Preview

Proceedings of the Voronezh State University of Engineering Technologies

Advanced search

In vitro release studies of rilpivirine from in situ forming polymeric implants in buffer solution and in a gel phantom of muscle tissue

https://doi.org/10.20914/2310-1202-2023-4-70-75

Abstract

Development of in situ forming implants (ISFI) based on PLGA polymers is one of the most promising approaches to long-acting injectables. Evaluation of the drug release rate from such depot formulations requires methods that most closely simulate in vivo conditions. Gel phantoms mimic the elastic properties of muscle tissue and appear to be a promising replacement for conventional methods using physiologically relevant buffer solutions. Accordingly, the aim of the study was to select the optimal composition for the gel phantom formation and evaluate the effect of the phantom matrix on the release rate of rilpivirin used as a model drug from the PLGA ISFI. According to the results of the study, a 1% agarose gel was the best suited for a tissue phantom preparation and implant formation. It was also shown that the release profile of rilpivirin from the ISFI matrix depended on how the implant was formed (in a gel or freely in buffer). In the case of a phantom, the structure of the implant was less porous and retained its shape for 28 days of incubation at 37 °C. During this period, the ISFI formed in an agarose gel released considerably less rilpivirin compared to the ISFI formed without gel (11% vs 80%).

About the Authors

Y. V. Ulianova
D. Mendeleev University of Chemical Technology of Russia
Russian Federation

Cand. Sci. (Chem.), assistant, chemistry and technology of biomedical preparations department, Miusskaya square 9, Moscow, 125047, Russia



Y. V. Ermolenko
D. Mendeleev University of Chemical Technology of Russia

Cand. Sci. (Chem.), associate professor, chemistry and technology of biomedical preparations department, Miusskaya square 9, Moscow, 125047, Russia



L. V. Vanchugova
A.V. Topchiev Institute of Petrochemical Synthesis Russian Academy of Sciences

Cand. Sci. (Chem.), leading researcher, laboratory of chemistry of polyelectrolytes and biomedical polymers, Leninsky prospect 29, Moscow, 119991, Russia



A. V. Mityukov
A.V. Topchiev Institute of Petrochemical Synthesis Russian Academy of Sciences

Cand. Sci. (Chem.), junior researcher, laboratory of polymer rheology, Leninsky prospect 29, Moscow, 119991, Russia



S. E. Gelperina
D. Mendeleev University of Chemical Technology of Russia

Dr. Sci. (Chem.), professor, chemistry and technology of biomedical preparations department, Miusskaya square 9, Moscow, 125047, Russia



References

1. Ibrahim T.M., El-Megrab N.A., El-Nahas H.M. Optimization of injectable PLGA in-situ forming implants of anti-psychotic risperidone via Box-Behnken Design. Journal of Drug Delivery Science and Technology. 2020. vol. 58. pp. 101803.

2. Ibrahim T.M., El-Megrab N.A., El-Nahas H.M. An overview of PLGA in-situ forming implants based on solvent exchange technique: effect of formulation components and characterization. Pharmaceutical Development and Technology. 2021. vol. 26. no. 7. pp. 709-728.

3. Muddineti O. S., Omri A. Current trends in PLGA based long-acting injectable products: The industry perspective. Expert Opinion on Drug Delivery. 2022. vol. 19. no. 5. pp. 559-576.

4. Pandya A., Vora L., Umeyor C., Surve D. et al. Polymeric in situ forming depots for long-acting drug delivery systems. Advanced Drug Delivery Reviews. 2023. P. 115003. doi: 10.1016/j.addr.2023.115003

5. Wang X., Burgess D.J. Drug release from in situ forming implants and advances in release testing. Advanced Drug Delivery Reviews. 2021. vol. 178. pp. 113912. doi: 10.1016/j.addr.2021.113912

6. Kožák J., Rabišková M., Lamprecht A. In-vitro drug release testing of parenteral formulations via an agarose gel envelope to closer mimic tissue firmness. International Journal of Pharmaceutics. 2021. vol. 594. pp. 120142. doi: 10.1016/j.ijpharm.2020.120142

7. Patel R.B., Solorio L., Wu H., Krupka T. et al. Effect of injection site on in situ implant formation and drug release in vivo. Journal of controlled release. 2010. vol. 147. №. 3. pp. 350-358. doi: 10.1016/j.jconrel.2010.08.020

8. Sun Y., Jensen H., Petersen N.J., Larsen S.W. et al. Concomitant monitoring of implant formation and drug release of in situ forming poly (lactide-co-glycolide acid) implants in a hydrogel matrix mimicking the subcutis using UV–vis imaging. Journal of pharmaceutical and biomedical analysis. 2018. vol. 150. pp. 95-106. doi: 10.1016/j.jpba.2017.11.065

9. Klose D., Azaroual N., Siepmann F., Vermeersch G. et al. Towards more realistic in vitro release measurement techniques for biodegradable microparticles. Pharmaceutical research. 2009. vol. 26. pp. 691-699.

