Self emulsifying drug delivery system
View Patent ↗The present invention claims and discloses a pharmaceutical composition suitable for oral administration, in form of an emulsion pre-concentrate, comprising (i) one or more NO-releasing NSAID(s); (ii) one or more surfactants, of which at least one is phospholipid; said composition forming an in-situ oil-in-water emulsion upon contact with gastrointestinal fluids. The composition may optionally also comprise an additional oil or semi-solid fat. Further, one or more short-chain alcohols can optionally be included in the composition. Also within the scope of the invention is a combination with a proton pump inhibitor. The pharmaceutical composition is useful in the treatment of pain and inflammation. Further within the scope of the invention is kit comprising a pharmaceutical composition according to the invention in a unit dosage form, in combination with a proton pump inhibitor, and said proton pump inhibitor is enteric coated.
1. An emulsion pre-concentrate in the form of a liquid consisting essentially of:
(i) one or more NO-releasing NSAID(s);
(ii) a phospholipid; and
(iii) one or more short-chain alcohols,
and
wherein the emulsion pre-concentrate forms an in-situ oil-in-water emulsion upon contact with aqueous media.
2. The emulsion pre-concentrate according to claim 1 , wherein the NO-releasing NSAID is a compound of the formula I,
wherein:
X is a spacer; and
M is a structure selected from the group consisting of:
3. The emulsion pre-concentrate according to claim 2 , wherein the spacer X of the NO-releasing NSAID is selected from the group consisting of:
a linear, branched or cyclic alkylene group;
—(CH 2 )— n wherein n is an integer from 2 to 10;
—(CH 2 ) m —O—(CH 2 ) p — wherein m and p are integers from 2 to 10; and
—(CH 2 ) p —C—6H 4 —CH 2 — wherein p is an integer from 2 to 10.
4. The emulsion pre-concentrate according to claim 1 , wherein the NO-releasing NSAID is a compound selected from the group consisting of:
5. The emulsion pre-concentrate according to claim 1 , wherein the amount of the NO-releasing NSAID is from 50-1500 mg per unit dose.
6. The emulsion pre-concentrate according to claim 5 , wherein the amount of the NO-releasing NSAID is from 125-500 mg per unit dose.
7. The emulsion pre-concentrate according to claim 1 , wherein the phospholipid is lecithin.
8. The emulsion pre-concentrate according to claim 7 , wherein the lecithin is egg lecithin, soya lecithin, or a mixture thereof.
9. The emulsion pre-concentrate according to claim 1 , wherein the short-chain alcohol is ethanol, propylene glycol, or glycerol.
10. A unit dosage form comprising the emulsion pre-concentrate of claim 1 and excipients for formulating the unit dosage form.
11. The unit dosage form according to claim 10 , wherein the dosage form is a capsule.
12. The unit dosage form according to claim 11 , wherein the capsule is a hard gelatine capsule.
13. The unit dosage form according to claim 11 , wherein the capsule is a soft gelatine capsule.