Modulating drug release and matrix erosion of alginate matrix capsules by microenvironmental interaction with calcium ion.
Effect of calcium gluconate (CG) content on release of dextromethorphan hydrobromide (DMP), model drug, from capsules containing low and medium viscosity grades of sodium alginate (SA) was investigated in different dissolution media. Matrix erosion of the SA matrix capsules in distilled water and pH 7.4 phosphate buffer was compared. Molecular interaction of SA with calcium ion in surface gel layer of the SA matrix capsules was examined using Fourier transform infrared spectroscopy and differential scanning calorimetry. In distilled water and pH 7.4 phosphate buffer, DMP release rate depended on the viscosity grade of SA, whereas a comparable DMP release rate was found in 0.1N HCl. Incorporation of CG into the SA matrix capsules caused a faster drug release in acidic medium because CG acted as a channeling agent in the hydrated insoluble gel matrix of alginic acid. Interaction of calcium ions with carboxyl groups of SA could be formed in surface gel layer of hydrated matrix capsules in distilled water. This led to a more rigid matrix gel structure that caused a slower drug release and matrix erosion. In contrast, the extent of this interaction in pH 7.4 phosphate buffer was less than that in distilled water because the common ion effect and high concentration of sodium ion retarded the hydration of SA and the binding of calcium ions with carboxyl groups of SA. Thus, a small change in drug release and matrix erosion was observed. This finding suggests that microenvironmental interaction between hydrated SA and calcium ion in distilled water could be created in the formulations prepared using low compression force. Moreover, incorporation of CG could moderate drug release and matrix erosion of the SA matrix capsules.
Pongjanyakul
Thaned
T
Faculty of Pharmaceutical Sciences, Khon Kaen University, Khon Kaen, Thailand. thaned@kku.ac.th
Puttipipatkhachorn
Satit
S
D000464:Alginates / Q000737:chemistry*; D000996:Antitussive Agents / Q000008:administration & dosage / Q000737:chemistry*; D002125:Calcium Gluconate / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002214:Capsules; D003915:Dextromethorphan / Q000008:administration & dosage / Q000737:chemistry*; D004777:Environment; D005079:Excipients; D012995:Solubility; D012997:Solvents; D017550:Spectroscopy, Fourier Transform Infrared; D014783:Viscosity
D000464:Alginates; D000996:Antitussive Agents; D002214:Capsules; D005079:Excipients; D012997:Solvents; D003915:Dextromethorphan; D002125:Calcium Gluconate