A NOVEL VESICULAR APPROACH FOR TRANSDERMAL ADMINISTRATION OF ENALAPRIL MALEATE LOADED NANOPRONIOSOMAL GEL: FORMULATION, EX VIVO EVALUATION AND IN VIVO ANTIHYPERTENSIVE STUDY
DOI:
https://doi.org/10.22159/ijap.2020v12i5.38463Keywords:
Cholesterol, Enalapril maleate, Ex vivo Permeation studies, In vivo antihypertensive studies, Lecithin, Nonionic surfactants, Proniosomes, Skin irritation studies, Transdermal gelAbstract
Objective: The objective of the study was to formulate and evaluate the nanoproniosomal gel of Enalapril maleate (EM) for the treatment of hypertension through the transdermal administration and to provide better bioavailability.
Methods: The nanoproniosomal gel of the EM was formulated by Lecithin, Cholesterol, Non-ionic surfactants using the Coacervation-phase separation method. The prepared nanoproniosomal gels were evaluated for pH and viscosity, vesicle size analysis, rate of spontaneity, entrapment efficiency, zeta potential, ex vivo skin permeation studies, skin irritation test, stability studies and in vivo antihypertensive studies.
Results: Physical characterization was found to be within acceptable limits. The ex vivo skin permeation studies showed the cumulative permeation of 58.75 % to 89.72 % through the albino rat skin in 24 h for all the formulations, which indicate the zero-order drug permeation with diffusion, non-fickian release. Among all formulations, EMNP7 was selected as best formulation because it showed better characteristics than other formulations in several aspects like physicochemical characterization, ex vivo skin permeation studies, permeation kinetics, and other evaluation parameters. The skin irritation study revealed that there was no irritation after topical application and it was found to be safer to use. The In vivo antihypertensive study revealed that the formulation of EMNP7 was successful to regress the rat blood pressure (BP) to normal values in experimental hypertensive rats.
Conclusion: The nanoproniosomal gel is an efficient transdermal therapeutic system for the delivery of EM for the treatment of hypertension. It is suitable for once a day controlled release formulation.
Downloads
References
Radha GV, Sudha Rani T, Sarwani B. A review on proniosomal drug delivery system for targeted drug action. J Basic Clin Pharm 2013;4:42-8.
Jangam Payal R, Thombre Nilima A, Gaikwad Pallavi N. A review: proniosomes as a novel drug delivery system. Asian J Pharm Tech 2017;7:166-74.
Srikanth, Anand Kumar Y, Mallikarjuna Setty C. Formulation and evaluation of maltodextrin based doxorubicin HCl proniosomes. Res J Pharm Technol 2019;12:2776-80.
Indira U, Uma Shankar MS. Proniosomes as a drug carrier: a review. Int J Pharm Sci Res 2012;3:4617-25.
Venkata Ramesh Yasam, Satya Lavanya Jakki, Jawahar Natarajan, Gowthamarajan Kuppusamy. A review on novel vesicular drug delivery: proniosomes. Drug Delivery 2013;1-7. DOI:10.3109/10717544.2013.841783
Swati Mittal, Amit Chaudhary, Anjali Chaudhary, Ankit Kumar. Proniosomes: the effective and efficient drug-carrier system. Ther Delivery 2020. https://doi.org/10.4155/tde-2019-0065
Maryam Khatoon, Kiyafat Ullah Shah, Fakhar Ud Din, Shefaat Ullah Shah, Asim Ur Rehman, Naz Dilawar, et al. Proniosomes derived niosomes: recent advancements in drug delivery and targeting. Drug Delivery 2017;24:56-69.
Kondawar MS, Kamble KG, Malusare MK, Waghmare JJ, Shah ND. Proniosome based drug delivery system for clotrimazole. Res J Pharm Technol 2011;4:1284-87.
Ankur Gupta, Sunil Kumar Prajapati, Bala Murugan M, Mamta Singh, Daksh Bhatia. Design and development of a proniosomal transdermal drug delivery system for captopril. Trop J Pharm Res 2007;6:687-93.
Waghmode Maya, Shruthi Ashar. Proniosomal drug delivery systems: an overview. Int J Pharm Chem Sci 2012;1:1044-56.
Gopala Krishna Murthy TE, Sai Kishore V. Formulation and evaluation of transdermal gels of diltiazem hydrochloride. Indian J Pharm Educ Res 2008;42:272-6.
Sean C Sweetman. Martindale: the complete drug reference. 35th ed. China: Pharmaceutical Press; 2007. p. 1146-8.
