SOLUBILITY ENHANCEMENT OF ROSUVASTATIN VIA NANOSPONGES: PREPARATION AND IN-VITRO CHARACTERIZATION
Main Article Content
Keywords
Rosuvastatin, solubility enhancement, oral bioavailability, nanosponges, in-vitro drug release
Abstract
Rosuvastatin is regarded as super statin and being a member of BCS class Ⅱ exhibit low aqueous solubility and dissolution rate with poor oral bioavailability of less than 20%. The current study involved rosuvastatin loaded nano-sponges preparation utilizing polyvinyl alcohol (surfactant), ethyl cellulose (polymer) while dichloromethane was used as cross linker. Nanosponge represents a scaffold structure of size less than 100 um demonstrating an excellent approach to deliver drugs that are poorly absorbed or show low solubility in GIT. The formulations were crafted by emulsion solvent evaporation method, initially screened via pre-formulation studies and finally were characterized by various physico-chemical tests. FTIR analysis showed no interaction among pure drug and formulation excipients. Zeta experiment revealed the stable formulations having droplet sizes in the range of 270-343 nm further confirmed by SEM indicating the porous sponge like appearance. There were high percent yield values of 80-87% with 62-74% entrapment efficiency of prepared formulations. Additionally dissolution and kinetic model analysis was established on the formulated nano-sponges to further examine their sustained release property, highlighting initial burst release of surface adhered drug followed by controlled release with anomalous non-Fickian diffusion mechanism. The findings of this study advocated successful fabrications of rosuvastatin loaded nanosponges that could improve low solubility and oral bioavailability of the drug.
References
2. Noh G, Keum T, Bashyal S, Seo JE, Shrawani L, Kim JH. Recent progress in hydrophobic ion-pairing and lipid-based drug delivery systems for enhanced oral delivery of biopharmaceuticals. J Pharm Investig [Internet]. 2022 Jan 1 [cited 2023 May 3];52(1):75–93. Available from: https://link.springer.com/article/10.1007/s40005-021-00549-5
3. Verma V, Ryan KM, Padrela L. Production and isolation of pharmaceutical drug nanoparticles. Int J Pharm. 2021 Jun 15;603:120708.
4. Danaei M, Dehghankhold M, Ataei S, Hasanzadeh Davarani F, Javanmard R, Dokhani A. Impact of Particle Size and Polydispersity Index on the Clinical Applications of Lipidic Nanocarrier Systems. Pharmaceutics [Internet]. 2018 May 18 [cited 2022 Sep 26];10(2):57. Available from: https://www.mdpi.com/1999-4923/10/2/57/htm
5. Khan MI, Shah S, Faisal S, Gul S, Khan S, Abdullah. Monotheca buxifolia Driven Synthesis of Zinc Oxide Nano Material Its Characterization and Biomedical Applications. Micromachines [Internet]. 2022 Apr 24 [cited 2022 May 25];13(5):668. Available from: https://www.mdpi.com/2072-666X/13/5/668/htm
6. Ramadon D, McCrudden MTC, Courtenay AJ, Donnelly RF. Enhancement strategies for transdermal drug delivery systems: current trends and applications. Drug Deliv Transl Res 2021 [Internet]. 2021 Jan 20 [cited 2022 Feb 21];1–34. Available from: https://link.springer.com/article/10.1007/s13346-021-00909-6
7. Darandale SS, Vavia PR. Cyclodextrin-based nanosponges of curcumin: Formulation and physicochemical characterization. J Incl Phenom Macrocycl Chem [Internet]. 2013 Apr 1 [cited 2024 May 14];75(3–4):315–22. Available from: https://link.springer.com/article/10.1007/s10847-012-0186-9
