Preparation of multiple-unit floating-bioadhesive cooperative minitablets for improving the oral bioavailability of famotidine in rats.
Abstract The aims of this study were to prepare fine famotidine-containing floating-bioadhesive cooperative minitablets and to investigate the possibility of using those minitablets as a delivery system for promoting the oral bioavailability of famotidine. Nine minitablet formulations were designed using hydroxypropylmethylcellulose (HPMC K4M) as release-retarding polymers, Carbopol 971P as bioadhesive materials and sodium bicarbonate (NaHCO3) as gas formers. The prepared 3 ± 0.02 mm minitablets were evaluated in terms of their swelling ability, floating behavior, bioadhesion test and in vitro release. The optimized minitablets (F6) containing HPMC K4M (50.00%, w/w), Carbopol 971P (10.00%, w/w) and NaHCO3 (10.00%, w/w) were found to float in 1 min and remain lastingly buoyant over a period of 8 h in vitro, with excellent bioadhesive properties (20.81 g) and sustained drug release characteristics (T50% = 46.54%) followed one-order model. In addition, plasma concentration-time profiles from pharmacokinetic studies in rats dosed with minitablets showed 1.62-fold (p < 0.05) increased absorption of famotidine, compared to the market tablets XinFaDing®. These studies demonstrated that the multiple-unit floating-bioadhesive cooperative minitablets may be a promising gastro-retentive delivery system for drugs that play a therapeutic role in the stomach.
Key Laboratory of Modern Chinese Medicines, China Pharmaceutical University , Nanjing , PR China and.
Xuehua
X
Zhu
Xiaole
X
Qi
Zhenghong
Z
Wu
Ziwei
Z
Zhang
Jiayu
J
Xing
Xiangbo
X
Li
D000179:Acrylates / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D000269:Adhesives / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D000284:Administration, Oral; D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods; D015738:Famotidine / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism; D008297:Male; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017693:Sodium Bicarbonate / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D013607:Tablets / Q000008:administration & dosage* / Q000737:chemistry* / Q000378:metabolism
D000179:Acrylates; D000269:Adhesives; D003692:Delayed-Action Preparations; D011108:Polymers; D013607:Tablets; C492577:carbopol 971P; D015738:Famotidine; D017693:Sodium Bicarbonate
Famotidine; floating-bioadhesive cooperative; gastro-retentive; minitablets; sustained-release