Medicines compendium. Datapharam Communications Ltd. Great Britain: Vitual Health Network Ltd., and Pharmaceutical Press; 2002. p. 994-7.
https://www.drugbank.ca/drugs/DB00584 [Last accessed on 20 Apr 2020]
Lokesh BVS, Raghava Naidu S. New dissolution method for the evaluation of enalapril maleate tablets using ph 7.2 phosphate buffer in vitro and determination of its content by validated uv spectrophotometric method. JASA 2007;5:34-7.
Simona Gherman, Daniela Zavastin, Adrian Spac, Vasile Dorneanu. Development and validation of UV spectrophotometric method for the determination of enalapril maleate from commercial dosage forms. Farmacia 2015;63:934-7.
Ragaa El Sheikh, Ayman A Gouda, Nancy Gouda. Validated spectrophotometric methods for the determination of enalapril maleate in pure and dosage forms. Int J Pharm Pharm Sci 2015;7:190-7.
Venkata Ramesh Yasam, Satya Lavanya Jakki, Jawahar Natarajan, Senthil Venkatachalam, Gowthamarajan Kuppusamy, Sumeet Sood, et al. A novel vesicular transdermal delivery of nifedipine-preparation, characterization and in vitro/in vivo evaluation. Drug Delivery 2016;23:619-30.
Prem Kumar Y, Vinod Kumar K, Sai Kishore V. Preparation and evaluation of diclofenac niosomes by various techniques. Res J Pharm Technol 2013;6:1097-101.
Umekar MJ, Biyani DM, Amgaonkar YM, Bhoyar PK, Lade UB, Kalsait RP. Formulation development and evaluation of transdermal drug delivery system of antihypertensive drug. Res J Pharm Technol 2010;3:753-7.
Ming Ming Wen, Ragwa M Farid, Abeer A Kassem. Nano-proniosomes enhancing the transdermal delivery of mefenamic acid. J Liposome Res 2014;24:280-9.
Viney Lather, Dharmpal Sharma, Deepti Pandita. Proniosomal gel-mediated transdermal delivery of bromocriptine: in vitro and ex vivo evaluation. J Exp Nanosci 2016;11:1044-57.
Soujanya C, Ravi Prakash P. Formulation and evaluation of proniosomal gel-based transdermal delivery of atorvastatin calcium by box-behnken design. Asian J Pharm Clin Res 2019;12:335-43.
Khanderao R Jadhav, Ashish Y Pawar, Ashwini A Bachhav, Satish A Ahire. Proniosome: a novel non-ionic provesicules as potential drug carrier. Asian J Pharm 2016;10:S210-22.
Nadeem Farooqui, Mousumi Kar, Ravindra Pal Singh. Formulation and development of proniosomal gel for transdermal delivery of ketorolac tromethamine. Asian J Pharm 2016;10:S394-400.
Rishu Kakkar, Rao Rekha, Dahiya Navin Kumar, Nanda Sanju. Formulation and characterisation of valsartan proniosomes. Maejo Int J Sci Technol 2011;5:146-58.
Ashish Kute, Prakash Goudanavar, Doddayya Hiremath, Reddy SR. Development and characterization of perindopril erbumine loaded proniosomal gel. Asian J Pharm Tech 2012;2:54-8.
Amol Shete, Priyanka Thorat, Rajendra Doijad, Sachin Sajane. Formulation and in vitro, in vivo evaluation of proniosomal gel of neomycin sulphate. Int J Appl Pharm 2019;11:156-63.
Eman A Mazyed, Sherin Zakaria. Enhancement of dissolution characteristics of clopidogrel bisulphate by proniosomes. Int J Appl Pharm 2019;11:77-85.
Faiyaz Shakeel, Sanjula Baboota, Alka Ahuja, Javed Ali, Mohammed Aqil, Sheikh Shafiq. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech 2007;8:E1-9.
Sadashivaiah R, Dinesh BM, Uma A Patil, Desai BG, Raghu KS. Design and in vitro evaluation of haloperidol lactate transdermal patches containing ethyl cellulose-povidone as film polymers. Asian J Pharm 2008;2:43-9.
Sandeep Gupta, Dheeraj Ahirwar, Neeraj K Sharma, Deenanath Jhade. Proniosomal gel as a carrier for improved transdermal delivery of griseofulvin: preparation and in vitro characterization. Res J Pharma Dosage Forms Tech 2009;1:33-7.
