Aceclofenac nanocrystals with enhanced in vitro, in vivo performance: Formulation optimization, characterization, analgesic and acute toxicity studies

• Main Authors: Hussain, Z. (Author), Ibrahim, K. (Author), Khan, M.A (Author), Khan, S. (Author), Rahim, H. (Author), Sadiq, A. (Author), Shah, S.M.H (Author), Shahat, A.A (Author), Ullah, R. (Author)
• Format: Article
• Language: English
• Published: Dove Medical Press Ltd. 2017
• Subjects: aceclofenac; Aceclofenac nanocrystals; albino rabbit; analgesic activity; analogs and derivatives; animal; animal experiment; Animals; Anti-Inflammatory Agents, Non-Steroidal; antinociception; Area Under Curve; area under the curve; Article; bioavailability; Biological Availability; chemistry; Chemistry, Pharmaceutical; comparative study; controlled study; diclofenac; Diclofenac; differential scanning calorimetry; dispersity; Dissolution rate; dodecyl sulfate sodium; dose response; Dose-Response Relationship, Drug; drug absorption; drug bioavailability; drug screening; drug solubility; drug stability; drug structure; excipient; Excipients; hydroxypropylmethylcellulose; in vitro study; In vivo studies; in vivo study; Leporidae; male; Male; maximum plasma concentration; medicinal chemistry; Mice; mouse; nanocrystal; nanoparticle; Nanoparticles; nonhuman; nonsteroid antiinflammatory agent; particle size; Particle Size; povidone derivative; Precipitation–ultrasonication; procedures; process optimization; Rabbits; scanning electron microscopy; solubility; Solubility; structure analysis; tablet formulation; toxicity testing; Toxicity Tests, Acute; transmission electron microscopy; venlafaxine; X ray diffraction; zeta potential
• Online Access: View Fulltext in Publisher; View in Scopus

 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 Cmaxwere 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. © 2017 Rahim et al.