Supervisors info:
Βλάχου Μαριλένα, Αναπληρώτρια Καθηγήτρια, Τμήμα Φαρμακευτικής, ΕΚΠΑ,
Δεμέτζος Κωνσταντίνος, Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ,
Καραλής Ευάγγελος, Αναπληρωτής Καθηγητής, Τμήμα Φαρμακευτικής, ΕΚΠΑ
Summary:
In the context of the present postgraduate research project, the in vitro release of omeprazole (API) was studied from uncoated tablets with 20 mg of active substance/tablet and uncoated tablets with 5 mg of the API/tablet, in a pH 6.8 dissolution medium, as well as from commercial gastro-resistant capsules of omeprazole (LOSEC®) with 20 mg of active substance/capsule and from coated tablets of omeprazole with 5 mg of the API/tablet, in pH 4.5 and 6.8 dissolution media. The design of the experiments conducted was based on deciphering which amount of omeprazole is released from each drug delivery system, the effect of the pH-value of the dissolution medium and the use of different combinations of the excipients affecting the API’s release rate. Of the pharmaceutical forms studied, the omeprazole tablets containing 20 mg of the active substance/tablet were prepared by the Laboratory of Polymer and Colour Chemistry and Technology of the Section of Chemical Technology and Industrial Chemistry of the Depatment of Chemistry of Aristotle University of Thessaloniki, while the tablets, coated and uncoated, whilst those with 5 mg of the API/tablet were prepared by the Laboratory of Pharmaceutical Technology of the Section of Pharmaceutical Technology of the Department of Pharmacy of National and Kapodistrian University of Athens. The tablets are matrix systems and the excipients used for their preparation are: Chitosan in three different types (neat, copolymer of Chitosan with Oxidized Dextran and copolymer of Chitosan with Oxidized Cellulose NanoCrystals), Sodium Alginate, Magnesium Stearate, Lactose monohydrate and Eudragit® L100-55.
Omeprazole is a pharmaceutical substance, which belongs to the class of proton pump inhibitors, namely, the hydrogen/potassium ATPase, which is found in the parietal cells of the stomach. In particular, omeprazole binds covalently to the pump and inhibits the secretion of acid (hydrogen ions) in the gastric lumen, resulting in the reduction of stomach acidity. This action makes omeprazole useful in the treatment of pathological conditions associated with increased stomach acidity, such as gastritis and peptic ulcers, gastroesophageal reflux disease and Zollinger-Ellison disease.
In order to exert its effect, omeprazole needs to be protected from gastric acid, to be released into the small intestine and absorbed and to reach the parietal cells of the stomach. More specifically, omeprazole is unstable in the acidic environment of the stomach, because it is converted into a form that cannot be absorbed by the small intestine. Therefore, the pharmaceutical dosage forms of omeprazole are usually solid, by reason of better stability, and gastro-resistant. In more detail, the capsules are prepared with a gastro-resistant shell and, correspondingly, the tablets are coated with a gastro-resistant coating. Gastro-resistance is achieved by the appropriate choice of excipients for capsule shells or tablet coating, which keep the pharmaceutical dosage form intact in the acidic environment of the stomach, preventing the release of the active substance. Conversely, when the pharmaceutical dosage form comes into contact with the more alkaline environment of the small intestine, it disintegrates and immediately releases the active substance, due to the properties of the aforementioned excipients. Therefore, the ideal omeprazole delivery system is a delayed-release system, which does not release the active substance into the gastric environment, while releasing it directly into the small intestine.
The main reasons for the development of new pharmaceutical dosage forms of omeprazole, especially for pediatric patients, are its increased use, the need to limit the long-term adverse effects of the active substance and the safer, more effective and easier use of dosage forms by pediatric patients, leading to better compliance. To this end, the production of mini-tablets, which have suitable dimensions for safe ingestion by children, have been developed.
From the results obtained in the context of this work, it is concluded that the choice of the type and quantity of excipients, polymeric and non-polymeric, for use in the preparation of pharmaceutical dosage forms is decisive for the release of the active substance. Thus, LOSEC® capsules with 20 mg of active substance/capsule are a model of an effective pharmaceutical form of omeprazole for the development of new systems with more improved properties. Regarding the tablet matrix, it was found that, at pH 6.8, the copolymers endow the omeprazole delivery system with increased and faster release capacity, compared to the neat Chitosan polymer, while, in tablets with the neat Chitosan polymer, the increase in the content of Lactose monohydrate in combination with the simultaneous decreased quantity of Chitosan and Sodium Alginate also has an enhancing effect on the release. Regarding the coating of the tablets, the following have been concluded: a) the effective gastro-resistance of the coating (at pH=4.5), when Eudragit® L100-55 is used as the main component in combination with Lactose monohydrate or alone, b) the enhanced release at pH 6.8, due to the increase of the content of Lactose monohydrate combined with the concomitant decrease of the content of Eudragit® L100-55, and c) the deceleration of release, at pH 6.8, when the total amount of coating increases, with Eudragit® L100-55 as the main component and Lactose monohydrate as a secondary component.
Keywords:
Omeprazole, Chitosan, Oxidized Dextran, Oxidized Cellulose, Copolymer, Sodium Alginate, Lactose Monohydrate, Eudragit®L100-55, Gastro-resistance, Capsules, Tablets, Mini-tablets
