Solid carriers for improved delivery of active ingredients in pharmaceutical compositions

• US 6,923,988 B2
• Filed: 05/01/2003
• Issued: 08/02/2005
• Est. Priority Date: 11/23/1999
• Status: Expired due to Term

• Current Assignee: Lipocine Inc.
• Original Assignee: Lipocine Inc.
• Inventors: Chen, Feng-Jing, Patel, Mahesh V.
• Primary Examiner(s): Spear, James M.
• Application Number:
  US10/428,341
• Publication Number:
  US 20030215496A1
• Time in Patent Office: 824 Days
• Field of Search: 424/489, 424/422, 424/430, 424/433, 424/427, 424/436, 424/434, 424/435, 424/441, 424/443, 424/451, 424/457, 424/464, 424/466, 424/490, 424/468, 424/470, 424/465, 424/474, 424/476, 424/482, 424/498
• US Class Current: 424/489
• CPC Class Codes: A61K 31/352 condensed with carbocyclic rings, e.g. methantheline cannabinoids A61K31/658
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/496 Non-condensed piperazines containing further heterocyclic rings, e.g. rifampin, thiothixene or sparfloxacin
• CPC Class Codes: A61K 31/5383 ortho- or peri-condensed with heterocyclic ring systems
• CPC Class Codes: A61K 31/5513 1,4-Benzodiazepines, e.g. diazepam or clozapine
• CPC Class Codes: A61K 31/568 substituted in positions 10 and 13 by a chain having at least one carbon atom, e.g. androstanes, e.g. testosterone
• CPC Class Codes: A61K 31/7048 having oxygen as a ring hetero atom, e.g. leucoglucosan, hesperidin, erythromycin, nystatin , digitoxin or digoxin
• CPC Class Codes: A61K 47/10 Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
• CPC Class Codes: A61K 47/14 Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
• CPC Class Codes: A61K 9/1617 Organic compounds, e.g. phospholipids, fats
• CPC Class Codes: A61K 9/1676 having a drug-free core with discrete complete coating layer containing drug adsorbates of liquid drug formulations on inert powders without simultaneous granulation step A61K9/141; with further drug-free outer coating A61K9/5078; drug conjugated to non-active particles A61K47/6921
• CPC Class Codes: A61K 9/4858 Organic compounds
• CPC Class Codes: A61K 9/5015 Organic compounds, e.g. fats, sugars
• CPC Class Codes: A61K 9/5026 obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyvinyl pyrrolidone, poly(meth)acrylates
• CPC Class Codes: A61K 9/5078 with drug-free core
• CPC Class Codes: A61K 9/5084 Mixtures of one or more drugs in different galenical forms, at least one of which being granules, microcapsules or (coated) microparticles according to A61K9/16 or A61K9/50, e.g. for obtaining a specific release pattern or for combining different drugs tablets containing such a mixture A61K9/2077
• CPC Class Codes: A61P 1/04 for ulcers, gastritis or reflux esophagitis, e.g. antacids, inhibitors of acid secretion, mucosal protectants
• CPC Class Codes: A61P 13/08 of the prostate
• CPC Class Codes: A61P 15/10 for impotence
• CPC Class Codes: A61P 17/12 Keratolytics, e.g. wart or anti-corn preparations
• CPC Class Codes: A61P 19/06 : Antigout agents, e.g. antihyperuricemic or uricosuric agents
• CPC Class Codes: A61P 19/10 : for osteoporosis
• CPC Class Codes: A61P 21/02 : Muscle relaxants, e.g. for tetanus or cramps
• CPC Class Codes: A61P 25/04 : Centrally acting analgesics, e.g. opioids
• CPC Class Codes: A61P 25/06 : Antimigraine agents
• CPC Class Codes: A61P 25/08 : Antiepileptics; Anticonvulsants
• CPC Class Codes: A61P 25/16 : Anti-Parkinson drugs
• CPC Class Codes: A61P 25/20 : Hypnotics; Sedatives
• CPC Class Codes: A61P 25/22 : Anxiolytics
• CPC Class Codes: A61P 25/26 : Psychostimulants, e.g. nicotine, cocaine
• CPC Class Codes: A61P 25/28 : for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
• CPC Class Codes: A61P 29/00 : Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
• CPC Class Codes: A61P 3/04 : Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/06 : Antihyperlipidemics
• CPC Class Codes: A61P 3/10 : for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/04 : Antibacterial agents
• CPC Class Codes: A61P 31/10 : Antimycotics
• CPC Class Codes: A61P 31/12 : Antivirals
• CPC Class Codes: A61P 33/06 : Antimalarials
• CPC Class Codes: A61P 33/10 : Anthelmintics
• CPC Class Codes: A61P 35/00 : Antineoplastic agents
• CPC Class Codes: A61P 37/06 : Immunosuppressants, e.g. drugs for graft rejection
• CPC Class Codes: A61P 43/00 : Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: A61P 5/16 : for decreasing, blocking or antagonising the activity of the thyroid hormones
• CPC Class Codes: A61P 5/24 : of the sex hormones
• CPC Class Codes: A61P 5/40 : Mineralocorticosteroids, e.g. aldosterone; Drugs increasing or potentiating the activity of mineralocorticosteroids
• CPC Class Codes: A61P 7/02 : Antithrombotic agents; Anticoagulants; Platelet aggregation inhibitors
• CPC Class Codes: A61P 7/10 : Antioedematous agents; Diuretics
• CPC Class Codes: A61P 9/04 : Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure
• CPC Class Codes: A61P 9/06 : Antiarrhythmics
• CPC Class Codes: A61P 9/10 : for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
• CPC Class Codes: A61P 9/12 : Antihypertensives
• CPC Class Codes: B82Y 5/00 : Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
• CPC Class Codes: Y02A 50/30 : Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
• CPC Class Codes: Y10S 977/906 : Drug delivery
• CPC Class Codes: Y10S 977/927 : Diagnostic contrast agent

