Stabilised solid drug dispersions in an organic carrier and a process for preparing the same
New solid drug dispersions are described in which a drug is present in amorphous form and dispersed within the particles of an organic carrier selected from cross-linked polymers and/or complexing agents. These dispersions are obtainable by mixing the drug and the carrier and applying an oscillating electromagnetic field in the microwave region according to a specific heating cycle wherein the drug-carrier mixture is heated at a temperature higher than the melting point of the drug for at least 5 minutes.
1. A process for the preparation of a composite containing a drug dispersed in a particulate organic carrier, comprising:
a) mixing a drug and a particulate organic carrier selected from the group consisting of water-soluble complexing agents, water-insoluble cross-linked polymers, and mixtures thereof; and
b) applying an oscillating electromagnetic field to the mixture, wherein the oscillating electromagnetic field is microwave irradiation modulated to increase the temperature of the mixture to a temperature greater than the melting temperature of the drug and maintained at the temperature greater than the melting temperature of the drug for at least 5 minutes to provide a composite containing the drug, wherein the drug is dispersed inside of the organic carrier particles as well as on the external surface of the particles, wherein the drug is present in the composite in amorphous form in a quantity greater than or equal to 50% by weight based on the total amount of the drug.
2. The process of claim 1 , wherein mixing a drug and a particulate organic carrier further comprises adding a solvent to provide a wet mixture.
3. The process of claim 2 , wherein said solvent is water.
4. The process of claim 3 , wherein said wet mixture is formed by adding water to the drug and particulate organic carrier in a quantity between 0.1 ml/g and 5 ml/g based on the weight of drug and particulate organic carrier.
5. The process of claim 2 , wherein the oscillating electromagnetic field is applied to the mixture at a the pressure between 1 and 20 bar.
6. The process of claim 1 , wherein the oscillating electromagnetic field is applied to the mixture in a container comprising a dielectric material having coupling capacity with microwaves.
7. The process of claim 6 , wherein said dielectric material is polytetrafluoroethylene loaded with graphite.
8. The process of claim 1 , wherein the microwave irradiation is carried out with power in the range between 100 W and 5000 W, for a time up to 120 minutes.
9. The process of claim 1 , wherein said cross-linked polymer is selected from the group consisting of cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethylcellulose, cross-linked starch, cross-linked dextran, cross-linked polystyrene and cross-linked β-cyclodextrin.
10. The process of claim 1 , wherein said drug is a drug sparingly soluble in water.
11. The process of claim 1 , wherein said water-soluble complexing agents are selected from the group consisting of cyclodextrins, maltodextrins, and mixtures thereof.