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Letters in Drug Design & Discovery

Author(s): Deepika Joshi*, Manish Tiwari, Bhawana Singh and Nidhi Semwal

DOI: 10.2174/1570180819666220903154109

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Design and Characterisation of Rosuvastatin Calcium Nanosuspension Loaded Transdermal Patch

Page: [943 - 956] Pages: 14

  • * (Excluding Mailing and Handling)

Abstract

Objective: The present investigation highlights the formulation and evaluation of nanosuspension- loaded transdermal patches of poorly soluble antilipidemic drug (rosuvastatin).

Methods: Dissolution characteristics of drug was improved by preparation of nanosuspension employing precipitation–ultrasonication technique using a different blend of water-soluble film forming polymers such as hydroxyl propyl methyl cellulose (HPMC K4M), Eudragit and were further characterized by fourier transformation infrared spectroscopy (FTIR), Malvern zetasizer and SEM. Propylene glycol and tween 80 were used as stabilizers. Based on the particle size of the formulation, the best one of NS4 was selected and fabricated into the transdermal patch by solvent casting method. The prepared formulations were evaluated for various parameters like drug excipient compatibility, appearance, morphology, thickness, tensile strength, folding endurance, % elongation, % moisture content, % moisture uptake, % drug content, in-vitro drug permeation, and stability studies were performed for the optimized formula according to the ICH Q1A (R2) guideline under 4°C and 25°C RH for three months.

Results: Amongst all formulation, P4 transdermal patches were considered the optimized formulation. It has the highest in-vitro drug permeation (86.01±0.05%), thickness (0.86±0.09), weight uniformity (475.0±8.60 mg), folding endurance (279.3±9.39), moisture uptake (7.06±1.75%), moisture content (6.81±2.34 %) and stable formula.

Conclusion: Therefore, transdermal patches were considered to be potentially suitable for the sustained release of drugs to improve patient compliance.

Keywords: Transdermal patch, Nanosuspension, Rosuvastatin, Fourier transformation infrared spectroscopy, folding endurance, in-vitro drug permeation.

