JOURNAL OF THE CZECH PHARMACEUTICAL SOCIETY AND THE SLOVAK PHARMACEUTICAL SOCIETY

Čes. slov. farm. 2021, 70(2):66-78 | DOI: 10.5817/CSF2021-2-66

Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach

Oleksii Yakovenko1, Tetiana Kolisnyk1,*, Lena Ruban1, Natalia Fil2
1 Department of Industrial Technology of Drugs, National University of Pharmacy, Kharkiv, Ukraine
2 Department of Automation and Computer-Integrated Technologies, Kharkiv National Automobile and Highway University, Kharkiv, Ukraine

The aim of this work was to develop anti-stress compressed lozenges containing 100 mg of glycine and 250 mg of magnesium citrate obtained by the direct compression method. To choose optimal excipient composition providing the sufficient pharmaco-technical properties of the tablet blend, mechanical strength of tablets and non-disintegrating, slow-dissolving behavior of compressed lozenges during sucking, 27 experimental formulations according to fractional factorial Latin cube design were prepared and tested. The excipients used in the study were: Mannogem® EZ, Cellactose® 80 and GalenIQ™ 721 (fillers); Plasdone™ S-630, Kollidon® 90 F and Avicel® PH-101 (dry binders); Metolose® 90SH-4000SR and guar gum (gel-forming binders); PRUV®, Neusilin® US2, and Compritol® 888 CG ATO (antifriction excipients). The following parameters were investigated as responses: bulk density, Carr's index, friability, resistance to crushing, and in vitro disintegration time. ANOVA approach was applied for statistical processing, which allowed to reveal the individual effects of each excipient and several interaction effects observed for the excipient amounts used in this study. Isomalt (GalenIQ™ 721), copovidone (Plasdone™ S-630), and glyceryl behenate (Compritol® 888 CG ATO) were selected to be incorporated in the final formulation of compressed lozenges.

Keywords: compressed lozenges; glycine; magnesium citrate; stress-protective activity; formulation development; design of experiment; Analysis of variance

Received: February 28, 2021; Accepted: April 13, 2021; Published: February 1, 2021  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Yakovenko O, Kolisnyk T, Ruban L, Fil N. Formulation development of anti-stress compressed lozenges using a fractional factorial Latin cube design and ANOVA approach. Čes. slov. farm. 2021;70(2):66-78. doi: 10.5817/CSF2021-2-66.
Share...
Download citation
  • BibTeX (.bib)
  • Bookends (.ris)
  • EasyBib (.ris)
  • EndNote (.enw)
  • EndNote 8 (.xml)
  • ISI WoS (.isi)
  • Medlars (.medlars)
  • Mendeley (.ris)
  • MODS (.xml)
  • Papers (.ris)
  • RefWorks (.txt)
  • RefManager (.ris)
  • RIS (.ris)
  • MS Word (.xml)
  • Zotero (.ris)
    • Open full article

