrotestosterone. Andrologia. 2007;39: 216–22.

Bernice Asiedu, Yvonne Anang, Adraina Nyarko, Derek Amartey Doku, Brodrick Y. Amoah, Sheila Santa, Robert A. Ngala & George A. Asare (2017): The role of sex steroid hormones in benign prostatic hyperplasia, The Aging Male, DOI: 10.1080/13685538.2016.1272101

Tiwari A, Krishna NS, Nanda K and Chugh A. Benign prostatic hyperplasia: an insight into current investigational medical therapies. Exp. Opin. Invest. Drugs 2005 14: 1359-1372.

Dull P, Reagan Jr RW and Bahnson RR. Managing benign prostatic hyperplasia. Am. Fam. Physician. 2002; 66: 77-84

Li Y, Ma J, Qin X, Yi Hu C. The Efficacy and Safety of Dutasteride and Finasteride in Patients with Benign Prostatic Hyperplasia. Translational Andrology and Urology Journal. 2022; 11 (3): 313-324. Doi: 10.21037/tau-22-5.

Sakhri S, Gooren LJ. Safety aspects of androgen treatment with 5α-dihydrotestosterone. Andrologia. 2007;39: 216–22.

Eun HC, Kwon OS, Yeon JH, et al. Efficacy, safety, and tolerability of dutasteride 0.5 mg once daily in male patients with male pattern hair loss: A randomized, double-blind, placebo-controlled, phase III study. J Am Acad Dermatol. 2010;63: 252–8

Treatments for Benign Prostatic Hyperplasia. Agency for Healthcare Research and Quality (US); Rockville (MD):02, 2004.

Zito PM, Bistas KG, Syed K. StatPearls. StatPearls Publishing; Treasure Island (FL): 25, 2022. Finasteride.

Shin JW, Chung EH, Kim MB, Kim TO, Kim WI, Huh CH. Evaluation of long-term efficacy of finasteride in Korean men with androgenetic alopecia using the basic and specific classification system. J Dermatol. 2019 ;46(2):139-143.

Lee DH, Yeom DW, Song YS, Cho HR, Choi YS, Kang MJ, ChoiYW. Improved oral absorption of dutasteride via Soluplus®-based supersaturable self-emulsifying drug delivery system(S-SEDDS). International journal of pharmaceutics. 2015; 478(1):341-347.

Siddalingam R, Subramaniam P. Self-Nanoemulsifying Drug Delivery Systems of Poorly Soluble Drug Dutasteride: Formulation and In-Vitro characterization. J App Pharm Sci, 2017; 7 (04): 011-022.

Barret ER. Nanosuspensions in drug delivery. Nat Rev. 2004;3: 785–96.

Ma Y, Gong Z, Gao P, Wang Y. Nanosuspensions technology as a master key for nature products drug delivery and In vivo fate. European Journal of Pharmaceutical Sciences. 2023; 185: 1-17. https://doi.org/10.1016/j.ejps.2023.106425.

Grau MJ, Kayser O, Muller RH. Nanosuspensions of poorly soluble drugs reproducibility of small-scale production. Int J Pharm. 2000;196: 155–7.

Elsharkawy EE. Nanotechnology Applications of Pesticide Formulations. Nanomedicine. 2020;3(c):1029.

Chingunpituk J. Nanosuspension technology for drug delivery. Walailak J Sci Tech. 2007;4: 139–53.

Pu X, Sun J, Li M, He Z. Formulation of nanosuspensions as a new approach for the delivery of poorly soluble drugs. Curr Nanosci. 2009;5: 417–27.

Al-lami MS, Oudah MH, Rahi FA. Preparation and characterization of domperidone nanoparticles for dissolution improvement. Iraqi Journal of Pharmaceutical Sciences. 2018;27(1):39-52

Mansour Mansouri, Hamid Reza Pouretedal , Vida Vosoughi .Preparation and Characterization of Ibuprofen Nanoparticles By Usingsolvent/ Antisolvent Precipitation The Open Conference Proceedings Journal. 2011; 2: 88-94.

Hergert, W. and Wriedt, T. (eds.) 2012. The Mie Theory: Baiscs and Applications. Springer, 2012

Muhesen R A, Rajab NA. Formulation and characterization of olmesartan medoxomil as a nanoparticle. Research J. Pharm. and Tech. 2023; 16 (7): 1-7.

Toma NM, Abdulrasool AA. Formulation and Evaluation of Montelukast Sodium Nanoparticles for Transdermal Delivery. International Journal of Drug Delivery Technology. 2021;11(2):530-538.

Noor AH, Ghareeb MM. Formulation and Evaluation of Ondansetron HCl Nanoparticles for Transdermal Delivery. Iraqi Journal of Pharmaceutical Science.2020; 29 (2).

Lee, D.H., et al., Improved oral absorption of dutasteride via Soluplus1-based supersaturable self-emulsifying drug delivery system (S-SEDDS). Int J Pharmaceut 2014, http://dx.doi.org/10.1016/j.ijpharm.2014.11.060.

