Compositions and methods for improved delivery of ionizable hydrophobic therapeutic agents

• US 6,383,471 B1
• Filed: 04/06/1999
• Issued: 05/07/2002
• Est. Priority Date: 04/06/1999
• Status: Expired due to Term

• Current Assignee: Spriaso, LLC
• Original Assignee: Lipocine Inc.
• Inventors: Chen, Feng-Jing, Patel, Mahesh V.
• Primary Examiner(s): Bawa, Raj
• Application Number:
  US09/287,043
• Time in Patent Office: 1,127 Days
• Field of Search: 424/401, 424/45, 424/46, 424/451, 424/436, 514/944
• US Class Current: 424/45
• CPC Class Codes: A61K 47/02 Inorganic compounds
• CPC Class Codes: A61K 9/1075 Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers A61K9/0026 takes precedence
• CPC Class Codes: A61K 9/485 Inorganic compounds
• CPC Class Codes: A61K 9/4858 Organic compounds

Abstract

The present invention is directed to a pharmaceutical composition including a hydrophobic therapeutic agent having at least one ionizable functional group, and a carrier. The carrier includes an ionizing agent capable of ionizing the functional group, a surfactant, and optionally solubilizers, triglycerides, and neutralizing agents. The invention further relates to a method of preparing such compositions by providing a composition of an ionizable hydrophobic therapeutic agent, an ionizing agent, and a surfactant, and neutralizing a portion of the ionizing agent with a neutralizing agent. The compositions of the invention are particularly suitable for use in oral dosage forms.

Claims

1. A pharmaceutical composition comprising:

(a) a hydrophobic theraputic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight; and

(b) a carrier comprising;

(i) an ionizing agent capable of ionizing the at least one ionizable functional group, wherein the ionizing agent is present in an amount of at least about 0.1 mole equivalents per mole of the at least one functional group;

(ii) a surfactant selected from the group consisting of non-ionic hydrophilic surfactants having an HLB value greater than or equal to about 10, ionic hydrophilic surfactants, hydrophobic surfactants having an HLB value less than 10, and mixtures thereof; and

(iii) a triglyceride.

2. The pharmaceutical composition of claim 1, wherein the at least one ionizable functional group is an acidic functional group, and the ionizing agent is a pharmaceutically acceptable base.

3. The pharmaceutical composition of claim 2, wherein the acidic functional group is selected from the group consisting of carboxylic acids, imidazolidinediones, thiazolidinediones, pyrimidinetriones, hydroxyheteroaromatics, phenols, phosphoric acids, sulfuric acids, sulfonic acids, sulfonamides, aminosulfones, sulfonylureas, tetrazoles and thiols.

4. The pharmaceutical composition of claim 2, wherein the hydrophobic therapeutic agent is selected from the group consisting of acetazolamide, acetohexamide, acrivastine, alatrofloxacin, albuterol, alclofenac, aloxiprin, alprostadil, amodiaquine, amphotericin, amylobarbital, aspirin, atorvastatin, atovaquone, baclofen, barbital, benazepril, bezafibrate, bromfenac, bumetanide, butobarbital, candesartan, capsaicin, captopril, cefazolin, celecoxib, cephadrine, cephalexin, cerivastatin, cetrizine, chlorambucil, chlorothiazide, chlorpropamide, chlorthalidone, cinoxacin, ciprofloxacin, clinofibrate, cloxacillin, cromoglicate, cromolyn, dantrolene, dichlorophen, diclofenac, dicloxacillin, dicumarol, diflunisal, dimenhydrinate, divalproex, docusate, dronabinol, enoximone, enalapril, enoxacin, enrofloxacin, epalrestat, eposartan, essential fatty acids, estramustine, ethacrynic acid, ethotoin, etodolac, etoposide, fenbufen, fenoprofen, fexofenadine, fluconazole, flurbiprofen, fluvastatin, fosinopril, fosphenytoin, fumagillin, furosemide, gabapentin, gemfibrozil, gliclazide, glipizide, glybenclamide, glyburide, glimepiride, grepafloxacin, ibufenac, ibuprofen, imipenem, indomethacin, irbesartan, isotretinoin, ketoprofen, ketorolac, lamotrigine, levofloxacin, levothyroxine, lisinopril, lomefloxacin, losartan, lovastatin, meclofenamic acid, mefenamic acid, mesalamine, methotrexate, metolazone, montelukast, nalidixic acid, naproxen, natamycin, nimesulide, nitrofurantoin, non-essential fatty acids, norfloxacin, nystatin, ofloxacin, oxacillin, oxaprozin, oxyphenbutazone, penicillins, pentobarbital, perfloxacin, phenobarbital, phenytoin, pioglitazone, piroxicam, pramipexol, pranlukast, pravastatin, probenecid, probucol, propofol, propylthiouracil, quinapril, rabeprazole, repaglinide, rifampin, rifapentine, sparfloxacin, sulfabenzamide, sulfacetamide, sulfadiazine, sulfadoxine, sulfamerazine, sulfamethoxazole, sulfafurazole, sulfapyridine, sulfasalazine, sulindac, sulphasalazine, sulthiame, telmisartan, teniposide, terbutaline, tetrahydrocannabinol, tirofiban, tolazamide, tolbutamide, tolcapone, tolmetin, tretinoin, troglitazone, trovafloxacin, undecenoic acid, ursodeoxycholic acid, valproic acid, valsartan, vancomycin, verteporfin, vigabatrin, vitamin K-S (II), zafirlukast, and pharmaceutically acceptable salts thereof.

5. The pharmaceutical composition of claim 4, wherein the hydrophobic therapeutic agent is selected from the group consisting of acetohexamide, acrivastine, alatrofloxacin, albuterol, alclofenac, amodiaquine, amphotericin, aspirin, atorvastatin, atovaquone, baclofen, benazepril, bezafibrate, bromfenac, butobarbital, candesartan, capsaicin, captopril, celecoxib, cerivastatin, cetrizine, chlorambucil, chlorpropamide, chlorthalidone, clinofibrate, cinoxacin, ciprofloxacin, clinofibrate, cloxacillin, cromoglicate, cromolyn, dantrolene, diclofenac, dicumarol, divalproex, docusate, dronabinol, enalapril, enoxacin, epalrestat, eposartan, etodolac, etoposide, fenbufen, fenoprofen, fexofenadine, fluconazole, flurbiprofen, fluvastatin, fosphenytoin, fumagillin, gabapentin, gemfibrozil, gliclazide, glipizide, glyburide, glimepiride, grepafloxacin, ibufenac, ibuprofen, imipenem, indomethacin, irbesartan, isotretinoin, ketoprofen, ketorolac, lamotrigine, levofloxacin, levothyroxine, lisinopril, lomefloxacin, losartan, lovastatin, mesalamine, methotrexate, montelukast, naproxen, nimesulide, non-essential fatty acids, norfloxacin, ofloxacin, oxaprozin, phenytoin, pioglitazone, piroxicam, pramipexol, pravastatin, probucol, propofol, rabeprazole, repaglinide, rifampin, rifapentine, sparfloxacin, sulfadiazine, sulfamethoxazole, sulfasalazine, sulindac, sulphasalazine, telmisartan, teniposide, terbutaline, tetrahydrocannabinol, tirofiban, tolazamide, tolbutamide, tolcapone, tolmetin, tretinoin, troglitazone, trovafloxacin, undecenoic acid, valproic acid, valsartan, vancomycin, verteporfin, vigabatrin, vitamin K-S (II), zafirlukast, and pharmaceutically acceptable salts thereof.

