Parameters affecting the drug release from in situ gelling nasal inserts

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 63; no. 3; pp. 310 - 319
• Main Authors: Bertram, Ulrike, Bodmeier, Roland
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.07.2006; Elsevier Science
• Subjects: Administration, Intranasal; Biological and medical sciences; Carrageenan; Carrageenan - administration & dosage; Delayed-Action Preparations - chemistry; Drug–polymer interaction; Extended drug release; Gels - chemistry; General pharmacology; HPMC; Hydrogen-Ion Concentration; Hypromellose Derivatives; Inserts; Medical sciences; Methylcellulose - administration & dosage; Methylcellulose - analogs & derivatives; Nasal drug delivery; Nasal Mucosa - metabolism; Osmolar Concentration; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Release medium; Solubility; Static Electricity; Nasal drug delivery; Release medium; Drug–polymer interaction; Inserts; Carrageenan; Extended drug release; HPMC; Drug; Pharmaceutical technology; Controlled release form; In situ; Polymer; Intranasal administration; Insert; Dosage form; Drug interaction; Drug-polymer interaction; Release
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2005.11.008

The purpose of the study was to investigate the influence of physicochemical drug properties, drug loading, and composition of the release medium on the drug release from in situ gelling nasal inserts. Sponge-like nasal inserts of carrageenan and HPMC K15M with the model drugs oxymetazoline HCl, diprophyllin, and acetaminophen (APAP) were prepared by lyophilization. Drug release studies at different drug loadings were performed in various release media. Raman analysis, DSC, and SEM were conducted to analyze the physical state of the drugs in the inserts. All drugs were dissolved in the solid HPMC inserts and were released at similar rates at all investigated loadings except for the least soluble APAP. APAP concentrations in the hydrating HPMC K15M inserts in excess of its solubility limit resulted in reduced relative release rates at higher drug loadings. Drug–polymer interactions (formation of less soluble drug–polymer salts) resulted in a slower release of oxymetazoline HCl from carrageenan inserts than from HPMC K15M inserts. Changes in the composition of the release medium affected the water uptake of carrageenan but not of HPMC K15M inserts. Oxymetazoline release from carrageenan inserts increased with higher Na +-content of the medium because of ion exchange and at low (pH 2) as well as at high pH (pH 10). The osmolality of the release medium had no effect. The solubility of the drug, its physical state in the polymer matrix, and drug–polymer interactions governed the drug release from nasal inserts. The release from inserts prepared with oppositely charged polymers and drugs was influenced by electrostatic drug–polymer interactions and by the composition of the release medium.