RESEARCH ARTICLE
A Systematic Study on Manufacturing of Prilled Microgels into Lipids for Oral Protein Delivery
Jan Kendall De Kruif,
Felipe Varum, Roberto Bravo,
Martin Kuentz,
Jan Kendall De Kruif
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
Search for more papers by this authorRoberto Bravo
Tillotts Pharma AG, Rheinfelden, 4310 Switzerland
Search for more papers by this authorCorresponding Author
Martin Kuentz
Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, 4132 Switzerland
Telephone: +41-61-467-46-88; Fax: +41-61-467-47-01; E-mail: [email protected]Search for more papers by this authorJan Kendall De Kruif,
Felipe Varum, Roberto Bravo,
Martin Kuentz,
Jan Kendall De Kruif
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
Search for more papers by this authorRoberto Bravo
Tillotts Pharma AG, Rheinfelden, 4310 Switzerland
Search for more papers by this authorCorresponding Author
Martin Kuentz
Institute of Pharma Technology, University of Applied Sciences and Arts Northwestern Switzerland, Muttenz, 4132 Switzerland
Telephone: +41-61-467-46-88; Fax: +41-61-467-47-01; E-mail: [email protected]Search for more papers by this authorFirst published: 24 June 2015
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. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 104:3351–3365, 2015
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