Physicochemical characterization and evaluation of buccal adhesive tablets containing omeprazole.
The objective of this study was to develop an effective omeprazole buccal adhesive tablet with excellent bioadhesive force and good drug stability in human saliva. The omeprazole buccal adhesive tablets were prepared with various bioadhesive polymers, alkali materials, and croscarmellose sodium. Their physicochemical properties, such as bioadhesive force and drug stability in human saliva, were investigated. The release and bioavailability of omeprazole delivered by the buccal adhesive tablets were studied. As bioadhesive additives for the omeprazole tablet, a mixture of sodium alginate and hydroxypropylmethylcellulose (HPMC) was selected. The omeprazole tablets prepared with bioadhesive polymers alone had bioadhesive forces suitable for a buccal adhesive tablet, but the stability of omeprazole in human saliva was not satisfactory. Among alkali materials, only magnesium oxide could be an alkali stabilizerfor omeprazole buccal adhesive tablets due to its strong waterproofing effect. Croscarmellose sodium enhanced the release of omeprazole from the tablets; however, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet composed of omeprazole/sodium alginate/HPMC/magnesium oxide/croscarmellose sodium (20/24/6/50/10 mg) could be attached on the human cheek without disintegration, and it enhanced the stability of omeprazole in human saliva for at least 4 h and gave fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to a maximum of 370 ng/ml at 45 min after buccal administration and continuously maintained a high level of 146-366 ng/ml until 6 h. The buccal bioavailability of omeprazole in hamsters was 13.7% +/- 3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful for delivery of an omeprazole that degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration.
Yong
C S
CS
College of Pharmacy, Yeungnam University, Dae-Dong, Gyongsan, South Korea.
Jung
J H
JH
Rhee
J D
JD
Kim
C K
CK
Choi
H G
HG
D000269:Adhesives; D000284:Administration, Oral; D000328:Adult; D000464:Alginates / Q000008:administration & dosage; D000897:Anti-Ulcer Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D002266:Carboxymethylcellulose Sodium / Q000008:administration & dosage; D016503:Drug Delivery Systems; D004355:Drug Stability; D020723:Glucuronic Acid; D006603:Hexuronic Acids; D006801:Humans; D007785:Lactose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008277:Magnesium Oxide / Q000008:administration & dosage; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives*; D009853:Omeprazole / Q000008:administration & dosage* / Q000493:pharmacokinetics; D010078:Oxazines; D011108:Polymers; D012463:Saliva / Q000378:metabolism*; D012995:Solubility; D013607:Tablets
D000269:Adhesives; D000464:Alginates; D000897:Anti-Ulcer Agents; D006603:Hexuronic Acids; D010078:Oxazines; D011108:Polymers; D013607:Tablets; D008277:Magnesium Oxide; D020723:Glucuronic Acid; D008747:Methylcellulose; C071191:MK 458; D007785:Lactose; D002266:Carboxymethylcellulose Sodium; D009853:Omeprazole