8. Gad S, Alhussini S, Gardouh AR. Polymeric nano sponge drug delivery system: A review. Rec Pharm Biomed Sci [Internet]. 2022 Apr 1 [cited 2024 May 14];6(3):34–58. Available from: https://rpbs.journals.ekb.eg/article_231964.html
9. Martwong E, Chuetor S, Junthip J. Adsorption of Paraquat by Poly(Vinyl Alcohol)-Cyclodextrin Nanosponges. Polymers (Basel) [Internet]. 2021 Nov 25 [cited 2024 May 19];13(23):4110. Available from: https://www.mdpi.com/2073-4360/13/23/4110/htm
10. Jeong SM, Choi S, Kim K, Kim SM, Lee G, Son JS, et al. Association of change in total cholesterol level with mortality: A population-based study. PLoS One [Internet]. 2018 Apr 1 [cited 2024 May 19];13(4):e0196030. Available from: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0196030
11. Elsayed MMA, Aboelez MO, Mohamed MS, Mahmoud RA, El-Shenawy AA, Mahmoud EA, et al. Tailoring of Rosuvastatin Calcium and Atenolol Bilayer Tablets for the Management of Hyperlipidemia Associated with Hypertension: A Preclinical Study. Pharmaceutics [Internet]. 2022 Aug 4 [cited 2023 Jan 3];14(8):1629. Available from: https://www.mdpi.com/1999-4923/14/8/1629/htm
12. Pandya KD, Shah N V., Gohil DY, Seth AK, Aundhia CJ, Patel SS. Development of Risedronate Sodium-loaded Nanosponges by Experimental Design: Optimization and in vitro Characterization. Indian J Pharm Sci [Internet]. 2019 [cited 2024 May 19];81(2):309–16. Available from: https://www.researchgate.net/publication/332858328
13. Tanwar D, Chandra Rathi J, Sharma R. FORMULATION DEVELOPMENT AND EVALUATION OF FLOATING TABLET OF LEVOFLOXACIN. World J Pharm Res [Internet]. 2021 [cited 2023 Aug 12];10(10):726–41. Available from: www.wjpr.net
14. Ilyas F, Jamsahid M, Bashir I, Aslam R, Mehboob T, Tabassam N, et al. Solvent Diffusion Method: An Effective Approach to Formulate Nanosponges Loaded with Naproxen Sodium. RADS J Pharm Pharm Sci [Internet]. 2020 Nov 11 [cited 2024 May 15];8(2):74–80. Available from: https://jpps.juw.edu.pk/index.php/jpps/article/view/338
15. Varan C, Anceschi A, Sevli S, Bruni N, Giraudo L, Bilgiç E, et al. Preparation and characterization of cyclodextrin nanosponges for organic toxic molecule removal. Int J Pharm. 2020 Jul 30;585:119485.
16. Kumar S, Prasad M, Rao R. Topical delivery of clobetasol propionate loaded nanosponge hydrogel for effective treatment of psoriasis: Formulation, physicochemical characterization, antipsoriatic potential and biochemical estimation. Mater Sci Eng C. 2021 Feb 1;119:111605.
17. Rao MRP, Chaudhari J, Trotta F, Caldera F. Investigation of Cyclodextrin-Based Nanosponges for Solubility and Bioavailability Enhancement of Rilpivirine. AAPS PharmSciTech [Internet]. 2018 Jul 1 [cited 2024 May 14];19(5):2358–69. Available from: https://link.springer.com/article/10.1208/s12249-018-1064-6
18. Dai Y, Li Q, Zhang S, Shi S, Li Y, Zhao X, et al. Smart GSH/pH dual-bioresponsive degradable nanosponges based on β-CD-appended hyper-cross-linked polymer for triggered intracellular anticancer drug delivery. J Drug Deliv Sci Technol. 2021 Aug 1;64:102650.
19. Almoshari Y, Iqbal H, Razzaq A, Ahmad KA, Khan MK, Alqahtani SS, et al. Development of nanocubosomes co-loaded with dual anticancer agents curcumin and temozolomide for effective Colon cancer therapy. Drug Deliv. 2022;29(1):2633–43.
