Evaluasi In Vitro dan In Vivo Pemakaian Cangkang Kapsul Alginat Sebagai Sediaan Floating Simetidin

Abstract

Background:Cimetidine is a Histamine H2 receptor antagonist, which is widely prescribed in gastric ulcers, duodenal ulcers and gastroesophageal reflux disease. It is poorly absorbed from the lower gastrointestinal tract and has short elimination half-life about 2 hours. Purpose: To evaluate in vitro and in vivo of floating dosage form of cimetidine using alginate capsules shell. Methods: Alginate capsule shell made from sodium alginate 80-120 cP, 300-400 cP and 500-600 cP. Dissolution test was tested to alginate capsules shell contained cimetidine 200 mg with paddle method dissolution apparatus in artificial gastric fluid pH 1.2. Concentration of cimetidine were measured using UV spectrophotometer with wavelength 218.4 nm. The best profile release of alginate capsules shell formulation was evaluated the bioavailability and antiulcer. In vivo bioavailability studies were conducted in healthy male rabbits, the rabbits given floating alginate capsules 500-600 cP contained cimetidine (9.3 mg/kg per oral) and gelatin capsules contained cimetidine (9.3 mg/kg per oral). The antiulcer studies was conducted in rat and evaluated by HCl-induced ulcer method. One hour after induction, the rats were given floating alginate capsules 500-600 cP contained cimetidine (18 mg/kg per oral once a day) for 2 and 4 days. Cimetidine suspension (18 mg/kg per oral) was used as standard to comparison. Gastric ulcers were evaluated by macroscopic and microscopic observation. Results: The results of dissolution test showed that cimetidine using alginate capsules shell 500-600 cP caused sustained release for 12 hours. In vivo bioavailability studies showed that the alginate capsules shell made of sodium alginate 500-600 cP contained cimetidine gave the higher AUC, Cmax, Tmax than cimetidine from gelatin capsules. The result of antiulcer studies showed that the number of gastric ulcers and ulcer index in the rats received floating alginate capsules 500-600 cP contained cimetidine at the 2nd day were 0.33 ± 0.81 and 0.007 ± 0.01, histopathologically less erosion mucosacompared to rats received cimetidine suspension which were 2.5 ± 1.76 and 0.15 ± 0.18, histopathologically showed much erosion mucosa. The number of gastric ulcer in the rats that received floating alginate capsules 500-600 cP contained cimetidine was with no ulcer after 4 days treatment and histopathologically showed normal mucosa while the average number of gastric ulcer in rats that received cimetidine suspension was 2.4 ± 1.14 with ulcer index 0.036 ± 0.024 and histopathologically still showed erosion mucosa. Conclusion: The results of this study suggest that release of cimetidine from the alginate capsules shell 500-600 cP as a floating dosage form is a sustained release with better bioavailability of floating alginate capsules shell contain cimetidine than cimetidine of gelatin capsules and more effective in antiulcer than cimetidine suspension.

Background:Cimetidine is a Histamine H2 receptor antagonist, which is widely prescribed in gastric ulcers, duodenal ulcers and gastroesophageal reflux disease. It is poorly absorbed from the lower gastrointestinal tract and has short elimination half-life about 2 hours. Purpose: To evaluate in vitro and in vivo of floating dosage form of cimetidine using alginate capsules shell. Methods: Alginate capsule shell made from sodium alginate 80-120 cP, 300-400 cP and 500-600 cP. Dissolution test was tested to alginate capsules shell contained cimetidine 200 mg with paddle method dissolution apparatus in artificial gastric fluid pH 1.2. Concentration of cimetidine were measured using UV spectrophotometer with wavelength 218.4 nm. The best profile release of alginate capsules shell formulation was evaluated the bioavailability and antiulcer. In vivo bioavailability studies were conducted in healthy male rabbits, the rabbits given floating alginate capsules 500-600 cP contained cimetidine (9.3 mg/kg per oral) and gelatin capsules contained cimetidine (9.3 mg/kg per oral). The antiulcer studies was conducted in rat and evaluated by HCl-induced ulcer method. One hour after induction, the rats were given floating alginate capsules 500-600 cP contained cimetidine (18 mg/kg per oral once a day) for 2 and 4 days. Cimetidine suspension (18 mg/kg per oral) was used as standard to comparison. Gastric ulcers were evaluated by macroscopic and microscopic observation. Results: The results of dissolution test showed that cimetidine using alginate capsules shell 500-600 cP caused sustained release for 12 hours. In vivo bioavailability studies showed that the alginate capsules shell made of sodium alginate 500-600 cP contained cimetidine gave the higher AUC, Cmax, Tmax than cimetidine from gelatin capsules. The result of antiulcer studies showed that the number of gastric ulcers and ulcer index in the rats received floating alginate capsules 500-600 cP contained cimetidine at the 2nd day were 0.33 ± 0.81 and 0.007 ± 0.01, histopathologically less erosion mucosacompared to rats received cimetidine suspension which were 2.5 ± 1.76 and 0.15 ± 0.18, histopathologically showed much erosion mucosa. The number of gastric ulcer in the rats that received floating alginate capsules 500-600 cP contained cimetidine was with no ulcer after 4 days treatment and histopathologically showed normal mucosa while the average number of gastric ulcer in rats that received cimetidine suspension was 2.4 ± 1.14 with ulcer index 0.036 ± 0.024 and histopathologically still showed erosion mucosa. Conclusion: The results of this study suggest that release of cimetidine from the alginate capsules shell 500-600 cP as a floating dosage form is a sustained release with better bioavailability of floating alginate capsules shell contain cimetidine than cimetidine of gelatin capsules and more effective in antiulcer than cimetidine suspension.