6. The pharmaceutical composition of claim 5, wherein the hydropeutic agent is selected from the group consisting of acrivastine, alatrofloxacin, albuterol, alclofenac, aspirin, atorvastatin, atovaquone, baclofen, benazepril, bezafibrate, bromfenac, butobarbital, celecoxib, cerivastatin, cetrizine, chlorpropamide, ciprofloxacin, cromoglicate, cromolyn, dantrolene, diclofenac, dicumarol, divalproex, dronabinol, enoxacin, epalrestat, etodolac, etoposide, fenoprofen, fexofenadine, fluconazole, flurbiprofen, fluvastatin, fosphenytoin, gemfibrozil, glipizide, glybunde, glimepiride, grepafloxacin, ibufenac, ibuprofen, isotretinoin, ketoprofen, ketorolac, lamotrigine, levofloxacin, levothyroxine, lomefloxacin, lovastatin, methotrexate, montelukast, naproxen, nimesulide, non-essential fatty acids, norfloxacin, ofloxacin, oxaprozin, phenytoin, pioglitazone, piroxicam, pravastatin, probucol, rabeprazole, repaglinide, rifampin, rifapentine, sulfamethoxazole, sulfasalazine, teniposide, tetrahydrocannabinol, tolcapone, tolmetin, tretinoin, troglitazone, trovafloxacin, valproic acid, vancomycin, vitamin K-S (II), zafirlukast, and pharmaceutically acceptable salts thereof.

7. The pharmaceutical composition of claim 6, wherein the hydrophobic therapeutic agent is selected from the group consisting of alclofenac, aspirin, atorvastatin, atovaquone, benazepril, bromfenac, celecoxib, cromoglicate, cromolyn, diclofenac, dronabinol, epalrestat, etodolac, fexofenadine, flurbiprofen, glimepiride, ibufenac, ibuprofen, isotretinoin, ketorolac, levothyroxine, naproxen, non-essential fatty acids, oxaprozin, phenytoin, pioglitazone, rabeprazole, repaglinide, teniposide, tetrahydrocannabinol, tolmetin, tretinoin, troglitazone, trovafloxacin, vitamin K-S (II), and pharmaceutically acceptable salts thereof.

8. The pharmaceutical composition of claim 2, wherein the base is selected from the group consisting of an amino acid, an amino acid estcr, ammonium hydroxide, potassium hydroxide, sodium hydroxide, sodium hydrogen carbonate, aluminum hydroxide, calcium carbonate, magnesium hydroxide, magnesium aluminum silicate, synthetic aluminum silicate, synthetic hydrotalcite, magnesium aluminum hydroxide, diisopropylethylamine, ethanolamine, ethylenediamine, triethanolamine, triethylamine, triisopropanolamine, salts of a pharmaceutically acceptable cation and acetic acid, acrylic acid, adipic acid, alginic acid, alkanesulfonic acid, an amino acid, ascorbic acid, benzoic acid, boric acid, butyric acid, carbonic acid, citric acid, a fatty acid, formic acid, fumaric acid, gluconic acid, hydroquinosulfonic acid, isoascorbic acid, lactic acid, maleic acid, methanesulfonic acid, oxalic acid, parabromophenylsulfonic acid, propionic acid, p-toluenesulfonic acid, salicylic acid, stearic acid, succinic acid, tannic acid, tartaric acid, thioglycolic acid, toluenesulfonic acid, or uric acid, and mixtures of any of the foregoing.

9. The pharmaceutical composition of claim 1, wherein the at least one ionizable functional group is a basic functional group, and the ionizing agent is a pharmaceutically acceptable acid.

10. The pharmaceutical composition of claim 9, wherein the basic functional group is selected from the group consisting of aliphatic amines, aromatic amines, C-substituted aromatic amines, N-substituted aromatic amines, heterocyclic amines, C-substituted heterocyclic amines and N-substituted heterocyclic amines.

