title: Importance of air bubbles in the core of coated pellets: Synchrotron X-ray microtomography allows for new insights.
abstract: High-resolution X-ray microtomography was used to get deeper insight into the underlying mass transport mechanisms controlling drug release from coated pellets. Sugar starter cores were layered with propranolol HCl and subsequently coated with Kollicoat SR, plasticized with 10% TEC. Importantly, synchrotron X-ray computed microtomography (SR-μCT) allowed direct, non-invasive monitoring of crack formation in the film coatings upon exposure to the release medium. Propranolol HCl, as well as very small sugar particles from the pellets' core, were expulsed through these cracks into the surrounding bulk fluid. Interestingly, SR-μCT also revealed the existence of numerous tiny, air-filled pores (varying in size and shape) in the pellet cores before exposure to the release medium. Upon water penetration into the system, the contents of the pellet cores became semi-solid/liquid. Consequently, the air-pockets became mobile and fused together. They steadily increased in size (and decreased in number). Importantly, "big" air bubbles were often located in close vicinity of a crack within the film coating. Thus, they play a potentially crucial role for the control of drug release from coated pellets.
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, 59000 Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Fahier
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, 59000 Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Muschert
authors.affiliation: Novitom, 1 Place Firmin Gautier, 38000 Grenoble, France.
authors.forename: B
authors.initials: B
authors.lastname: Fayard
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, 59000 Lille, France.
authors.forename: C
authors.initials: C
authors.lastname: Velghe
authors.affiliation: Early Development Center, Merck Sharp & Dohme, Hertford Road, Hoddesdon EN11 9BU, UK.
authors.forename: G
authors.initials: G
authors.lastname: Byrne
authors.affiliation: Novitom, 1 Place Firmin Gautier, 38000 Grenoble, France.
authors.forename: J
authors.initials: J
authors.lastname: Doucet
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, 59000 Lille, France.
authors.forename: F
authors.initials: F
authors.lastname: Siepmann
authors.affiliation: Univ. Lille, Inserm, CHU Lille, U1008 - Controlled Drug Delivery Systems and Biomaterials, 59000 Lille, France. Electronic address: juergen.siepmann@univ-lille2.fr.
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
mesh_terms: D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000737:chemistry; D002951:Citrates / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000737:chemistry*; D065546:Drug Liberation; D010968:Plasticizers / Q000737:chemistry; D011145:Polyvinyls / Q000737:chemistry*; D011433:Propranolol / Q000008:administration & dosage* / Q000737:chemistry; D017356:Synchrotrons; D055114:X-Ray Microtomography
chemical_list: D000959:Antihypertensive Agents; D002951:Citrates; D003692:Delayed-Action Preparations; D010968:Plasticizers; D011145:Polyvinyls; C013215:polyvinyl acetate; C023001:ethyl citrate; D011433:Propranolol
keywords: Air bubble; Coated pellets; Drug release mechanisms; Film coating; X-ray microtomography