Graphical Abstract

[1]
Müller, R.H.; Runge, S.; Ravelli, V.; Mehnert, W.; Thünemann, A.F.; Souto, E.B. Oral bioavailability of cyclosporine: Solid lipid nanoparticles (SLN) versus drug nanocrystals. Int. J. Pharm., 2006, 317(1), 82-89.
[http://dx.doi.org/10.1016/j.ijpharm.2006.02.045] [PMID: 16580159]
[2]
Patravale, V.B.; Date, A.A.; Kulkarni, R.M. Nanosuspensions: A promising drug delivery strategy. J. Pharm. Pharmacol., 2004, 56(7), 827-840.
[http://dx.doi.org/10.1211/0022357023691] [PMID: 15233860]
[3]
Todo, H. Transdermal permeation of drugs in various animal species. Pharmaceutics, 2017, 9(3), 33.
[http://dx.doi.org/10.3390/pharmaceutics9030033] [PMID: 28878145]
[4]
Hussain, S.M.; Ahmed, A.B.; Debnath, J. Nanosuspension: A promising drug delivery system for poorly water soluble drug and enhanced bioavailability. Int. J. Pharm. Sci. Res., 2020, 11(10), 4822-4832.
[5]
Nayak, S.; Panda, D.S.; Sahoo, J. Nanosuspension: A novel drug delivery system. J. Pharm. Res., 2010, 3(12), 410-433.
[6]
Gupta, A.; Simple, U.V. Spectrophotometric determination of rosuvastatin calcium in pure form and in pharmaceutical formulations. E-J. Chem., 2009, 6(1), 89-92.
[http://dx.doi.org/10.1155/2009/956712]
[7]
Divya, A.; Rao, M.K.; Gnanprakash, K.; Sowjanya, A.; Vidyasagar, N. A review on current scenario of transdermal drug delivery system. Int. J.Res. Pharm. Sci., 2012, 3(4), 494-502.
[8]
Gavali, P.; Gaikwad, A.; Radhika, P.R.; Sivakumar, T. Design and development of hydroxypropyl methylcellulose based polymeric film of enalapril maleate. Int. J. Pharm. Tech. Res., 2010, 2(1), 274-282.
[9]
Martin, P.D.; Warwick, M.J.; Dane, A.L.; Brindley, C.; Short, T. Absolute oral bioavailability of rosuvastatin in healthy white adult male volunteers. Clin. Ther., 2003, 25(10), 2553-2563.
[http://dx.doi.org/10.1016/S0149-2918(03)80316-8] [PMID: 14667956]
[10]
Rubba, P.; Marotta, G.; Gentile, M. Efficacy and safety of rosuvastatin in the management of dyslipidemia. Vasc. Health Risk Manag., 2009, 5(1), 343-352.
[http://dx.doi.org/10.2147/VHRM.S3662] [PMID: 19436657]
[11]
Singh, V.; Chandra, D.; Singh, P.; Kumar, S.; Singh, A. Nanosuspension: Way to enhance the bioavailibility of poorly soluble drug. Int. J. Curr. Trends Pharm. Res., 2013, 1, 277-287.
[12]
Zainab, E.; Nawal, A.R. Review on preparation, characterization, and pharmaceutical application of nanosuspension as an approach of solubility and dissolution enhancement. J. Pharm. Res., 2018, 12(5), 771-774.
[13]
Aher, S.S.; Malsane, S.T.; Saudagar, R.B. Nanosuspension: An overview. Int. J. Curr. Pharm. Res., 2017, 9(3), 19-23.
[http://dx.doi.org/10.22159/ijcpr.2017.v9i3.19584]
[14]
Pastore, M.N.; Kalia, Y.N.; Horstmann, M.; Roberts, M.S. Transdermal patches: History, development and pharmacology. Br. J. Pharmacol., 2015, 172(9), 2179-2209.
[http://dx.doi.org/10.1111/bph.13059] [PMID: 25560046]
[15]
Raturi, A.; Bhatt, G.; Kothiyal, P. Formulation and evaluation of nanosuspension of rosuvastatin calcium. Int. J. Drug Regul. Affairs, 2013, 1(3), 14-18.
[http://dx.doi.org/10.22270/ijdra.v1i3.115]
[16]
Muller, R.H.; Gohla, S.; Dingler, A.; Schneppe, T.; Wise, D. Handbook of pharmaceutical controlled release technology. Largescale production of solid-lipid nanoparticles (SLN) and nanosuspension (Dissocubes); Marcel Dekker: New York, 2000, 18, pp. 359-375.
[17]
