title: Role of Lipid Blooming and Crystallite Size in the Performance of Highly Soluble Drug-Loaded Microcapsules.
abstract: Hot-melt coating is of growing interest, because it does not require solvents, resulting in reduced process times and costs. However, excipients for this technology are mainly triacylglycerides (TAGs) or their derivatives, which exhibit polymorphism, surface disruption, and complex crystallite networks, affecting the release profile of produced microcapsules. In this work, anhydrous citric acid crystals were coated with molten tristearin using conventional inlet air temperatures (microcapsules A) and temperatures above the melting point of α-form (microcapsules B). Additionally, microcapsules A were tempered to achieve polymorphic stability (microcapsules AB). The product yield and coating efficacy were above 90% and 97%, respectively, demonstrating the feasibility and efficacy of the process. Small angle X-ray scattering analysis confirmed that the tristearin shell of microcapsules B is in the β-form with a larger average crystallite size than microcapsules A and AB. Scanning electron microscopy images revealed a nonbloomed surface of microcapsules B. We showed that blooming does not play a critical role in the drug release, but the apparent diffusion coefficient of drug is dramatically reduced by increasing TAGs crystallite size and resulting tortuosity. This work brings new insights on the micrometric properties of solid lipid dosage forms, being an important step to prevent the overuse of excipients with unknown toxicity.
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria; Karl-Franzens-University Graz, Department of Pharmaceutical Technology, Graz, Austria.
authors.forename: Diogo G
authors.initials: DG
authors.lastname: Lopes
authors.affiliation: Karl-Franzens-University Graz, Department of Pharmaceutical Technology, Graz, Austria.
authors.forename: Karin
authors.initials: K
authors.lastname: Becker
authors.affiliation: Cremer Oleo GmbH and Company KG, Witten, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Stehr
authors.affiliation: Cremer Oleo GmbH and Company KG, Witten, Germany.
authors.forename: Dirk
authors.initials: D
authors.lastname: Lochmann
authors.affiliation: Hermes Arzneimittel GmbH, Großelohe, Germany.
authors.forename: Detlev
authors.initials: D
authors.lastname: Haack
authors.affiliation: Karl-Franzens-University Graz, Department of Pharmaceutical Technology, Graz, Austria.
authors.forename: Andreas
authors.initials: A
authors.lastname: Zimmer
authors.affiliation: Research Center Pharmaceutical Engineering GmbH, Graz, Austria. Electronic address: sharareh.salar-behzadi@tugraz.at.
authors.forename: Sharareh
authors.initials: S
authors.lastname: Salar-Behzadi
mesh_terms: D002214:Capsules / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D019343:Citric Acid / Q000737:chemistry; D004304:Dosage Forms; D005079:Excipients / Q000737:chemistry; D008055:Lipids / Q000737:chemistry*; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D012995:Solubility; D013696:Temperature; D014280:Triglycerides / Q000737:chemistry
chemical_list: D002214:Capsules; D004304:Dosage Forms; D005079:Excipients; D008055:Lipids; D014280:Triglycerides; D019343:Citric Acid; C022618:tristearin
keywords: crystal growth; crystal structure; dissolution; excipients; lipids; microencapsulation; polymorphism; solid state