Formulation and treatment methods
The invention relates to pharmaceutical compositions comprising 6-thioguanidine (6-TG) wherein the composition is formulated for release of 6-TG in the distal intestine. Methods for treating a disease or condition of the distal ileum that responds to 6-TG wherein the 6-TG is released in the distal intestine are also disclosed.
1. A pharmaceutical composition comprising 6-TG and a homogeneous erodible hydrophilic polymer matrix, wherein the composition is formulated for oral administration and provides release of at least 35% of the 6-TG in vitro at about pH 6 to about pH 7.5 after approximately 12 hours.
2. A pharmaceutical composition according to claim 1 in solid dosage form.
3. A pharmaceutical composition according to claim 1 comprising an enteric coating.
4. A pharmaceutical composition according to claim 1 wherein the composition is adapted to provide substantially zero order kinetics of 6-TG release between approximately 12 hours and 24 hours from oral administration.
5. A pharmaceutical composition according to claim 1 wherein the composition provides release of at least 60% of the 6-TG in vitro at about pH 6 to about pH 7.5 after approximately 12 hours.
6. A pharmaceutical composition according to claim 1 , wherein the composition is adapted to avoid substantial systemic concentrations of 6-TG.
7. The pharmaceutical composition according to claim 1 , wherein the composition provides release of at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90% or 95% of the 6-TG in vitro at about pH 6 to about pH 7.5 after approximately 12 hours.
8. A pharmaceutical composition according to claim 1 in microparticulate dosage form.
9. The pharmaceutical composition according to claim 1 wherein the composition provides release of at least 45% of the 6-TG in vitro at about pH 6 to about pH 7.5 after approximately 12 hours.
10. A pharmaceutical composition according to claim 1 , wherein the pH is about 6.
11. A pharmaceutical composition according to claim 1 , wherein the pH is about 7.5.
12. A pharmaceutical composition according to claim 1 , wherein the homogeneous erodible hydrophilic polymer matrix comprises polyethylene oxides.
13. A pharmaceutical composition according to claim 1 , wherein the homogeneous erodible hydrophilic polymer matrix comprises both a hydrophilic and a hydrophobic polymer.
14. A pharmaceutical composition according to claim 13 , wherein the homogeneous erodible hydrophilic polymer matrix comprises ethyl cellulose.
15. A pharmaceutical composition according to claim 1 , wherein the homogeneous erodible hydrophilic polymer matrix comprises polyethylene oxides and the pharmaceutical composition comprises an enteric coating.
16. A pharmaceutical composition according to claim 1 , wherein the homogeneous erodible hydrophilic polymer matrix comprises polyethylene oxides and ethyl cellulose, and the pharmaceutical composition comprises an enteric coating.