A NOVEL APPROACH TO INCREASE THE BIOAVAILABILITY OF CANDESARTAN CILEXETIL BY PRONIOSOMAL GEL FORMULATION: IN-VITRO AND IN-VIVO EVALUATION


Ankit Acharya, Kiran Kumar G. B., Mohammed Gulzar Ahmed, Saroj Paudel

Abstract


Objective: The oral bioavailability of Candesartan cilexetil is less (<15%), so in this study an approach has been made to increase its bioavailability by proniosomal gel formulation.

Methods: The proniosomal formulation of Candesartan cilexetil was prepared by slurry method, using span 60 and Tween 60 as non-ionic surfactants, maltodextrin as carrier and cholesterol and soya lecithin as stabilizers. Prepared gel formulations were evaluated for compatibility study, entrapment efficiency, vesicle size, surface morphology, in-vitro diffusion studies, in-vitro skin permeation studies, in-vivo pharmacokinetics studies, various release kinetic studies and stability studies.

Results: FT-IR study showed no interaction between drugs and other excipients, drugs and excipients are compatible. Mean vesicles size of proniosome derived niosome was found in the range of 16.34 µm-32.48 µm and 7.25-16.45 µm before and after shaking. An optimized formulation A3 containing a 2:1 ratio of span 60 and cholesterol showed maximum entrapment (86.17%) and in-vitro drug release (93.8%) compared to other formulations. In-vitro skin permeation studies were carried out using Albino rat skin and results showed that formulation A3 exhibited 88.65% drug permeation in a steady-state manner over a period of 24 h with a flux value of 1.94 µg/cm2/h and enhancement ratio of 3.73. In-vivo pharmacokinetics studies of proniosomal gel formulation A3 showed a significant increase in bioavailability (1.425 folds) compared with an oral formulation of Candesartan cilexetil. Stability studies showed that proniosomal gel formulation was stable throughout its study period.

Conclusion: Physiochemically stable Candesartan cilexetil proniosomal gel was formulated, which could deliver significant amount of the drug across the skin in a steady-state manner for the prolong period of time in the treatment of hypertension.

 


Keywords


Bioavailability, Candesartan cilexetil, proniosomal gel, In-vitro diffusion studies, Entrapment efficiency, Span 60, Tween 60

| PDF | HTML |

References


Martinoho N, Christiane D, Reis CP. Recent advances in drug delivery systems. J Biomed Nanotechnol 2011;2:510-26.

Rangasamy M, Parthiban KG. Recent advances in novel drug delivery systems. Int J Res Ayurveda Pharm 2010;1:316-26.

Alsarra IA, Bosela AA, Ahmed SM, Mahrous GM. Proniosomes as a drug carrier for transdermal delivery of ketorolac. Eur J Pharm Biopharm 2005;59:485-90.

Akhilesh D, Faishal G, Kamant JV. Comparative study of carriers used in proniosomes. Int J Pharma Chem Sci 2012;1:164-73.

Nekkanti VK, Karatgi P, Prabhu R, Pillai R. Solid self-microemulsifying formulation for candesartan cilexetil. AAPS Pharm Sci Tech 2010;11:9-17.

Mohan H. Textbook of pathology. 6th edition; 2010. p. 685-6.

Sudhamani T, Ganesan V, Priyadarsini N, Radhakrishnan M. Formulation and evaluation of ibuprofen loaded maltodextrin based proniosome. Int J Biopharm 2010;1:75-81.

Ajay S, Jolly P, Rajesh P. Preparation, characterization, optimization, and stability studies of aceclofenac proniosomes. Iran J Pharm Res 2008;7:237-46.

Mittal S, Mittal A, Sharma K, Alam S. Proniosomes as a drug carrier for transdermal delivery of candesartan cilexetil. Int J Nano Stud Technol 2013;2:1-7.

Mohammed Haneefa KP, Anu A, Saraswathi R, Guru PM, Nayar C. Formulation and evaluation of herbal gel of Basella alba for wound healing activity. J Pharm Sci Res 2012;4:1642-8.

Solanki AB, Parikh JR. Preparation, optimization and characterization of ketoprofen proniosomes for transdermal delivery. Int J Pharm Sci Nanotechnol 2009;2:413-20.

Sundarapandian R, Challa MC, Yajamans S. Development and in-vitro permeation studies of proniosomal based transdermal delivery system of atenolol. Pak J Pharm Sci 2014;27:115-20.

Parthibarajan R, Rubinareichal C, Loganathan S. Formulation and evaluation of methotrexate proniosomal powder. Int J Pharm Pharm Sci 2012;4:175-8.

Baboota S, Shakeel F, Ahuja A, Ali J, Shafiq S. Design, development and evaluation of novel nano-emulsion formulation for transdermal potential of celecoxib. Acta Pharm 2007;57:315-32.

Xiao Y, Lin Z, Liu J, Zhang W, Wang L, Yu P. A transdermal microemulsion-based hydrogel of nisoldipine: preparation, in-vitro characterization and in-vivo pharmacokinetic evaluation. Asian J Pharm Sci 2012;7:316-28.

Jalalil MB, Adibkial K, Valizadeh H, Shadbad Mohammad RS, Nokhodchi A, Omidil Y, et al. Kinetic analysis of drug release from nanoparticles. J Pharm Pharm Sci 2008;11:167-77.

ICH Q1A (R2) Stability testing guidelines: Stability testing of new drug substances and products. Available from: URL: http://www.tga.health.gov.au/docs/pdf/euguide/inch/273699r2en.pdf. [Last accessed on 10 Nov 2008].




About this article

Title

A NOVEL APPROACH TO INCREASE THE BIOAVAILABILITY OF CANDESARTAN CILEXETIL BY PRONIOSOMAL GEL FORMULATION: IN-VITRO AND IN-VIVO EVALUATION

Keywords

Bioavailability, Candesartan cilexetil, proniosomal gel, In-vitro diffusion studies, Entrapment efficiency, Span 60, Tween 60

Date

25-11-2015

Additional Links

Manuscript Submission

Journal

International Journal of Pharmacy and Pharmaceutical Sciences
Vol 8, Issue 1, 2016 Page: 241-246

Online ISSN

0975-1491

Statistics

192 Views | 239 Downloads

Authors & Affiliations

Ankit Acharya
Department of Pharmaceutics, Sri Adichunchanagiri College of Pharmacy B. G. Nagara 571448, Karnataka, India
India

Kiran Kumar G. B.
Sri Adichunchanagiri College of Pharmacy B. G. Nagara
India

Mohammed Gulzar Ahmed
Sri Adichunchanagiri College of Pharmacy B. G. Nagara
India

Saroj Paudel
Sri Adichunchanagiri College of Pharmacy B. G. Nagara
India


Article Tools



Refbacks

  • There are currently no refbacks.