    References

    1. Zhang H., Zhang J., Streisand J. B. Oral mucosal drug delivery: clinical pharmacokinetics and therapeutic applications. Clin Pharmacokinet. 2002; 41(9), 661-680. Go to original source... Go to PubMed...
    2. Council of Europe. European Pharmacopoeia, 10th edition, Strasbourg: Council of Europe, 2019.
    3. Ashraf M., Sayeed V. A. Considerations in developing sublingual tablets - an overview. Pharm. Technol. 2014; 38(11), 38-47.
    4. Dawson D. V., Drake D. R., Hill J. R., Brogden K. A., Fischer C. L., Wertz P. W. Organization, barrier function and antimicrobial lipids of the oral mucosa. Int. J. Cosmet. Sci. 2013; 35(3), 220-223. Go to original source... Go to PubMed...
    5. Squier C. A. The permeability of oral mucosa. Crit. Rev. Oral. Biol. Med. 1991; 2(1), 13-32. Go to original source... Go to PubMed...
    6. Shinkar D. M, Dhake A. S, Setty C. M. Drug delivery from the oral cavity: a focus on mucoadhesive buccal drug delivery systems. PDA J. Pharm. Sci. Technol. 2012; 66(5), 466-500. Go to original source... Go to PubMed...
    7. Fonseca-Santos B., Chorilli M. An overview of polymeric dosage forms in buccal drug delivery: State of art, design of formulations and their in vivo performance evaluation. Mater Sci. Eng. C Mater Biol. Appl. 2018; 86, 129-143. Go to original source... Go to PubMed...
    8. Maheshwari R., Jain V., Ansari R., Mahajan S. C., Joshi G. A review on lozenges. Br. Biomed. Bull. 2013; 1, 35-43.
    9. Majekodunmi S. O. A review on lozenges. American Journal of Medicine and Medical Sciences 2015; 5(2), 99-104.
    10. Uvnäs-Moberg K., Prime D. K. Oxytocin effects in mothers and infants during breastfeeding. Infant. 2013; 9(6), 201-206.
    11. Uvnäs-Moberg K., Handlin L., Petersson M. Self-soothing behaviors with particular reference to oxytocin release induced by non-noxious sensory stimulation. Front. Psychol. 2015; 5, 1529. Go to original source... Go to PubMed...
    12. Guzmán Y. F., Tronson N. C., Jovasevic V., Sato K., Guedea A. L., Mizukami H., Nishimori K., Radulovic J. Fear-enhancing effects of septal oxytocin receptors. Nat. Neurosci. 2013; 16(9), 1185-1187. Go to original source... Go to PubMed...
    13. Kirsch P., Esslinger C., Chen Q., Mier D., Lis S., Siddhanti S., Gruppe H., Mattay V. S., Gallhofer B., Meyer-Lindenberg A. Oxytocin modulates neural circuitry for social cognition and fear in humans. J. Neurosci. 2005; 25(49), 11489-11493. Go to original source... Go to PubMed...
    14. Gundersen R. Y., Vaagenes P., Breivik T., Fonnum F., Opstad P. K. Glycine - an important neurotransmitter and cytoprotective agent. Acta Anaesthesiol. Scand. 2005; 49, 1108-1116. Go to original source... Go to PubMed...
    15. Petrat F., Boengler K., Schulz R., de Groot H. Glycine, a simple physiological compound protecting by yet puzzling mechanism(s) against ischaemia-reperfusion injury: current knowledge. Br. J. Pharmacol. 2012; 165(7), 2059-2072. Go to original source... Go to PubMed...
    16. Kawai N., Sakai N., Okuro M., Karakawa S., Tsuneyoshi Y., Kawasaki N., Takeda T., Bannai M., Nishino S. The sleep-promoting and hypothermic effects of glycine are mediated by NMDA receptors in the suprachiasmatic nucleus. Neuropsychopharmacology 2015; 40(6), 1405-1416. Go to original source... Go to PubMed...
    17. Bannai M., Kawai N. New therapeutic strategy for amino acid medicine: glycine improves the quality of sleep. J. Pharmacol. Sci. 2012; 118(2), 145-148. Go to original source... Go to PubMed...
    18. Gusev E. I., Skvortsova V. I., Dambinova S. A., Raevskiy K. S., Alekseev A. A., Bashkatova V. G., Kovalenko A. V., Kudrin V. S., Yakovleva E. V. Neuroprotective effects of glycine for therapy of acute ischaemic stroke. Cerebrovasc. Dis. 2000; 10(1), 49-60. Go to original source... Go to PubMed...
    19. El Hafidi M., Pérez I., Baños G. Is glycine effective against elevated blood pressure? Curr. Opin. Clin. Nutr. Metab. Care 2006; 9(1), 26-31. Go to original source... Go to PubMed...
    20. Imtiaz S., Ikram H., Ayaz M., Qadir M. I., Muhammad S. A. Effect of glycine: Studying memory and behavioral changes in mice. Pak. J. Pharm. Sci. 2018; 31(5), 1943-1949.
    21. Razak M. A., Begum P. S., Viswanath B., Rajagopal S. Multifarious Beneficial Effect of Nonessential Amino Acid, Glycine: A Review. Oxid Med. Cell Longev. 2017; 2017, 1716701. Go to original source... Go to PubMed...
