Development of omeprazole buccal adhesive tablets with stability enhancement in human saliva

Choi, Han-Gon,Kim, Chong-Kook 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

To develop an omeprazole buccal adhesive tablet, the absorption of omeprazole solutions from human oral cavity was evaluated and the physicochemical properties such as the bioadhesive forces of various omeprazole tablet formulations composed of bioadhesive polymers and alkali materials, and the stability of omeprazole tablets in human saliva were investigated. About 23% of the administered dose was absorbed from the oral cavity at 15 min after the administration of omeprazole solutions (1 mg/15 ml). A mixture of sodium alginate and HPMC was selected as the bioadhesive additive for the omeprazole tablet. Omeprazole tablets prepared with bioadhesive polymers alone had the bioadhesive forces suitable for buccal adhesive tablets, but the stability of omeprazole in human saliva was not satisfied. Among alkali materials, only magnesium oxide could be an alkali stabilizer for omeprazole buccal adhesive tablets due to its strong waterproofing effect. Two tablets composed of [omeprazole/sodium alginate/HPMC/magnesium oxide (20/24/6/50, mg/tab)] and [(20/30/0/50, mg/tab)] were suitable for omeprazole buccal adhesive tablets which could be attached to human cheeks without collapse and could be stabilized in human saliva for at leat 4 h. It was concluded that these two formulae were polential candidates for the subject of further study for the development of development of omeprazole buccal adhesive tablets. ⓒ 2000 Elsevier Science B.V. All rights reserved.

Physicochemical Characterization and Evaluation of Buccal Adhesive Tablets Containing Omeprazole

Yong, Chul Soon,Jung, Jae-Hee,Rhee, Jong-Dal,Kim, Chong-Kook,Choi, Han-Gon 영남대학교 약품개발연구소 2002 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

The objective of this study was to develop an effective omeprazole buccal adhesive toblet 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 stabilizer for omeprazole buccal adhesive tablets due to its strong waterproofing effect. Croscarmellose sodium enhanced the release of omeprazole from the tablets; howerver, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet composed of omeprazole/sodium alginate/HPMC/magnesium oxide/corscarmellose 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 4h 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 6h. The buccal bioavailability of omeprazole in hamsters was 13.7% ± 3.2%. These results demomstrate 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 adminstration.

Omeprazole-cholestyramine Resin 제제의 인체에 대한 약물동력학적 연구

이영욱,우종수,이태상,염지현,강희윤,신창열,손의동,허인회 중앙대학교 약학연구소 2000 약학 논총 Vol.14 No.-

We have performed the pharmacokinetic study of omeprazole- cholestyramine resinate, which has been developed to increase the stability of omeprazole, the well-known proton pump inhibitor, in an acidic condition. In the human experiments, AUC or T_max of oral administration of omeprazole-cholestyramine resinate is bioequivalent with omeprazole, but C_max was 20% higher in omeprazole-cholestyramine resinate than omeprazole. Omeprazole-cholestyramine resinate suppository showed higher C_max and shortened T_max, so it is expected to show a rapid absorption. These data suggest that omeprazole-cholestyramine resinate is more stable in acid and more rapidly absorbed than omeprazole.

Formulation and in vivo evaluation of omepraxole buccal adhesive tablet

Choi, Han-Gon,Jung, Jac-Hee,Yong, Chul Soon,Rhee, Chong-Dal,Lee, Mi-Kyung,Han, Jeong-Hee,Park, Kyung-Mi,Kim, Chong-Kook 영남대학교 약품개발연구소 2001 영남대학교 약품개발연구소 연구업적집 Vol.11 No.-

