title: A Systematic Study on Manufacturing of Prilled Microgels into Lipids for Oral Protein Delivery.
abstract: The development of novel systems with oral protein delivery as ultimate goal represents an important field of pharmaceutics. Prilling of protein-loaded polymeric solutions into lipid-based hardening baths could provide here an attractive formulating technology. As the obtained microgel dispersion can be directly capsule-filled, no drying step is required and thermal drug degradation is avoided. This study aims to find excipient combinations for the novel prilling process and investigate systematically diverse material and process factors. Bovine serum albumin and mono-N-carboxymethyl chitosan were selected as model protein and prilling polymer, respectively. The prilling suitability of 880 formulations was screened with 60 ternary phase diagrams comprising two co-solvents, 10 different glycerides, and three so-called complementary excipients. Preliminary capsule compatibility was tested for one month on 245 formulations in hard and soft capsules with different shell materials. Ternary phase diagrams' center points were used to evaluate morphology, encapsulation efficiency, and protein stability of the prilled microgels. As result, several formulations proved suitable for prilling and compatible for capsule filling. Statistical analysis using partial least square regression revealed significant factors regarding different quality attributes of microgel dispersions. Therefore, an improved understanding was obtained for this promising drug delivery approach.
authors.affiliation: Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, 4132, Switzerland.|Department of Pharmaceutical Sciences, University of Basel, Basel, 4056, Switzerland.
authors.forename: Jan Kendall
authors.initials: JK
authors.lastname: De Kruif
authors.affiliation: Tillotts Pharma AG, Rheinfelden, 4310, Switzerland.
authors.forename: Felipe
authors.initials: F
authors.lastname: Varum
authors.affiliation: Tillotts Pharma AG, Rheinfelden, 4310, 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, 4132, Switzerland.
authors.forename: Martin
authors.initials: M
authors.lastname: Kuentz
mesh_terms: D000284:Administration, Oral; D002626:Chemistry, Pharmaceutical; D016503:Drug Delivery Systems / Q000379:methods*; D004345:Drug Industry; D004355:Drug Stability; D005079:Excipients; D005782:Gels; D008055:Lipids / Q000737:chemistry*; D011506:Proteins / Q000008:administration & dosage*; D012710:Serum Albumin, Bovine / Q000737:chemistry
chemical_list: D005079:Excipients; D005782:Gels; D008055:Lipids; D011506:Proteins; D012710:Serum Albumin, Bovine
keywords: capsule compatibility; encapsulation; excipient compatibility; hydrogels; lipids; microgels; partial least squares; phase diagram; prilling; protein delivery