IMPLICATION OF CENTRAL COMPOSITE DESIGN IN THE DEVELOPMENT OF SIMVASTATIN-LOADED NANOSPONGES

SADHANA NOOTHI; NARENDER MALOTHU; ANKARA ARETI; PRASANNA KUMAR DESU; SARVAN KUMAR

doi:10.22159/ijap.2023v15i5.48453

Authors

SADHANA NOOTHI KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India. Department of Pharmaceutical engineering, B V Raju institute of technology, Narsapur, Medak, Telangana, India https://orcid.org/0000-0003-4992-3300
NARENDER MALOTHU KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India https://orcid.org/0000-0002-3069-5742
ANKARA ARETI KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India
PRASANNA KUMAR DESU KL College of Pharmacy, Koneru Lakshmaiah Education Foundation, Vaddeswaram, AP, India
SARVAN KUMAR Department of Pharmacology, G Pulla Reddy College of Pharmacy, Hyderabad, Telangana, India https://orcid.org/0000-0002-7065-1728

DOI:

https://doi.org/10.22159/ijap.2023v15i5.48453

Keywords:

Nanosponges, Eudragit L-100, Surface response method, Particle size, Central composite design

Abstract

Objective: The present study’s objective was to apply a central composite design to develop the simvastatin-loaded nanosponge formulation to improve its oral bioavailability.

Methods: With the help of a design expert (State-Ease version 13.0.1), a central composite design was selected for the formulation of simvastatin-loaded nanosponges by using a defined concentration of Eudragit L-100 (X1) and PVA (X2) as independent variables and particle size (Y1), percent (%) entrapment efficiency (EE) (Y2), in vitro drug release (Y3) as dependent variables. Fourteen (SF1-SF14) formulations were prepared using the emulsion solvent evaporation and evaluated for surface morphology, particle size, drug-excipient compatibility, %EE, and % drug release. The optimized model (SF14) obtained from a design expert was evaluated for in vivo pharmacokinetics in animal models.

Results: SF14 was formulated and evaluated for morphology (shape and size) of the particle, % EE, in vitro % drug release, and its kinetics. The formulation showed particle size of 163±0.45 nm, 80.54 %±0.57 of EE, and 97.13%±0.38 of drug release at 8h. The release kinetics followed the zero-order and Higuchi mechanisms with non-fiction diffusion. In vivo results showed C_max, T_max, AUC_0-t,AUC_0-α, and MRT_0-αfor nanosponges were 0.175 µg/ml, 6 h, 1.561 µg/mlh, 1.755 µg/mlh, 11.77 h, respectively.

Conclusion: The results indicated a significant increase in the bioavailability of the drug in nanosponges compared with standard drugs. The experimentally designed nanosponge formulations have been successfully developed, and evaluated parameters show that the nanosponge formulation of Simvastatin is a promising delivery through the oral route.

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References

Adepu S, Ramakrishna S. Controlled drug delivery systems: current status and future directions. Molecules. 2021;26(19):5095. doi: 10.3390/molecules26195905, PMID 34641447.

Alicia G, Villegas M, Analia R, Santiago D, Bermudez M. Nanotechnology applications in drug controlled release. Simonazzi1 A. In: Grumezescu A Mihai, editor. Drug targeting and stimuli-sensitive drug delivery systems. United States; 2018. p. 81-116. doi: 10.1016/B978-0-12-813689-8.00003-3.

SS, SA, Krishnamoorthy K, Rajappan M. Nanosponges: a novel class of drug delivery system-review. J Pharm Pharm Sci. 2012;15(1):103-11. doi: 10.18433/j3k308, PMID 22365092.

Simranjot Kaur, Sandeep Kumar. The nanosponges: an innovative drug delivery system. Asian J Pharm Clin Res 2019;12(7):60-7. doi: 10.22159/ajpcr.2019.v12i7.33879.

Sneha R, Omprakash G, Imran N, Sachin B, Nanosponges VB. A novel trend for targeted drug delivery. J Drug Deliv Ther. 2019;9:(3-s). doi: 10.22270/jddt.v9i3-s.2864.

Sharma P, Sharma A, Gupta A. Nanosponges: as a dynamic drug delivery approach for targeted delivery. Int J App Pharm. 2023;15(3):1-11. doi: 10.22159/ijap.2023v15i3.46976.