Wang, Y.; Wang, C.; Zhao, J.; Ding, Y.; Li, L. A cost-effective method to prepare curcumin nanosuspensions with enhanced oral bioavailability. J. Colloid Interface Sci., 2017, 485, 91-98.
[http://dx.doi.org/10.1016/j.jcis.2016.09.003] [PMID: 27657837]
[18]
Patel, D.J.; Vyas, A.M.; Rathi, S.G.; Shah, S.K. Formulation and evaluation of transdermal patch of Apixaban. Int. J. Pharm. Sci. Res., 2021, 69(2), 57-63.
[19]
Yadav, V. Transdermal drug delivery system. Int. J. Pharm. Sci. Res., 2012, 3(2), 376-382.
[20]
Szunerits, S.; Boukherroub, R. Heat: A highly efficient skin enhancer for transdermal drug delivery. Front. Bioeng. Biotechnol., 2018, 6(15), 15.
[http://dx.doi.org/10.3389/fbioe.2018.00015] [PMID: 29497609]
[21]
Geetha, G.; Poojitha, U.; Khan, K.A. Various techniques for preparation of nanosuspension-A review. Int. J. Pharma Res. Rev., 2014, 3(9), 30-37.
[22]
Shid, R.L.; Dhole, S.N.; Kulkarni, N.; Shid, S.L. Nanosuspension: A review. Int. J. Pharm. Sci. Rev. Res., 2013, 22(1), 98-106.
[23]
Arjun, S.; Karthik, S.; Arjunan, K.; Hariharan, S.; Seenivasan, P.; Sankar, V. Preparation and evaluation of rosuvastatin calcium nanosuspension and solid dispersion tablets by wet granulation and direct compression techniques using tamarind gum as a binder. Indian J. Pharm. Sci., 2020, 82(1), 32-40.
[24]
Geevarghese, R.B.; Shirolkar, S.V. Formulation development of rosuvastatin calcium drug in adhesive transdermal system. Int. J. Pharm. Sci. Res., 2020, 11(8), 3902-39011.
[25]
Santhosh, R.M.; Venkataramana, K. Formulation characterization, in-vitro, in-vivo and pharmacokinetic evaluation of stabilized rosuvastatin calcium nanosuspension. Int. J. Res. Pharmaceut. Sci., 2020, 11(2), 10-20.
[26]
Afrin, K.; Prajapati, S.K.; Prajapati, R.N.; Kumar, D.C.; Tiwari, S. Formulation and evaluation of nanosuspension of rosuvastatin using nanoprecipitation technique. Sch. Acad. J. Pharm., 2019, 8(7), 365-375.
[27]
Berthomieu, C.; Hienerwadel, R. Fourier transform infrared (FTIR) spectroscopy. Photosynth. Res., 2009, 101(2-3), 157-170.
[http://dx.doi.org/10.1007/s11120-009-9439-x] [PMID: 19513810]
[28]
Jadhav, P.; Yadav, A. Formulation, optimization, and in vitro evaluation of polymeric nanosuspension of flurbiprofen. Asian J. Pharm. Clin. Res., 2019, 12(11), 183-191.
[http://dx.doi.org/10.22159/ajpcr.2019.v12i11.35670]
[29]
Mujtaba, M.A.; Hassan, K.A. Development and evaluation of nanocrystals of rosuvastatin for enhancement of dissolution rate. Dusunen Adam, 2019, 10, 359-365.
[30]
Subramanian, S.; Devi, M.K.; Vaiyana, C.R.; Sakthi, M.; Suganya, G. Preparation, evaluation and optimization of atorvastatin nanosuspension incorporated transdermal patch. Asian J. Pharm., 2016, 10(4), S487-S491.
[31]
Morsy, M.A.; Abdel-Latif, R.G.; Nair, A.B.; Venugopala, K.N.; Ahmed, A.F.; Elsewedy, H.S.; Shehata, T.M. Preparation and evaluation of atorvastatin-loaded nanoemulgel on wound-healing efficacy. Pharmaceutics, 2019, 11(11), 1-15.
[http://dx.doi.org/10.3390/pharmaceutics11110609] [PMID: 31766305]
[32]
Pal, S.L.; Jana, U.; Manna, P.K.; Mohanta, G.P.; Manavalan, R. Nanoparticle: An overview of preparation and characterization. J. Appl. Pharm. Sci., 2011, 1, 228-234.
[33]
Attari, Z.; Kalvakuntla, S.; Reddy, M.S.; Deshpande, M.; Rao, C.M.; Koteshwara, K.B. Formulation and characterisation of nanosuspensions of BCS class 2nd and 4th drugs by combinative method. J. Exp. Nanosci., 2016, 11(4), 276-288.
