Login Register Cart 0
Generic placeholder image

Recent Advances in Anti-Infective Drug Discovery

Editor-in-Chief

ISSN (Print): 2772-4344
ISSN (Online): 2772-4352

Back
Journal Home About Journal Editorial Board Current Issue Volumes/Issues
Subscribe
Research Article

Assessment of the Anti-Malarial Properties of Dihydroartemisinin- Piperaquine Phosphate Solid Lipid-Based Tablets

Author(s): Chime Salome Amarachi*, Anthony Amaechi Attama and Godswill Chukwunweike Onunkwo

Volume 17, Issue 2, 2022

Published on: 13 September, 2022

Page: [103 - 117] Pages: 15

DOI: 10.2174/2772434417666220606105822

Price: $65

Abstract

Background: Artemisininbased combination therapies (ACTs) typified by dihydroartemisinin- piperaquine phosphate are first-line drugs used in the treatment of Plasmodium falciparum malaria. However, the emergence of drug resistance to ACTs shows the necessity to develop novel sustained release treatments in order to ensure maximum bioavailability.

Objectives: To formulate dihydroartemisinin (DHA)-piperaquine phosphate (PQ) sustained release tablets based on solidified reverse micellar solutions (SRMS).

Methods: The SRMS was prepared by fusion using varying ratios of Phospholipon® 90H and Softisan® 154 and characterised. The tablets were prepared by using an in-house made and validated mould. The formulations were tested for uniformity of weight, hardness, friability, softening time, erosion time and in vitro-in vivo dissolution rate. Antimalarial properties were studied using modified Peter’s 4-days suppressive test in mice. One-way analysis of variance (ANOVA) was used in the analysis of results.

Results: Smooth caplets, with average weight of 1300 ± 0.06 mg to 1312 ± 0.11 mg, drug content of 61 mg for DHA and t 450 mg for PQ. Tablet hardness ranged from 7.1 to 9.0 Kgf and softening time of 29.50 ± 1.90 min. Erosion time of 62.00 ± 2.58 to 152.00 ± 1.89 min were obtained for tablets formulated with Poloxamer 188 (Batches R2, S2 and T2) which significantly reduced the softening and erosion time (p < 0.05). In vitro release showed that the optimized formulations had a maximum release at 12 h. Formulations exhibited significantly higher parasitaemia clearance and in vivo absorption compared to marketed formulations at day 7 (p < 0.05).

Conclusion: DHA-PQ tablets based on SRMS were much easier and relatively cheaper to produce than compressed tablets. They also showed exceptionally better treatment of malaria owing to their sustained release properties and improved bioavailability and are recommended to Pharmaceutical companies for further studies.

Keywords: Artemisinin based combination therapy, dihydroartemisinin, malaria parasite, piperaquine phosphate, reverse micelles, solid lipids.