Sharda Sambharkar, Sarvesh Paliwal, Swapnil Sharma, Bishambar Singh. Formulation of risperidone loaded proniosomes for effective transdermal delivery: an in vitro and in vivo study. Bull Fac Pharm (Cairo Univ) 2017;55:239-47.
https://www.oecd.org/env/test-no-404-acute-dermal-irritation-corrosion-9789264242678-en.htm [Last accessed on 20 Apr 2020]
Singh S, Trivedi S, Jain S. Design and development of proniosome based transdermal delivery of ondansetron hydrochloride. Int J Appl Pharm Biol Res 2012;3:191-201.
Ali Nasr, Mona Qushawy, Shady Swidan. Spray-dried lactose based proniosomes as stable provesicular drug delivery carriers: screening, formulation, and physicochemical characterization. Int J Appl Pharm 2018;10:125-37.
Abdul Ahad, Mohd Aqil, Asgar Ali. Investigation of antihypertensive activity of carbopol valsartan transdermal gel containing 1,8-cineole. Int J Biol Macromol 2014;64:144-9.
Ramkanth S, Madhusudhana Chetty C, Sudhakar Y, Thiruvengadarajan VS, Anitha P, Gopinath C. Development, characterization, and in vivo evaluation of proniosomal based transdermal delivery system of atenolol. Future J Pharm Sci 2018;4:80-7.
Ankit Acharya, Kiran Kumar GB, Mohammed Gulzar Ahmed, Saroj Paudel. A novel approach to increase the bioavailability of candesartan cilexetil by proniosomal gel formulation: in vitro and in vivo evaluation. Int J Pharm Pharm Sci 2016;8:241-6.
Shanti Sagar, Sara Lavanya, Vaishali Sagar, Basavaraj K. Nanjwade. Formulation and evaluation of the proniosomal gel of capecitabine. Indo Am J Pharm Sci 2017;4:2513-20.
Ahmed M Samy, Afaf A Ramadan, Amal SM Abu El-Enin, Yasmin IM Mortagi. Formulation and optimization of itraconazole proniosomes using box behnken design. Int J Appl Pharm 2018;10:41-51.
Sunil Kumar, Pushpendra Kumar Jain, Nalini Pandey, Gyanendra Saxena. Comparative study of proniosomal drug delivery system of flurbiprofen. J Chem Pharm Res 2016;8:222-8.
Raja K, Jestin Palu Ukken, Athul PV, Tamizharasi S, Siva Kumar T. Formulation and evaluation of maltodextrin based proniosomal drug delivery system containing anti-diabetic (glipizide) drug. Int J PharmTech Res 2011;3:471-7.
Radha GV, Trideva Sastri K, Prathyusha P, Bhanu P, Jampala Rajkumar. Formulation and evaluation of aceclofenac proniosome loaded orabase for management of dental pain. Int J Appl Pharm 2018;10:204-10.
Prajapati SK, Kumar S, Sahu VK, Prakash G. Proniosomal gel of flurbiprofen: formulation and evaluation. J Drug Delivery Ther 2012;2:1-5.
Ashok Mateti, Mohammed Habibuddin, Raju Jukanti. Formulation and evaluation of proniosome based transdermal gel of sumatriptan succinate. Int J Pharm Biol Sci 2016;6:224-35.
Hardik A Shah, Disha R Patel, Rakshit N Sonapal, Paresh A Prajapati, Madhabhai M. Formulation and comparative evaluation of transdermal patch and proniosomal gel of ropinirole, an anti parkinson’s drug. Int J Pharm Sci Nanotech 2016;9:3091-101.
Ameerah A Radhi. Benazepril hydrochloride loaded niosomal formulation for oral delivery: formulation and characterization. Int J Appl Pharm 2018;10:66-70.
Didem Ag Seleci, Muharrem Seleci, Johanna Gabriela Walter, Frank Stahl, Thomas Scheper. Niosomes as nanoparticular drug carriers: fundamentals and recent applications. J Nanomater 2016;1-13. https://doi.org/10.1155/2016/7372306
Rishikesh Gupta, Santosh Kumar, Nikhil Gupta, Anurag Kumar. The new advancement nanotechnology: Proniosomes as a promising and potential drug carrier. Int J Res Dev Pharm Life Sci 2014;3:1258-65.
Saroha K, Lauchab A, Kumar D, Verma S, Pratibha, Nanda S. Proniosomes: a versatile drug delivery. Int J Res Pharm Pharm Sci 2016;1:43-8.
Published
How to Cite
Issue
Section
