Formulation development of SYN-004 (ribaxamase) oral solid dosage form, a β-lactamase to prevent intravenous antibiotic-associated dysbiosis of the colon
| Autor: | Felix Hofmann, Hans Baer, Andrew Bristol, Steven Hubert |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Drug medicine.drug_class Colon Polymers media_common.quotation_subject Chemistry Pharmaceutical 030106 microbiology Antibiotics Pharmaceutical Science Excipient Pharmaceutical formulation Pharmacology Dosage form beta-Lactamases Excipients 03 medical and health sciences chemistry.chemical_compound Drug Delivery Systems medicine Humans Cellulose media_common Dosage Forms Chemistry Hydroxypropyl cellulose Hydrogen-Ion Concentration medicine.disease Recombinant Proteins Anti-Bacterial Agents Intravenous antibiotics Delayed-Action Preparations Dysbiosis Administration Intravenous medicine.drug |
| Zdroj: | International journal of pharmaceutics. 534(1-2) |
| ISSN: | 1873-3476 |
| Popis: | SYN-004 (ribaxamase) delayed release drug product is a multi-particulate, hard capsule for oral delivery of a recombinant β-lactamase enzyme designed to degrade β-lactam antibiotics administered intravenously, and thus prevent colon dysbiosis. Here we describe the development of the SYN-004 enteric coated pellet formulation, which has been tested in multiple clinical trials. Since the SYN-004 drug substance is a buffered liquid, several binder excipients in different ratios were tested to facilitate binding of SYN-004 to sugar spheres. The binding systems were evaluated by droplet pre-evaluation and film casting tests. The most promising formulations were produced in small scale fluidized bed application runs and analyzed by dissolution tests and complementary analytical assays. Hydroxypropyl cellulose was selected as the preferred SYN-004 binding excipient. The formulation included a second, outer coat containing the enteric EUDRAGIT® L 30 D-55 polymer-based formulation to achieve gastric protection, and rapid SYN-004 release in the intestinal tract, when the pH rises above 5.5. Additional formulation improvements resulted in an increase in the SYN-004 load compared to a predecessor oral enzyme formulation (Ipsat P1A). Thus, a novel formulation and process for an orally administered enzyme was developed and used to manufacture drug product for clinical trials. |
| Databáze: | OpenAIRE |
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