title: On prilling of hydrophilic microgels in lipid dispersions using mono-N-carboxymethyl chitosan for oral biologicals delivery.
abstract: Oral delivery of biologicals is a thriving field in pharmaceutics and the first challenge is to achieve a stable drug product. Interesting is prilling of a drug-containing polymeric solution as microgel into an aqueous hardening bath where crosslinking occurs. However, to deliver a final dosage form, for example, soft gelatin capsules, the aqueous hardening bath must be removed, thus leading to manufacturing processes that are potentially harmful for the active. The current work introduces a prilling method with a lipid-based hardening bath, which could theoretically be filled directly into capsules. Bovine serum albumin (BSA) and mono-N-carboxymethyl chitosan (MCC) were selected as model biological and encapsulating polymer, respectively. Several nonaqueous formulations of the receiving bath were investigated; calcium chloride was added to these formulations to allow the MCC gelling. The obtained microgels had average diameters of ∼300 μm and spherical to toroidal shapes, according to the hardening bath composition. Along with a high encapsulation efficiency (>85%), the microgels protected the BSA from any denaturing effect of the hardening bath. The release study showed a rather fast BSA release within the first 10 min from most microgels. This novel approach demonstrated technical viability for encapsulation of biologicals using lipid formulations regarding oral delivery.
authors.affiliation: Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland; Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
authors.forename: Jan Kendall
authors.initials: JK
authors.lastname: De Kruif
authors.affiliation: Institute of Chemistry and Bioanalytics, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland.
authors.forename: Elizaveta
authors.initials: E
authors.lastname: Fasler-Kan
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Felipe
authors.initials: F
authors.lastname: Varum
authors.affiliation: Tillotts Pharma AG, Rheinfelden, Switzerland.
authors.forename: Roberto
authors.initials: R
authors.lastname: Bravo
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, Switzerland. Electronic address: martin.kuentz@fhnw.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D000284:Administration, Oral; D001688:Biological Products / Q000008:administration & dosage / Q000737:chemistry*; D002214:Capsules; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000737:chemistry*; D002942:Circular Dichroism; D004337:Drug Carriers; D004355:Drug Stability; D004591:Electrophoresis, Polyacrylamide Gel; D005782:Gels; D006244:Hardness; D057927:Hydrophobic and Hydrophilic Interactions; D007700:Kinetics; D008055:Lipids / Q000737:chemistry*; D011489:Protein Denaturation; D055550:Protein Stability; D012710:Serum Albumin, Bovine / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013050:Spectrometry, Fluorescence; D013678:Technology, Pharmaceutical / Q000379:methods
chemical_list: D001688:Biological Products; D002214:Capsules; D004337:Drug Carriers; D005782:Gels; D008055:Lipids; D012710:Serum Albumin, Bovine; C068302:N-(carboxymethyl)chitosan; D048271:Chitosan
keywords: chitosan; hydrogel; lipid-based dispersion; macromolecular drug delivery; microencapsulation; oral drug delivery; prilling; vibrating nozzle