Skip to main content
Log in

Investigation of Factors Affecting Particle Size Distribution and Sustained Release of a Water-Soluble Drug from Cellulose Derivatives Microspheres

  • Original Article
  • Published:
Chemistry Africa Aims and scope Submit manuscript

Abstract

Microspheres loaded by 2-aminopyrimidine (2-AP) and based on cellulose derivatives as polymeric matrices: ethylcellulose (EC) and cellulose acetate butyrate (CAB), were prepared by double emulsion solvent evaporation method (w/o/w). The main objective of this research is to conceptualize the fabrication of new formulations with high encapsulation efficiency and a large range of size for a controlled drug release of a water-soluble drug. The effects of the process variables, namely, nature of the matrix, stirring speed, surfactant nature and concentration on the mean particle size and distribution, drug loaded, encapsulation efficiency and drug release were investigated. The microspheres were characterized by SEM, optical microscopy, FT-IR spectroscopy and the size and size distribution (δ) were determined. SEM images showed spherical and porous microspheres with different structures. We have obtained systems with large ranges of size (d32, 45–219 µm with EC; d32, 37–160 µm with CAB using Polyvinyl alcohol (PVA) as emulsifier; and d32, 294–779 µm with Tween 80) by modifying the process parameters. Furthermore, the mean diameter d32 and the dispersion can be controlled particularly by stirring speed of emulsion and the emulsifier nature and concentration. The drug entrapment and encapsulation efficiency were improved by controlling certain factors, especially by using PVA as a stabilizer in the continuous phase, by increasing PVA concentration (2% PVA) and when using EC as a matrix. The drug release was established in simulated gastric medium at pH 1.2 and 37 °C by UV–Vis analysis to estimate the drug content. The kinetics results revealed that the drug release is governed by the diffusion mechanism and the release rate can be adjusted by varying the encapsulation factors that have a significant effect on the particle size and size distribution.

Graphical abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Gulcan M, Doğru U, Öztürk G, Levent A, Akbaş E (2014) Fluorescence properties and electrochemical behavior of some Schiff bases derived from N-amino-pyrimidine. J Fluoresc. https://doi.org/10.1007/s10895-013-1303-x

    Article  PubMed  Google Scholar 

  2. Kumar S, Deep A, Narasimhan B (2015) Pyrimidine derivatives as potential agents acting on central nervous system. Cent Nerv Syst Agents Med Chem. https://doi.org/10.2174/1871524914666140923130138

    Article  PubMed  Google Scholar 

  3. Shi M, Wang L, Zhang L, Wang K et al (2021) Synthesis and evaluation of antitumor activities of 4-selenopyrimidine derivatives. Nucleosides Nucleotides Nucleic Acids. https://doi.org/10.1080/15257770.2020.1833342

    Article  PubMed  Google Scholar 

  4. Ghannoum M, Abu Elteen K, El-Rayyes NR (1989) Antimicrobial activity of some 2-aminopyrimidines. Microbios 60:23–33

    CAS  PubMed  Google Scholar 

  5. Lindsey EA, Worthington RJ, Alcaraz C, Melander C (2012) 2-Aminopyrimidine as a novel scaffold for biofilm modulation. Org Biomol Chem. https://doi.org/10.1039/c2ob06871k

    Article  PubMed  PubMed Central  Google Scholar 

  6. Ozkan G, Franco P, De Marco I, Xiao J et al (2019) A review of microencapsulation methods for food antioxidants: principles, advantages, drawbacks and applications. Food Chem. https://doi.org/10.1016/j.foodchem.2018.07.205

    Article  PubMed  Google Scholar 

  7. Amasya G, Badilli U, Aksu B, Tarimci N (2016) Quality by design case study 1: design of 5-fluorouracil loaded lipid nanoparticles by the W/O/W double emulsion-solvent evaporation method. Eur J Pharm Sci. https://doi.org/10.1016/j.ejps.2016.01.003

    Article  PubMed  Google Scholar 

  8. Iqbal M, Zafar N, Fessi H, Elaissari A (2015) Double emulsion solvent evaporation techniques used for drug encapsulation. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2015.10.057

