Solubilization of the poorly water soluble drug, telmisartan, using supercritical anti-solvent (SAS) process

Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability....

Full description

Saved in:
Bibliographic Details
Published in:International journal of pharmaceutics 2013-01, Vol.441 (1-2), p.50-55
Main Authors: Park, Junsung, Cho, Wonkyung, Cha, Kwang-Ho, Ahn, Junhyun, Han, Kang, Hwang, Sung-Joo
Format: Article
Language:English
Subjects:
Angiotensin II Type 1 Receptor Blockers - administration & dosage
Angiotensin II Type 1 Receptor Blockers - chemistry
Benzimidazoles - administration & dosage
Benzimidazoles - chemistry
Benzoates - administration & dosage
Benzoates - chemistry
bioavailability
biopharmaceuticals
crystal structure
Crystallization
dispersions
Drug Stability
Drug Storage
Excipients - chemistry
gels
Hypromellose Derivatives
Methylcellulose - analogs & derivatives
Methylcellulose - chemistry
Nanoparticles
Particle Size
polymers
Povidone - chemistry
raw materials
Solid dispersion
Solubility
solubilization
solvents
Solvents - chemistry
stabilizers
Supercritical anti-solvent process
Telmisartan
Time Factors
water solubility
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Telmisartan is a biopharmaceutical classification system (BCS) class II drug that has extremely low water solubility but is freely soluble in highly alkalized solutions. Few organic solvents can dissolve telmisartan. This solubility problem is the main obstacle achieving the desired bioavailability. Because of its unique characteristics, the supercritical anti-solvent (SAS) process was used to BCS class II drug in a variety of ways including micronization, amorphization and solid dispersion. Solid dispersions were prepared using hydroxypropylmethylcellulose/polyvinylpyrrolidone (HPMC/PVP) at 1:0.5, 1:1, and 1:2 weight ratios of drug to polymer, and pure telmisartan was also treated using the SAS process. Processed samples were characterized for morphology, particle size, crystallinity, solubility, dissolution rate and polymorphic stability. After the SAS process, all samples were converted to the amorphous form and were confirmed to be hundreds nm in size. Solubility and dissolution rate were increased compared to the raw material. Solubility tended to increase with increases in the amount of polymer used. However, unlike the solubility results, the dissolution rate decreased with increases in polymer concentration due to gel layer formation of the polymer. Processed pure telmisartan showed the best drug release even though it had lower solubility compared to other solid dispersions; however, because there were no stabilizers in processed pure telmisartan, it recrystallized after 1 month under severe conditions, while the other solid dispersion samples remained amorphous form. We conclude that after controlling the formulation of solid dispersion, the SAS process could be a promising approach for improving the solubility and dissolution rate of telmisartan.
ISSN:0378-5173
1873-3476
DOI:10.1016/j.ijpharm.2012.12.020