20. Bajas D, Vlase G, Mateescu M, Grad OA, Bunoiu M, Vlase T, et al. Formulation and Characterization of Alginate-Based Membranes for the Potential Transdermal Delivery of Methotrexate. Polymers (Basel) [Internet]. 2021 Jan 4 [cited 2023 Jan 29];13(1):161. Available from: https://www.mdpi.com/2073-4360/13/1/161/htm
21. Mahajan N, Mujtaba MA, Fule R, Thakre S, Akhtar MS, Alavudeen SS, et al. Self-Emulsifying Drug Delivery System for Enhanced Oral Delivery of Tenofovir: Formulation, Physicochemical Characterization, and Bioavailability Assessment. ACS Omega [Internet]. 2024 [cited 2024 Feb 20]; Available from: https://pubs.acs.org/doi/full/10.1021/acsomega.3c08565
22. Rajput P, Gauniya A. Preformulation Studies of Rosuvastatin. J Drug Deliv Ther [Internet]. 2019 Jun 22 [cited 2024 May 19];9(3-s):729–35. Available from: https://www.jddtonline.info/index.php/jddt/article/view/2968
23. Shawky SM, Khalifa MKA, Eassa HA. Lornoxicam-Loaded Nanosponges for Controlled Antiinflammatoryneffect: In vitro/ in vivo Assessment. Int J Appl Pharm [Internet]. 2020 [cited 2022 Sep 29];12(6):217–23. Available from: http://creativecommons.org/licenses/by/4.0/
24. Naseem F, Shah SU, Rashid SA, Farid A, Almehmadi M, Alghamdi S. Metronidazole Based Floating Bioadhesive Drug Delivery System for Potential Eradication of H. pylori: Preparation and In vitro Characterization. Polymers (Basel) [Internet]. 2022 Jan 27 [cited 2022 Jan 28];14(3):519. Available from: https://www.mdpi.com/2073-4360/14/3/519/htm
25. Liu Q, Xu J, Liao K, Tang N. Oral Bioavailability Improvement of Tailored Rosuvastatin Loaded Niosomal Nanocarriers to Manage Ischemic Heart Disease: Optimization, Ex vivo and In vivo Studies. AAPS PharmSciTech [Internet]. 2021 Feb 1 [cited 2024 May 19];22(2):1–9. Available from: https://link.springer.com/article/10.1208/s12249-021-01934-x
26. Nandal R, Tahlan S, Verma R, Kumar D, Deep A. Evaluation Of SNEDDS For Poorly Water Soluble BCS Class 2 Rosuvastatin: Preparation, In-vitro And In-vivo Assessment. J Pharm Negat Results [Internet]. 2022 Dec 13 [cited 2024 May 19];13(8):3455–74. Available from: https://www.pnrjournal.com/index.php/home/article/view/4662
27. Verma R, Kaushik A, Almeer R, Habibur Rahman M, Abdel-Daim MM, Kaushik D. Improved pharmacodynamic potential of rosuvastatin by self-nanoemulsifying drug delivery system: An in vitro and in vivo evaluation. Int J Nanomedicine. 2021;16:905–24.
28. Phan NT, Tran YTH, Nguyen LT, Hoang YK, Bui CK, Nguyen HD, et al. Self Nanoelmusifying Drug Delivery System of Rosuvastatin: Bioavailability Evaluation and In vitro – In vivo Correlation. Curr Drug Deliv. 2022 Dec 22;21(5):734–43.
29. Elsayed I, El-Dahmy RM, Elshafeey AH, El Gawad NAA, El Gazayerly ON. Tripling the Bioavailability of Rosuvastatin Calcium Through Development and Optimization of an In-Situ Forming Nanovesicular System. Pharmaceutics [Internet]. 2019 Jun 11 [cited 2024 May 19];11(6):275. Available from: https://www.mdpi.com/1999-4923/11/6/275/htm
30. Kumar A, Rao R. Enhancing efficacy and safety of azelaic acid via encapsulation in cyclodextrin nanosponges: development, characterization and evaluation. Polym Bull [Internet]. 2021 Sep 1 [cited 2024 May 14];78(9):5275–302. Available from: https://link.springer.com/article/10.1007/s00289-020-03366-2
31. Jadon RS, Sharma M. Docetaxel-loaded lipid-polymer hybrid nanoparticles for breast cancer therapeutics. J Drug Deliv Sci Technol [Internet]. 2019;51(December 2018):475–84. Available from: https://doi.org/10.1016/j.jddst.2019.03.039
32. Kraisit P, Hirun N, Mahadlek J, Limmatvapirat S. Fluconazole-loaded solid lipid nanoparticles (SLNs) as a potential carrier for buccal drug delivery of oral candidiasis treatment using the Box-Behnken design. J Drug Deliv Sci Technol. 2021 Jun 1;63:102437.