    Article  PubMed  Google Scholar 

  9. Giri TK, Choudhary C, Ajazuddin AA, Badwaik H et al (2013) Prospects of pharmaceuticals and biopharmaceuticals loaded microparticles prepared by double emulsion technique for controlled delivery. Saudi Pharm J. https://doi.org/10.1016/j.jsps.2012.05.009

    Article  PubMed  Google Scholar 

  10. Chong-Cerda R, Levin L, Castro-Ríos R, Hernández-Luna CE et al (2020) Nanoencapsulated laccases obtained by double-emulsion technique. Effects on enzyme activity pH-dependence and stability. Catalysts. https://doi.org/10.3390/catal10091085

    Article  Google Scholar 

  11. Laffleur F, Krouská J, Tkacz J, Pekař M, Aghai F, Netsomboon K (2018) Buccal adhesive films with moisturizer- the next level for dry mouth syndrome. Int J Pharm. https://doi.org/10.1016/j.ijpharm.2018.08.032

    Article  PubMed  Google Scholar 

  12. Cazorla-Luna R, Notario-Pérez F, Martín-Illana A, Bedoya LM et al (2020) Development and in vitro/ex vivo characterization of vaginal mucoadhesive bilayer films based on ethylcellulose and biopolymers for vaginal sustained release of Tenofovir. Biomacromol. https://doi.org/10.1021/acs.biomac.0c00249

    Article  Google Scholar 

  13. Notario-Pérez F, Cazorla-Luna R, Martín-Illana A, Galante J et al (2020) Design, fabrication and characterisation of drug-loaded vaginal films: state-of-the-art. J Control Release. https://doi.org/10.1016/j.jconrel.2020.08.032

    Article  PubMed  Google Scholar 

  14. Jabar A, Madni A, Bashir S, Tahir N et al (2021) Statistically optimized pentazocine loaded microsphere for the sustained delivery application: Formulation and characterization. PLoS ONE. https://doi.org/10.1371/journal.pone.-0250876

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chen W, Palazzo A, Hennink WE, Kok RJ (2017) Effect of particle size on drug loading and release kinetics of gefitinib-loaded PLGA microspheres. Mol Pharm. https://doi.org/10.1021/acs.molpharmaceut.6b00896

    Article  PubMed  PubMed Central  Google Scholar 

  16. Kumar A, Chanda S, Agarwal S, Singh M et al (2021) Formulation and evaluation of gastro-retentive Tinidazole loaded floating microsphere for sustained release. Mater Today Proc. https://doi.org/10.1016/j.matpr.2021.05.616

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mouffok M, Mesli A, Abdelmalek I, Gontier E (2016) Effect of formulation parameters on encapsulation efficiency and release behavior of p-aminobenzoic acid-loaded ethylcellulose microspheres. J Serb Chem Soc. https://doi.org/10.2298/JSC160308068M

    Article  Google Scholar 

  18. Du L, Liu S, Hao G, Zhang L et al (2021) Preparation and release profiles in vitro/vivo of galantamine pamoate loaded poly (lactideco-glycolide) (PLGA) microspheres. Front Pharmacol. https://doi.org/10.3389/fphar.2020.619327

    Article  PubMed  PubMed Central  Google Scholar 

  19. Pang L, Gao Z, Feng H, Wang S (2019) Cellulose based materials for controlled release formulations of agrochemicals: a review of modifications and applications. J Control Release. https://doi.org/10.1016/j.jconrel.2019.11.004

    Article  PubMed  PubMed Central  Google Scholar 

  20. Zhou J, Walker J, Ackermann R, Olsen K et al (2020) Effect of manufacturing variables and raw materials on the composition-equivalent PLGA microspheres for 1 month controlled release of leuprolide. Mol Pharm. https://doi.org/10.1021/acs.molpharmaceut.9b01188

