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. 2022 Jan 3;23(1):45.
doi: 10.1208/s12249-021-02188-3.

Cyclodextrin/Adamantane-Grafted Polyethylene Glycol-Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies

Ahmed A H Abdellatif  1   2 , Ahmed M Mohammed  1 , Gamal Zayed  1 , Saleh Abd El-Rasoul  1   3 , Saud Almawash  4 , Mohamed A Safwat  5 , Shaaban K Osman  6
Affiliations

Cyclodextrin/Adamantane-Grafted Polyethylene Glycol-Based Self-assembling Constructs for Topical Delivery of Ketorolac Tromethamine: Formulation, Characterization, and In Vivo Studies

Ahmed A H Abdellatif et al. AAPS PharmSciTech. .

Abstract

Topical formulation of non-steroidal anti-inflammatory drugs (NSAIDs) exhibits many advantages over the oral administration route, such as avoiding the direct effect on GIT and avoiding the poor oral bioavailability of such drugs. Our study aims to develop a new self-assembling construct based on the hydrophobic interaction between adamantane terminated poly (ethylene glycol) polymers and polymerized β-cyclodextrin. The viscous constructs were developed from direct mixing of host and guest polymer solutions, indicating spontaneous formation without cross-linkers. The modified system was evaluated by different analyses, including X-ray diffractometry, electron microscopy, isothermal titration calorimetry, and rheological analysis. Moreover, such a system's ability for drug loading and release was investigated via the in vitro release of ketorolac tromethamine (KT) as a model of NSAIDs. Finally, the prepared formulas were applied on a rat paw edema model to prove the enhanced anti-inflammatory activities. The obtained results indicated that the modified constructs have a rubbery porous structure with an amorphous nature. Also, from rheological results, the modified system exhibited a viscous behavior with higher loss modulus (G″) compared with storage (G'). The inclusion complexation between cyclodextrin and adamantane moieties was proved by the recorded high binding constants with a 1:1 stoichiometric ratio. Furthermore, the results showed the successful KT incorporation into the modified system and quantitatively released through a semi-permeable membrane in a sustained fashion (over 24 h). Finally, the in vivo results of the medicated constructs showed a significant inhibition of the induced inflammation and swelling, indicating that the modified construct has a great utility for safe non-irritating topical delivery applications.

Keywords: adamantane; anti-inflammatory; construct; inclusion complex; ketorolac tromethamine; poly (ethylene glycol); β-CD.

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References

    1. Khurana S, Chhillar N, Gautam VKS. Inventory control techniques in medical stores of a tertiary care neuropsychiatry hospital in Delhi. Health. 2013;05(01):8–13.
    1. Cho YA, Gwak HS. Transdermal delivery of ketorolac tromethamine: effects of vehicles and penetration enhancers. Drug Dev Ind Pharm. 2004;30(6):557–64. - PubMed
    1. Pabreja K, Dua K, Gorajana A. Evaluation of topical gels containing ketorolac tromethamine on inflammation and hyperalgesia in rats. Anti-Inflamm Anti-Allergy Agents Med Chem. 2012;10(5):323–6.
    1. Brocks DR, Jamali F. Clinical pharmacokinetic of ketorolac tromethamine. Clin Pharmacokinet. 1992;23(6):415–27. - PubMed
    1. Del Valle EMM. Cyclodextrins and their uses: a review. Process Biochemistry. 2004;39(9):1033–46.

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