Uji Efek Iritasi Lambung pada Tikus Wistar Jantan dari Nanosuspensi Ketoprofen dengan Polimer Gom Xanthan

Abstract

Background: Ketoprofen can cause gastrointestinal complications that are locally caused by the direct contact of ketoprofen drug crystals with the gastric mucosa. Currently, ketoprofen is formulated in enteric-coated tablets, but it does not completely eliminate irritation. Based on previous research, some users of ketoprofen experience a greater increase in stomach ulcers compared to non-users. A solution that can be used to reduce gastric irritation effects is formulating it into a nanosuspension with xanthan gum polymer as a stabilizer. Objective: To prove that ketoprofen made using xanthan gum as a stabilizer has nanoscale particle size and can reduce gastric irritation effects compared to suspension preparations. Method: The research stages were carried out by preparing nanosuspension formulations using the evaporative precipitation method with 0.05% xanthan gum polymer and Tween 80 surfactant as stabilizers. Male Wistar rats were divided into 8 treatment groups with 3 rats in each group. The test animals were administered the preparation for 7 days and underwent surgery to obtain gastric specimens. The parameters for the gastric ulcer index were assessed macroscopically using the Image-J application and microscopically with the gastric histological score parameters. Results: The ketoprofen nanosuspension is liquid, clear, has a characteristic odor, and shows no sedimentation; pH 5,00,05; particle size of the nanosuspension with 0.05% xanthan gum polymer is 15.62±0.24 nm; polydispersity index 0.3854±0.03; zeta potential -35.64 mV. The nanosuspension groups (1, 2, 3) have an index value of 0.00±0.00 mm; the suspension groups (4, 5, 6) have values of 0.013±0.016; 0.059±0.020; 0.089±0.008 mm, respectively; the base (7) and normal (8) groups have values of 0.007±0.012 and 0.001±0.001 mm, respectively. The histological scores for groups 1, 2, 3, 4, 7, and 8 are 0.00±0.00; for groups 5 and 6, have values of 1.33±0.58 and 3.00±1.00, respectively. Conclusion: Ketoprofen can be formulated into a nanosuspension with a particle size of < 250 nm. Nanosuspensions of ketoprofen at doses of 50 mg, 100 mg, and 200 mg can reduce gastric irritation with lower ulcer index values and histological scores compared to ketoprofen suspension.