    Article  PubMed  PubMed Central  Google Scholar 

  21. Hwisa NT, Katakam P, Chandu B, Adiki SK (2013) Solvent evaporation techniques as promising advancement in microencapsulation. Vedic Res Int Biolog Medicin Chem. https://doi.org/10.14259/bmc.v1i1.29

    Article  Google Scholar 

  22. Thakare M, Israel B, Garner S, Ahmed H et al (2017) Nonionic surfactant structure on the drug release, formulation and physical properties of ethylcellulose microspheres. J Pharm Dev Technol. https://doi.org/10.1080/10837450.2016.1221431

    Article  Google Scholar 

  23. Hinze JO (1955) Fundamentals of the hydrodynamic mechanism of splitting in dispersion processes. AIChE J. https://doi.org/10.1002/aic.690010303

    Article  Google Scholar 

  24. Jégat C, Taverdet JL (2000) Stirring speed influence study on the microencapsulation process and on the drug release from microcapsules. Polym Bull. https://doi.org/10.1007/s002890050612

    Article  Google Scholar 

  25. Alexandridou S, Kiparissides C (1994) Production of oil-containing polyterephthalamide microcapsules by interfacial polymerization. An experimental investigation of the effect of process variables on the microcapsule size distribution. J Microencapsul. https://doi.org/10.3109/02652049409051110

    Article  PubMed  Google Scholar 

  26. Kaczmarski K, Bellot JC (2003) Effect of particle-size distribution and particle porosity changes on mass-transfer kinetics. Acta Chromatogr 13(13):22–37

    CAS  Google Scholar 

  27. El Bahri Z, Taverdet J-L (2007) Elaboration and characterisation of microparticles loaded by pesticide model. Powder Technol. https://doi.org/10.1016/j.powtec.2006.10.036

    Article  Google Scholar 

  28. Subedi G, Shrestha AK, Shakya S (2016) Study of effect of different factors in formulation of micro and nanospheres with solvent evaporation technique. Open Pharm Sci J. https://doi.org/10.2174/1874844901603010182

    Article  Google Scholar 

  29. Merdoud A, Mouffok M, Mesli A, Chafi N et al (2020) In vitro release study of 2-aminobenzothiazole from microspheres as drug carriers. J Serb Chem Soc. https://doi.org/10.2298/JSC190326132M

    Article  Google Scholar 

  30. Vankova N, Tcholakova S, Denkov N-D, Ivanov I-B et al (2007) Emulsification in turbulent flow 1. Mean and maximum drop diameters in inertial and viscous regimes. J Colloid Interface Sci. https://doi.org/10.1016/j.jcis.2007.03.059

    Article  PubMed  Google Scholar 

  31. Silverstein RM, Bassler GC, Morill TC (1981) Spectrometric identification of organic compounds, 4th edn. Wiley, New-York

    Google Scholar 

  32. Higuchi T (1963) Mechanism of sustained-action medication. Theoretical analysis of rate of release of solid drugs dispersed in solid matrices. J Pharm Sci. https://doi.org/10.1002/jps.2600521210

    Article  PubMed  Google Scholar 

  33. Korsmeyer RW, Peppas NA (1984) Solute and penetrant diffusion in swellable polymers III. Drug release from glassy P(HEMA-co-NVP) copolymers. J Control Release. https://doi.org/10.1016/0168-3659(84)90001-4

    Article  Google Scholar 

  34. Dash S, Murthy PN, Nath L, Chowdhury P (2010) Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol Pharm 67(3):217–223

    CAS  PubMed  Google Scholar 

  35. Crank J (1973) The mathematics of diffusion, 2nd edn. Brunel University Uxbridge, London

    Google Scholar 

  36. Albert A, Sergent E (1971) The determination of ionization constants. Chapman and Hall, Great Britain

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Meryem Mouffok.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mouffok, M., Abdelmalek, I., Mesli, A. et al. Investigation of Factors Affecting Particle Size Distribution and Sustained Release of a Water-Soluble Drug from Cellulose Derivatives Microspheres. Chemistry Africa 6, 163–173 (2023). https://doi.org/10.1007/s42250-022-00323-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s42250-022-00323-6

Keywords

Navigation