Sustained-release multiparticulates for oral delivery of a novel peptidic ghrelin agonist: Formulation design and in vitro characterization

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dc.contributor.authorHowick, Kenneth P.
dc.contributor.authorAlam, Ryan
dc.contributor.authorChruścicka, Barbara
dc.contributor.authorKandil, Dalia
dc.contributor.authorFitzpatrick, Dara
dc.contributor.authorRyan, Aoife M.
dc.contributor.authorCryan, John F.
dc.contributor.authorSchellekens, Harriët
dc.contributor.authorGriffin, Brendan T.
dc.contributor.funderEnterprise Irelanden
dc.date.accessioned2017-11-27T10:12:09Z
dc.date.available2017-11-27T10:12:09Z
dc.date.issued2017-11-23
dc.description.abstractThere is an impetus to provide appropriate sustained release oral delivery vehicles to protect biofunctional peptide loads from gastric degradation in vivo. This study describes the generation of a high load capacity pellet formulation for sustained release of a freely water-soluble dairy-derived hydrolysate, FHI-2571. The activity of this novel peptidic ghrelin receptor agonist is reported using in vitro calcium mobilization assays. Conventional extrusion spheronization was then used to prepare peptide-loaded pellets which were subsequently coated with ethylcellulose (EC) film coats using a fluid bed coating system in bottom spray (Wurster) mode. Aqueous-based EC coating dispersions produced mechanically brittle coats which fractured due to osmotic pressure build-up within pellets in simulated media. In contrast, an ethanolic-based EC coating solution provided robust, near zero-order release in both USP Type 1 and Type 4 dissolution studies. Interestingly, the functionality of aqueous-based EC film coats was restored by first layering pellets with a methacrylic acid copolymer (MA) subcoat, thereby hindering pellet core swelling in acidic media. Broadband Acoustic Resonance Dissolution Spectroscopy (BARDS) was utilised as a complementary technique to confirm the results seen in USP dissolution studies. Retention of activity of the ghrelinergic peptide hydrolysate in the final encapsulated product was confirmed as being greater than 80%. The described pellet formulation is amenable to oral dosing in small animal studies in order to assess in vivo efficacy of the whey-derived ghrelinergic hydrolysate. In more general terms, it is also suitable as a delivery vehicle for peptide-based bioactives to special population groups e.g paediatric and geriatric.en
dc.description.sponsorshipEnterprise Ireland (grant no. TC20130001)en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationHowick, K., Alam, R., Chruscicka, B., Kandil, D., Fitzpatrick, D., Ryan, A. M., Cryan, J. F., Schellekens, H. and Griffin, B. T. (2017) 'Sustained-Release Multiparticulates for Oral Delivery of a Novel Peptidic Ghrelin Agonist: Formulation Design and In Vitro Characterization', International Journal of Pharmaceutics, 536(1), pp. 63-72. doi: 10.1016/j.ijpharm.2017.11.051en
dc.identifier.doi10.1016/j.ijpharm.2017.11.051
dc.identifier.endpage72
dc.identifier.issn0378-5173
dc.identifier.issued1
dc.identifier.journaltitleInternational Journal of Pharmaceuticsen
dc.identifier.startpage63
dc.identifier.urihttps://hdl.handle.net/10468/5092
dc.identifier.volume536
dc.language.isoenen
dc.publisherElsevieren
dc.relation.urihttps://www.sciencedirect.com/science/article/pii/S0378517317311067
dc.rights© 2017 Elsevier B.V. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.en
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectPelleten
dc.subjectFilm coatingen
dc.subjectSustained-releaseen
dc.subjectBioactive peptideen
dc.subjectGhrelinen
dc.titleSustained-release multiparticulates for oral delivery of a novel peptidic ghrelin agonist: Formulation design and in vitro characterizationen
dc.typeArticle (peer-reviewed)en
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