''Modified release studies of melatonin from ulvan hydrophilic matrices and nanofiber systems"

Postgraduate Thesis uoadl:2768884 315 Read counter

Unit:
Κατεύθυνση Βιομηχανική Φαρμακευτική
Library of the School of Science
Deposit date:
2018-06-13
Year:
2018
Author:
Tragou Konstantina
Supervisors info:
Μαριλένα Βλάχου, Επίκουρη Καθηγήτρια του Τομέα Φαρμακευτικής Τεχνολογίας, Τμήμα Φαρμακευτικής, Εθνικό και Καποδιστριακό Πανεπιστήμιο Αθηνών
Original Title:
«Μελέτες τροποποιημένης αποδέσμευσης της μελατονίνης από υδρόφιλες μήτρες ουλβανών και νανοϊνώδη υποστρώματα»
Languages:
Greek
Translated title:
''Modified release studies of melatonin from ulvan hydrophilic matrices and nanofiber systems"
Summary:
Melatonin (N-acetyl-5-methoxy tryptamine) is synthesized primarily by the pineal gland from the essential amino acid tryptophan, follows a circadian rhythm with a periodicity of approximately 24h and maintains the internal clock of the body that regulate most of the major physiological systems. The synthesis of the neurohormone in humans is regulated from the prevailing light/dark environment and it is inextricably linked to the body adaptation to the day-night cycle, with the production and secretion of the neurohormone taking place almost only during the night, as the light signals inhibit its production. Melatonin participates in many physiological functions by acting through MT1 and MT2 receptors, that belong to the G-protein receptor family. Studies have shown, that exogenous administrated melatonin in patients with sleep disturbances can induce phase shifts in the circadian rhythm, encouraging sleep quality and duration. However, the use of melatonin in dosage forms, which mimic the physiologically secreted hormone concentration versus time model, is hampered by its short biοlogical half-life and poor bioavailability.
Ιn the context of this study, a series of melatonin modified released tablets and capsules was prepared and tested in order to treat sleep onset problems and also improve the sleep quality and maintenance. Melatonin's release characteristics from these new formulations were compared with those of the market drug Circadin®. In both cases, it was indented to achieve completion of the hormone's release within eight hours. The release studies were conducted in two media, initially at pH 1.2 dissolution media and then at pH 6.8 dissolution media, in order to simulate the in vivo transferation of the drug from the gastric fluids to the intestine fluids. In some tablets, except of some commonly used excipients, it was used a new polymeric biomaterial that is extracted from the green seaweeds, known as ulvan. Ulvan is a marine polysaccharide suitable for controlled release tablet matrices, that after the interaction with the physiological fluids, starts swelling and at the same time release the incorporated drug with a sustained release rate. According to the capsules, novel fibrous biocomposites comprising melatonin were successfully prepared using the electrospinning technique. These nanofibers were then introduced into commonly used and DRcapsTM capsules, from where was studied melatonin’s release. In summary, the results of the melatonin release from all the above dosage forms showed that these combinations of marine derived ulvan and classical excipients leads to a high rate of hydration, swelling and erosion of the polymeric matrix and in that way in a high rate release of melatonin from the tablets, even if compared with other marine polysaccharides, such as sodium alginate. The electrospun nanofibers developed in the present study show potential as promising drug delivery systems for the per os administration of melatonin. At pH 1.2, the formulations CA1, CA2, PV1, HP1, HP2 and the composite formulations CAPV1-CAPV5, with hard gelatin capsules, exhibited rapid MLT release, a suitable profile for alleviating sleep onset problems. In general, the same trend is followed at pH 6.8, with the exception of CAPV1 and CAPV2. On the other hand, all formulations, composite and not, with DRcapsTM capsules filled with the nanofiber: MLT systems, are suitable for delivering melatonin in a modified manner, with a potential for treating sleep maintenance dysfunctions.
Main subject category:
Science
Keywords:
melatonin, modified release, ulvan, nanofibers
Index:
Yes
Number of index pages:
10
Contains images:
Yes
Number of references:
95
Number of pages:
177
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