Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali

Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced b...

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Main Author:	Razali, Sharipah
Format:	Thesis
Language:	English
Published:	2022
Subjects:	Indexes (General)
Online Access:	https://ir.uitm.edu.my/id/eprint/76547/1/76547.pdf
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id	my-uitm-ir.76547
record_format	uketd_dc
spelling	my-uitm-ir.765472023-05-29T03:25:35Z Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali 2022 Razali, Sharipah Indexes (General) Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced by compressing pellets with cushioning agent unless otherwise stated. Dome matrix was assembly of modules with pre-determined compact formulation and drug release characteristics. Melatonin loaded alginate/chitosan-less matrix exhibited almost 100% melatonin release within 8 h gastrointestinal transit with low viscosity hydroxypropyl methylcellulose as cushioning agent. Delayed-release alginate-chitosan caffeine matrix was not attainable through polymer coating due to the premature coat detachment. Admixing of cushioning agent high viscosity hydroxypropyl methylcellulose and high viscosity ethyl cellulose (9:1 weight ratio) with coat-free caffeine loaded particulates introduced delayed-release response via hydroxypropyl methylcellulose swelled in early dissolution phase and ethyl cellulose sustained matrix hydrophobicity at prolonged phase. The caffeine was release substantially in colonic fluid in response to matrix polymers being degraded by rat colonic content. Dome matrix with gastric- specific sustained-release melatonin and intestinal-specific delayed-release caffeine was introduced as an alternative design to introduce melatonin-induced sleep phase then caffeine-stimulated wake phase in restoration of jet lag sleep-wake cycle. To enable efficient gastric and intestinal targeting, intermediate dispersible modules were introduced to detach the melatonin module from the caffeine module along the gastrointestinal transit. The Dome matrix was an assembly of caffeine module with melatonin modules capped at both ends via intermediate dispersible modules (75:25 weight ratio of crospovidone and low viscosity hydroxypropyl methylcellulose). Dome matrix was designed with melatonin module in void configuration and caffeine module in pile configuration to enable the melatonin module to float in the gastric cavity and caffeine module to transit downwards into the intestinal tract. Through using intermediate dispersible module, the melatonin module was detachable from the Dome matrix without incurring surface damages to the caffeine module. The detachment of melatonin module with minimal caffeine module damage further prolonged the caffeine release, with majority of caffeine being delivered in the colonic region (> 85 %). Dome matrix with dual drug release kinetics and targeting sites was produced to introduce melatonin-induced sleep phase then caffeine- stimulated wake phase 2022 Thesis https://ir.uitm.edu.my/id/eprint/76547/ https://ir.uitm.edu.my/id/eprint/76547/1/76547.pdf text en public phd doctoral Universiti Teknologi MARA (UiTM) Faculty of Pharmacy Wong, Tin Wui
institution	Universiti Teknologi MARA
collection	UiTM Institutional Repository
language	English
advisor	Wong, Tin Wui
topic	Indexes (General)
spellingShingle	Indexes (General) Razali, Sharipah Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali
description	Multi-particulate Dome matrix with sustained-release melatonin and delayed-release caffeine was designed to restore jet lag sleep-wake cycle. The polymeric pellets were produced using extrusion-spheronization technique and fluid-bed coated when applicable. The compact and Dome module were produced by compressing pellets with cushioning agent unless otherwise stated. Dome matrix was assembly of modules with pre-determined compact formulation and drug release characteristics. Melatonin loaded alginate/chitosan-less matrix exhibited almost 100% melatonin release within 8 h gastrointestinal transit with low viscosity hydroxypropyl methylcellulose as cushioning agent. Delayed-release alginate-chitosan caffeine matrix was not attainable through polymer coating due to the premature coat detachment. Admixing of cushioning agent high viscosity hydroxypropyl methylcellulose and high viscosity ethyl cellulose (9:1 weight ratio) with coat-free caffeine loaded particulates introduced delayed-release response via hydroxypropyl methylcellulose swelled in early dissolution phase and ethyl cellulose sustained matrix hydrophobicity at prolonged phase. The caffeine was release substantially in colonic fluid in response to matrix polymers being degraded by rat colonic content. Dome matrix with gastric- specific sustained-release melatonin and intestinal-specific delayed-release caffeine was introduced as an alternative design to introduce melatonin-induced sleep phase then caffeine-stimulated wake phase in restoration of jet lag sleep-wake cycle. To enable efficient gastric and intestinal targeting, intermediate dispersible modules were introduced to detach the melatonin module from the caffeine module along the gastrointestinal transit. The Dome matrix was an assembly of caffeine module with melatonin modules capped at both ends via intermediate dispersible modules (75:25 weight ratio of crospovidone and low viscosity hydroxypropyl methylcellulose). Dome matrix was designed with melatonin module in void configuration and caffeine module in pile configuration to enable the melatonin module to float in the gastric cavity and caffeine module to transit downwards into the intestinal tract. Through using intermediate dispersible module, the melatonin module was detachable from the Dome matrix without incurring surface damages to the caffeine module. The detachment of melatonin module with minimal caffeine module damage further prolonged the caffeine release, with majority of caffeine being delivered in the colonic region (> 85 %). Dome matrix with dual drug release kinetics and targeting sites was produced to introduce melatonin-induced sleep phase then caffeine- stimulated wake phase
format	Thesis
qualification_name	Doctor of Philosophy (PhD.)
qualification_level	Doctorate
author	Razali, Sharipah
author_facet	Razali, Sharipah
author_sort	Razali, Sharipah
title	Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali
title_short	Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali
title_full	Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali
title_fullStr	Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali
title_full_unstemmed	Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali
title_sort	design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / sharipah razali
granting_institution	Universiti Teknologi MARA (UiTM)
granting_department	Faculty of Pharmacy
publishDate	2022
url	https://ir.uitm.edu.my/id/eprint/76547/1/76547.pdf
_version_	1783736110518632448

Design of multi-particulate compact and “dome matrix” with sustained-release melatonin and delayed- release caffeine for jet lag treatment / Sharipah Razali

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