Satpathy TK, Chaubey N, Sri BU, Naidu VR. Nanosponges–novel emerging drug delivery system. Int J Pharm Sci Res. 2020;11(7):3087-100.

Hill MF, Bordoni B. Hyperlipidemia. StatPearls; 2022.

James R, Rod F, Graeme H, Yoon KL, David M, Humphrey R. Rang and Dale’s pharmacology. 9th ed; Nov 4, 2018.

Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19(1):117-25. doi: 10.1111/j.1472-8206.2004.00299.x. PMID 15660968.

Stancu C, Sima A. Statins: mechanism of action and effects. J Cell Mol Med. 2001;5(4):378-87. doi: 10.1111/j.1582-4934.2001.tb00172.x. PMID 12067471.

Tiwari R, Pathak K. Statins therapy: a review on conventional and novel formulation approaches. J Pharm Pharmacol. 2011;63(8):983-98. doi: 10.1111/j.2042-7158.2011.01273.x. PMID 21718281.

Mundhada DR, Patil S, Mhaiskar A, Mundhada D. A review on novel drug delivery system: a recent trend. Int J Curr Pharm Res. 2016;6(2):89-93.

Solunke RS, Borge UR, Murthy K, Deshmukh MT, Shete RV. Formulation and evaluation of gliclazide nanosponges. Int J App Pharm. 2010;11(6):181-9. doi: 10.22159/ijap.2019v11i6.35006.

Omar SM, Ibrahim F, Ismail A. Formulation and evaluation of cyclodextrin-based nanosponges of griseofulvin as a pediatric oral liquid dosage form for enhancing bioavailability and masking bitter taste. Saudi Pharm J. 2020;28(3):349-61. doi: 10.1016/j.jsps.2020.01.016, PMID 32194337.

Sadhana N, Narender M, Uma Sankar K, Rao GSNK, Reddy AR, Vishnu P. Preparation and evaluation of simvastatin nanosponges. IJPR. 2020;12(3):855-61. doi: 10.31838/IJPR/2020.12.03.047.

Srinivas P, Reddy AJ. Formulation and evaluation of isoniazid-loaded nanosponges for topical delivery. Pharm Nanotechnol. 2015;3(1):68-76. doi: 10.2174/2211738503666150501003906.

Chinthaginjala H, Ahad HA, Bhargav E, Pradeepkumar B. Central composite design aided formulation development and optimization of clarythromycin extended-release tablets. Ind J Pharm Educ Res. 2021;55(2):395-406. doi: 10.5530/ijper.55.2.77.

Barbalata CI, Porfire AS, Sesarman A, Rauca VF, Banciu M, Muntean D, Stiufiuc R, Moldovan A, Moldovan C, Tomuta IA. Screening study for the development of simvastatin-doxorubicin liposomes, a co-formulation with future perspectives in colon cancer therapy. Pharmaceutics. 2021;13:1526. doi: 10.3390/pharmaceutics13101526.

Devesh AB, Smita IR. QbD approach to analytical RP¬HPLC method development and its validation. Int J Pharm Pharm Sci. 2011;3(1):179-87.

Iriventi P, Gupta NV, Osmani RAM, Balamuralidhara V. Design and development of nanosponge loaded topical gel of curcumin and caffeine mixture for augmented treatment of psoriasis. Daru. 2020;28(2):489-506. doi: 10.1007/s40199-020-00352-x, PMID 32472531.

Bakliwal AA, Jat DS, Talele SG, Jadhav AG. Formulation and evaluation of nateglinide nanosponges. Indian Drugs. 2018;55(2):27-35. doi: 10.53879/id.55.02.10717.

Penjuri SCB, Ravouru N, Damineni S, Bns S, Poreddy SR. Formulation and evaluation of lansoprazole-loaded nanosponges. Turk J Pharm Sci. 2016;13(3):304-10. doi: 10.4274/tjps.2016.04.

Marian E, Jurca T. Compatibility study between simvastatin and excipients in their physical mixtures. Rev Chim. 2015;66(6):803-7.

Pawar S, Shende P. Dual drug delivery of cyclodextrin cross-linked artemether and lumefantrine nanosponges for synergistic action using 23 full factorial designs. Colloids and Surfaces A: Physicochemical and Engineering Aspects. 2020;602. doi: 10.1016/j.colsurfa.2020.125049.

Parthasarathi V, Thilagavathi G. Synthesis and characterization of zinc oxide nanopartilce and its application on fabrics for microbe resistant defence clothing. Int J Pharm Pharm Sci. 2011;3(4):392-8.