Abstract

The present invention provides solid pharmaceutical compositions for improved delivery of a wide variety of pharmaceutical active ingredients contained therein or separately administered. In one embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier including a substrate and an encapsulation coat on the substrate. The encapsulation coat can include different combinations of pharmaceutical active ingredients, hydrophilic surfactant, lipophilic surfactants and triglycerides. In another embodiment, the solid pharmaceutical composition includes a solid carrier, the solid carrier being formed of different combinations of pharmaceutical active ingredients, hydrophilic surfactants, lipophilic surfactants and triglycerides. The compositions of the present invention can be used for improved delivery of hydrophilic or hydrophobic pharmaceutical active ingredients, such as drugs, nutritional agents, cosmeceuticals and diagnostic agents.

Claims

1. A pharmaceutical composition in the form of a solid carrier comprising an admixture of:

(a) a pharmaceutical active ingredient selected from the group consisting of;

analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents, erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxiolytic agents, sedatives, hypnotics, neuroleptics, β

-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, keratolyptics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opiod analgesics, protease inhibitors, sex hormones, stimulants, muscle relaxants, anti-osteoporosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, nutritional oils, anti-benign prostate hypertrophy agents, essential fatty acids, non-essential fatty acids, and mixtures thereof, (b) an effective solubilizing amount of at least one hydrophiliac surfactant, which is effective to partially or fully solubilize the pharmaceutically active ingredient in the solid carrier, and optionally (c) an additive, wherein the at least one hydrophilic surfactant is selected from;

(i) a hydrophilic surfactant that solidifies at ambient room temperature;

(ii) a mixture of hydrophilic surfactants that in combination solidify at ambient room temperature;

(iii) a hydrophilic surfactant that solidifies at ambient room temperature in the presence of the additive; and

(iv) a combination of two or more of (i), (ii), and (iii), wherein the effective solubilizing amount of the at least one hydrophilic surfactant is an amount effective to facilitate sustained solubilization of the active ingredient upon administration, with the proviso that when the at least one hydrophilic surfactant includes (iii), the composition then includes the optional additive.