For the development of omeprazole buccal adhesive tablets, we studied the release and biovailability of omeprazole delivered by buccal adhesive tablets composed of sodium alginate, hydroxypropylmethylcellulose (HPMC), magnesium oxide and croscamellose sodium. Croscarmellose sodium enhanced the release of omeprazole from tablests. The analysis of the release mechanism showed that croscarmellose sodium changed the release profile of omeprazole from first- to zero-order release kinetics by forming porous channels in the tablet matrix. However, it decreased the bioadhesive forces and stability of omeprazole tablets in human saliva. The tablet is composed of omeprazole-sodium alginate-HPMC-magnesium oxide-croscarmellose sodium (20:24:6:50:10 mg). It may be attached to the human cheek without collapse and it enhance the stability of omeprazole in human saliva for at lest 4h, giving a fast release of omeprazole. The plasma concentration of omeprazole in hamsters increased to reach a maximum of 370 ng/ml at 45 min after buccal administration and remained at the high level of 146-366 ng/ml for 6 h. The buccal bioavailability of emeprazole in hamsters was 13.7±3.2%. These results demonstrate that the omeprazole buccal adhesive tablet would be useful to deliver omeprazole which degrades very rapidly in acidic aqueous medium and undergoes hepatic first-pass metabolism after oral administration. ⓒ 2000 Elsevier Science B.B. All rights reserved.

Omeprazole-cholestyramine Resin 직장투여와 정맥주사시의 토끼에 대한 약물 동력화 연구

이영욱,우종수,김진학,이율표,조성호,금찬,성지현,임성혁,손의동,허인회 중앙대학교 약학연구소 2000 약학 논총 Vol.14 No.-

We have performed the pharmacokinetic study of omeprazole- cholestyramine resinate in rabbits, which has been developed to increase the stability of omeprazole, the well-known proton pump inhibitor, in an acidic condition. In this experiments, omeprazole-cholestyramine resinate suppository seemed to have more rapid absorption than omeprazole. AUC and C_max of omeprazole-cholestyramine resinate were 2.3 and 3.7 times greater than omeprazole, respectively. T_max was almost half of omeprazole. Compared with i.v. bolus, i.v. infusion showed three times greater bioavailability. As a result omeprazole-cholestyramine resinate suppository had 74% bioavailability of i.v. infusion, suggesting i.v. infusion could be replaced by suppositories.

관상동맥 스텐트 삽입술을 시행한 환자에서 Omeprazole과의 병용이 Clopidogrel의 효능에 미치는 영향

최고운,이소영,오정미,손인자,이혜숙 한국병원약사회 2012 병원약사회지 Vol.29 No.1

Clopidogrel is converted to an active metabolite by hepatic cytochrome P450 isoenzymes,with cytochrome P450 2C19 (CYP2C19) playing a major role. Because omeprazole is the main substrate of this enzyme, the concomitant use of clopidogrel and omeprazole is associated with reduced plasma concentration of clopidogrel. However, there has been no definite conclusion yet to whether this drug-drug interaction results in significant clinical outcomes, such as cardiovascular events. Further, the expression rate of CYP2C19, which is a poor metabolizer, in Koreans is higher than in Caucasians. So this trial sought to assess the influence of omeprazole on clopidogrel efficacy in Korean patients. We conducted a retrospective study, among patients who received aspirin clopidogrel, following coronary artery stent insertion, between January 1, 2000, and December 31, 2008. ㄴWe performed a follow-up for a year after the surgical procedure and divided patients into two groups,the clopidogrel with omeprazole group (experimental group) and the clopidogrel alone group (control group). The former were 39 patients who take this combination therapy for more than a week, and the latter (at a ratio of 2:1) comprised of 65 patients that were matched to patients had with the same age, same sex, and no PPI history during the follow-up period. Date difference in the surgical procedure is within a year between the matched patients. We regarded the impact of omeprazole on clopidogrel efficacy as the frequency of the cardiovascular events, which are Major Adverse Cardiac Events and Stent Restenosis in Coronary Angiogram, during the follow-up period. Higher frequency appeared of these events in the clopidogrel,with omeprazole group, than in the clopidogrel alone group. However, there was no significant difference between the two groups. (35.9% vs 29.2%, p=0.48)In our study, co-administration of clopidogrel and omeprazole showed a negative effect on clopidogrel’s efficacy, but the result did not show statistical significance. Thereafter, a prospective study should be done in more patients in the near future.

