Modulation of microenvironmental pH and crystallinity of ionizable telmisartan using alkalizers in solid dispersions for controlled release.
The present work is an original evaluation of the microenvironmental pH (pH(M)) and crystallinity of an ionizable drug in order to enhance its dissolution using alkalizers in polyethylene glycol 6000 (PEG 6000) based solid dispersions (SDs). Telmisartan (TEL) was chosen as a model drug due to its poor and pH-dependent water solubility. The nine alkalizers used to modify the pH of TEL were MgO, NaOH, KOH, Na2CO3, NaHCO, bentonite, Na2HPO4, K2HPO4 and arginine. MgO, NaOH, KOH and Na2CO3 in the SD system significantly increased the drug dissolution rate in intestinal fluid (pH 6.8) and water. Modulation of pH(M) was clearly observed as a function of time at different fractional dimensions of tablet. Structural change in drug crystallinity to an amorphous form was also a contributing factor based on differential scanning calorimetry (DSC) thermograms and powder X-ray diffraction (PXRD) patterns. The drug frequency of the CO band decreased and the O-H broad band in the Fourier transform infrared (FTIR) spectra disappeared when these alkalizers were added. It was evident that the alkalizers in PEG 6000 based SDs synergistically enhanced dissolution of TEL not only by modulating pH(M) but also by changing drug crystallinity to an amorphous form via molecular interactions.
Tran
Phuong Ha Lien
PH
National Research Lab. for Bioavailability Control, College of Pharmacy, Kangwon National University, Chuncheon, Republic of Korea.
Tran
Huyen Thi Thanh
HT
Lee
Beom-Jin
BJ
D000468:Alkalies / Q000737:chemistry*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000737:chemistry*; D001562:Benzimidazoles / Q000737:chemistry*; D001565:Benzoates / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003460:Crystallization; D018360:Crystallography, X-Ray; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D011092:Polyethylene Glycols / Q000737:chemistry; D033362:Powder Diffraction; D012995:Solubility; D017550:Spectroscopy, Fourier Transform Infrared; D013678:Technology, Pharmaceutical / Q000379:methods; D000077333:Telmisartan
D000468:Alkalies; D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001565:Benzoates; D003692:Delayed-Action Preparations; D011092:Polyethylene Glycols; D000077333:Telmisartan