3. The pharmaceutical composition of claim 1, wherein the effective solubilizing amount of the hydrophilic surfactant is an amount effective to facilitate rapid dispersion of the active ingredient upon administration.

4. The pharmaceutical composition of claim 3, wherein the rapid dispersion comprises micellization and/or emulsification.

5. The pharmaceutical composition of claim 1, wherein the carrier further comprises a substrate and wherein the admixture is in the form of an encapsulation coat on the substrate.

6. The pharmaceutical composition of claim 5, wherein the substrate is a powder or a multiparticulate.

7. The pharmaceutical composition of claim 6, wherein the substrate is a multiparticulate selected from the group consisting of granules, pellets, beads, spherules, beadlets, microcapsules, millispheres, nonocapsules, microspheres, platelets, tablets, and capsules.

8. The pharmaceutical composition of claim 1, wherein the composition includes the additive.

9. The pharmaceutical composition of claim 8, wherein the additive is selected from the group consisting of solubilizers, enzyme inhibitors, anti-adherents, anticoagulants, antifoaming agents, antioxidants, binders, bufferants, chelating agents, coagulants, colorants, opaquants, coolants, cryoprotectants, diluents, fillers, disintegrants, super disintegrants, hydrogen bonding agents, flavorants, desensitizers, ion-exchange resins, plasticizers, preservatives, solvents, sweeteners, thickeners, and mixtures thereof.

10. The pharmaceutical composition of claim 9, wherein the additive is selected from the group consisting of anti-adherents, binders, and disintegrants.

11. The pharmaceutical composition of claim 10, wherein the additive is an anti-adherent selected from the group consisting of talc, magnesium stearate, fumed silica, micronized silica, polyethylene glycols, surfactants, waxes, stearic acid, stearic acid salts, stearic acid derivatives, starch, hydrogenated vegetable oils, sodium benzoate, sodium acetate, leucine, PEG-4000 and magnesium lauryl sulfate.

12. The pharmaceutical composition of claim 10, wherein the additive is a binder selected from the group consisting of matrix binders, film binders, and chemical binders.

13. The pharmaceutical composition of claim 10, wherein the additive is a disintegrant selected from the group consisting of croscarmellose sodium, starch, starch derivatives, clays, gums, cellulose, cellulose derivates, alginates, crosslinked polyvinylpyrrolidone, sodium starch glycolate and microcrystalline cellulose.

14. The pharmaceutical composition of claim 8, wherein the additive is polyvinylpyrrolidone.

15. The pharmaceutical composition of claim 8, wherein the additive is cyclodextrin.

16. The pharmaceutical composition of claim 8, wherein the additive is polyethylene glycol.

17. The pharmaceutical composition of claim 16, wherein the additive is a cellulosic polymer.

18. The pharmaceutical composition of claim 17, wherein the cellulosic polymer is selected from the group consisting of sodium carboxymethyl cellulose, hydroxypropyl cellulose, and hydroxypropylmethyl cellulose.

19. The pharmaceutical composition of claim 18, wherein the cellulosic polymer is hydroxypropylmethyl cellulose.

20. The pharmaceutical composition of claim 1, wherein the active ingredient is a drug, a nutrient, a cosmeceutical, a diagnostic agent, a salt thereof, an isomer thereof, a derivative thereof, or a mixture thereof.

21. The pharmaceutical composition of claim 1, wherein the active ingredient has an intrinsic aqueous solubility of less than about 1 mg/mL.

