Abstract

At present, the use of benzimidazole drugs in veterinary medicine is strongly limited by both pharmacokinetics and formulative issues. In this research, the possibility of applying an innovative semi-solid extrusion 3D printing process in a co-axial configuration was speculated, with the aim of producing a new gastro-retentive dosage form loaded with ricobendazole. To obtain the drug delivery system (DDS), the ionotropic gelation of alginate in combination with a divalent cation during the extrusion was exploited. Two feeds were optimized in accordance with the printing requirements and the drug chemical properties: the crosslinking ink, i.e., a water ethanol mixture containing CaCl2 at two different ratios 0.05 M and 0.1 M, hydroxyethyl cellulose 2% w/v, Tween 85 0.1% v/v and Ricobendazole 5% w/v; and alginate ink, i.e., a sodium alginate solution at 6% w/v. The characterization of the dried DDS obtained from the extrusion of gels containing different amounts of calcium chloride showed a limited effect on the ink extrudability of the crosslinking agent, which on the contrary strongly influenced the final properties of the DDS, with a difference in the polymeric matrix toughness and resulting effects on floating time and drug release.

Highlights

  • Benzimidazole composites, due to their wide spectrum of action, good tolerability, and low toxicity are at present the first-choice drugs for the treatment of helminthic parasites such us nematode and trematode in domestic and livestock animals [1,2]

  • The drug was dispersed into the ethanol and the alcoholic dispersion was added to the aqueous calcium chloride solution to obtain an hydroalcoholic suspension stabilized with Tween

  • Drug delivery systems able to float while releasing the drug in simulated gastric fluids were successfully obtained by 3D printing semi-solid extrusion, exploiting the alginate ionotropic gelation immediately after ink extrusion

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Summary

Introduction

Benzimidazole composites, due to their wide spectrum of action, good tolerability, and low toxicity are at present the first-choice drugs for the treatment of helminthic parasites such us nematode and trematode in domestic and livestock animals [1,2]. The pharmacokinetic properties of these anthelmintic drugs, in particular the rate and extent of gastrointestinal absorption, are strongly influenced by some extrinsic parameters, i.e., species, dosage, and function of the esophageal groove reflex [3] For this reason, the control and the improvement of the benzimidazole pharmacokinetic profile represent an important challenge to allow for efficacious parasite control in animals [4,5]. The control and the improvement of the benzimidazole pharmacokinetic profile represent an important challenge to allow for efficacious parasite control in animals [4,5] To achieve this goal, for more than three decades the benzimidazole backbone underwent to chemical modifications to develop several subclasses: triazoles, probenzimidazoles and methylcarbamates [6]. GRDDS are oral dosage forms able to resist gastric emptying, remaining in the stomach for a long period of time thanks to different physical processes, such as bioadhesion, swelling, or floating [9,11]

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