A Pharmaceutical study on gastroretentive pulsatile delivery systems for certain chronological drugs / A Thesis presented by M.Sc. Rasha Salaheldin Mahmoud Elbatanony, (Assistant lecturer, Department of Pharmaceutics and Pharmaceutical Technology, Future University in Egypt)

Supervision of Prof. Dr. Seham Abdel Khalek Elkheshen, (Professor of Pharmaceutics and Industrial Pharmacy, Dean of Faculty of Pharmacy, Future University in Egypt), Dr. Mina Ibrahim Tadros, (Associate Professor of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Cairo University)

Thesis (Ph.D.)-Cairo university, Faculty of pharmacy, Department of pharmaceutics and industrial pharmacy, 2016.

Includes bibliographical references.

It is now well established that maintaining a relatively constant plasma drug level throughout the dosage interval is not considered as an optimum situation in many conditions. Relationships between drug presence, duration of action and safety may be influenced by, among other factors, circadian rhythms. Pulsatile delivery systems may release drug at the correct time as programmed from the system, but drug may be released into a region of the gastrointestinal tract where it is only poorly absorbed or, worse, not absorbed at all. These considerations led to the development of oral pulsatile release dosage forms possessing gastric retention capabilities that allow the systems to remain above or within the window of absorption, and extend the period of absorption of drugs exhibiting limited window of absorption in the upper gastrointestinal tract. A combination of gastroretentive and pulsatile principles offers an advantage that the system can achieve long residence time in the stomach, sufficient for delivering an adequate amount of drug at the right time, particularly in diseases requiring medication during sleeping and awakening. The press-coated tablet can be considered an example from Chrontropic system. It consists of a fast disintegration or modified release core, coated by compression with a solid barrier, commonly made of polymeric material, a diluent (as a release modifier) and drug (for both rapid and extended release). Press coated tablets may be modified to provide different release patterns, by varying the drug distribution and type of polymers used in the core and outer coating shell. It can be classified as a chronopharmaceutical technology, in that it provides a solid dosage form for drug delivery in a pulsatile fashion rather than continuously, and at predetermined times and sites following oral administration. Core in cup could be also considered as approach for gastroretentive pulsatile drug delivery. It consists of a core tablet containing the drug, an impermeable outer shell and top cover layer barrier of hydrophilic polymer. Water ingress into the osmotic core causes it to swell, rupturing the external coat and releasing the drug in pulsatile mode. In a trial to prepare a gastroretentive dosage form with pulsatile drug release profile, two approaches were investigated in this thesis. The oral bioavailabilities of the drugs from two selected formulae were compared to the commercial products in healthy human volunteers.

Text in English, abstracts in English and Arabic.