11. The pharmaceutical composition of claim 9, wherein the hydrophobic therapeutic agent is selected from the group consisting of abacavir, acebutolol, acrivastine, alatrofloxacin, albuterol, albendazole, alprazolam, alprenolol, amantadine, amiloride, aminoglutethimide, amiodarone, amitriptyline, amlodipine, amodiaquine, amoxapine, amphetamine, amphotericin, amprenavir, amrinone, amsacrine, astemizole, atenolol, atropine, azathioprine, azelastine, azithromycin, baclofen, benethamine, benidipine, benzhexol, benznidazole, benztropine, biperiden, bisacodyl, bisanthrene, bromazepam, bromocriptine, bromperidol, brompheniramine, brotizolam, bupropion, butenafine, butoconazole, cambendazole, camptothecin, carbinoxamine, cephadrine, cephalexin, cetrizine, cinnarizine, chlorambucil, chlorpheniramine, chlorproguanil, chlordiazepoxide, chlorpromazine, chlorprothixene, chloroquine, cimetidine, ciprofloxacin, cisapride, citalopram, clarithromycin, clemastine, clemizole, clenbuterol, clofazimine, clomiphene, clonazepam, clopidogrel, clozapine, clotiazepam, clotrimazole, codeine, cyclizine, cyproheptadine, dacarbazine, darodipine, decoquinate, delavirdine, demeclocycline, dexamphetamine, dexchlorpheniramine, dexfenfluramine, diamorphine, diazepam, diethylpropion, dihydrocodeine, dihydroergotamine, diltiazem, dimenhydrinate, diphenhydramine, diphenoxylate, diphenylimidazole, diphenylpyraline, dipyridamole, dirithromycin, disopyramide, dolasetron, domperidone, donepezil, doxazosin, doxycycline, droperidol, econazole, efavirenz, ellipticine, enalapril, enoxacin, enrofloxacin, eperisone, ephedrine, ergotamine, erythromycin, ethambutol, ethionamide, ethopropazine, etoperidone, famotidine, felodipine, fenbendazole, fenfluramine, fenoldopam, fentanyl, fexofenadine, flecainide, flucytosine, flunarizine, flunitrazepam, fluopromazine, fluoxetine, fluphenthixol, fluphenthixol decanoate, fluphenazine, fluphenazine decanoate, flurazepam, flurithromycin, frovatriptan, gabapentin, granisetron, grepafloxacin, guanabenz, halofantrine, haloperidol, hyoscyamine, imipenem, indinavir, irinotecan, isoxazole, isradipine, itraconazole, ketoconazole, ketotifen, labetalol, lamivudine, lanosprazole, leflunomide, levofloxacin, lisinopril, lomefloxacin, loperamide, loratadine, lorazepam, lormetazepam, lysuride, mepacrine, maprotiline, mazindol, mebendazole, meclizine, medazepam, mefloquine, melonicam, meptazinol, mercaptopurine, mesalamine, mesoridazine, metformin, methadone, methaqualone, methylphenidate, methylphenobarbital, methysergide, metoclopramide, metoprolol, metronidazole, mianserin, miconazole, midazolam, miglitol, minoxidil, mitomycins, mitoxantrone, molindone, montelukast, morphine, moxifloxacin, nadolol, nalbuphine, naratriptan, natamycin, nefazodone, nelfinavir, nevirapine, nicardipine, nicotine, nifedipine, nimodipine, nimorazole, nisoldipine, nitrazepam, nitrofurazone, nizatidine, norfloxacin, nortriptyline, nystatin, ofloxacin, olanzapine, omeprazole, ondansetron, omidazole, oxamniquine, oxantel, oxatomide, oxazepam, oxfendazole, oxiconazole, oxprenolol, oxybutynin, oxyphencyclimine, paroxetine, pentazocine, pentoxifylline, perchlorperazine, perfloxacin, perphenazine, phenbenzamine, pheniramine, phenoxybenzamine, phentermine, physostigmine, pimozide, pindolol, pizotifen, pramipexol, pranlukast, praziquantel, prazosin, procarbazine, prochlorperazine, proguanil, propranolol, pseudoephedrine, pyrantel, pyrimethamine, quetiapine, quinidine, quinine, raloxifene, ranitidine, remifentanil, repaglinide, reserpine, ricobendazole, rifabutin, rifampin, rifapentine, rimantadine, risperidone, ritonavir, rizatriptan, ropinirole, rosiglitazone, roxaditine, roxithromycin, salbutamol, saquinavir, selegiline, sertraline, sibutramine, sildenafil, sparfloxacin, spiramycins, stavudine, sulconazole, sulphasalazine, sulpiride, sumatriptan, tacrine, tamoxifen, tamsulosin, temazepam, terazosin, terbinafine, terbutaline, terconazole, terfenadine, tetramisole, thiabendazole, thioguanine, thioridazine, tiagabine, ticlopidine, timolol, tinidazole, tioconazole, tirofiban, tizanidine, tolterodine, topotecan, toremifene, tramadol, trazodone, triamterene, triazolam, trifluoperazine, trimethoprim, trimipramine, tromethamine, tropicamide, trovafloxacin, vancomycin, venlafaxine, vigabatrin, vinblastine, vincristine, vinorelbine, vitamin K₅, vitamin K₆, vitamin K₇, zafirlukast, zolmitriptan, zolpidem, zopiclone, and pharmaceutically acceptable salts thereof.

12. The pharmaceutical composition of claim 11, wherein the hydrophobic therapeutic agent is selected from the group consisting of abacavir, acebutolol, acrivastine, alatrofloxacin, albendazole, albuterol, alprazolam, amiodarone, amlodipine, amodiaquine, amphetamine, amphotericin, amprenavir, astemizole, atenolol, azathioprine, azelastine, azithromycin, baclofen, benztropine, bisacodyl, bromazepam, bromperidol, brompheniramine, bupropion, butenafine, butoconazole, cambendazole, camptothecin, carbinoxamine, cetrizine, cinnarizine, chlorpheniramine, chlorambucil, chlorpromazine, cimetidine, ciprofloxacin, cisapride, citalopram, clarithromycin, clemastine, clemizole, clomiphene, clonazepam, clopidogrel, clozapine, clotiazepam, clotrimazole, codeine, cyclizine, delavirdine, dexamphetamine, dexchlorpheniramine, diamorphine, diazepam, diethylpropion, dihydrocodeine, dihydroergotamine, diltiazem, diphenhydramine, diphenylimidazole, diphenylpyraline, dipyridamole, dirithromycin, disopyramide, dolasetron, domperidone, donepezil, doxazosin, droperidol, econazole, efavirenz, ellipticine, enalapril, enoxacin, eperisone, ergotamine, famotidine, felodipine, fenfluramine, fenoldopam, fexofenadine, fentanyl, flecainide, flunarizine, fluopromazine, fluoxetine, frovatriptan, gabapentin, granisetron, halofantrine, imipenem, indinavir, irinotecan, isoxazole, isradipine, itraconazole, ketoconazole, ketotifen, labetalol, lamivudine, lanosprazole, leflunomide, levofloxacin, lisinopril, lomefloxacin, loperamide, loratadine, lorazepam, lormetazepam, mazindol, mebendazole, mefloquine, mercaptopurine, mesalamine, metformin, methadone, methaqualone, methylphenidate, methysergide, metoclopramide, metoprolol, metronidazole, miconazole, midazolam, miglitol, minoxidil, mitoxantrone, montelukast, naratriptan, nelfinavir, nevirapine, nicardipine, nicotine, nifedipine, nimodipine, nimorazole, nisoldipine, nizatidine, norfloxacin, ofloxacin, olanzapine, omeprazole, ondansetron, oxamniquine, oxiconazole, paroxetine, perchlorperazine, phenbenzamine, pheniramine, phentermine, physostigmine, pizotifen, pramipexol, prazosin, prochlorperazine, pseudoephedrine, quetiapine, quinidine, raloxifene, ranitidine, remifentanil, repaglinide, rifabutin, rifampin, rifapentine, rimantadine, risperidone, ritonavir, rizatriptan, rosiglitazone, roxaditine, saquinavir, sibutramine, sildenafil, sparfloxacin, stavudine, sulphasalazine, sumatriptan, tacrine, tamoxifen, tamsulosin, terazosin, terbinafine, terbutaline, terconazole, terfenadine, tiagabine, ticlopidine, tinidazole, tioconazole, tirofiban, tizanidine, tolterodine, topotecan, toremifene, tramadol, trazodone, trovafloxacin, vancomycin, venlafaxine, vigabatrin, vinblastine, vincristine, vinorelbine, vitamin K₅, vitamin K₆, vitamin K₇, zafirlukast, zolmitriptan, zolpidem, zopiclone, and pharmaceutically acceptable salts thereof.

