ROSUVASTATIN CALCIUM PRONIOSOME POWDER: A NOVEL APPROACH TO IMPROVE INTESTINAL ABSORPTION AND BIOAVAILABILITY
Objective: The main objective of the present study was to develop proniosomal formulations to enhance the oral bioavailability of rosuvastatin calcium by improving solubility, dissolution, and/or intestinal permeability.
Methods: Proniosomal powder formulations were prepared with rosuvastatin calcium drug varying the Span 40 and cholesterol ratio in the range of 0.8:0.2–0.2:0.8 using maltodextrin as carrier by slurry method. The prepared proniosomal powder was filled into capsules. The bioavailability enhancement of proniosomes loaded with drug was studied focusing on non-ionic surfactants composition and drug:Span 40 ratio. Prepared proniosomes were characterized for their particle size distribution, zeta potential, entrapment efficiency, in vitro dissolution study, and thermal characteristics to understand the phase transition behavior. Further, the formulated proniosomes were subjected to stability behavior, ex vivo permeation studies using rat intestine followed by in vivo studies.
Results: Physicochemical studies help in optimization of formulations. Enhancement in dissolution is due to incorporation of rosuvastatin calcium into the non-ionic surfactant and change in the physical state from crystalline to amorphous, thus improving oral bioavailability. Ex vivo studies show significant permeation enhancement across gastrointestinal membrane compared to control.
Conclusion: Proniosomes provide a powerful and functional way of distribution of inadequately soluble rosuvastatin calcium drug which is proved from in vivo studies based on the enhanced oral delivery.
2. Smitha G, Areefulla SH, Swamy PV. Enhancement of in vitro dissolution characteristics of nifedipine by co-grinding technique. Int J Pharm Chem Sci 2012;1:1279-85.
3. Nadia HN, Ebtessam AE, Gamal ME. Enhancing dissolution rate of indomethacin by in situ crystalization; development of orally disintegrating tablets. Int J Pharm Pharm Sci 2018;10:18-23.
4. Mudit D, Abdul R, Narayana C, Fijaz R, Sudi D. Enhancing solubility and dissolution of fenofibrate by spray drying technique. Int J Pharm Pharm Sci 2014;7:173-7.
5. Driscoll CM, Griffin BT. Biopharmaceutical challenges associated with drugs with low aqueous solubility-the potential impact of lipid-based formulations. Adv Drug Deliv Rev 2008;60:617-24.
6. Tang B, Cheng G, Gu JC, Xu CH. Development of solid self-emulsifying drug delivery systems: Preparation techniques and dosage forms. Drug Discov Today 2008;13:606-12.
7. Jha AK, Kumar R, Kumar S, Jha SS. Vesicular system-carrier for drug delivery. Pharm Sin 2011;2:192-202.
8. Schreier H, Bouwstra J. Liposomes and niosomes as topical drug carriers: Dermal and transdermal drug delivery. J Control Release 1994;30:1-15.
9. Ijeoma FU, Vyas SP. Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm 1998;17:33-70.
10. Annakula D, Errabelli MR, Jukanti R, Bandari S, Veerareddy PR. Provesicular drug delivery systems: An overview and appraisal. Arch Appl Sci Res 2010;2:135-46.
11. Sarala Y, Natarajan V, Veeran GK, Zhijun W, Manish I, Guru VB. Proliposomes as a drug delivery system to decrease the hepatic first-pass metabolism: Case study using a model drug. Eur J Pharm Sci 2014;64:26-36.
12. Yasam VR, Jakki SL, Natarajan J, Kuppusamy G. A review on novel vesicular drug delivery: Proniosomes. Drug Deliv 2014;21:243-9.
13. Gangadharappa HV, Gangadhar V, Nagashubha B. Approaches for improvement of vesicular system-pro-vesicular drug delivery. Am J Pharm Tech Res 2014;4:16-57.
14. Bayindir ZS, Yuksel N. Provesicles as novel drug delivery systems. Curr Pharm Biotechnol 2015;16:344-64.
15. Hu C, Rhodes DG. Proniosomes: A novel drug carrier preparation. Int J Pharm 1999;185:23-35.
16. Gannu PK, Pogaku R. Nonionic surfactant vesicular systems for effective drug delivery-an overview. Acta Pharm Sin B 2011;1:8-219.
17. Abd-Elbary A, El-laithy HM, Tadros MI. Sucrose stearate-based proniosome-derived niosomes for the nebulisable delivery of cromolyn sodium. Int J Pharm 2008;357:189-98.
18. Sankar V, Ruckmani K, Durga S, Jailani S. Proniosomes as drug carriers. Pak J Pharm Sci 2010;23:103-7.
19. Akhilesh D, Hazel G, Kamath JV. Proniosomes-a propitious provesicular drug carrier. Int J Pharm Pharm Sci Res 2011;1:98-103.
20. Uyar B, Celebier M, Altinoz S. Spectrophotometric determination of rosuvastatin calcium in tablets. Pharmazie 2007;62:411-3.