10. Mathur A.B., Collinsworth A.M., Reichert W.M., Kraus W.E. et al. Endothelial, cardiac muscle and skeletal muscle exhibit different viscous and elastic properties as determined by atomic force microscopy. Journal of biomechanics. 2001. vol. 34. no. 12. pp. 1545-1553. doi: 10.1016/S0021-9290(01)00149-X

11. Lozinsky V.I. Cryogels on the basis of natural and synthetic polymers: preparation, properties and application. Russian Chemical Reviews. 2002. vol. 71. no. 6. pp. 489-511. doi: 10.1070/RC2002v071n06ABEH000720

12. Solorio L., Babin B.M., Patel R.B., Mach J. et al. Noninvasive characterization of in situ forming implants using diagnostic ultrasound. Journal of Controlled Release. 2010. vol. 143. no. 2. pp. 183-190. doi: 10.1016/j.jconrel.2010.01.001

13. Kumskova N., Ermolenko Y., Osipova N., Semyonkin A. et al. How subtle differences in polymer molecular weight affect doxorubicin-loaded PLGA nanoparticles degradation and drug release. Journal of microencapsulation. 2020. vol. 37. no. 3. pp. 283-295.

14. Ye F., Larsen S.W., Yaghmur A., Jensen H. et al. Drug release into hydrogel-based subcutaneous surrogates studied by UV imaging. Journal of pharmaceutical and biomedical analysis. 2012. vol. 71. pp. 27-34. doi: 10.1016/j.jpba.2012.07.024

15. Li Z., Mu H., Larsen S.W., Jensen H. et al. An in vitro gel-based system for characterizing and predicting the long-term performance of PLGA in situ forming implants. International Journal of Pharmaceutics. 2021. vol. 609. pp. 121183. doi: 10.1016/j.ijpharm.2021.121183

16. Bassand C., Verin J., Lamatsch M., Siepmann F., et al. How agarose gels surrounding PLGA implants limit swelling and slow down drug release. Journal of Controlled Release. 2022. vol. 343. pp. 255-266. doi: 10.1016/j.jconrel.2022.01.028

17. Lefol L.A., Bawuah P., Zeitler J.A., Verin J. et al. Drug release from PLGA microparticles can be slowed down by a surrounding hydrogel. International Journal of Pharmaceutics: X. 2023. vol. 6. pp. 100220. doi: 10.1016/j.ijpx.2023.100220

18. Larsen C., Larsen S.W., Jensen H., Yaghmur A. et al. Role of in vitro release models in formulation development and quality control of parenteral depots. Expert opinion on drug delivery. 2009. vol. 6. №. 12. pp. 1283-1295. doi: 10.1517/17425240903307431

19. Ulianova Y., Ermolenko Y., Tkachenko S., Trukhan V. et al. Tuning the release rate of rilpivirine from PLGA-based in situ forming implants. Polymer Bulletin. 2023. vol. 80. no. 10. pp. 11401-11420.

20. Hopkins K.A., Vike N., Li X., Kennedy J.et al. Noninvasive characterization of in situ forming implant diffusivity using diffusion-weighted MRI. Journal of Controlled Release. 2019. vol. 309. pp. 289-301. doi: 10.1016/j.jconrel.2019.07.019


Review

For citations:


Ulianova Y.V., Ermolenko Y.V., Vanchugova L.V., Mityukov A.V., Gelperina S.E. In vitro release studies of rilpivirine from in situ forming polymeric implants in buffer solution and in a gel phantom of muscle tissue. Proceedings of the Voronezh State University of Engineering Technologies. 2023;85(4):70-75. (In Russ.) https://doi.org/10.20914/2310-1202-2023-4-70-75

Views: 249


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2226-910X (Print)
ISSN 2310-1202 (Online)