Dynamic suspension drying (DSD) to control Ostwald Ripening
The present invention relates to a process for the control of Ostwald Ripening phenomenon occurring in particle suspensions without the need for addition of stabilizing agents, by using high pressure homogenization at mild conditions in a way that no increase or decrease in particle size occurs, thus allowing the stabilization of the suspension during the isolation step in the form of a dried powder.
1. A method for processing particles of a pharmaceutical ingredient in suspension comprising the steps of:
a) reducing the particle size of the pharmaceutical ingredient in the suspension under high pressure conditions by using a high pressure homogenization apparatus, wherein the suspension is formed by adding the pharmaceutical ingredient to an anti-solvent, which is any media where the pharmaceutical ingredient shows none or low solubility; and
b) isolating the particles from the suspension in the form of a powder, characterized in that during the isolation step at least a portion of the suspension is recycled to the high pressure homogenization apparatus under mild pressure conditions.
2. The method according to claim 1 wherein the high pressure condition is a pressure in the range of from 500 to 3500 bar.
3. The method according to claim 1 wherein the mild pressure condition is a pressure lower than the high pressure applied to the particle size reduction.
4. The method according to claim 2 , wherein the mild pressure condition is below 500 bar.
5. The method according to claim 1 wherein the high pressure homogenization apparatus comprises gap valve, rotor stator, ultrasonic, homogenization cell or high sheer fluid processing.
6. The method according to claim 1 wherein the particle isolation step comprises a drying process for obtaining the particles in the form of a dry powder.
7. The method according to claim 6 wherein the drying process comprises spray drying, lyophilization, evaporation to dryness or a fluid bed drying step.
8. The method according to claim 7 wherein the drying step is a spray drying process.
9. The method according to claim 1 wherein the anti-solvent is methanol, ethanol, acetone, ethyl acetate, n-heptane or water.
10. The method according to claim 1 wherein the suspension is continuously recycled to the high pressure homogenization apparatus at optimized mild pressure conditions.
11. The method according to claim 1 wherein the suspension does not contain a stabilizing agent or a surfactant.
12. The method according to claim 1 wherein there are no time constraints regarding completion of the particle isolation step.
13. The method according to claim 1 wherein the particle size is stabilized during the pharmaceutical ingredient isolation step.
14. A method of minimizing Ostwald Ripening in a process for producing powder particles of a pharmaceutical ingredient from a suspension of said pharmaceutical ingredient, wherein said process comprises the steps of:
a) reducing the particle size of the pharmaceutical ingredient in the suspension under high pressure conditions by using a high-pressure homogenization apparatus, wherein the suspension is formed by adding the pharmaceutical ingredient to an anti-solvent, which is any medium where the pharmaceutical ingredient shows none or low solubility; and
b) isolating the particles from the suspension in the form of a powder, characterized in that during the isolation step, at least a portion of the suspension is recycled to the high-pressure homogenization apparatus under mild pressure conditions.
15. A method for processing particles of a pharmaceutical ingredient in suspension comprising the steps of:
a) reducing the particle size of the pharmaceutical ingredient in the suspension under high pressure conditions by using a high pressure homogenization apparatus, wherein the suspension is formed by adding the pharmaceutical ingredient to an anti-solvent, which is any media where the pharmaceutical ingredient shows none or low solubility, such as methanol, ethanol, acetone, ethyl acetate, n-heptane or water; and
b) isolating the particles from the suspension in the form of a powder, characterized in that during the isolation step at least a portion of the suspension is recycled to the high pressure homogenization apparatus under mild pressure conditions.