Next »
Graphical Abstract

[1]
WHO. World malaria report, 2020.https://www.who.int/news-room/fact-sheets/detail/malaria
[2]
Lewinson, G.; Srivastava, D. Malaria research, 1980 – 2004, and the burden of pigment beta-haematin. Nature, 2008, 404, 307-310.
[3]
Manel, O.; Jean-Michel, A.; Lucie, P.; Françoise, B. Plasmodium falciparum resistance to artemisinin-based combination therapies: A sword of damocles in the path toward malaria elimination. Parasites, 2018, 25(24), 1-12.
[4]
WHO. World Malaria report; , 2018. Available from: http://www.who.int/malaria/media/world-malaria-day-2018/en/
[5]
Umeyor, C; Kenechukwu, F; Uronnachi, E; Chime, S; Reginald-Opara, J; Attama, A Recent advances in particulate anti-malarial drug delivery systems: A review. Int J Drug Del, 2013, 5, 01-14.
[6]
Woodrow, C.J.; Haynes, R.K.; Krishna, S. Artemisinins. Postgrad. Med. J., 2005, 81(952), 71-78.
[http://dx.doi.org/10.1136/pgmj.2004.028399] [PMID: 15701735]
[7]
White, N.J. Delaying antimalarial drug resistance with combination chemotherapy. Parassitologia, 1999, 41(1-3), 301-308.
[PMID: 10697872]
[8]
Agbo, C.; Umeyor, C.; Kenechukwu, F. Formulation design, in vitro characterizations and anti-malarial investigations of artemether and lumefantrine-entrapped solid lipid microparticles. Drug Dev. Ind. Pharm., 2016, 42(10), 1708-1721.
[http://dx.doi.org/10.3109/03639045.2016.1171331] [PMID: 27095388]
[9]
Hou, D.; Xie, C.; Huang, K.; Zhu, C. The production and characteristics of Solid Lipid Nanoparticles (SLNs). Biomaterials, 2003, 24(10), 1781-1785.
[http://dx.doi.org/10.1016/S0142-9612(02)00578-1] [PMID: 12593960]
[10]
Reithmeier, H.; Herrmann, J.; Gopferich, A. Development and characterisation of lipid microparticles as a drug carrier for somatostatin. Int. J. Pharm., 2001, 218, 133-143.
[http://dx.doi.org/10.1016/S0378-5173(01)00620-2] [PMID: 11337157]
[11]
Friedrich, I.; Müller-Goymann, C.C. Characterization of Solidified Reverse Micellar Solutions (SRMS) and production development of SRMS-based nanosuspensions. Eur. J. Pharm. Biopharm., 2003, 56(1), 111-119.
[http://dx.doi.org/10.1016/S0939-6411(03)00043-2] [PMID: 12837489]
[12]
Schneeweis, A.; Müller-Goymann, C.C. Controlled release of Solid-Reversed-Micellar-Solution (SRMS) suppositories containing metoclopramide-HCl. Int. J. Pharm., 2000, 196(2), 193-196.
[http://dx.doi.org/10.1016/S0378-5173(99)00419-6] [PMID: 10699716]
[13]
Tärning, J. Piperaquine bioanalysis, drug metabolism and pharmacokinetics., 2007, 1-56.
[14]
Pfeil, J.; Borrmann, S.; Tozan, Y. Dihydroartemisinin-piperaquine vs. artemether-lumefantrine for first-line treatment of uncomplicated malaria in African children: A cost-effectiveness analysis. PLoS One, 2014, 9(4), e95681.
[http://dx.doi.org/10.1371/journal.pone.0095681] [PMID: 24748395]
[15]
Zhang, X.Y.; Liu, P.; Qiao, H. Increased stability and solubility of dihydroartemisinin in aqueous solution through the formation of complexes with 2 hydroxypropyl βcyclodextrin. J. Chin. Pharm. Sci., 2009, 18, 170-176.
[16]
Kenechukwu, F.C.; Attama, A.A.; Ibezim, E.C. Novel intravaginal drug delivery system based on molecularly pegylated lipid matrices for improved antifungal activity of miconazole nitrate. BioMed Res. Int., 2018, 2018, 3714329.
[http://dx.doi.org/10.1155/2018/3714329] [PMID: 29977910]
[17]
Bouwstra, J.A.; Gooris, G.S.; Vries, M.A.S.; van der Spek, J.A.; Bras, W. Structure of human stratum corneum as a function of temperature and hydration: A wide-angle X-ray diffraction study. Int. J. Pharm., 1992, 84(3), 205-216.
[http://dx.doi.org/10.1016/0378-5173(92)90158-X]
[18]
Umeyor, E.C.; Kenechukwu, F.C.; Ogbonna, J.D.N.; Chime, S.A.; Attama, A.A. Investigation of solidified reverse micellar systems as novel carriers for oral delivery of gentamicin. J. Pharm. Res., 2012, 5(9), 4914-4920.