Abbas IK. Rajab NA. Formulation and In-Vitro Evaluation of Darifenacin Hydrobromide as Buccal Films. International Journal of Drug Delivery Technology.2019; 28 (2).

Srivastava R. Synthesis and characterization techniques of nanomaterials. Int J Green Nanotechnol. 2012;4(1):17–27.

Jacobsen AC, Ejskjær L, Brandl M, Holm R, Bauer-Brandl A. Do phospholipids boost or attenuate drug absorption? In vitro and in vivo evaluation of mono- and diacyl phospholipid-based solid dispersions of celecoxib. Journal of Pharmaceutical Sciences. 2021;110(1):198–207.

Al-Mahmood, A. A., & Alhammid, S. N. A. 2022. Formulation and characterization of floating biphasic tablet consisting of cefdinir nanosuspension. International Journal of Health Sciences, 6(S4), 12154–12172.

Al-Sarraf MA, Hussein AA, Al-Kinani KK. Formulation, Characterization, and Optimization of Zaltoprofen Nanostructured Lipid Carriers (NLCs). International Journal of Drug Delivery Technology. 2021;11(2):434-442.

Alhagiesa AW, Ghareeb MM. Formulation and Characterization of Nimodipine Nanoparticles for the Enhancement of Solubility and Dissolution rate. Iraqi Journal of Pharmaceutical Science .2021;30(2):143-152.

Al-Obaidy RAR, Rajab NA. Preparation and In-vitro Evaluation of Darifenacin HBr as Nanoparticles Prepared as Nanosuspension. International Journal of Drug Delivery Technology. 2022;12(2):775-781.

Jassim ZE, Hussein AA. Formulation and evaluation of clopidogrel tablet incorporating drug nanoparticles. Int J Pharm Pharm Sci.2014;6(1):838–51.

Liu D, Xu H, Tian B, Yuan K, Pan H, Ma S, et al. Fabrication of carvedilol nanosuspensions through the anti-solvent precipitation ultrasonication method for the improvement of dissolution rate and oral bioavailability. AAPS Pharm SciTech. 2012;13(1):295–304.

Dalvi, S., Dave, R., 2009. Controlling Particle Size of a Poorly Water-Soluble Drug Using Ultrasound and Stabilizers in Antisolvent Precipitation. Ind. Eng. Chem. Res. 48, 7581-7593.

Zhao, H., et al., 2009a. Facile preparation of danazol nanoparticles by high-gravity anti-solvent precipitation (HGAP) method. Chinese J. Chem. Eng. 17, 318-323.

RH. Chen,M.L Tsaih, Effect of temperature on the intrinsic viscosity and coninitial burst release of drug [29-31]. This is partly associated with formation of chitosans in dilute HCI solution, International Journal of Biological the low mechanical strength of the chitosan/TPP particles, and the Macromolecules 23 1998: 135-141.

Kumar P, Arivuchelvan A, Jagadeeswaran A, Subramanian N, Kumar C, Mekala P. Formulation, optimization and evaluation of enrofloxacin solid lipid nanoparticles for sustained oral delivery. Asian J Pharm Clin Res 2015;8: 231-6 Lee J, Choi JY, Park CH. Characteristics of polymers enabling nanocomminution of water – insoluble drugs. Int J of Pharmaceuticals 2008; 355.

Lee J, Choi JY, Park CH. Characteristics of polymers enabling nanocomminution of water – insoluble drugs. Int J of Pharmaceuticals 2008; 355.

Zuo J, Gao Y, Bou-Chacra N, Löbenberg R. Evaluation of the DDSolver software applications. Biomed Res Int. 2014;2014: 1-9.

Taghi HS, Abdulbaqi MR, Jabar EG. Enhancement Solubilization of Dutasteride using Microsponge Formulation. International Journal of Drug Delivery Technology. 2020; 10(1): 60-67.

Muhammed SA and Al-Kinani KK. Formulation and in vitro evaluation of meloxicam as a self microemulsifying drug delivery system [version 2; peer review: 2 approved] F1000Research 2023, 12:315.

https://doi.org/10.12688/f1000research.130749.2.

Al-hassnaui LS eldin, Rahi FA, Al-lami MS, V. Dissolution Enhancement of Danazol Nanoparticles prepared by Nanoprecipitation Method. Kerbala journal of pharmacy and pharmaceutical science. 2021;1(19).

Ingham B. X-ray scattering characterisation of nanoparticles. Crystallogr Rev. 2015;21(4):229–303.

Rashid AM, Abd-Alhammid SN. Formulation and characterization of itraconazole as nanosuspension dosage form for enhancement of solubility. Iraqi J Pharm Sci. 2019;28(2):124–133.

Seçilmiş Canbay H, Polat M, Doğantürk M. Study of Stability and Drug-Excipient Compatibility of Estriol. Bilge Int J Sci Technol Res. 2019;3: 102-7.

Downloads

Published

2025-03-29