Unit:
Κατεύθυνση Βιομηχανική ΦαρμακευτικήLibrary of the School of Science
Author:
Χαρκοφτάκη Γεωργία
Dissertation committee:
Παναγιώτης Μαχαίρας, Καθηγητής ΕΚΠΑ (Επιβλέπων), Μιχαήλ Κουπάρης, Καθηγητής ΕΚΠΑ, Γεωργία Βαλσαμή, Επίκουρη καθηγήτρια ΕΚΠΑ, Σοφία Τσελένη-Μπαλαφούτα, Καθηγήτρια ΕΚΠΑ, Σοφία Αντιμησιάρη, Καθηγήτρια Πανεπιστημίου Πατρών, Ζωή Παπαδοπούλου Νταϊφώτη, Καθηγήτρια ΕΚΠΑ, Δημήτριος Φατούρος, Επίκουρος καθηγητής ΑΠΘ
Original Title:
In vitro και in vivo μελέτες για την ανάπτυξη per os χορηγούμενων διαλυμάτων Μη Στεροειδών Αντιφλεγμονωδών Φαρμάκων με βάση το γάλα.
Summary:
The aim of this study was to develop milk-based formulations for ionized drugs
by adding alkaline drug containing solution into 150 mL full fat milk in order
to present the drug in a dissolved form and take advantage of the
gastroprotective characteristics of milk. Solubility studies of the following
non-steroidal anti-inflammatory drugs (NSAIDs): mefenamic acid, tolfenamic
acid, ketoprofen, meloxicam, tenoxicam and nimesulide in phosphate and
glycine-NaOH buffers at nominal pH 8–12, were performed. Using pH-dependent
solubility profiles the formation of drug aggregates in phosphate buffer
solution was explored. All the non-steroidal anti-inflammatory drugs exhibited
increased solubility in the alkaline buffers and high concentration NSAIDs–
alkaline buffer solutions were prepared containing the corresponding
therapeutic dose. These solutions were added in 150 mL full fat ultra-high
temperature processing (UHT) milk. The actual pH values (range 6.7–7.7) of the
final NSAIDs–milk formulations were very close to milk pH. Long term and
accelerated stability studies were performed in order to determine the drug
concentration and the pH changes of the alkaline solutions, according to the
FDA stability guidelines. The physicochemical characteristics of full fat UHT
milk after the
addition of strong alkaline aqueous buffer solutions containing various
concentrations of non steroidal anti-inflammatory were investigated. Stability
and content uniformity studies of meloxicam/milk formulation were performed.
The meloxicam/milk formulation was orally administered to one healthy volunteer
and the pharmacokinetic parameters were calculated. In vivo studies were
performed in order to study gastric ulceration of the meloxicam/milk
formulation in comparison to a commercial tablet (Movatec®), in male Wistar
albino rats.
In conclusion:
The high concentration alkaline buffer solutions of NSAIDs are stable.
The final milk-based formulations of the NSAIDs have physiologic pH
values for per os administration.
The in vivo studies of the NSAIDs milk-based formulations are
promising, thanks to their good pharmacokinetic properties and their
gastroprotective properties.
Keywords:
NSAIDs, Milk, Solubility, Stomach irritation, Meloxicam
Number of references:
180