[http://dx.doi.org/10.1080/17458080.2015.1055841]
[34]
Castaneda, P.S.; Chavez, J.; Aguado, A.T.; Cruz, I.M.; Contreras, L.M. Design and evaluation of a transdermal patch with atorvastatin. Farmacia, 2017, 65(6), 90-98.
[35]
Lakshmi, S.S.; Rao, Y.S.; Asha, D.; Kumari, K.; Allikarjun, P.N. Formulation and evaluation of rosuvastatin-calcium drug transdermal patch. Research J. Pharm. And Tech, 2020, 13(10), 4784-4790.
[http://dx.doi.org/10.5958/0974-360X.2020.00841.0]
[36]
Tanwar, H.; Sachdeva, R. Transdermal drug delivery system: A review. Int. J. Pharm. Sci. Res., 2016, 7(6), 2274-2290.
[37]
Singh, A.; Bali, A. Formulation and characterization of transdermal patches for controlled delivery of duloxetine hydrochloride. J. Anal. Sci. Technol., 2016, 7(25), 1-13.
[http://dx.doi.org/10.1186/s40543-016-0105-6]
[38]
Gaikwad, A.K. Transdermal drug delivery system: Formulation aspects and evaluation. Comprehensive J. Pharm. Sci., 2013, 1(1), 1-10.
[39]
Kondamudi, P.K.; Tirumalasetty, P.P.; Malayandi, R.; Mutalik, S.; Pillai, R. Lidocaine transdermal patch: Pharmacokinetic modeling and in vitro–in vivo correlation (IVIVC). AAPS PharmSciTech, 2016, 17(3), 588-596.
[40]
Sachan, B.; Bajpai, M. Transdermal drug delivery system: A review. Int. J Res. Dev. Pharm and life Sci, 2013, 3(1), 748-765.
[41]
Evane, B.; Singh, S.; Mishra, A.; Pathak, A.K. Formulation and evaluation of transdermal drug delivery system of simvastatin. J. Pharm. Res., 2012, 5(2), 813-810.
[42]
Guang, M.; Wang, L. In-vitro and in-vivo characterization of clonidine transdermal patch treatment of attention deficit hyperactivity disorder in children. Biol. Pharm. Bull., 2004, 28(2), 305-310.
[PMID: 15684489]
[43]
Rowe, C.R.; Sheskey, J.P.; Weller, J.P. Handbook of Pharmaceutical Excipients, 4th ed; Varghese Publication: Mumbai, 2003.
[44]
Dash, S.; Murthy, P.N.; Nath, L.; Chowdhury, P. Kinetic modeling on drug release from controlled drug delivery systems. Acta Pol. Pharm., 2010, 67(3), 217-223.
[PMID: 20524422]
[45]
Bharkatiya, M.; Nema, R.; Bhatnagar, M. Designing and characterization of drug free patches for transdermal application. Int. J. Pharm. Sci. Drug Res., 2010, 2(1), 35-39.
[46]
Singh, A.; Baghel, U.S.; Sinha, M. Pharmaceutical dosage forms using green and rapid fourier-transform infrared spectroscopic method. Indian J. Pharm. Sci., 2020, 82(4), 632-639.
[47]
Bowen, P. Particle size distribution measurement from millimeters to nanometers and from rods to platelets. J. Dispers. Sci. Technol., 2002, 23(5), 631-645.
[http://dx.doi.org/10.1081/DIS-120015368]
[48]
Tinke, A.P.; Govoreanu, R.; Vanhoutte, K. Particle size and shape characterization of nano- and submicron liquid dispersions. Am. Pharm. Rev., 2006, 9(5), 45-56.
[49]
Bayat, A.; Larijani, B.; Ahmadian, S.; Junginger, H.E.; Rafiee-Tehrani, M. Preparation and characterization of insulin nanoparticles using chitosan and its quaternized derivatives. Nanomedicine, 2008, 4(2), 115-120.
[http://dx.doi.org/10.1016/j.nano.2008.01.003] [PMID: 18339584]
[50]
Lu, X.Y.; Wu, D.C.; Li, Z.J.; Chen, G.Q. Polymer nanoparticles. Prog. Mol. Biol. Transl. Sci., 2011, 104, 299-323.
[http://dx.doi.org/10.1016/B978-0-12-416020-0.00007-3] [PMID: 22093222]
[51]
Hunter, R.J. Ed. Zeta Potential in Colloid Science: Principles and Applications; Academic Press: London, 2013, Vol. 2, pp. 4-26.
[52]