13. The pharmaceutical composition of claim 12, wherein the hydrophobic therapeutic agent is selected from the group consisting of abacavir, acrivastine, alatrofloxacin, albuterol, amiodarone, amlodipine, amphetamine, amprenavir, astemizole, atenolol, azathioprine, azelastine, azithromycin, baclofen, benztropine, bisacodyl, bromazepam, bromperidol, brompheniramine, bupropion, butenafine, butoconazole, cambendazole, camptothecin, carbinoxamine, cetrizine, cinnarizine, chlorpheniramine, chlorpromazine, cimetidine, ciprofloxacin, cisapride, clarithromycin, clemastine, clemizole, clonazepam, clopidogrel, clotrimazole, codeine, dexchlorpheniramine, dihydrocodeine, dihydroergotamine, diphenhydramine, diphenylimidazole, diphenylpyraline, dirithromycin, dolasetron, domperidone, doxazosin, econazole, efavirenz, ellipticine, enoxacin, eperisone, ergotamine, famotidine, fenoldopam, fentanyl, fexofenadine, flunarizine, fluoxetine, frovatriptan, granisetron, grepafloxacin, halofantrine, indinavir, irinotecan, isradipine, itraconazole, ketoconazole, ketotifen, lamivudine, lanosprazole, leflunomide, levofloxacin, loperamide, loratadine, metformin, methadone, methylphenidate, methysergide, metronidazole, miconazole, midazolam, miglitol, mitoxantrone, montelukast, naratriptan, nelfinavir, nicotine, nifedipine, nimorazole, nizatidine, norfloxacin, ofloxacin, omeprazole, perchlorperazine, phenbenzamine, physostigmine, pizotifen, pseudoephedrine, quetiapine, quinidine, raloxifene, ranitidine, remifentanil, repaglinide, rifabutin, rifampin, rifapentine, rimantadine, ritonavir, rizatriptan, rosiglitazone, roxaditine, saquinavir, sibutramine, sildenafil, stavudine, sumatriptan, tacrine, tamoxifen, tamsulosin, terazosin, terbinafine, tinidazole, tizanidine, tolterodine, topotecan, toremifene, tramadol, trovafloxacin, vancomycin, vinblastine, vincristine, vinorelbine, vitamin K₅, vitamin K₆, vitamin K₇, zafirlukast, zolmitriptan, zolpidem, and pharmaceutically acceptable salts thereof.

14. The pharmaceutical composition of claim 13, wherein the hydrophobic therapeutic agent is selected from the group consisting of amlodipine, astemizole, brompheniramine, bupropion, carbinoxamine, cetrizine, cimetidine, cisapride, clemastine, clemizole, dihydroergotamine, diphenhydramine, diphenylimidazole, diphenylpyraline, domperidone, eperisone, famotidine, fexofenadine, frovatriptan, granisetron, itraconazole, ketoconazole, ketotifen, lanosprazole, leflunomide, loperamide, loratadine, methysergide, miglitol, montelukast, naratriptan, nizatidine, omeprazole, ondansetron, phenbenzamine, pseudoephedrine, raloxifene, ranitidine, repaglinide, rifabutin, rimantadine, ritonavir, rizatriptan, rosiglitazone, roxaditine, saquinavir, sibutramine, sildenafil, sumatriptan, tamsulosin, terbinafine, tizanidine, tramadol, trovafloxacin, vitamin K₅, vitamin K₆, vitamin K₇, zafirlukast, zolmitriptan, zolpidem, and pharmaceutically acceptable salts thereof.

15. The pharmaceutical composition of claim 9, wherein the acid is a pharmaceutically acceptable inorganic acid.

16. The pharmaceutical composition of claim 15, wherein the inorganic acid is selected from the group consisting of hydrochloric acid, hydrobromic acid, hydriodic acid, sulfiric acid, carbonic acid, nitric acid boric acid and phosphoric acid.

17. The pharmaceutical composition of claim 9, wherein the acid is a pharmaceutically acceptable organic acid.

18. The pharmaceutical composition of claim 17, wherein the organic acid is selected from the group consisting of acetic acid, acrylic acid, adipic acid, alginic acid, alkanesulfonic acid, an amino acid, ascorbic acid, benzoic acid, boric acid, butyric acid, carbonic acid, citric acid, a fatty acid, formic acid, fumaric acid, gluconic acid, hydroquinosulfonic acid, isoascorbic acid, lactic acid, maleic acid, methanesulfonic acid, oxalic acid, para-bromophenylsulfonic acid, propionic acid, p-toluenesulfonic acid, salicylic acid, stearic acid, succinic acid, tannic acid, tartaric acid, thioglycolic acid, toluenesulfonic acid, uric acid, and mixtures thereof.

19. The pharmaceutical composition of claim 1, wherein the hydrophobic therapeutic agent is present in an amount that is solubilized by the carrier.

20. The pharmaceutical composition of claim 1, wherein the hydrophobic therapeutic agent is present in a first amount that is solubilized by the carrier and a second amount that is suspended but not solubilized in the carrier.

21. The pharmacetical composition of claim 1, wherein the surfactant is a hydropililic surfactant selected from the group consisting of non-ionic hydrophilic surfactants having an HLB value greater than equal to about 10, ionic hydrophilie surfactants, and mixtures thereof.

22. The pharmaceutical composition of claim 21, wherein the hydrophilic surfactant is a non-ionic hydrophilic surfactant having an HLB value greater than or equal to about 10.

23. The pharmaceutical composition of claim 22, wherein the non-ionic hydrophilic surfactant is selected from the group consisting of:

alkylgluceosides;

alkylmaltosides;

alkylthioglucosides;

lauryl macrogolglycenides;

polyoxyethylene alkyl ethers;

polyoxyethylene alkylphenols;

polyethylene glycol fatty acids esters;

polyethylene glycol glycerol fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

polyglyceryl fatty acid csters;

polyoxyethylene glycerides;

polyoxyethylene sterols and analogues thereof;

polyoxyethylene vegetable oils, polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member selected from the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, in sterols;

sugar esters, sugar ethers;

sucroglycerides; and

mixtures thereof.

24. The pharmaceutical composition of claim 22, wherein the non-ionic hydrophilic surfactant is selected from the group consisting of polyoxyethylene alkylethers;

polyethylene glycol fatty acids csters;

polyethylene glycol glycerol fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

polyglyceryl fatty acid esters;

polyoxyethylene glycerides;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member selected front the group consisting of fatty acids, glycerides, vegetable oil hydrogenated vegetable oils, and sterols; and

mixtures thereof.

25. The pharmaceutical composition of claim 16, wherein the reaction mixture comprises a transcstcrification product of a polyol and at least one member selected from the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols.

26. The pharmaceutical composition of claim 25, wherein the polyol is glycerol, ethylene glycol, polyethylene glycol, sorbitol, propylene glycol, pentaerythritol or a mixture thereof.

