Controlled-release effervescent floating matrix tablets of ciprofloxacin hydrochloride: development, optimization and in vitro-in vivo evaluation in healthy human volunteers.
Ciprofloxacin hydrochloride has a short elimination half-life, a narrow absorption window and is mainly absorbed in proximal areas of GIT. The purpose of this study was to develop a gastroretentive controlled-release drug delivery system with swelling, floating, and adhesive properties. Ten tablet formulations were designed using hydroxypropylmethylcellulose (HPMC K15M) and/or sodium alginate (Na alginate) as release-retarding polymer(s) and sodium bicarbonate (NaHCO(3)) or calcium carbonate (CaCO(3)) as a gas former. Swelling ability, floating behaviour, adhesion period and drug release studies were conducted in 0.1 N HCl (pH 1.2) at 37+/-0.5 degrees C. The tablets showed acceptable physicochemical properties. Drug release profiles of all formulae followed non-Fickian diffusion. Statistical analyses of data revealed that tablets containing HPMC K15M (21.42%, w/w), Na alginate (7.14%, w/w) and NaHCO(3) (20%, w/w) (formula F7) or CaCO(3) (20%, w/w) (formula F10) were promising systems exhibiting excellent floating properties, extended adhesion periods and sustained drug release characteristics. Both formulae were stored at 40 degrees C/75% RH for 3months according to ICH guidelines. Formula F10 showed better physical stability. Abdominal X-ray imaging of formula F10, loaded with barium sulfate, in six healthy volunteers revealed a mean gastric retention period of 5.50+/-0.77h.
Tadros
Mina Ibrahim
MI
Department of Pharmaceutics and Industrial Pharmacy, Cairo University, Egypt. mina_ebrahim@yahoo.com
D000328:Adult; D000464:Alginates / Q000737:chemistry / Q000493:pharmacokinetics; D001466:Barium Sulfate / Q000493:pharmacokinetics; D002119:Calcium Carbonate / Q000737:chemistry; D055598:Chemical Phenomena; D002939:Ciprofloxacin / Q000493:pharmacokinetics*; D003287:Contrast Media / Q000493:pharmacokinetics; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D004339:Drug Compounding / Q000379:methods*; D004355:Drug Stability; D005753:Gastric Mucosa / Q000378:metabolism; D020723:Glucuronic Acid / Q000737:chemistry / Q000493:pharmacokinetics; D006603:Hexuronic Acids / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D065347:Hypromellose Derivatives; D008297:Male; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D011860:Radiography, Abdominal; D017693:Sodium Bicarbonate / Q000737:chemistry; D013270:Stomach / Q000000981:diagnostic imaging; D013607:Tablets / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000493:pharmacokinetics; D013997:Time Factors
D000464:Alginates; D003287:Contrast Media; D003692:Delayed-Action Preparations; D006603:Hexuronic Acids; D013607:Tablets; D001466:Barium Sulfate; D065347:Hypromellose Derivatives; D002939:Ciprofloxacin; D020723:Glucuronic Acid; D017693:Sodium Bicarbonate; D008747:Methylcellulose; D002119:Calcium Carbonate