Murdock, R.C.; Braydich-Stolle, L.; Schrand, A.M.; Schlager, J.J.; Hussain, S.M. Characterization of nanomaterial dispersion in solution prior to in vitro exposure using dynamic light scattering technique. Toxicol. Sci., 2008, 101(2), 239-253.
[http://dx.doi.org/10.1093/toxsci/kfm240] [PMID: 17872897]
[53]
Gmoshinski, I.V.; Khotimchenko, S.A.; Popov, V.O.; Dzantiev, B.B.; Zherdev, A.V.; Demin, V.F.; Buzulukov, Y.P. Nanomaterials and nanotechnologies: Methods of analysis and control. Russ. Chem. Rev., 2013, 2(1), 48-76.
[http://dx.doi.org/10.1070/RC2013v082n01ABEH004329]
[54]
Patel, V.R.; Agrawal, Y.K. Nanosuspension: An approach to enhance solubility of drugs. J. Adv. Pharm. Technol. Res., 2011, 2(2), 81-87.
[http://dx.doi.org/10.4103/2231-4040.82950] [PMID: 22171298]
[55]
Sattar, A.; Chen, D.; Jiang, L.; Pan, Y.; Tao, Y.; Huang, L.; Liu, Z.; Xie, S.; Yuan, Z. Preparation, characterization and pharmacokinetics of cyadox nanosuspension. Sci. Rep., 2017, 7(1), 2289.
[http://dx.doi.org/10.1038/s41598-017-02523-4] [PMID: 28536446]
[56]
Sharma, N.; Sharma, S.; Kaushik, R. Formulation and evaluation of lornoxicam transdermal patches using various permeation enhancers. IJDDT, 2019, 9(4), 597-607.
[57]
Shivhare, U.; Dorlikar, V.; Bhusari, K.; Mathur, V.; Mirani, B. Effect of polymeric compositions on pharmacotechnical properties of carvedilol transdermal film. Int. J. Pharm. Sci. Nanotechnol., 2009, 2(1), 457-463.
[http://dx.doi.org/10.37285/ijpsn.2009.2.1.10]
[58]
Parivesh, S.; Sumeet, D.; Abhishek, D. Design, evaluation, parameters and marketed products of transdermal patches: A review. J. Pharm. Res., 2010, 3(2), 235-240.
[59]
Matteucci, M.; Casella, M.; Bedoni, M.; Donetti, E.; Fanetti, M.; De Angelis, F.; Gramatica, F.; Di Fabrizio, E. A compact and disposable transdermal drug delivery system. Microelectron. Eng., 2008, 85(5-6), 1066-1073.
[http://dx.doi.org/10.1016/j.mee.2007.12.067]
[60]
Bhatia, C.; Sachdeva, M.; Bajpai, M. Formulation and evaluation of transdermal patch of pregabalin. IJPSR, 2012, 3(2), 569-575.
[61]
Saroha, K.; Yadav, B.; Sharma, B. Transdermal patch: A discrete dosage form. Int. J. Curr. Pharm. Res., 2011, 3(3), 98-108.
[62]
Kalia, Y.N.; Guy, R.H. Modeling transdermal drug release. Adv. Drug Deliv. Rev., 2001, 48(2-3), 159-172.
[http://dx.doi.org/10.1016/S0169-409X(01)00113-2] [PMID: 11369080]
[63]
Kapoor, D. Innovations in transdermal drug delivery system. Int. Pharmaceut. Sci., 2011, 1(1), 56-67.
[64]
Patel, D.M.; Kavitha, K. Formulation and evaluation aspect of transdermal drug delivery system. Int. J. Pharm. Sci. Rev. Res., 2011, 6(2), 83-90.
[65]
Prabhakar, D.; Sreekanth, J.; Jayaveera, K.N. Transdermal drug delivery patches: A review. J. Drug Deliv. Ther., 2013, 3(4), 59-80.
[http://dx.doi.org/10.22270/jddt.v3i4.590]
[66]
Roy, C.; Gandhi, A. Formulation aspects, approaches and evaluation of transdermal drug delivery system: A concise review. Indian Res. J. Pharm. Sci., 2017, 4(2), 963-971.
[http://dx.doi.org/10.21276/irjps.2017.4.2.3]
[67]
Sharma, S.; Aggarwal, G.; Dhawan, S. Design and evaluation of olanzapine transdermal patches containing vegetable oils as permeation enhancers. Pharm. Lett., 2010, 2(6), 84-98.
[68]
Parhi, R.; Padilam, S. In vitro permeation and stability studies on developed drug-in-adhesive transdermal patch of simvastatin. Bull. Fac. Pharm. Cairo Univ., 2018, 56(1), 26-33.
[http://dx.doi.org/10.1016/j.bfopcu.2018.04.001]