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.2018 Sep;26(6):845-851.
doi: 10.1016/j.jsps.2018.03.014. Epub 2018 Mar 27.

Novel in-situ gel for intravesical administration of ketorolac

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Novel in-situ gel for intravesical administration of ketorolac

Abdelrahman Y Sherif et al. Saudi Pharm J.2018 Sep.

Abstract

The urinary bladder stores urine until the time of urination. Systemic administration of drugs to treat bladder diseases faces several limitations. Therefore, intravesical drug delivery is a promising alternative route of administration. An in-situ gel is used to form a gel inside the bladder cavity and ensure continuous release of the drug even after urination. The objective of the present study was to optimize an in-situ gel formulation of poloxamer and chitosan for intravesical delivery of ketorolac tromethamine. The gelling temperature of the prepared combinations ranged from 20.67 to 25.8 °C. In-vitro release of KT was sustained for up to 7 h using a poloxamer concentration ranging from 17% to 19% and a chitosan concentration ranging from 1% to 2%. Design-Expert® 10 was used to select the optimized formulation (poloxamer/chitosan 17/1.589% w/w) which significantly (p < 0.05) extended the drug release more than each polymer alone. Anex-vivo study showed the ability of the optimized formulation to sustain drug release after emptying two times to mimic urination. Furthermore, the formed gel adhered to the bladder tissue throughout the time period of the experiment. Intravesical administration of the optimized formulation to rabbits via catheter showed no obstruction of urine flow and continuous release of the drug for 12 h.

Keywords: Chitosan; In-situ gel; Intravesical; Ketorolac; Poloxamer 407.

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Figures

Fig. 1
Fig. 1
Three dimensional surface plot represent (A) gelling temperature (B, C and D) percent of drug released at 2, 4 and 7 h respectively of poloxamer/chitosan combinations.
Fig. 2
Fig. 2
(A) In-vitro release of KT from F1 - F9 in SUF at 37 °C, (B) In-vitro release of KT from Fopt, 17% poloxamer and 1.589% chitosan in SUF at 37 °C and (C)Ex-vivo release of KT from Fopt.
Fig. 3
Fig. 3
(A) Mean pH and volume of urine for rabbits before and after intravesical administration of Fopt, (B) KT released fromin-situ gel after intravesical administration of Fopt (C) Photographs of formed gel inside bladder cavity after intravesical administration of Fopt.
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References

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