Kapileshwari GR, Barve AR, Kumar L, Bhide PJ, Joshi M, Shirodkar RK. Novel drug delivery system of luliconazole–formulation and characterisation. J Drug Deliv Sci Technol. 2020;55:101302. doi: 10.1016/j.jddst.2019.101302.

Moin A, Roohi NKF, Rizvi SMD, Ashraf SA, Siddiqui AJ, Patel M. Design and formulation of polymeric nanosponge tablets with enhanced solubility for combination therapy. RSC Adv. 2020;10(57):34869-84. doi: 10.1039/d0ra06611g, PMID 35514416.

Ahmed MM, Fatima F, Anwer MK, Ibnouf EO, Kalam MA, Alshamsan A. Formulation and in vitro evaluation of topical nanosponge-based gel containing butenafine for the treatment of fungal skin infection. Saudi Pharm J. 2021;29(5):467-77. doi: 10.1016/j.jsps.2021.04.010. PMID 34135673.

Ghurghure SM, Surwase P. Fabrication and evaluation of simvastatin Nano sponges for oral delivery. Indo Am J Pharm. 2019;9(4):1982-92.

Mihailiasa M, Caldera F, Li J, Peila R, Ferri A, Trotta F. Preparation of functionalized cotton fabrics by means of melatonin loaded β-cyclodextrin nanosponges. Carbohydr Polym. 2016;142:24-30. doi: 10.1016/j.carbpol.2016.01.024. PMID 26917369.

Sundar Devendiran, Pamu Divya, Magharla Dasaratha Dhanaraju. Design, formulation and evaluation of nanosuspension for drug delivery of celecoxib. IJPR. 2019;11(1):139-46. doi: 10.31838/ijpr/2019.11.01.013.

Baishya H. Application of mathematical models in drug release kinetics of carbidopa and levodopa er tablets. J Dev Drugs 2017;06(2):1-8. doi: 10.4172/2329-6631.1000171.

Rahamathulla M, HG, Veerapu G, Hani U, Alhamhoom Y, Alqahtani A. Characterization, optimization, in vitro and in vivo evaluation of simvastatin proliposomes, as drug delivery. AAPS PharmSciTech. 2020;21(4):129. doi: 10.1208/s12249-020-01666-4, PMID 32405982.

Babu MS, Murthy TEG. Comparative in vivo study of pure drug and fast dissolving tablets of Simvastatin. J Drug Delivery Ther 2019;9(4-A):490-6. doi: 10.22270/jddt.v9i4-A.3508.

Brito Raj SB, Chandrasekhar KB, Reddy KB. Formulation, in vitro and in vivo pharmacokinetic evaluation of simvastatin nanostructured lipid carrier loaded transdermal drug delivery system. Futur J Pharm Sci. 2019;5(1):9. doi: 10.1186/s43094-019-0008-7.

Chavhan SS, Petkar KC, Sawant KK. Simvastatin nanoemulsion for improved oral delivery: design, characterization, in vitro and in vivo studies. J Microencapsul. 2013;30(8):771-9. doi: 10.3109/02652048.2013.788085, PMID 23631382.

Shringirishi M, Mahor A, Gupta R, Prajapati SK, Bansal K, Kesharwani P. Fabrication and characterization of nifedipine loaded β-cyclodextrin nanosponges: an in vitro and in vivo evaluation. J Drug Deliv Sci Technol. 2017;41:344-50. doi: 10.1016/j.jddst.2017.08.005.

Ahsan Hafiz M, Abbas N, Bukhari NI. Quality by design approach for formulation development and evaluation of carboplatin-loaded ethylcellulose nanosponges. International Journal of Polymeric Materials and Polymeric Biomaterials. 2022;71(13):1012-24. doi: 10.1080/00914037.2021.1933978.

Bachir Y, Medjekane M, Benaoudj F, Sahraoui N, Hadj Ziane A. Formulation of β-cyclodextrin nanosponges by polycondensation method: application for natural drugs delivery and preservation. J Mater Environ. 2017;5:81-5.

Prabhu PP, Prathvi, Gujaran TV, Mehta CH, Suresh A, Koteshwara KB. Development of lapatinib nanosponges for enhancing bioavailability. J Drug Deliv Sci Technol. 2021;65. doi: 10.1016/j.jddst.2021.102684.