Formulation and Evaluation of Polymeric Nanoparticles as Carriers of Rosuvastatin Calcium for Oral Administration
Authors
-
Department of Pharmaceutics, College of Pharmacy, Madurai Medical College, Madurai - 625020, Tamil Nadu ,IN
M. Thenmozhi -
Department of Pharmaceutics, College of Pharmacy, Madurai Medical College, Madurai - 625020, Tamil Nadu ,INT. Suganya
-
Department of Pharmacology, Captain Srinivasamurthi Central Ayurveda Research Institute, Arignar Anna Hospital campus, Arumbakkam, Chennai - 600106, Tamil Nadu ,INGokul Marimuthu
DOI:
https://doi.org/10.18311/ti/2023/v30i4/33447Keywords:
Eudragit L100, Eudragit S100, Entrapment Efficiency, Ex vivo Intestinal Permeability, Nanoparticles, SolubilityAbstract
Aim of this research was to formulate and evaluate the polymeric nanoparticle as carriers of rosuvastatin calcium for oral administration. Rosuvastatin calcium-loaded nanoparticles were formulated by nanoprecipitation method using different ratios of polymers (Eudragit L100 and Eudragit S100) and different concentrations of stabilizers (Pluronic F68 and PVA) with constant drug concentration. The formulations were evaluated for particle size, zeta potential, drug content, entrapment efficiency, in vitro release, kinetics, solubility, ex vivo intestinal permeability and Transmission Electron Microscopy (TEM). Fourier Transform-Infrared (FT-IR) spectroscopy and Differential Scanning Calorimetry (DSC) studies were carried out to check compatibility between the drug and polymers. No significant drug-polymer interactions were found. To enhance drug entrapment particle size range from 100-250 nm were prepared and entrapment efficiencies were found be 28-79 %. In vitro release studies showed a biphasic release pattern of rosuvastatin calcium from nanosuspensions: One initial burst release in the first 2 hours which could be helpful to improve the penetration of drug followed by a second slow release phase consistent with a Higuchi diffusion mechanism. The solubility of rosuvastatin calcium loaded polymeric nanoparticles compared to pure drug form was increased to about two-fold. Intestinal permeability of rosuvastatin calcium entrapped in Eudragit L100 an Eudragit S100 nanoparticles across rat small intestinal segments was significantly improved compared with rosuvastatin calcium in solution. Nanoparticles observed by TEM showed extremely spherical shapes. Results indicated that nanoparticle formulations could be a promising delivery system for oral administration of rosuvastatin calcium with enhanced solubility, intestinal permeability and improved oral bioavailability.
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2023 M. Thenmozhi, T. Suganya, Gokul Marimuthu
This work is licensed under a Creative Commons Attribution 4.0 International License.
Accepted 2023-07-30
Published 2023-11-10
References
Adepu S, Ramakrishna S. Controlled drug delivery systems: current status and future directions. Molecules. 2021; 26(19):5905. PMID: 34641447; PMCID: PMC8512302. https://doi.org/10.3390/molecules26195905 DOI: https://doi.org/10.3390/molecules26195905
Couvreur P. Polyalkylcyanoacrylates as colloidal drug carriers. Crit Rev Ther Drug Carrier Syst. 1988; 5(1):1-20. PMID: 3293806.
Kumar G, Shafiq N, Malhotra S. Drug-loaded PLGA nanoparticles for oral administration: Fundamental issues and challenges ahead. Crit Rev Ther Drug Carrier Syst. 2012; 29(2):149-82. PMID: 22475089. https://doi. org/10.1615/CritRevTherDrugCarrierSyst.v29.i2.20 DOI: https://doi.org/10.1615/CritRevTherDrugCarrierSyst.v29.i2.20
McClean S, Prosser E, Meehan E, O’Malley D, Clarke N, Ramtoola Z, Brayden D. Binding and uptake of biodegradable poly-DL-lactide micro- and nanoparticles in intestinal epithelia. Eur J Pharm Sci. 1998; 6(2):153-63. PMID: 9795038. https://doi.org/10.1016/S0928-0987(97)10007-0 DOI: https://doi.org/10.1016/S0928-0987(97)10007-0
Benoit JP, Couvreur P, Devissaguet JP, Fessi H, Puisieux F, Roblot-Treupel L. Les formes “vectorisées” ou à “distribution modulée”, nouveaux systèmes d’administration des médicaments [“Carrier” or “modulated distribution” forms, new systems for drug administration]. J Pharm Belg. 1986; 41(5):319-29. French. PMID: 3543289.
