DEVELOPMENT OF HEMOSTATIC GELATIN SPONGE WITH MIRAMISTIN USING THE "QUALITY BY DESIGN" METHOD (QbD)
DOI:
https://doi.org/10.11603/2312-0967.2023.3.14168Keywords:
hemostatic sponge, gelatin, miramistin, technology, mathematical planning of the experimentAbstract
The aim of the work. Development of the composition of a medical/hemostatic sponge based on gelatin, study of the influence of miramistin and auxiliary substances on critical quality attributes.
Materials and Methods. During the experimental study, the active pharmaceutical ingredient Miramistin was used, as well as auxiliary substances medical gelatin, propylene glycol, and formaldehyde. Hemostatic sponges were obtained using the lyophilization method and examined according to six reviews: thickness, cm; pH; appearance, points; in vitro degradation, %; percentage of water absorption, %; time of complete dissolution, hours.
Results and Discussion. Using the assessment of the quality target product profile the quality and efficiency of the developed hemostatic sponges were determined. At the first stage of research, a quality target product profile was developed. Critical quality attributes are time of complete dissolution and percentage of water absorption. On the basis of previous studies, the influence of independent variables, that is, the amount of medical gelatin (x1) and the amount of aldehyde (x2), on the dependent variables was studied. The results clearly indicate that all dependent variables are strongly related to the selected independent variables.
Optimization of the composition of hemostatic sponges with miramistin was carried out using the quadratic model of the response surface. As a result of a number of conducted experiments and based on the limitations set by independent variables using the Design-Expert 10.0.0 program, the composition of the developed form with miramistin for external use was proposed and scientifically substantiated.
Conclusions. An experimental study was conducted on the development of a hemostatic sponge with miramistin for external use. The effect of the amount of auxiliary substances on the technological and physico-chemical indicators was studied, and their optimal amount was selected, which ensures the compliance of the hemostatic sponge with the quality target product profile. As a result of a number of conducted experiments and based on the limitations set by independent variables using the Design-Expert 10.0.0 program, the composition of the developed form with miramistin for external use was proposed and scientifically substantiated.
References
Zhao X, Guo B, Wu H, Liang Y, Ma PX. Injectable an-tibacterial conductive nanocomposite cryogels with rapid shape recovery for noncompressible hemor-rhage and wound healing. Nature Communications. 2018;9(1). DOI: https://doi.org/10.1038/s41467-018-04998-9
Johnson D, Bates Sh, Nukalo S, Staub A, Hines A, Leishman T, Michel J, Sikes D, Gegel B, Burgert J. The effects of QuikClot Combat Gauze on hemorrhage control in the presence of hemodilution and hypothermia. Annals of Medicine and Surgery. 2014;3(2): 21-5. DOI: https://doi.org/10.1016/j.amsu.2014.03.001
Gabay M. Absorbable hemostatic agents. American Journal of Health-System Pharmacy. 2006;63(13): 1244-53. DOI: https://doi.org/10.2146/ajhp060003
American College of Surgeons. Hemostatic Agents in the Surgical Toolbox. Bulletin of the American College of Surgeons, 2014;99(8): 20-8. doi: 10.1016/j.jamcollsurg.2004.03.018. DOI: https://doi.org/10.1016/j.jamcollsurg.2004.03.018
Rachal M. MedTech Dive [Internet]. FDA consults surgical device experts on down-classing certain hemostatic agents; [cited 2023 Jan 27]. Available from: https://www.medtechdive.com/news/fda-consults-surgical-device-experts-on-down-classing-certain-hemostatic-ag/555768/.
Hroshovyi TA. Mathematical planning of the experiment in conducting research in pharmacy. [Математичне планування експерименту при проведенні наукових досліджень у фармації] Ternopil: TSMU “Ukrmedknyha”; 2008. Ukrainian.
Pavliuk B, Chubka M, Hroshovyi T, Stechyshyn I. Characteristics of structured medical hemostatic sponges as a medical devices for stop bleeding and for close the wound. Pol Merkur Lekarski. 2020;22,48(288): 422-26. PMID: 33387430.
Pavliuk B, Chubka M, Hroshovyi T. The development of composition and characterization of biodegradable hemostatic and absorbable sponges for medical application. Farmacia. 2020;3,68(3): 419-25. DOI: https://doi.org/10.31925/farmacia.2020.3.6
State Pharmacopoeia of Ukraine: 3 Vol. Kharkiv: Ukrainian Scientific Pharmacopoeia Center of Qual-ity of Medicinal Products. Ed.2. Vol.3. [Державна Фармакопея України: в 3 т./ Державне підприємство «Український науковий фармакопейний центр якості лікарських засобів». – 2-е вид., Т.3]: Kharkiv: Ukrainian Scientific Pharmacopoeia Center of Quality of Medicinal Products; 2014. Ukrainian.
Vijayanand K, Deepak K. Interpreting Blood-biomaterial interactions from surface free energy and work of adhesion. Trends Biomater: Artif Organs 2005;18: 73-84.
Choi YS, Hong SR. Study on gelatin-containing artificial skin: Biomaterials. 1999;20: 409-17. DOI: https://doi.org/10.1016/S0142-9612(98)00180-X
Long H, Ma K, Xiao Z, Ren X, Yang G. Preparation and characteristics of gelatin sponges crosslinked by microbial transglutaminase. PeerJ. 2017;9,5: e3665. doi: 10.7717/peerj.3665. PMID: 28828260; PMCID: PMC5554441. DOI: https://doi.org/10.7717/peerj.3665
The United States Pharmacopoeia, 36th ed., NF 31., New York, 2013.
Guidance. Pharmaceutical development (ICH Q8). [Настанова СТ-Н 42-3.0:2011. Лікарські засоби. Фармацевтична розробка (ICH Q8)] Кyiv; 2011. Ukrainian.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 Pharmaceutical Review / Farmacevtičnij časopis
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
The authors who publish their materials in this journal agree with the following terms:
- Authors reserve the right to authorship of their work and assign to the journal the right to first publish this work under the terms of the Creative Commons Attribution License, which allows other persons to freely distribute the published work with a mandatory reference to the authors of original work and the first publication of work in this journal
. - Authors have the right to make independent extra-exclusive work agreements in the form they are published by this journal (for example, posting work in an electronic repository of an institution or publishing as part of a monograph), provided that the link to the first publication of the work in this journal is maintained.
Journal policy allows and encourages publication of manuscripts on the Internet (for example, in institutions repositories or on personal websites), both before the publication of this manuscript and during its editorial review, as it contributes to productive scientific discussion and positively affects the efficiency and dynamics of the citation of the published work (see The Effect of Open Access).