27. The pharmaceutical composition of claim 22, wherein the non-ionic hydropililic surfactant is selected from the group consisting of PEG-10 laurate, PEG-12 laurate, PEG-20 laurate, PEG-32 laurate, PEG-32 dilaurate, PEG-12 oleate, PEG-15 olcatc, PEG-20 olcatc, PEG-20 dioleate, PEG-32 oleate, PEG-200 oleate, PEG-400 oleate, PEG-15 stearate, PEG-32 distearate, PEG-40 stearate, PEG-100 stearate, 20 dilaurate, PEG-25 glyceryl trioleate, PEG-32 dioleate, PEG-20 glyceryl laurate, PEG-30 glyceryl laurate, 20 glyceryl stearate, PEG-20 glycidyl oleate, PEG-30 glyceryl oleate, PEG-30 glyceryl laurate, PEG-40 glyceryl laurate, PEG-40 palm kernel oil, PEG-50 hydrogenated castor oil, PEG-40 castor oil, PEG-35 castor oil, PEG-60 castor oil, PEG-40 hydrogenated castor oil, PEG-60 hydrogenated castor oil, PEG-60 corn oil, PEG-6 caprate/caprylate glycerides, PEG-8 caprate/caprylate glycerides, polyglyceryl-10 laurate, PEG-30 cholesterol, PEG-25 phyto sterol, PEG-30 soya sterol, PEG-20 trioleate, PEG-40 sorl itaii oleate, PEG-80 sorbitan laurate, polysorbate 20, polysorbate 80, POE-9 lauryl ether, POE-23 lauryl ether, POE-10 oleyl ether, POE-20 oleyl ether, POE-20 stearyl ether, tocopheryl PEG-100 succinate, PEG-24 cholesterol, polyglyceryl-10 olcatc, Tween 40, Tween 60, sucrose monostearate, sucrose monolaurate, sucrose monopalmitate, PEG 10-100 lionyl phenol series, PEG 15-100 octyl phenol series, apoloxamcr, and mixtures thereof.

28. The pharmaceutical composition of claim 22, wherein the non-ionic hydrophilic surfactant is selected from the group consisting of PEG-20 laurate, PEG-20 oleate, PEG-35 castor oil, PEG-40 palm kernel oil, PEG-40 hydrogenated castor oil, PEG-60 corn oil, PEG-25 glyceryl trioleate, polyglyceryl-10 laurate, PEG-6 caprate/caprylate glycerides, PEG-8 caprate/caprylate glycerides, PEG-30 cholesterol, polysorbate 20, polysorbate 80, POE-9 lauryl ether, POE-23 lauryl ether, POE-10 oleyl ether, PEG-24 cholesterol, sucrose monostearate, sucrose monolaurate, a poloxamer, and mixtures thereof.

29. The pharmaceutical composition of claim 22, wherein the non-ionic hydrophilic surfactant is selected from the group consisting or PEG-35 castor oil, PEG-40 hydrogenated castor oil, PEG-60 corn oil, PEG-25 glyceryl trioleate, PEG-6 caprate/caprylate glycerides, PEG-8 caprate/caprylate glycerides, polysorbate 20, polysorbate 80, tocopheryl PEG-1000 succinate, PEG-24 cholesterol, a poloxamer, and mixtures thereof.

30. The pharmaceutical composition of claim 21, wherein the hydrophilic surfactant is an ionic surfactant.

31. The pharmaceutical composition of claim 30, wherein the ionic surfactant is selected from the group consisting of fatty acid salts, bile salts, phospholipids, phosphoric acid esters, carboxylates, sulfates, sulfonates, and mixtures thereof.

32. The pharmaceutical composition of claim 21, wherein the hydrophilic surfactant is a mixture of at least one ionic surfactant and at least one non-ionic hydrophilic surfactant.

33. The pharmaceutical composition of claim 1, wherein the surfactant is a hydrophobic surfactant or mixture of hydrophobic surfactants having an HLB value of less than about 10.

34. The pharmaceutical composition of claim 33, wherein the hydrophobic surfactant is selected from the group consisting of:

alcohols;

polyoxymethylene alkylethers;

polyglyceryl fatty acid esters, fatty acids;

glyccrol fatty acid esters;

acetylated glycerol fatty acid esters;

lower alcohol fatty acids esters;

polyethylene glycol fatty acids esters;

polyethylene glycol glycerol fatty acid esters;

polypropylene glycol fatty acid esters;

polyoxyethylene glycerides;

lactic acid conjugates of mono- and diglycerides;

propylene glycol diglycerides;

sorbitan fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

transesteriefcd vegetable oils;

sterols;

sugar esters;

sugar ethers;

sucroglycerides;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member selected from the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols; and

mixtures thereof.

35. The pharmaceutical composition of claim 33, wherein the hydrophobic surfactant is selected from the group consisting of fatty acids;

lower alcohol fatty acid esters;

polyethylene glycol glycerol fatty acid esters, polypropylene glycol fatty acid esters;

polyoxyethylene glycerides;

glycerol fatty acid esters;

acetylated glycerol fatty acid esters;

polyglyceryl fatty acid esters;

lactic acid conjugates of mono- and diglycerides;

sorbitan fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene-polyoxypropylene block copolymers;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member selected from the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols; and

mixtures thereof.

36. The pharmaceutical composition of claim 33, wherein the hydrophobic surfactant is selected from the group consisting of lower alcohol fatty acids esters;

polypropylene glycol fatty acid esters;

propylene glycol fatty acid esters;

glycerol fatty acid esters;

polyglyceryl fatty acid esters;

acetylated glycerol fatty acid esters;

lactic acid conjugates of mono- and diglycerides;

sorbitan fatty acid esters;

polyoxyethylene vegetable oils; and

mixtures thereof.

37. The pharmaceutical composition of claim 33, wherein the hydrophobic surfactant is selected from the group consisting of a glycerol fatty acid ester, a polyglyceryl fatty acid ester, an acetylated glycerol fatty acid ester, and mixtures thereof.

38. The pharmaceutical composition of claim 37, wherein the glycerol fatty acid ester is selected from the group consisting of a monoglyceride, a diglyceride, and mixtures thereof.

39. The pharmaceutical composition of claim 38, wherein the fatty acid of the glycerol fatty acid ester is selected from the group consisting of C₆ to C₂₀ fatty and mixtures thereof.

40. The pharmaceutical composition of claim 33, wherein the hydrophobic surfactant comprises a reaction mixture of a polyol and at least one member selected from the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols.

41. The pharmaceutical composition of claim 40, wherein the reaction mixture comprises a transesterification product of a polyol and at least one member selected from the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols.

42. The pharmaceutical composition of claim 41, wherein the polyol is selected from the group consisting of polyethylene glycol, sorbitol, propylene glycol, pentaerythritol and mixtures thereof.