Soppimath KS, Aminabhavi TM, Kulkarni AR, Rudzinski WE. Biodegradable polymeric nanoparticles as drug delivery devices. J Control Release. 2001; 70(1-2):1-20. PMID: 11166403. https://doi.org/10.1016/S0168-3659(00)00339-4 DOI: https://doi.org/10.1016/S0168-3659(00)00339-4
Jung T, Kamm W, Breitenbach A, Kaiserling E, Xiao JX, Kissel T. Biodegradable nanoparticles for oral delivery of peptides: Is there a role for polymers to affect mucosal uptake? Eur J Pharm Biopharm. 2000; 50(1):147-60. PMID: 10840198. https://doi.org/10.1016/S0939-6411(00)00084-9 DOI: https://doi.org/10.1016/S0939-6411(00)00084-9
Lennernäs H. Modeling gastrointestinal drug absorption requires more in vivo biopharmaceutical data: Experience from in vivo dissolution and permeability studies in humans. Curr Drug Metab. 2007; 8(7):645-57. PMID: 17979653. https://doi.org/10.2174/138920007782109823. DOI: https://doi.org/10.2174/138920007782109823
Pauletti GM, Gangwar S, Knipp GT, Nerurkar MM, Okumu FW, Tamura K, Borchard RT. Structural requirements for intestinal absorption of peptide drugs. In Journal of Controlled Release. 1996; 41:3–17. https://doi. org/10.1016/0168-3659(96)01352-1 DOI: https://doi.org/10.1016/0168-3659(96)01352-1
Khin SY, Soe HMSH, Chansriniyom C, Pornputtapong N, Asasutjarit R, Loftsson T, Jansook P. Development of fenofibrate/randomly methylated β-cyclodextrinloaded eudragit® rl 100 nanoparticles for ocular delivery. Molecules. 2022; 27(15):4755. https://doi. org/10.3390/molecules27154755 DOI: https://doi.org/10.3390/molecules27154755
Poovi G, Dhana leks UM, Narayanan N, Neelakanta P. Preparation and characterization of repaglinide loaded chitosan polymeric nanoparticles. Res J Nanosci Nanotechnol. 2011; 1(1):12-24. https://doi.org/10.3923/ rjnn.2011.12.24 DOI: https://doi.org/10.3923/rjnn.2011.12.24
Samy M, Abd El-Alim SH, Rabia AEG, Amin A, Ayoub MMH. Formulation, characterization and in vitro release study of 5-fluorouracil loaded chitosan nanoparticles. Int J Biol Macromol. 2020; 156:783-791. Epub 2020 Apr 19. PMID: 32320805. https://doi.org/10.1016/j. ijbiomac.2020.04.112 DOI: https://doi.org/10.1016/j.ijbiomac.2020.04.112
Adibkia K, Javadzadeh Y, Dastmalchi S, Mohammadi G, Niri FK, Alaei-Beirami M. Naproxen–eudragit® RS100 nanoparticles: Preparation and physicochemical characterization. Colloids Surf B. 2011; 83(1):155-9. https:// doi.org/10.1016/j.colsurfb.2010.11.014 DOI: https://doi.org/10.1016/j.colsurfb.2010.11.014
Fessi H, Puisieux F, Devissaguet JP, Ammoury N, Benita S. Nanocapsule formation by interfacial polymer deposition following solvent displacement. Int J Pharm. 1989; 55(1):R1— R4. https://doi.org/10.1016/0378-5173(89)90281-0 DOI: https://doi.org/10.1016/0378-5173(89)90281-0
Das S, Suresh PK, Desmukh R. Design of eudragit RL 100 nanoparticles by nanoprecipitation method for ocular drug delivery. Nanomedicine. 2010; 6(2):318-23. https://doi. org/10.1016/j.nano.2009.09.002 DOI: https://doi.org/10.1016/j.nano.2009.09.002
Legrand P, Lesieur S, Bochot A, Gref R, Raatjes W, Barratt G, Vauthier C. Influence of polymer behaviour in organic solution on the production of polylactide nanoparticles by nanoprecipitation. Int J Pharm. 2007; 344(1-2):33-43. https://doi.org/10.1016/j.ijpharm.2007.05.054 DOI: https://doi.org/10.1016/j.ijpharm.2007.05.054
Govender T. PLGA nanoparticles prepared by nanoprecipitation: Drug loading and release studies of a water-soluble drug. J Control Release. 1999; 57(2):171-85. https://doi.org/10.1016/S0168-3659(98)00116-3 DOI: https://doi.org/10.1016/S0168-3659(98)00116-3
Song X, Zhao Y, Hou S, Xu F, Zhao R, He J, Cai Z, Li Y, Chen Q. Dual agents loaded PLGA nanoparticles: Systematic study of particle size and drug entrapment efficiency. Eur J Pharm Biopharm. 2008; 69(2):445-53. https://doi.org/10.1016/j.ejpb.2008.01.013 DOI: https://doi.org/10.1016/j.ejpb.2008.01.013