21. Navin KK. Rosuvastatin: A highly potent statin for the prevention and management of coronary artery disease. Expert Rev Cardiovasc Ther 2007;5:161-75.
22. Crouse JR 3rd. An evaluation of rosuvastatin: Pharmacokinetics, clinical efficacy and tolerability. Expert Opin Drug Metab Toxicol 2008;4:287-304.
23. Grosser N, Erdmann K, Hemmerle A, Berndt G, Hinkelmann U, Smith G, et al. Rosuvastatin upregulates the antioxidant defense protein heme oxygenase-1. Biochem Biophys Res Commun 2004;325:871-6.
24. White CM. A review of the pharmacologic and pharmacokinetic aspects of rosuvastatin. J Clin Pharmacol 2002;42:963-70.
25. Venkatesh DN, Priyanka VS, Tulasi K, Kalyani K, Ali SA, Harikrishna J. Proniosomes: A superior drug delivery system. Int J Pharm Sci Drug Res 2014;6:178-82.
26. Bangham AD, Standish MM, Watkins JC. Diffusion of univalent ions across the lamellae of swollen phospholipids. J Mol Biol 1965;13:238-52.
27. Staniforth J. Powder flow. In: Aulton M, editor. Pharmaceutics: The Science of Dosage form Design. 2nd ed. Edinburgh: Longman Group; 2002. p. 197-210.
28. Lieberman HA, Lachman L, Schwartz JB. Pharmaceutical Dosage Forms: Tablets. 2nd ed. New York: Marcel Dekker; 1990. p. 201-43.
29. Carr RL. Evaluation flow properties of solids. Chem Eng 1965;72:163-8.
30. Manjunath K, Venkateswarlu V. Pharmacokinetics, tissue distribution and bioavailability of clozapine solid lipid nanoparticles after intravenous and intraduodenal administration. J Control Release 2005;107:215-28.
31. Jukanti R, Sheela S, Bandari S, Veerareddy PR. Enhanced bioavailability of exemestane via proliposomes based transdermal delivery. J Pharm Sci 2011;100:3208-22.
32. Swathi T, Krishna MV, Kumar DS, Krishnaveni J. Enhancement of solubility and dissolution rate of rosuvastatin by using solid dispersion technique. JPSI 2013;2:36-40.
33. Blazek-Welsh AI, Rhodes DG. SEM imaging predicts quality of niosomes from maltodextrin-based proniosomes. Pharm Res 2001;18:656-61.
34. El-Ridy MS, Badawi AA, Safar MM, Mohsen AM. Niosomes as a novel pharmaceutical formulation encapsulating the hepatoprotective drug silymarin. Int J Pharm Pharm Sci 2012;4:549-59.
35. Pradip KG, Rita JM, Manish LU, Rayasa SR. Design and development of microemulsion drug delivery system of acyclovir for improvement of oral bioavailability. AAPS Pharm Sci Tech 2006;7:E1-5.
36. Smitha G, Reddy SS, Kumar DS, Kumar JS, Jukanti R. Rosuvastatin calcium quantification in rat serum with the aid of RP-HPLC: Method development and validation. IOSR J Pharm Bioallied Sci 2015;10:23-8.
37. Nel I, Gauler TC, Eberhardt WE, Nickel AC, Schuler M, Thomale J, et al. Formation and repair kinetics of Pt-(GpG) DNA adducts in extracted circulating tumour cells and response to platinum treatment. Br J Cancer 2013;109:1223-9.
38. Blamek-Welsh AI, Rhodes DG. Maltodextrin-based proniosomes. Pharm Sci 2001;3:1-8.
39. Gupta A, Prajapati SK, Singh M, Balamurugan M. Proniosomal powder of captopril: Formulation and evaluation. Mol Pharm 2007;4:596-9.
40. Solanki AB, Parikh JR, Parikh RH. Formulation and optimization of piroxicam proniosomes by 3-factor, 3-level box-behnken design. AAPS Pharm Sci Tech 2007;8:43.
41. Plessis J, Ramachandran C, Weiner N, Miller DG. The influence of particle size of liposomes on deposition of drug into skin. Int J Pharm 1991;103:277-82.
42. Namdeo A, Jain NK. Niosomal delivery of 5-fluorouracil. J Microencapsul 1999;16:731-40.
43. Uchegbu IF, Florence AT. Non-ionic surfactant vesicles (niosomes): Physical and pharmaceutical chemistry. Adv Colloid Interface Sci 1995;58:1-55.
44. Praveen SH, Kumaresh SS, Guru VB. Proliposomes of exemestane for improved oral delivery: Formulation and in vitro evaluation using PAMPA, Caco-2 and rat intestine. Int J Pharm 2009;380:96-104.
45. Bradbury S, Joy DC, Ford BJ. Transmission Electron Microscope (TEM). Edinburgh: Encyclopedia Britannica; 2011.
46. Cornaire G, Woodley J, Hermann P, Cloarec A, Arellano C, Houin G. Impact of excipients on the absorption of P-glycoprotein substrates in vitro and in vivo. Int J Pharm 2004;278:119-31.
This work is licensed under a Creative Commons Attribution 4.0 International License.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.