43. The pharmaceutical composition of claim 33, wherein the hydrophobic surfactant is selected from the group consisting of myristic acid;

oleic acid;

lauric acid;

stearic acid;

palmitic acid;

PEG 1-4 stearate;

PEG 2-4 oleate;

PEG-4 dilaurate;

PEG-4 dioleate;

PEG-4 distearate;

PEG-6 dioleate;

PEG-6 distearate;

PEG-8 dioleate;

PEG 3-16 castor oil;

PEG 5-10 hydrogenated castor oil;

PEG 6-20 corn oil;

PEG 6-20 almond oil;

PEG-6 olive oil;

PEG-6 peanut oil;

PEG-6 palm kernel oil;

PEG-6 hydrogenated palm kernel oil;

PEG-4 capric/caprylic triglyceride, mono, di, tri, tetra esters of vegetable oil and sorbitol;

pentaerythritol di, tetra stearate, isostearate, oleate, caprylatc, or caprate;

polyglyceryl 2-4 oleate, stearate, or isostearate;

polyglyceryl 4-10 pentaoleate;

polyglyceryl-3 dioleate;

polyglyceryl-6 dioleate;

polyglyceryl-10 trioleate;

polyglyceryl-3 distearate;

propylene glycol mono- or diesters of a C₆ to C₂₀ fatty acid;

monoglycerides of a C₆ to C₁₀ fatty acid;

acetylated monoglycerides of C₆ to C₂₀ fatty acid;

diglycerides of C₆ to C₂₀ fatty acids;

lactic acid conjugates of monoglycerides;

lactic acid conjugates of diglycerides;

cholesterol;

phytosterol;

PEG 5-20 soya sterol;

PEG-6 sorbitan tetra, hexastearate;

PEG-6 sorbitan tetraoleate;

sorbitan monolaurate;

sorbitan monopalmitate;

sorbitan mono, trioleate;

sorbitan mono, tristearate;

sorbitan monoisostearate;

sorbitan sesquioleate;

sorbitan sesquistearate;

PEG 2-5 oleyl ether;

POE 2-4 lauryl ether;

PEG-2 cetyl ether;

PEG-2 stearyl ether;

sucrose distearate;

sucrose dipalmitate;

ethyl oleate;

isopropyl myristate;

isopropyl palmitate;

ethyl linoleate;

isopropyl linoleate;

poloxamers; and

mixtures thereof.

44. The pharmaceutical composition of claim 34, wherein the hydrophobic surfactant is selected from the group consisting of oleic acid;

lauric acid;

glyceryl monocaprate;

glyceryl monocaprylate;

glyceryl monolaurate;

glyceryl monooleate;

glyceryl dicaprate;

glyceryl dicaprylate;

glyceryl dilaurate;

glyceryl dioleate;

acetylated monoglycerides;

propylene glycol oleate;

propylene glycol laurate;

polyglyceryl-3 oleate;

polyglyceryl-6 dioleate;

PEG-6 corn oil;

PEG-20 corn oil;

PEG-20 almond oil;

sorbitan monooleate;

sorbitan monolaurate;

POE-4 lauryl ether;

POE-3 oleyl ether;

ethyl oleate;

poloxamers; and

mixtures thereof.

45. The pharmaceutical composition of claim 1, wherein the triglyceride is selected from the group consisting of a pharmaceutically acceptable oil, a hydrogenated oil, a partially hydrogenated oil, a medium chain triglyceride, a long chain triglyceride, a structured triglyceride, and mixtures thereof.

46. The pharmaceutical composition of claim 1, which further comprises a solubilizer.

47. The pharmaceutical composition of claim 46, wherein the solubilizer is selected from the group consisting of alcohols, polyols, amides, esters, propylene glycol ethers and mixtures thereof.

48. The pharmaceutical composition of claim 47, wherein the alcohol or polyol is selected from the group consisting of ethanol, isopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol, butanediols and isomers thereof, glyccrol, pentaerythritol, sorbitol, transcutol, mannitol, dimethyl isosorbide, polyethylene glycol, polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose, maltodextrins, cyclodextrins, and mixtures thereof.

49. The pharmaceutical composition of claim 47, wherein the amide is selected from the group consisting of 2-pyrrolidone, 2-piperidone, ε

caprolactam, N-alkylpyrrolidone, N-hydroxyalkylpyrrolidone, N-alkylpiperidone, N-alkylcaprolactam, dimethylacetamide, polyvinylpyrrolidone, and mixtures thereof.

50. The pharmaceutical composition of claim 47, wherein the ester is selected from the group consisting of ethyl propionate, tributylcitrate, acetyl triethylcitrate, acetyl tributyl citrate, triethylcitrate, ethyl oleate, ethyl caprylate, ethyl butyrate, triacetin, propylene glycol monoacetate, propylene glycol diacetate, ε

-caprolactone and isomers thereof, δ

valerolactone and isomers thereof, β

butyrolactone and isomers thereof, and mixtures thereof.

51. The pharmaceutical composition of claim 46, wherein the solubilizer is selected from the group consisting of ethanol, isopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol, butanediol and isomers thereof, glycerol, pentaerythritol, sorbitol, transcutol, mannitol, dimethyl isosorbide, polyethylene glycol, polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose, maltodextrins, cyclodextrins, ethyl propionate, tributylcitrate, acetyl triethylcitrate, acetyl tributyl citrate, triethylcitrate, ethyl oleate, ethyl caprylate, ethyl butyrate, triacetin, propylene glycol diacetate, ε

caprolactone and isomers thereof, δ

-valerolactone and isomers thereof, β

-butyrolactone and isomers thereof, 2-pyrrolidone, 2-piperidone, ε

-caprolactam, N-methylpyrrolidone, N-ethylpyrrolidone, N-hydroxyethyl pyrrolidone, N-octylpyrrolidone, N-laurylpyrrolidone, dimethylacetamide, polyvinylpyrrolidone, glycofurol, methoxy PEG, and mixtures thereof.

52. The pharmaceutical composition of claim 46, wherein the solubilizer is selected from the group consisting of ethanol, isopropanol, benzyl alcohol, ethylene glycol, propylene glycol, 1,3-butanediol, glycerol, pentaerythritol, sorbitol, transcutol, glycofurol, dimethyl isosorbide, polyethylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose, methylcellulose, ethylcellulose, hydroxypropylcyclodextrins, sulfobutyl ether conjugates of cyclodextrins, ethyl propionate, tributylcitrate, triethylcitrate, ethyl oleate, ethyl caprylate, triacetin, β

-butyrolactone and isomers thereof, 2-pyrrolidone, N-methylpyrrolidinone, N-cthylpyrrolidone, N-hydroxyalkylpyrrolidone, N-octylpyrrolidone, N-laurylpyrrolidone, dimethylacetamide, polyvinylpyrrolidone, and mixtures thereof.

53. The pharmaceutical composition of claim 46, wherein the solubilizer is selected from the group consisting of triacctin, triethylcitrate, ethyl oleate, ethyl caprylate, dimethylacetamide, N-methylpyrrolidone, N-hydroxyalkylpyrrolidone, polyvinylpyrrolidone, hydroxypropyl methylcellulose, hydroxypropyl cyclodextrins, ethanol, polyethylene glycol 200-600, transcutol, glycofurol, propylene glycol, dimethyl isosorbide, and mixtures thereof.

54. The pharmaceutical composition of claim 46, wherein the solubilizer is selected from the group consisting of triacctin, ethanol, polyethylene glycol 400, glycofurol, propylene glycol and mixtures thereof.

