Formulation of Aceclofenac Tablets Using Nanosuspension as Granulating Agent: An Attempt to Enhance Dissolution Rate and Oral Bioavailability

Abstract

Haroon Rahim,1 Abdul Sadiq,2 Riaz Ullah,3 Ahmed Bari,4 Fazli Amin,1 Umar Farooq,5 Naeem Ullah Jan,1 Hafiz Majid Mahmood6 1Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Khyber Pakhtunkhwa, Pakistan; 2Department of Pharmacy, University of Malakand, Chakdara, Khyber Pakhtunkhwa, Pakistan; 3Department of Pharmacognosy (MAPPRC), College of Pharmacy, King Saud University Riyadh, Riyadh, Saudi Arabia; 4Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University Riyadh, Riyadh, Saudi Arabia; 5Legacy Pharmaceutical (Pvt.) Ltd., Peshawar, Khyber Pakhtunkhwa, Pakistan; 6Department of Pharmacology, College of Pharmacy, King Saud University Riyadh, Riyadh, Saudi ArabiaCorrespondence: Haroon RahimDepartment of Pharmacy, Sarhad University of Science and Information Technology Peshawar, Peshawar 25000, Khyber Pakhtunkhwa, PakistanTel [phone]Email [email protected]: The aim of the studies was to fabricate aceclofenac (AC) tablets using nanosuspension as granulating fluid to boost its rate of in vitro dissolution and eventually its oral bioavailability.Methods: The optimized nanosuspension with particle size of 112± 2.01 nm was fabricated using HPMC 1% (w/v), PVP-K30 1% (w/v) and SLS 0.12% (w/v) at 400 watts of ultrasonication energy for 15 min duration and 3 sec pause. Then, the optimized aceclofenac nanosuspension was used as granulating fluid for aceclofenac tablets formulation. The characterization was performed using Malvern zetasizer, SEM, TEM, DSC and P-XRD. The granules were evaluated for the bulk and tapped densities, Hausner’s ratio, angle of repose and their resulted values were found within limit. The prepared tablets were tested for average weight, hardness, friability, disintegration, dissolution and in vivo bioavailability in rabbits.Results: The in vitro dissolution data showed the boosted rate of nanosuspension-based tablets compared to the microsuspension-based tablets. The in vivo bioavailability (in rabbits model) of aceclofenac nanosuspension-based tablets (ACN-1, ACN-2) proved an improved absorption as in comparison to the marketed formulation. The Cmax and AUC0→ 24 of ACN-1 and ACN-2 were 1.53-fold, 1.48-fold and 2.23-fold, 2.0-fold greater than that of the marketed drug, and were 1.74-fold, 1.68-fold and 2.3-fold, 2.21-fold greater in comparison to raw drug.Conclusion: This boosted in vitro and in vivo bioavailability may be attributed to reduced particle size of aceclofenac nanoformulations used in tablets. Finally, this will result in faster absorption of these fabricated tablets.Keywords: nanosuspension-based tablets, release kinetics, enhanced oral bioavailability

Keywords

• nanosuspension-based tablets
• release kinetics
• enhanced oral bioavailability.