title: Nano-engineering chitosan particles to sustain the release of promethazine from orodispersables.
abstract: Orally dispersing tablets (ODTs), also known as orodispersibles, were first introduced into the market in 1980s to overcome dysphagia problems amongst pediatrics and geriatrics. Despite their abilities to avoid swallowing difficulties, frequency of dosing stood as a barrier for these formulations. The aim of the current study is to produce and optimize a sustained release orally disintegrating tablets (SR-ODT), with the aid of chitosan. A design of experiment (DoE) was first performed using Minitab to determine the effect of five independent variables on three dependent responses when producing the nanoparticles using ionotopic gelation. The variables studied were (tripolyphosphate concentration TPP, chitosan concentration CS, acetic acid concentration, chitosan: tripolyphosphate ratios and stirring time) and the responses were (particle size, surface charge and encapsulation efficiency). A formulation with optimum particle size, surface charge and encapsulation efficiency was prepared and further coated with polyvinylpyrolidine (PVP), polyethylene glycol (PEG) and polyethylene co-acrylic acid (PEAA). Minitab studies revealed that the nanoparticles' particle size was affected by most of the independent variables except stirring time and the ratios of CS to TPP. The optimized nanoparticles showed particle size of 153.8±14nm, surface charge of 31.4±0.9mV and encapsulation efficiency of 99.7±0.06%. The DSC showed that PMZ was solubilized within chitosan nanoparticle, whereas SEM images indicated that all the samples were spherical in shape with smooth surface and had similar size to that measured by DLS. After coating and dispersing into the tablets' matrices, the tablets were evaluated to determine their friability, disintegration time and tensile strength. All tablets were at an appropriate friability (less than 1%) and had tensile strength above 2.5N/mm(2). Besides, all the tablets managed to disintegrate within 40s whilst sustaining the drug release over 24h.
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC), School of Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, Surrey KT1 2EE, UK.
authors.forename: Arwa Matoug
authors.initials: AM
authors.lastname: Elwerfalli
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC), School of Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, Surrey KT1 2EE, UK.
authors.forename: Ali
authors.initials: A
authors.lastname: Al-Kinani
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC), School of Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, Surrey KT1 2EE, UK; School of Pharmacy, The University of Auckland, Auckland, New Zealand.
authors.forename: Raid G
authors.initials: RG
authors.lastname: Alany
authors.affiliation: Drug Discovery, Delivery and Patient Care (DDDPC), School of Pharmacy and Chemistry, Kingston University London, Kingston Upon Thames, Surrey KT1 2EE, UK. Electronic address: a.elshaer@kingston.ac.uk.
authors.forename: Amr
authors.initials: A
authors.lastname: ElShaer
mesh_terms: D018938:Caco-2 Cells; D002152:Calorimetry, Differential Scanning; D016923:Cell Death / Q000187:drug effects; D048271:Chitosan / Q000737:chemistry*; D003692:Delayed-Action Preparations; D006244:Hardness; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D036103:Nanotechnology / Q000379:methods*; D010316:Particle Size; D011398:Promethazine / Q000737:chemistry / Q000494:pharmacology*; D012235:Rhodamines / Q000378:metabolism; D055672:Static Electricity; D013696:Temperature; D013718:Tensile Strength; D013818:Thermogravimetry; D013997:Time Factors
chemical_list: D003692:Delayed-Action Preparations; D012235:Rhodamines; C022027:lissamine rhodamine B; D048271:Chitosan; D011398:Promethazine
keywords: Chitosan; Design of experiment; Orally disintegrating tablets; Polymers; Sustained release