55. The pharmaceutical composition of claim 1, wherein the ionizing agent is present in a pre-reaction amount of greater than about 1.5 mole equivalents per mole of the at least one ionizable functional group.

56. The pharmaceutical composition of claim 55, which further comprises a neutralizing agent capable of neutralizing a portion of the ionizing agent.

57. The pharmaceutical composition of claim 56, wherein the at least one ionizable functional group is an acidic functional group, the ionizing agent is a pharmaceutically acceptable base, and the neutralizing agent is a pharmaceutically acceptable acid.

58. The pharmaceutical composition of claim 56, wherein the at least one ionizable functional group is a basic functional group, the ionizing agent is a pharmaceutically acceptable acid, and the neutralizing agent is a pharmaceutically acceptable base.

59. The pharmaceutical composition of claim 56, wherein the neutralizing agent is present in an amount sufficient to neutralize the ionizing agent so that any non-neutralized ionizing agent is less than 1.5 mole equivalents per mole of the at least one ionizable functional group.

60. The pharmaceutical composition of claim 59, wherein the amount of the neutralizing agent is sufficient to neutralize the ionizing agent so that any non-neutralized ionizing agent is less than about 1.0 mole equivalents per mole of the at least one ionizable functional group.

61. The pharmaceutical composition of claim 1, wherein the ionizing agent is present in an amount of greater than about 1.0 mole equivalents per mole of ionizable functional group.

62. The pharmaceutical composition of claim 1, wherein the ionizing agent is present in an amount of about 0.1 to about 1.5 mole equivalents per mole of ionizable functional group.

63. The pharmaceutical composition of claim 1, wherein the ionizing agent is present in an amount of about 0.1 to about 1.0 mole equivalents per mole of ionizable functional group.

64. The pharmaceutical composition of claim 1, which further comprises an additive selected from the group consisting of an antioxidant, a preservative, a chelating agent, a viscomodulator, a tonicifier, a flavorant, a colorant, an odorant, an opacifier, a suspending agent, a binder, and mixtures thereof.

65. The pharmaceutical composition of claim 1 having a form selected from the group consisting of a preconcentrate, a diluted preconcentrate, a semi-solid dispersion, a solid dispersion, and a sprayable solution.

66. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 1.

67. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 59.

68. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 60.

69. A dosage form comprising a solid particulate carrier coated with or formed from the pharmaceutical composition of claim 1.

70. A dosage form comprising the pharmaceutical composition of claim 1 formulated as a solution, a cream, a lotion, an ointment, a suppository, a spray, an aerosol, a paste or a gel.

71. The dosage form of claim 66, wherein the capsule is selected from the group consisting of a hard gelatin capsule, a soft gelatin capsule, and a starch capsule, and is optionally enteric coated.

72. The pharmaceutical composition of claim 1, which further comprises water or an aqueous solution.

111. The pharmaceutical composition of claim 24, wherein the non-ionic hydrophilic surfactant is a reaction mixture of a polyol and at least one member selected from the group consisting of the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols.

112. The pharmaceutical composition of claim 25, wherein the reaction mixture comprises a transesterification product of a polyol and a glyceride.

114. The pharmaceutical composition of claim 112, wherein the glyceride is a monoglyceride, diglyceride, triglyceride, or a mixture thereof.

73. A pharmaceutical composition comprising:

(a) a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight; and

(b) a carrier comprising;

(i) an ionizing agent capable of ionizing the at least one ionizable functional group and present in an amount of greater than about 1.5 mole equivalents per mole of the at least one ionizable functional group; and

(ii) a surfactant selected from the group consisting of nonionic hydrophilic surfactants having an HLB value greater than or equal to about 10, ionic hydrophilic surfactants, hydrophobic surfactants having an HLB value less than 10, and mixtures thereof.

74. The pharmaceutical composition of claim 73, which further comprises a neutralizing agent capable of neutralizing a portion of the ionizing agent.

75. The pharmaceutical composition of claim 74, wherein the at least one ionizable functional group is an acidic functional group, the ionizing agent is a pharmaceutically acceptable base, and the neutralizing agent is a pharmaceutically acceptable acid.

76. The pharmaceutical composition of claim 74, wherein the at least one ionizable functional group is a basic functional group, the ionizing agent is a pharmaceutically acceptable acid, and the neutralizing agent is a pharmaceutically acceptable base.

77. The pharmaceutical composition of claim 74, wherein the neutralizing agent is present in an amount sufficient to neutralize the ionizing agent so that any non-neutralized ionizing agent is less than 1.5 mole equivalents per mole of the at least one ionizable functional group.

78. The pharmaceutical composition of claim 77, wherein the amount of the neutralizing agent is sufficient to neutralize the ionizing agent so that any non-neutralized ionizing agent is less than about 1.0 mole equivalents per mole of the at least one ionizable functional group.

79. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 77.

80. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 78.

81. The dosage form of claim 79, wherein the capsule is a hard gelatin capsule, a soft gelatin capsule, a starch capsule or an enteric coated capsule.

82. The pharmaceutical composition of claim 73, which further comprises water or an aqueous solution.

83. The pharmaceutical composition of claim 73, which further comprises a solubilizer.

84. A pharmaceutical composition comprising:

(a) a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight; and

(b) a carrier comprising;

(i) an ionizing agent capable of ionizing the at least one ionizable functional group, wherein the ionizing agent is present in an amount of at least about 0.1 mole equivalents per mole of the at least one functional group;

(ii) a surfactant selected from the group consisting of alkylglucosides;

alkylmaltosides;

alkylthioglucosides;

lauryl macrogolglycerides;

polyoxyalkylene alkyl ethers;

fatty acids;

lower alcohol fatty acid csters, polyoxyethylene, alkylphenols;

polyethylene glycol fatty acids esters;

polypropylene glycol fatty acid esters;

glycerol fatty acid esters;

acetylated glyccrol fatty acid esters;

polyethylene glycol glycerol fatty acid esters;

polyglyceryl fatty acid esters;

polyoxyethylene glycerides;

polyoxyethylene sterols and analogues thereof;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member selected from the group consisting of fatty acids, vegetable oils, hydrogenated vegetable oils, and sterols;

sugar esters, sugar others;

sucroglycerides;

fatty acid salts;

bile salts;

phospholipids;

phosphoric acid esters;

carboxylates;

sulfates; and

sulfonates; and

(iii) a solubilizer present in an amount of greater than about 10% by weight, based on the total weight of the composition.

85. The pharmaceutical composition of claim 84, wherein the solubilizer is selected from the group consisting of alcohols, polyols, amides, esters, propylene glycol ethers and mixtures thereof.

