Microemulsion pharmaceutical composition comprising a macrolide immunosuppressant drug
The invention provides novel pharmaceutical compositions of macrolide immunosuppressants. The compositions comprise a hydrophilic component, a lipophilic component, and an amphiphilic component. Preferably, the compositions are formulated as liquid microemulsion. Furthermore, the invention provides uses of such compositions, such as for the topical treatment of inflammatory and autoimmune diseases. Methods for preparing the compositions are also provided.
1. A pharmaceutical composition comprising:
a therapeutically active ingredient selected from the group consisting of sirolimus, everolimus, tacrolimus, pimecrolimus, ridaforolimus, temsirolimus, and zotarolimus,
a hydrophilic component;
a lipophilic component; and
an amphiphilic component,
wherein the composition is formulated as a microemulsion; and
wherein the hydrophilic component comprises a combination of water and a liquid glycol which is preferably selected from glycerol, propylene glycol, 1,2-pentylene glycol, and polyethylene glycol, further characterized in that the ratio of water to the liquid glycol is in the range from about 1:10 to about 10:1.
2. The pharmaceutical composition of claim 1 , comprising tacrolimus, or a salt or derivative thereof, wherein essentially all of the tacrolimus is in solubilised form.
3. The pharmaceutical composition of claim 1 , wherein the microemulsion is in liquid form.
4. The pharmaceutical composition of claim 1 , wherein the hydrophilic component is present at an amount of at least about 20 wt.-%, relative to the weight of the composition.
5. The pharmaceutical composition of claim 1 , wherein the weight ratio of the hydrophilic component to the amphiphilic component is 1:1 or higher.
6. The pharmaceutical composition of claim 1 , wherein the lipophilic component comprises at least one excipients selected from isopropyl myristate, isopropyl palmitate, dibutyl adipate, diisopropyl adipate, and triglycerides.
7. The pharmaceutical composition of claim 1 , wherein the amphiphilic component comprises at least one surfactant selected from phospholipids, alkyl polyglucosides, sorbitan esters with fatty acids, polyalkyleneglycol ethers of fatty alcohols, and pegylated mono- and diesters of glycerol with fatty acids.
8. The pharmaceutical composition of claim 1 , wherein the amphiphilic component comprises at least two surfactants.
9. The pharmaceutical composition of claim 2 , wherein
the hydrophilic component comprises a combination of water and propylene glycol or pentylene glycol;
the lipophilic component is selected from dibutyl adipate and isopropylmyristate;
the amphiphilic component comprises a lecithin combined with an alkyl polyglucoside, or a lecithin combined with sorbitan monooleate, or a lecithin combined with polyoxyethyleneglycol monostearate.
10. The pharmaceutical composition of claim 9 , wherein the ratio of water to propylene glycol or pentylene glycol is in the range of about 3:1 to 1:3.
11. The pharmaceutical composition of claim 9 , wherein the hydrophilic component comprises at least 20 wt % of water relative to the total composition.
12. The pharmaceutical composition of claim 1 , wherein the composition is formulated for topical use in the prophylaxis and/or treatment of atopic dermatitis, psoriasis, or collagenosis.