Modulation of buspirone HCl release from hypromellose matrices using chitosan succinate: implications for pH-independent release.
Chitosan succinate (CS) was synthesized through the acylation of chitosan with succinic anhydride. The interaction of CS with buspirone HCl (BUSP) was evaluated using dialysis experiments and shown to result in complex with a stability constant of 2.26 mM and a capacity of 0.0362 micromol BUSP/mg CS. The extent of complexation upon dry and wet mixing of CS and BUSP was determined quantitatively using differential scanning calorimetry. The extent of the interaction was highest in wet mixtures and was found to be dependent on the pH of the granulation liquid. CS was incorporated in BUSP-containing hypromellose (HPMC) tablets using dry mixing and wet granulation with BUSP. Tablet dissolution was tested in 0.1N HCl and phosphate buffer, pH 6.8. According to f(2) and mean dissolution time results, the similarity of profiles increased as CS content increased with the highest f(2) value observed when CS was wet granulated with BUSP. Dissolution was also tested in deionized water and 5% NaCl; where increased ionic strength resulted in faster dissolution suggesting an ion exchange involvement in drug release. CS was proved effective in modulating BUSP release from HPMC matrices for pH-independent release through ionic complex formation.
Alkhatib
Hatim S
HS
Faculty of Pharmacy, University of Jordan, Amman, Jordan. h.khatib@ju.edu.jo
Aiedeh
Khaled M
KM
Bustanji
Yasser
Y
Hamed
Saja
S
Mohammad
M K
MK
Alkhalidi
Bashar
B
Najjar
Samer
S
D002065:Buspirone / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D048271:Chitosan / Q000138:chemical synthesis*; D004337:Drug Carriers; D004339:Drug Compounding; D065347:Hypromellose Derivatives; D007700:Kinetics; D008747:Methylcellulose / Q000031:analogs & derivatives* / Q000737:chemistry; D009994:Osmolar Concentration; D012965:Sodium Chloride / Q000737:chemistry; D012995:Solubility; D013055:Spectrophotometry, Infrared; D013607:Tablets; D013678:Technology, Pharmaceutical / Q000379:methods
D004337:Drug Carriers; D013607:Tablets; C119690:chitosan succinate; D065347:Hypromellose Derivatives; D012965:Sodium Chloride; D008747:Methylcellulose; D048271:Chitosan; D002065:Buspirone