[19]
Chime, S.A.; Attama, A.A.; Onunkwo, G.C. Application of SRMS 154 as sustained release matrix for the delivery of stavudine: In vitro and in vivo evaluation and effect of poloxamer 188 on the properties of the tablets. Infect. Disord. Drug Targets, 2020, 20(1), 76-87.
[http://dx.doi.org/10.2174/1871526519666190313162635] [PMID: 30868966]
[20]
European Pharmacopoeia. Strasbourg: Council of Europe , 2005; pp. 225-258.
[21]
British Pharmacopoeia; Her Majesty’s Stationery Office: London, 2009, Vol. III, pp. 6578-6585.
[22]
International Pharmacopia. In: SNP Best-set/Policrom – 6500. , 2012; 5, pp. 214-222.
[23]
Kamal, A.H.; Samah, F.; Hammad, S.F. A review on UV spectrophotometric methods for simultaneous multicomponent analysis. Eur. J. Pharm. Med. Res., 2016, 3(2), 348-360.
[24]
Peters, W.; Robinson, B.L.; Tovey, G.; Rossier, J.C.; Jefford, C.W. The chemotherapy of rodent malaria. L. The activities of some synthetic 1,2,4-trioxanes against chloroquine-sensitive and chloroquine-resistant parasites. Part 3: Observations on ‘Fenozan-50F’, a difluorinated 3,3′-spirocyclopentane 1,2,4-trioxane. Ann. Trop. Med. Parasitol., 1993, 87(2), 111-123.
[http://dx.doi.org/10.1080/00034983.1993.11812745] [PMID: 8561518]
[25]
Dikasso, D.; Makonnen, E.A.; Abebe, D.; Urga, K. In vivo anti-malaria activity of hydroalcoholic extract from Asparaginus Africanus in mice infected with plasmodium berghei. Ethiop. J. Health Dev., 2006, 20(2), 112-118.
[26]
Chinaeke, E.E.; Chime, S.A.; Kenechukwu, F.C.; Attama, A.A.; Okore, V.C. Formulation of novel artesunate-loaded Solid Lipid Microparticle (SLMs) based on dika wax matrices: In vitro and in vivo evaluation. J. Drug Deliv. Sci. Technol., 2014, 24(1), 1-9.
[http://dx.doi.org/10.1016/S1773-2247(14)50010-X]
[27]
Santosh, B.; Rohidas, M.; Manmohan, N.; Rajendra, P.I.; Rajiv, S. An industrially feasible process for the manufacture of bisquinoline derivatives by using substantially pure n-monosubstituted piperazines. Int. J. Electrochem., 2006.
[28]
Attama, A.A.; Schicke, B.C.; Müller-Goymann, C.C. Further characterization of theobroma oil-beeswax admixtures as lipid matrices for improved drug delivery systems. Eur. J. Pharm. Biopharm., 2006, 64(3), 294-306.
[http://dx.doi.org/10.1016/j.ejpb.2006.06.010] [PMID: 16949805]
[29]
Joshi, N.H.; Shah, N. Review of lipids in pharmaceutical drug delivery system, part I. Amer Pharm Rev Russel Public, 2005, 8(3), 70-78.
[30]
Kuentz, M. Lipid-based formulations for oral delivery of lipophilic drugs. Drug Discov. Today. Technol., 2012, 9(2), e71-e174.
[http://dx.doi.org/10.1016/j.ddtec.2012.03.002] [PMID: 24064269]
[31]
Aungst, B.J.; Saitoh, H.; Burcham, D.L.; Huang, S.M.; Mousa, S.A.; Hussain, M.A. Enhancement of the intestinal absorption of peptides and non-peptides. J. Control. Release, 1996, 41(1-2), 19-31.
[http://dx.doi.org/10.1016/0168-3659(96)01353-3]
[32]
Bogman, K.; Erne-Brand, F.; Alsenz, J.; Drewe, J. The role of surfactants in the reversal of active transport mediated by multidrug resistance proteins. J. Pharm. Sci., 2003, 92(6), 1250-1261.
[http://dx.doi.org/10.1002/jps.10395] [PMID: 12761814]
[33]
Pang, K.S.; Lichuan, L.; Huadong, S. Interaction of drug transporters with excipients. Role of lipid excipients in modifying oral and parenteral drug delivery; Wiley, John Wiley and Sons, 2007, pp. 1-31.
[34]
Patro, M.N.; Ajit, S.B.; Sachin, U.R.; Yadav, A.V. Oral lipid based formulation: A review Int J Pharma Bio Sci , 2010, 1(2), 1-14.
[35]
Fouad, EA; El-badry, M; Mahrous, GM; Alsarra, V; Alashbban, Z; Alanazi, FK In vitro investigation for embedding dextromethorphan in lipids using spray drying. Digest J Nano Bio, 2011, 6(3), 1129-39.

Rights & Permissions Print Cite
Article Metrics
1
© 2024 Bentham Science Publishers | Privacy Policy