Self-microemulsifying dosage forms of low solubility active ingredients such as co-enzyme Q10
The invention includes dosage formulations, dosage forms and related methods for providing oral dosage forms of low solubility active ingredients such as coenzyme Q10. The present invention includes a Self-Microemulsifying Drug Delivery System (SMEDDS) in the form of a self-microemulsifying mixture that comprises a combination of a hydrophilic surfactant and a lipophilic co-surfactant (forming a surfactant pair). The preferred surfactant pair comprises a hydrophilic surfactant and a lipophilic co-surfactant with respective HLB (Hydrophile-Lipophile Balance) values of more than 12 and less than 8 respectively. The systems also contain at least one lipophilic solvent. The formulations exhibited excellent dissolution properties and storage stability.
1. A soft capsule containing an active ingredient comprising the active ingredient contained in a stable self-microemulsifying mixture, said mixture comprising:
(1) at least one hydrophilic surfactant having a hydrophile-lipophile balance of greater than 12;
(2) at least one lipophilic co-surfactant having a hydrophile-lipophile balance of less than 8; and
(3) at least one hydrophobic solvent;
wherein the weight ratio of said at least one hydrophilic surfactant to said at least one lipophilic co-surfactant is in the range of from 30:1 to 3:1;
wherein the concentration of said at least one hydrophobic solvent in said self-microemulsifying mixture is in the range of from 2 to 50% by weight and comprises a mixture of isopropyl myristate and lemon oil or a mixture of isopropyl myristate and orange oil; and
wherein the self-microemulsifying mixture exhibits a dissolution of up to 100% and storage stability of more than 80 days.
2. The soft capsule according to claim 1 , wherein the concentration of said at least one hydrophilic surfactant in said self-microemulsifying mixture is in the range of from 20 to 70% by weight.
3. The soft capsule according to claim 1 , wherein the concentration of said at least one lipophilic co-surfactant in said self-microemulsifying mixture is in the range of from 1.5 to 50% by weight.
4. The soft capsule according to claim 1 , wherein said mixture is substantially free of water.
5. The soft capsule according to claim 1 additionally comprising optionally at least one hydrophilic solvent.
6. The soft capsule according to claim 5 , wherein said at least one hydrophilic solvent is selected from the group consisting of glycol ethers.
7. The soft capsule according to claim 5 , wherein the weight ratio of said hydrophilic solvent to the total of said at least one hydrophilic surfactant, said at least one lipophilic co-surfactant and said at least one hydrophobic solvent is about 0.02-1:1.
8. A soft capsule containing a dosage form of a low water-solubility active ingredient comprising: at least one low water-solubility active ingredient contained in a stable self-microemulsifying mixture, said mixture comprising:
(1) at least one hydrophilic surfactant having a hydrophile-lipophile balance of greater than 12;
(2) at least one lipophilic co-surfactant having a hydrophile-lipophile balance of less than 8; and
(3) at least one hydrophobic solvent
wherein the weight ratio of said at least one hydrophilic surfactant to said at least one lipophilic co-surfactant is in the range of from 30:1 to 3:1;
wherein the concentration of said at least one hydrophobic solvent in said self-microemulsifying mixture is in the range of from 2 to 50% by weight and comprises a mixture of isopropyl myristate and lemon oil or a mixture of isopropyl myristate and orange oil; and
wherein the self-microemulsifying mixture exhibits a dissolution of up to 100% and storage stability of more than 80 days.
9. A soft capsule containing a dosage form of coenzyme Q10 comprising: coenzyme Q10 contained in a stable self-microemulsifying mixture, said mixture comprising:
(1) at least one hydrophilic surfactant having a hydrophile-lipophile balance of greater than 12;
(2) at least one lipophilic co-surfactant having a hydrophile-lipophile balance of less than 8; and
(3) at least one hydrophobic solvent;
wherein the weight ratio of said at least one hydrophilic surfactant to said at least one lipophilic co-surfactant is in the range of from 30:1 to 3:1;
wherein the concentration of said at least one hydrophobic solvent in said self-microemulsifying mixture is in the range of from 2 to 50% by weight and comprises a mixture of isopropyl myristate and lemon oil or a mixture of isopropyl myristate and orange oil; and
wherein the self-microemulsifying mixture exhibits a dissolution of up to 100% and storage stability of more than 80 days.
10. The soft capsule according to claim 9 , wherein the capsule wall is a non-gelatin composition.