소화성궤양 환자에 있어서 Omeprazole(오엠피®)의 치료효과

권중구,이창형,김영탁,금민수,권영오,김성국,최용환,정준모 慶北大學校 醫科大學 1995 慶北醫大誌 Vol.36 No.1

목적 : 소화성궤양 환자의 치료제중 하나인 benzimidazole유도체인 Omeprazole은 강력한 위산분비억제기능을 가지고 있는 것으로 알려져 있다. Omeprazole의 소화성궤양에 대한 치료효과를 관찰하기 위하여 본 연구를 실시하였다. 대상 및 방법 : 1994년 8월부터 12월까지 경북대학교병원 내과를 방문한 환자중 상부소화관내시경 검사로 확진된 위궤양 및 십이지장궤양 15예를 대상으로 omeprazole(OMP®) 20㎎을 1일 1회 투여하고, 4주후에 내시경검사를 실시하고 그 치유효과를 관찰하였다. 결과 : 소화성궤양에 대한 4주후의 내시경상의 치유율이 93.4%(8예 중 8예)였고 완전치유율은 62.5%(8예 중 5예)였다. 소화성궤양에 대한 4주후의 증상의 변화를 보면 저명개선이 66.7%(15예중 10예)였고 개선이 33.3%(15예 중 5예)였다. 4주후에 임상적으로 특기할만한 부작용이 관찰되지 않았다. 결론 : Omeprazole이 소화성궤양에 뚜렷한 효과가 있고 비교적 안전하게 사용할 수 있는 약물로 생각된다. For the evaluation of clinical efficacy of omeprazole in the treatment of patient with gastric and duodenal ulcer, 15 patients with upper GI endoscopically proved active gastric ulcer(14 patients) and duodenal ulcer(1 patient) were admitted to this trial. Omeprazole was administered 20㎎ daily for 4 weeks and then follow up was done by endoscopy. The observed results were as follows: (1) Overall improvement of peptic ulcers by endoscopy was noted in 93.4% of the patients. 7 out of 8 cases of peptic ulcers had been healed up in 4 weeks. The complete healing rates of peptic ulcer by endoscopic examination at 4 weeks were 62.5% of the patients. (2) Clinical manifestations of peptic ulcer had been markedly improved in 10 out of 15 cases (66.7%) after 4 weeks medication with omeprazole and had been improved in 5 out of 15 cases (33.3%) (3) No significant clinical side effects had been noticed with 4 weeks medication. According to this study, omeprazole appears to be fairly effective and safe for the treatment of patient with peptic ulcer-diseases.

소화성궤양 환자에서 omeprazole, amoxicillin, clarithromycin 삼제요법의 Helicobacter pylori 박멸 효과

정규,김재규,박실무 중앙대학교 의과대학 의과학연구소 2000 中央醫大誌 Vol.25 No.4

소화성궤양환자에서 Omeprazole과 Ranitidine의 효과에 대한 비교 연구

이정선,이성걸,최창환,박문규,김용기,이호심,이기호,김종숙 해성병원 1992 海星病院論文集 Vol.1 No.-

Omeprazole 장기투여가 에탄올에 의한 흰쥐의 위십이지장점막손상에 미치는 영향

장린(Rin Chang),김병호(Byung Ho Kim),장영운(Young Woon Chang),이정일(Jung Il Lee),김효종(Hyo Jong Kim),김영관(Young Kwan Kim),동석호(Seok Ho Dong),김성배(Sung Bae Kim) 대한소화기학회 1993 대한소화기학회지 Vol.25 No.5

N/A Chronic suppression of acid delivery to the ducdenal mucosa might down-regulate endogenou. protective mechanisms of the duodenum. We investigated whether long-term omeprazole-induced hypochlorhydria would increase the susceptibility of the gastroduodenal mucosa to ethanol injury in rats. Spraguc-Dawely rats were given omeprazole in varying doses of ompeprazole (5, 10, 20 mg/kg) b gavage at every morning for 29 days. Control rats were given buffer alone. After fasting overnight, rats were given 2 ml of 50% ethanol by gavage. Three hours later the rats were killed and macro- scopic injury to the gastric mucosa and microscopic injury to the duodenal mucosa was quantitated. With respect to the gastric mueosal injury, no significant difference was found between thomeprazole and control groups. With respect to the duodenal rnucosal injury, dose dependent worsening was found in the omeprazole group, and difference between the omepra.zole and control groups was significant at all dose of the omeprazole. These results suggest that chronic suppression of acid delivery to the duodenal mucosa might down-regulate endogenous protective mechanisms of the duodenal in rats.