Method for Reducing Side Effects from Administration of Phosphodiesterase-4 Inhibitors
A method for altering the PK profile of a pharmaceutical formulation containing a PDE-4 inhibitor, such as roflumilast, to reduce the spike in Cmax. The spike in Cmax is reduced by topically administering the PDE-4 inhibitor in combination with one or more phosphate ester surfactants. Reducing the spike in Cmax will reduce gastrointestinal side effects and result in better patient compliance.
1 . A pharmaceutical composition for topical administration comprising:
(i) a phosphodiesterase 4 (PDE4) inhibitor in an amount of 0.05-1% w/w;
(ii) a phosphate ester surfactant comprising cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate;
(iii) diethylene glycol monoethyl ether; and
(iv) water,
wherein said pharmaceutical composition is in the form of a foam, and
wherein the C max of the PDE4 inhibitor from the topical composition is reduced relative to an oral roflumilast formulation of the PDE4 inhibitor.
2 . The composition of claim 1 , wherein said composition further comprises a propellant.
3 . The composition of claim 1 , wherein said propellant is a blend of propane, isobutane, and n-butane.
4 . The composition of claim 1 , wherein said phosphate ester surfactant is in an amount of 1.0 to 25% w/w.
5 . The composition of claim 1 , wherein said diethylene glycol monoethyl ether is in an amount of 10-40% w/w.
6 . The composition of claim 1 , wherein the plasma concentration curve of the PDE4 inhibitor has no spike at C max .
7 . A pharmaceutical composition for topical administration comprising:
(i) a phosphodiesterase 4 (PDE4) inhibitor in an amount of 0.05-1% w/w;
(ii) a phosphate ester surfactant comprising one or more of cetostearyl alcohol, dicetyl phosphate and ceteth-10 phosphate; and
(iii) water,
wherein said pharmaceutical composition is in the form of a foam, and
wherein the C max of the PDE4 inhibitor from the topical composition is reduced relative to an oral roflumilast formulation of the PDE4 inhibitor.
8 . The composition of claim 7 , wherein said composition further comprises a propellant.
9 . The composition of claim 7 , wherein said propellant is a blend of propane, isobutane, and n-butane.
10 . The composition of claim 7 , wherein said phosphate ester surfactant is in an amount of 1.0 to 25% w/w.
11 . The composition of claim 7 , wherein the plasma concentration curve of the PDE4 inhibitor has no spike at C max .
12 . A pharmaceutical composition for topical administration comprising:
(i) a phosphodiesterase 4 (PDE4) inhibitor in an amount of 0.05-1% w/w;
(ii) diethylene glycol monoethyl ether; and
(iii) water,
wherein said pharmaceutical composition is in the form of a foam, and
wherein the C max of the PDE4 inhibitor from the topical composition is reduced relative to an oral roflumilast formulation of the PDE4 inhibitor.
13 . The pharmaceutical composition of claim 12 , further comprising a hydrophobic component.
14 . The topical pharmaceutical foam composition of claim 13 , wherein the hydrophobic component comprises mineral oil and light mineral oil.
15 . The topical pharmaceutical foam composition of claim 14 , wherein the hydrophobic component comprises olive oil.
16 . The topical pharmaceutical foam composition of claim 15 , wherein the hydrophobic component comprises medium chain triglycerides.
17 . The topical pharmaceutical foam composition of claim 16 , wherein the composition comprises 5-15% w/w of diethylene glycol monoethyl ether.
18 . The topical pharmaceutical foam composition of claim 17 , wherein the composition comprises 10-40% w/w of diethylene glycol monoethyl ether.
19 . The composition of claim 12 , wherein said composition further comprises a propellant.
20 . The composition of claim 13 , wherein said composition further comprises a propellant.