33. Malkawi A, Jalil A, Nazir I, Matuszczak B, Kennedy R, Schnurch AB. Self-emulsifying drug delivery systems: Hydrophobic drug polymer complexes provide a sustained release in vitro. Mol Pharm [Internet]. 2020 Oct 5 [cited 2024 Feb 29];17(10):3709–19. Available from: https://pubs.acs.org/doi/full/10.1021/acs.molpharmaceut.0c00389
34. Rashid SA, Bashir S, Naseem F, Farid A, Rather IA. Olive Oil Based Methotrexate Loaded Topical Nanoemulsion Gel for the Treatment of Imiquimod Induced Psoriasis-like Skin Inflammation in an Animal Model. Biology (Basel) [Internet]. 2021 Oct 31 [cited 2021 Dec 9];10(11):1121. Available from: https://www.mdpi.com/2079-7737/10/11/1121/htm
35. Ullah H, Khattak M, Khan M, Zulfiqar S, Khan MJ, Arshad Y, et al. Evaluation Of Photoactivated Curcumin Loaded Self Emulsifying Drug Delivery System In In vitro Microbial Caries Model Against Enterococcus Faecalis. J Pharm Negat Results [Internet]. 2023 Jun 16 [cited 2024 Feb 20];14(4):185–202. Available from: https://www.pnrjournal.com/index.php/home/article/view/10282
36. Shah H, Nair AB, Shah J, Bharadia P, Al-Dhubiab BE. Proniosomal gel for transdermal delivery of lornoxicam: optimization using factorial design and in vivo evaluation in rats. DARU, J Pharm Sci [Internet]. 2019 Jun 1 [cited 2023 Mar 9];27(1):59–70. Available from: https://link.springer.com/article/10.1007/s40199-019-00242-x
37. Shoaib QUA, Abbas N, Irfan M, Hussain A, Arshad MS, Hussain SZ, et al. Development and evaluation of scaffold-based nanosponge formulation for controlled drug delivery of naproxen and ibuprofen. Trop J Pharm Res [Internet]. 2018 Oct 5 [cited 2024 May 14];17(8):1465–74. Available from: https://www.ajol.info/index.php/tjpr/article/view/178153
38. Merwe J van der, Steenekamp J, Steyn D, Hamman J. The Role of Functional Excipients in Solid Oral Dosage Forms to Overcome Poor Drug Dissolution and Bioavailability. Pharmaceutics [Internet]. 2020 Apr 25 [cited 2023 Jun 22];12(5):393. Available from: https://www.mdpi.com/1999-4923/12/5/393/htm
39. Rajitha P, Shammika P, Aiswarya S, Gopikrishnan A, Jayakumar R, Sabitha M. Chaulmoogra oil based methotrexate loaded topical nanoemulsion for the treatment of psoriasis. J Drug Deliv Sci Technol. 2019 Feb 1;49:463–76.
Article Sidebar
Article Details
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
All articles published in JPTCP are licensed under Copyright Creative Commons Attribution-NonCommercial 4.0 International License.
Afifa Tariq
Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan, Allama Iqbal Campus, Lahore 54000
Rimsha Liaqat
Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan, Allama Iqbal Campus, Lahore 54000
Pervaiz Akhtar Shah
Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan, Allama Iqbal Campus, Lahore 54000
Hashmat Ullah
Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan
Syed Atif Raza
Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan, Allama Iqbal Campus, Lahore 54000
Sheikh Abdur Rashid
Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan
Qaiser Iqbal
Department of Pharmaceutics, Faculty of Biological, Pharmaceutical and Health Sciences, University of Balochistan, Quetta, Pakistan
Aamna Naz
Punjab University College of Pharmacy, University of the Punjab, Lahore, Pakistan, Allama Iqbal Campus, Lahore 54000
Sadia Haider
University of Lahore, Lahore, Pakistan
Saima Mahmood
Gomal Centre of Pharmaceutical Sciences, Faculty of Pharmacy, Gomal University, Dera Ismail Khan, 29050, Pakistan
Mobina Manzoor
Lahore College for Women University
Ghulam Mustafa Khan
Department of Chemistry, University of Balochistan, Quetta