Solubilization and preformulation of carbendazim

• Published in: International journal of pharmaceutics Vol. 244; no. 1; pp. 99 - 104
• Main Authors: Ni, Nina, Sanghvi, Tapan, Yalkowsky, Samuel H.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 05.09.2002; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antifungal agents; Antineoplastic agents; Benzimidazoles - chemistry; Biological and medical sciences; Buffer; Carbamates; Carbendazim; Chemistry, Pharmaceutical; Chemotherapy; Chromatography, High Pressure Liquid; Fungicides, Industrial - chemistry; General pharmacology; Hydrogen-Ion Concentration; Medical sciences; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Solubility; Solvents; Surfactant and Complexant; Buffer; Surfactant and Complexant; Carbendazim; Solubility; Antineoplastic agent; Non ionic surfactant; Oligosaccharide; Solubilization; Physical properties; Property formulation relationship; Antifungal agent; Cosolvent; Cyclodextrin; pH; Inclusion compound
• ISSN: 0378-5173; 1873-3476
• DOI: 10.1016/S0378-5173(02)00318-6

The solubilization of carbendazim by pH in combination with cosolvents, surfactants or complexants was investigated. At pH 7 the total drug solubility is 6.11±0.45 μg/ml which increases by 1–7 fold with cosolvent, surfactant or complexant. However, at pH 2 the solubility increases by 250 times. Cosolvents have a negligible effect (50% increase) on the total drug solubility at pH 2 because of the high polarity of the cationic drug. Also pH combined with nonionic surfactants does not improve solubility, as relatively less polar micelles are not able to accommodate the cationic drug. Interestingly, the total drug solubility increases by combining pH 2 with complexants, as they can form a complex with the isolated aromatic ring of both the unionized and the ionized drug. The proposed oral formulation of 1 mg/ml carbendazim at pH 2 does not precipitate in the presence of Seven Up or water. But it does precipitate with pH 7 buffer when diluted 1:10 but not 1:100 or 1:250.