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Physicomechanical, stability, and pharmacokinetic evaluation of aceclofenac dimethyl urea cocrystals

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Abstract

Poor physicomechanical properties and limited aqueous solubility restrict the bioavailability of aceclofenac when given orally. To improve its above properties, aceclofenac (ACE) was cocrystallized with dimethyl urea (DMU) in 1:2 molar ratio by dry and solvent assisted grinding. The cocrystals were characterized by ATR-FTIR, DSC, and PXRD, and their surface morphology was studied by SEM. There was enhancement in intrinsic dissolution rate (IDR) (~eight- and ~fivefold in cocrystals prepared by solvent assisted grinding (SAG) and solid state grinding (SSG), respectively, in 0.1 N HCl, pH 1.2) and similarly (~3.42-fold and ~1.20-fold in phosphate buffer, pH 7.4) as compared to pure drug. Additionally, mechanical properties were assessed by tabletability curves. The tensile strength of ACE was < 1 MPa in contrast to the cocrystal tensile strength (3.5 MPa) which was ~1.98 times higher at 6000 psi. The tablet formulation of cocrystal by direct compression displayed enhanced dissolution profile (~36% in 0.1 N HCl, pH 1.2, and ~100% in phosphate buffer, pH 7.4) in comparison to physical mixture (~ 30% and ~ 80%) and ACE (~18% and ~50%) after 60 min, respectively. Stability studies of cocrystal tablets for 3 months indicated a stable formulation. Pharmacokinetic studies were performed by using rabbit model. The AUC0-∞ (37.87±1.3 μgh/ml) and Cmax (6.94±2.94 μg/ml) of the selected cocrystal C1 prepared by SAG were significantly enhanced (p < 0.05) and were ~3.43 and ~1.63-fold higher than that of ACE. In conclusion, new cocrystal of ACE-DMU was successfully prepared with improved tabletability, in vitro and in vivo properties.

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Acknowledgements

We would like to pay special thanks to Mr. Mohammad Moqeet Khan, from University of Veterinary and Animal Sciences, for his cooperation and help in pharmacokinetic studies.

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Authors and Affiliations

  1. Punjab University College of Pharmacy, University of the Punjab, Allama Iqbal Campus, Lahore, 54000, Pakistan

    Hafsa Afzal, Nasir Abbas, Amjad Hussain, Kanwal Fatima & Nadeem Irfan Bukhari

  2. Institute of Pharmacy, Faculty of Pharmaceutical and Allied Health Sciences, Lahore College for Women University, Jail Road, Lahore, Pakistan

    Hafsa Afzal & Sumera Latif

  3. Department of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan

    Muhammad Sohail Arshad

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  1. Hafsa Afzal
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Correspondence to Nadeem Irfan Bukhari.

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Afzal, H., Abbas, N., Hussain, A. et al. Physicomechanical, stability, and pharmacokinetic evaluation of aceclofenac dimethyl urea cocrystals. AAPS PharmSciTech 22, 68 (2021). https://doi.org/10.1208/s12249-021-01938-7

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