Ion exchange resin treated to control swelling
The present invention provides a method and composition are provided for loading one or more drugs in a solution onto one or more ion exchange resin particles to form a drug-loaded resin particle. The drug-loaded resin particle is a sustained-release coated layered pharmaceutical drug-ion exchange resin having a one or more pharmaceutically active drugs applied directly to a non-equilibrated ion exchange resin to form a drug-resin complex. The drug-resin complex then coated is shelf stable.
1. A method of forming a coated pharmaceutical drug-ion exchange resin composition, comprising the steps of:
dissolving the pharmaceutically active drug in a solvent to form a solution or suspending the pharmaceutically active drug in a vehicle to form a suspension; and
applying the solution or suspension directly to the ion exchange resin to form the coated pharmaceutical drug-ion exchange resin composition,
wherein the method is carried out without equilibrating the ion exchange resin to ionically bind with the pharmaceutically active drug.
2. The method of claim 1 , further comprising contacting the ion exchange resin with between about 0.01% and 10% by weight of one or more sugar alcohols, based on the combined weight of the sugar alcohol and the ion exchange resin.
3. The method of claim 2 , wherein the one or more sugar alcohols are dissolved in an aqueous solution.
4. The method of claim 3 , wherein the one or more sugar alcohols are selected from mannitol, sorbitol, xylitol, maltitol, lactitol, 1,3-dihydroxypropane, inositol glucose, sucrose, mixtures and combinations thereof.
5. The method of claim 1 , wherein the ion exchange resin comprises a sulfonic acid cationic exchange resin particles.
6. The method of claim 1 , wherein the ion exchange resin comprises dipropylene glycol diallyl ether, polyglycol diallyl ether, triethylene glycol divinyl ether, hydroquinone diallyl ether, tetraallyloxyethanoyl, vinyl ether, vinyl acetate, vinyl butylbenzoate, crotonic acid, polyfunctional alcohol, tetraethylene glycol diacrylate, triallylamine, trimethylolpropane diallyl ether, methylenebisacrylamide, divinylbenzene, phthalic, sulphonphthalic acid, ethylene glycol, polymethyl siloxane .alpha., .gamma.-hydroxypropyl or combination thereof.
7. The method of claim 1 , wherein the pharmaceutically active drug is selected from narcotic analgesics, sympathomimetics, antitussives, analgesics antiemetics, anticholinergics, muscle relaxants, bronchodilators, antibiotics, antidepressants, antiasthmatics, antineoplastics, antiepileptics, cardiovascular agents, mixtures and combinations thereof.
8. The composition of claim 1 , wherein the pharmaceutically active drug is selected from codeine, dihydrocodeine, hydromorphone, morphine, pentazocine, propoxyphene, norephedrine, pseudoephedrine, dextromethorphan, phenylephrine, gauifenesin, aspirin, tramadol, metoclopramide, atropine, ipratropium bromide, scopolamine, cyclobenzaprine, papaverine, salbutamol, terbutaline and theophylline, amoxycillin, ampicillin, azlocillin, bacampicillin, cefamandole, cefonicid, cefotaxime, cefotetan, cefoxitin, ceftriaxone, mezlocillin, piperacillin, bupropion, nomifensine, nortriptyline, cromolyn, tamoxifen, valproic acid and phenvtoin, propranolol mixtures and combinations thereof.
9. A method of forming a coated pharmaceutical drug-ion exchange resin composition, comprising the steps of:
dissolving the pharmaceutically active drug in a solvent to form a solution or suspending the pharmaceutically active drug in a vehicle to form a suspension,
applying the solution or suspension directly to the ion exchange resin to form the coated pharmaceutical drug-ion exchange resin composition by spraying the solution or suspension directly onto the ion exchange resin in a fluid bed coating apparatus or with a planetary mixer or with a ribbon blender,
wherein the method is carried out without equilibrating the ion exchange resin to ionically bind with the pharmaceutically active drug.
10. The method of claim 1 , further comprising the steps of:
dissolving a second pharmaceutically active drug in a solution second solvent to form a second solution or suspending a second pharmaceutically active drug substance in a vehicle to form a second suspension;
further coating the coated pharmaceutical drug-ion exchange resin composition by applying the second solution or second suspension to the coated pharmaceutical drug-ion exchange composition without equilibrating the ion exchange resin with the second pharmaceutically active drug.
11. The method of claim 1 wherein the coated pharmaceutical drug-ion exchange resin composition is not washed after applying the solution or suspension.
12. A method of preparing a pharmaceutical formulation, comprising the steps of:
a) dissolving the pharmaceutically active drug in a solvent to form a solution or suspending the pharmaceutically active drug in a vehicle to form a suspension;
b) applying the solution or suspension directly to the ion exchange resin to form the coated pharmaceutical drug-ion exchange resin composition,
c) coating the drug coated resin formed in step b) with a rate controlling membrane to form a sustained release composition; and
d) suspending the sustained release composition formed in step c) in a pharmaceutically acceptable liquid or syrup;
wherein the method is carried out without equilibrating the ion exchange resin to ionically bind with the pharmaceutically active drug.