Beltrán Pineda ME, Lizarazo Forero LM, Sierra YCA. Mycosynthesis of silver nanoparticles: A review. Biometals. 2022. PMID: 36482125. https://doi.org/10.1007/s10534- 022-00479-1
Lopedota A, Trapani A, Cutrignelli A, Chiarantini L, Pantucci E, Curci R, Manuali E, Trapani G. The use of Eudragit RS 100/cyclodextrin nanoparticles for the transmucosal administration of glutathione. Eur J Pharm Biopharm. 2009; 72(3):509-20. Epub 2009 Mar 10. PMID: 19281845. https://doi.org/10.1016/j.ejpb.2009.02.013 DOI: https://doi.org/10.1016/j.ejpb.2009.02.013
Singare DS, Marella S, Gowthamrajan K, Kulkarni GT, Vooturi R, Rao PS. Optimization of formulation and process variable of nanosuspension: An industrial perspective. Int J Pharm. 2010; 402(1-2):213-20. PMID: 20933066. https:// doi.org/10.1016/j.ijpharm.2010.09.041 DOI: https://doi.org/10.1016/j.ijpharm.2010.09.041
Muthu MS, Rawat MK, Mishra A, Singh S. PLGA nanoparticle formulations of risperidone: Preparation and neuropharmacological evaluation. Nanomedicine. 2009; 5(3):323-33. PMID: 19523427. https://doi.org/10.1016/j. nano.2008.12.003 DOI: https://doi.org/10.1016/j.nano.2008.12.003
Mishra B, Arya N, Tiwari S. Investigation of formulation variables affecting the properties of lamotrigine nanosuspension using fractional factorial design. Daru. 2010; 18(1):1-8. PMID: 22615586; PMCID: PMC3232085.
Leroueil-Le Verger M, Fluckiger L, Kim YI, Hoffman M, Maincent P. Preparation and characterization of nanoparticles containing an antihypertensive agent. Eur J Pharm Biopharm. 1998; 46(2):137-43. PMID: 9795032. https://doi.org/10.1016/S0939-6411(98)00015-0 DOI: https://doi.org/10.1016/S0939-6411(98)00015-0
Korsmeyer RW, Gurny R, Doelker E, Buri P, Peppas NA. Mechanisms of solute release from porous hydrophilic polymers. 1983; 15(1):25-35. https://doi.org/10.1016/0378- 5173(83)90064-9 DOI: https://doi.org/10.1016/0378-5173(83)90064-9
Costa P, Sousa Lobo JM. Modeling and comparison of dissolution profiles. Eur J Pharm Sci. 2001; 13(2):123- 33. PMID: 11297896. https://doi.org/10.1016/ S0928-0987(01)00095-1 DOI: https://doi.org/10.1016/S0928-0987(01)00095-1
Kommavarapu P, Maruthapillai A, Palanisamy K, Sunkara M. Preparation and characterization of rilpivirine solid dispersions with the application of enhanced solubility and dissolution rate. Beni Suef Univ J Basic Appl Sci [Internet]. 2015; 4(1):71-9. https://doi.org/10.1016/j. bjbas.2015.02.010 DOI: https://doi.org/10.1016/j.bjbas.2015.02.010
Rezaei Mokarram A, Kebriaee Zadeh A, Keshavarz M, Ahmadi A, Mohtat B. Preparation and in vitro evaluation of indomethacin nanoparticles. Daru. 2010; 18(3):185-92. PMID: 22615616; PMCID: PMC3304364.
Akbari B, Valaki BP, Maradiya VH, Akbari AK, Vidyasagar G. Development and evaluation of orodispersible tablets of rosuvastatin calcium-HP-β-CD inclusion complex by using different super disintegrants. International Journal of Pharmacy and Technology. 2011; 3:1842-59.
Chitneni M, Peh KK, Darwis D, Abdulkarim M, Abdullah GZ, Qureshi MJ. Intestinal permeability studies of sulpiride incorporated into Self-Micro Emulsifying Drug Delivery System (SMEDDS). Pak J Pharm Sci. 2011; 24(2):113-21. PMID: 21454158.
Shishu, Maheshwari M. Comparative bioavailability of curcumin, turmeric and Biocurcumax™ in traditional vehicles using non-everted rat intestinal sac model. J Funct Foods [Internet]. 2010; 2(1):60-5. https://doi.org/10.1016/j. jff.2010.01.004 DOI: https://doi.org/10.1016/j.jff.2010.01.004
Chudasama A, Patel V, Nivsarkar M, Vasu K, Shishoo C. A novel lipid-based oral drug delivery system of nevirapine. International Journal of PharmTech Research. 2011; 3(2): 1159–68.