    22. Yakovenko O., Ruban O., Devyatkina N., Devyatkina T. Study of the stress-protective effect of the combination of glycine with magnesium citrate. Norwegian Journal of development of the International Science 2020; 48, 52-58.
    23. Sartori S. B., Whittle N., Hetzenauer A., Singewald N. Magnesium deficiency induces anxiety and HPA axis dysregulation: modulation by therapeutic drug treatment. Neuropharmacology 2012; 62(1), 304-312. Go to original source... Go to PubMed...
    24. Tarasov E. A., Blinov D. V., Zimovina U. V., Sandakova E. A. Magnesium deficiency and stress: Issues of their relationship, diagnostic tests, and approaches to therapy. Ter. Arkh. 2015; 87(9), 114-122. Russian. Go to original source... Go to PubMed...
    25. Hroshovyi T. A., Martsenyuk V. P., Kucherenko L. I., Vronska L. V., Huryeyeva S. M. Mathematical planning of experiment in pharmacy. Ternopil, Ukraine: Ternopil State Medical University 2008. Ukrainian.
    26. Singh B., Kumar R., Ahuja N. Optimizing drug delivery systems using systematic "design of experiments." Part I: fundamental aspects. Crit. Rev. Ther. Drug Carrier Syst. 2005; 22(1), 27-105. Go to original source... Go to PubMed...
    27. Dennison T. J., Smith J., Hofmann M. P., Bland C. E., Badhan R. K., Al-Khattawi A., Mohammed A. R. Design of Experiments to Study the Impact of Process Parameters on Droplet Size and Development of Non-Invasive Imaging Techniques in Tablet Coating. PLoS One 2016; 11(8), e0157267. Go to original source... Go to PubMed...
    28. Politis S. N., Colombo P., Colombo G., Rekkas D. M. Design of experiments (DoE) in pharmaceutical development. Drug Dev. Ind. Pharm. 2017; 43(6), 889-901. Go to original source... Go to PubMed...
    29. Fukuda I. M., Pinto C. F. F., Moreira C. S., Saviano A. M., Lourenço F. R. Design of Experiments (DoE) applied to Pharmaceutical and Analytical Quality by Design (QbD). Braz. J. Pharm. Sci. 2018; 54(Special), e01006. Go to original source...
    30. Saydam M., Takka S. Development and in vitro evaluation of pH-independent release matrix tablet of weakly acidic drug valsartan using quality by design tools. Drug Dev. Ind. Pharm. 2018; 44(12), 1905-1917. Go to original source... Go to PubMed...
    31. Wang Q., Wong C. H., Chan H. Y. E., Lee W. Y., Zuo Z. Statistical Design of Experiment (DoE) based development and optimization of DB213 in situ thermosensitive gel for intranasal delivery. Int. J. Pharm. 2018; 539(1-2), 50-57. Go to original source... Go to PubMed...
    32. Tietz K., Gutknecht S. I., Klein S. Bioequivalence of locally acting lozenges: Evaluation of critical in vivo parameters and first steps towards a bio-predictive in vitro test method. Eur. J. Pharm. Biopharm. 2018; 123, 71-83. Go to original source... Go to PubMed...
    33. Ruban O., Pidpruzhnykov Y., Kolisnyk T. Excipient risk assessment: possible approaches to assessing the risk associated with excipient function. J. Pharm. Investig. 2018; 48, 421-429. Go to original source...
    34. Hancock B. C., Colvin J. T., Mullarney M. P., Zinchuk A. V. The relative densities of pharmaceutical powders, blends, dry granulations, and immediate-release tablets. Pharm Technol. 2003; 27(4), 64-80.
    35. Pandeya A., Puri V. M. Relationships between tablet physical quality parameters and granulated powder properties: feasibility study. Particul. Sci. Technol. 2012; 30(5), 482-496. Go to original source...
    36. Sarraguça M. C., Cruz A. V., Soares S. O., Amaral H. R., Costa P. C., Lopes J. A. Determination of flow properties of pharmaceutical powders by near infrared spectroscopy. J. Pharm. Biomed. Anal. 2010; 52, 484-492. Go to original source... Go to PubMed...
    37. Paul S., Sun C. C. Dependence of Friability on Tablet Mechanical Properties and a Predictive Approach for Binary Mixtures. Pharm. Res. 2017; 34, 2901-2909. Go to original source... Go to PubMed...

    Return to the content


    Czech and Slovak Pharmacy

    Madam, Sir,
    please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
    Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

    I declare:

    1. that I have met the above instruction
    2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited

    No
    Yes

    If your statement is not true, please be aware
    that brings the risk of danger to their health or the health of others.