Drug Design, Development and Therapy (Aug 2017)
Aceclofenac nanocrystals with enhanced in vitro, in vivo performance: formulation optimization, characterization, analgesic and acute toxicity studies
Abstract
Haroon Rahim,1 Abdul Sadiq,1 Shahzeb Khan,1 Mir Azam Khan,1 Syed Muhammad Hassan Shah,2 Zahid Hussain,3 Riaz Ullah,4 Abdelaaty Abdelaziz Shahat,4,5 Khalid Ibrahim6 1Department of Pharmacy, University of Malakand, Chakdara, 2Department of Pharmacy, Sarhad University of Science and Information Technology Peshawar, Khyber Pakhtunkhwa, Pakistan; 3Faculty of Pharmacy, Department of Pharmaceutics, Universiti Teknologi, Mara, Selangor, Malaysia; 4Department of Pharmacognosy and Medicinal, Aromatic and Poisonous Plants Research Center, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Phytochemistry Department, National Research Center, Dokki, Giza, Egypt; 6Department of Chemical Engineering, College of Engineering, Al-Muzahmeiah Branch, King Saud University, Riyadh, Saudi Arabia Abstract: This study was aimed to enhance the dissolution rate, oral bioavailability and analgesic potential of the aceclofenac (AC) in the form of nanosuspension using cost-effective simple precipitation–ultrasonication approach. The nanocrystals were produced using the optimum conditions investigated for AC. The minimum particle size (PS) and polydispersity index was found to be 112±2.01 nm and 0.165, respectively, using hydroxypropyl methylcellulose (1%, w/w), polyvinylpyrrolidone K30 (1%, w/w) and sodium lauryl sulfate (0.12%, w/w). The characterization of AC was performed using zeta sizer, scanning electron microscopy, transmission electron microscopy, powder X-ray diffraction and differential scanning calorimetry. The saturation solubility of the AC nanocrystals was substantially increased 2.6- and 4.5-fold compared to its unprocessed active pharmaceutical ingredient in stabilizer solution and unprocessed drug. Similarly, the dissolution rate of the AC nanocrystals was substantially enhanced compared to its other counterpart. The results showed that >88% of AC nanocrystals were dissolved in first 10 min compared to unprocessed AC (8.38%), microsuspension (66.65%) and its marketed tablets (17.65%). The in vivo studies of the produced stabilized nanosuspension demonstrated that the Cmax were 4.98- and 2.80-fold while area under curve from time of administration to 24 h (AUC0→24 h) were found 3.88- and 2.10-fold greater when compared with unprocessed drug and its marketed formulation, respectively. The improved antinociceptive activity of AC nanocrystals was shown at much lower doses as compared to unprocessed drug, which is purely because of nanonization which may be attributed to improved solubility and dissolution rate of AC, ultimately resulting in its faster rate of absorption. Keywords: aceclofenac nanocrystals, precipitation–ultrasonication, dissolution rate, in vivo studies