Alsarra IA, Bosela AA, Al-Mohizea AM, Mahrous GM, Neau SH. Modulating intestinal uptake of Atenolol using niosomes as drug permeation enhancers. Scientia Pharmaceutica. 2005; 73(3):81–93. https://doi.org/10.3797/ scipharm.aut-05-07 DOI: https://doi.org/10.3797/scipharm.aut-05-07
Ruan LP, Chen S, Yu BY, Zhu DN, Cordell GA, Qiu SX. Prediction of human absorption of natural compounds by the non-everted rat intestinal sac model. Eur J Med Chem. 2006; 41(5):605-10. PMID: 16546303. https://doi. org/10.1016/j.ejmech.2006.01.013 DOI: https://doi.org/10.1016/j.ejmech.2006.01.013
Zheng Y, Zuo Z, Chow AH. Lack of effect of betacyclodextrin and its water-soluble derivatives on in vitro drug transport across rat intestinal epithelium. Int J Pharm. 2006; 309(1-2):123-8. PMID: 16359834. https://doi. org/10.1016/j.ijpharm.2005.11.022 DOI: https://doi.org/10.1016/j.ijpharm.2005.11.022
Al-Mohizea AM. Influence of intestinal efflux pumps on the absorption and transport of furosemide. Saudi Pharm J. 2010; 18(2):97-101. PMID: 23960725; PMCID: PMC3730994. https://doi.org/10.1016/j.jsps.2010.02.005 DOI: https://doi.org/10.1016/j.jsps.2010.02.005
Dillen K, Vandervoort J, Van den Mooter G, Ludwig A. Evaluation of ciprofloxacin loaded Eudragit RS100 or RL100/PLGA nanoparticles. Int J Pharm. 2006; 314(1):72- 82. Epub 2006 Apr 5. PMID: 16600538. https://doi. org/10.1016/j.ijpharm.2006.01.041 DOI: https://doi.org/10.1016/j.ijpharm.2006.01.041
Galindo-Rodríguez SA, Puel F, Briançon S, Allémann E, Doelker E, Fessi H. Comparative scale-up of three methods for producing ibuprofen-loaded nanoparticles. Eur J Pharm Sci. 2005; 25(4-5):357-67. PMID: 15916889. https://doi. org/10.1016/j.ejps.2005.03.013 DOI: https://doi.org/10.1016/j.ejps.2005.03.013
Cohen-Sela E, Chorny M, Koroukhov N, Danenberg HD, Golomb G. A new double emulsion solvent diffusion technique for encapsulating hydrophilic molecules in PLGA nanoparticles. J Control Release. 2009; 133(2):90-5. Epub 2008 Sep 24. PMID: 18848962. https://doi.org/10.1016/j. jconrel.2008.09.073. DOI: https://doi.org/10.1016/j.jconrel.2008.09.073
Avadi MR, Sadeghi AM, Mohammadpour N, Abedin S, Atyabi F, Dinarvand R, Rafiee-Tehrani M. Preparation and characterization of insulin nanoparticles using chitosan and Arabic gum with ionic gelation method. Nanomedicine. 2010; 6(1):58-63. Epub 2009 May 15. PMID: 19447202. https://doi.org/10.1016/j.nano.2009.04.007 DOI: https://doi.org/10.1016/j.nano.2009.04.007
Sharma K, Porat Z, Gedanken A. Designing natural polymer-based capsules and spheres for biomedical applications-a review. Polymers (Basel). 2021; 13(24):4307. PMID: 34960858; PMCID: PMC8708131. https://doi. org/10.3390/polym13244307 DOI: https://doi.org/10.3390/polym13244307
Bernardy N, Romio AP, Barcelos EI, Dal Pizzol C, Dora CL, Lemos-Senna E, Araujo PH, Sayer C. Nanoencapsulation of quercetin via mini emulsion polymerization. J Biomed Nanotechnol. 2010; 6(2):181-6. PMID: 20738073. https:// doi.org/10.1166/jbn.2010.1107 DOI: https://doi.org/10.1166/jbn.2010.1107
Severino P, da Silva CF, Andrade LN, de Lima Oliveira D, Campos J, Souto EB. Alginate nanoparticles for drug delivery and targeting. Curr Pharm Des. 2019; 25(11):1312- 34. PMID: 31465282. https://doi.org/10.2174/13816128256 66190425163424 DOI: https://doi.org/10.2174/1381612825666190425163424
Sonavane G, Tomoda K, Sano A, Ohshima H, Terada H, Makino K. In vitro permeation of gold nanoparticles through rat skin and rat intestine: Effect of particle size. Colloids Surf B Biointerfaces. 2008; 65(1):1-10. PMID: 18499408. https://doi.org/10.1016/j.colsurfb.2008.02.013 DOI: https://doi.org/10.1016/j.colsurfb.2008.02.013