86. The pharmaceutical composition of claim 84, wherein the solubilizer is selected from the group consisting of ethanol, isopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol, butanediol and isomers thcrcof, glycerol, pentaerythritol, sorbitol, mannitol, dimethyl isosorbide, polyethylene glycol, polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose, cyclodextrins, cyclodextrins, cthyl propionate, tributylcitrate, acetyl triethylcitrate, acetyl tributyl citrate, triethylcitrate, ethyl oleate, ethyl caprylate, ethyl butyrate, triacetin, propylene glycol diacetate, ε

-caprolactone and isomers thereof, δ

-valerolactone and isomers thereof, β

-butyrolactone and isomers thereof, 2-pyrrolidone, 2-piperidone, ε

-caprolactam, N-methylpyrrolidone, N-ethylpyrrolidone, N-hydroxyethyl pyrrolidone, N-octylpyrrolidone, N-laurylpyrrolidone, dimethylacetamide, polyvinylpyrrolidone, glycofurol, methoxy PEG, and mixtures thereof.

87. The pharmaceutical composition of claim 84, wherein the solubilizer is present in an amount of at least about 15% by weight, based on the total weight of the composition.

88. The pharmaceutical composition of claim 84, wherein the ionizing agent is present in an amount of greater than about 1.5 mole equivalents per mole of ionizable functional group.

89. The pharmaceutical composition of claim 84, wherein the ionizing agent is present in an amount of greater than about 1.0 mole equivalents per mole of ionizable functional group.

90. The pharmaceutical composition of claim 84, wherein the ionizing agent is present in an amount of about 0.1 to about 1.5 mole equivalents per mole of ionizable functional group.

91. The pharmaceutical composition of claim 84, wherein the ionizing agent is present in an amount of about 0.1 to about 1.0 mole equivalents per mole of ionizable functional group.

92. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 90.

93. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 91.

94. A pharmaceutical composition comprising:

(a) a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight; and

(b) a carrier comprising;

(i) an ionizing agent capable of ionizing the at least one ionizable functional group, wherein the ionizing agent is present in an amount of at least about 0.1 mole equivalents per mole of the at least one functional group;

(ii) a surfactant selected from the group consisting of alkylglucosides;

alkylmaltosides;

alkylthioglucosides;

lauryl macrogolglycerides;

fatty acids;

lower alcohol fatty acid esters;

polyoxyethylene alkylphenols;

polyethylene glycol fatty acids esters;

polypropylene glycol fatty acid esters;

glycerol fatty acid esters;

acetylated glycerol fatty acid esters;

polyethylene glycol glycerol fatty acid esters;

polyglyceryl fatty acid esters;

polyoxyethylene sorbitan fatty acid esters;

polyoxyethylene glycerides;

polyoxyethylene sterols and analogues thereof, polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

reaction mixtures of polyols and at least one member selected from the group consisting of fatty acids, vegetable oils, hydrogenated vegetable oils, and sterols;

sugar esters;

sugar ethers;

sucroglycerides;

fatty acid salts;

bile salts;

phospholipids;

phosphoric acid esters;

carboxylates;

sulfates; and

sulfonates; and

(iii) a solubilizer comprising at least one compound selected from the group consisting of alcohols, polyols, amides, esters, and propylene glycol ethers, the alcohol or polyol being selected from the group consisting of ethanol, isopropanol, butanol, benzyl alcohol, ethylene glycol, propylene glycol, butanediols and isomers thereof, glycerol, pentaerythritol, sorbitol, mannitol, dimethyl isosorbide, polypropylene glycol, polyvinylalcohol, hydroxypropyl methylcellulose, maltodextrins, and cyclodextrins.

95. The pharmaceutical composition of claim 94, wherein the ionizing agent is present in a pre-reaction amount of greater than about 1.5 mole equivalents per mole of ionizable functional group.

96. The pharmaceutical composition of claim 94, wherein the ionizing agent is present in a an amount of greater than about 1.0 mole equivalents per mole of ionizable functional group.

97. The pharmaceutical composition of claim 94, wherein the ionizing agent is present in an amount of about 0.1 to about 1.5 mole equivalents per mole of ionizable functional group.

98. The pharmaceutical composition of claim 94, wherein the ionizing agent is present in an amount of about 0.1 to about 1.0 mole equivalents per mole of ionizable functional group.

99. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 97.

100. A dosage form comprising a capsule filled with the pharmaceutical composition of claim 98.

101. A method of preparing a pharmaceutical composition of an ionizable hydrophobic therapeutic agent, the method comprising

(I) providing a pharmaceutical composition comprising;

(a) a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight; and

(b) a carrier comprising;

(i) an ionizing agent capable or ionizing the at least one ionizable functional group, and

(ii) a surfactant selected from the group consisting of nonionic hydrophilic surfactants having an HLB value greater than or equal to about 10, ionic hydrophilic surfactants, hydrophobic surfactants having an HLB value less than 10, and mixtures thereof; and

(II) providing a neutralizing agent in an amount sufficient to neutralize at least a fraction of the ionizing agent, wherein the non-neutralized fraction of the ionizing agent is present in an mount of at least about 0.1 mole equivalents per mole of the at least one functional group.

102. The method of claim 101, wherein the ionizing agent is present in the carrier in an amount of greater than about 1.5 mole equivalents per mole of ionizable functional group.

103. The method of claim 102, wherein the neutralizing agent is present in an amount sufficient to neutralize the ionizing agent so that any non-neutralized ionizing agent is less than 1.5 mole equivalents per mole of the at least one ionizable functional group.

104. The method of claim 103, wherein the amount of the neutralizing agent is sufficient to neutralize the ionizing agent so that any non-neutralized ionizing agent is less than about 1.0 mole equivalents per mole of the at least one ionizable functional group.

105. A method of treating an animal with an ionizable hydrophobic therapeutic agent, the method comprising:

(I) providing a dosage form of a pharmaceutical composition comprising;

(a) a hydrophobic therapeutic agent having at least one ionizable functional group and an intrinsic water solubility of less than about 1% by weight; and

(b) a carrier comprising;

(i) an ionizing agent capable of ionizing the at least one ionizable functional group, wherein the ionizing agent is present in an amount of at least about 0.1 mole equivalents per mole of the at least one functional group; and

(ii) a surfactant selected from the group consisting of nonionic hydrophilic surfactants having an HLB value greater than or equal about 10, ionic hydrophilic surfactant, hydrophobic surfactants having an HLB value less than 10, and mixtures thereof; and

(II) administering said dosage form to said animal.

106. The method of claim 105, wherein the pharmaceutical composition further comprises a triglyceride.

107. The method of claim 105, wherein the dosage form is selected from the group consisting of a capsule, a solution, a cream, a lotion, an ointment, a suppository, a spray, an aerosol, a paste and a gel.

108. The method of claim 105, wherein the dosage form is administered by route selected from the group consisting of oral, parenteral, topical, transdermal, ocular, pulmonary, vaginal, rectal and transmucosal.

109. The method of claim 105, wherein the animal is a mammal.

110. The method of claim 109, wherein the mammal is a human.

113. The method of claim 105, wherein the dosage form is administered orally.