23. The pharmaceutical composition of claim 1, wherein the active ingredient is selected from the group consisting of analgesics, anti-bacterial agents, anti-viral agents, anti-inflammatory agents, anti-depressants, anti-diabetics, anti-epileptics, anti-hypertensive agents, anti-migraine agents, immunosuppressants, anxiolytic agents, sedatives, hypnotics, neuroleptics, β

-blockers, gastro-intestinal agents, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, opioid analgesics, protease inhibitors, sex hormones, cognition enhancers, anti-urinary incontinence agents, and mixtures thereof.

24. The pharmaceutical composition of claim 1, wherein the active ingredient is selected from the group consisting of acetretin, albendazole, albuterol, aminoglutethimide, amiodarone, amlodipine, amphetamine, amphotericin B, atorvastatin, atovaquone, azithromycin, baclofen, beclomethasone, benezepril, benzonatate, betamethasone, bicalutanide, budesonide, bupropion, busulfan, butenafine, calcifediol, calcipotriene, calcitriol, camptothecin, candesartan, capsaicin, carbamezepine, carotenes, celecoxib, cerivastatin, cetirizine, chlorpheniramine, cholecalciferol, cilostazol, cimetidine, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clemastine, clomiphene, clomipramine, clopidogrel, codeine, coenzyme Q10, cyclobenzaprine, cyclosporin, danazol, dantrolene, dexchlorpheniramine, diclofenac, dicoumarol, digoxin, dehydroepiandrosterone, dihydroergotamine, dihydrotachysterol, dirithromycin, donezepil, efavirenz, eprosartan, ergocalciferol, ergotamine, essential fatty acid sources, etodolac, etoposide, famotidine, fenofibrate, fentanyl, fexofenadine, finasteride, fluconazole, flurbiprofen, fluvastatin, fosphenytoin, frovatriptan, furazolidone, gabapentin, gemfibrozil, glibenclamide, glipizide, glyburide, glimepiride, griseofulvin, halofantrine, ibuprofen, irbesartan, irinotecan, isosorbide dinitrate, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lansoprazole, leflunomide, lisinopril, loperamide, loratadine, lovastatin, L-thryroxine, lutein, lycopene, medroxyprogesterone, mifepristone, mefloquine, megestrol acetate, methadone, methoxsalen, metronidazole, miconazole, midazolam, miglitol, minoxidil, mitoxantrone, montelukast, nabumetone, nalbuphine, naratriptan, nelfinavir, nifedipine, nilsolidipine, nilutanide, nitrofurantoin, nizatidine, omeprazole, oprevelkin, oestradiol, oxaprozin, paclitaxel, paracalcitol, paroxetine, pentazocine, pioglitazone, pizofetin, pravastatin, prednisolone, probucol, progesterone, pseudoephedrine, pyridostigmine, rabeprazole, raloxifene, rofecoxib, repaglinide, rifabutine, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sertraline, sibutramine, sildenafil citrate, simvastatin, sirolimus, spironolactone, sumatriptan, tacrine, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, telmisartan, teniposide, terbinafine, terazosin, tetrahydrocannabinol, tiagabine, ticlopidine, tirofibran, tizanidine, topiramate, topotecan, toremitfene, tramadol, tretinoin, troglitazone, trovafloxacin, ubidecarenone, valsartan, venlafaxine, verteporfin, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, zolpidem, zopiclone, pharmaceutically acceptable salts, isomers, and derivatives thereof, and mixtures thereof.

25. The pharmaceutical composition of claim 24, wherein the active ingredient is selected from the group consisting of acetretin, albendazole, albuterol, aminoglutethimide, amiodarone, amlodipine, amphetamine, amphotericin B, atorvastatin, atovaquone, azithromycin, baclofen, benzonatate, bicalutanide, busulfan, butenafine, calcifediol, calcipotriene, calcitriol, camptothecin, capsaicin, carbamezepine, carotenes, celecoxib, cerivastatin, chlorpheniramine, cholecaliferol, cimetidine, cinnarizine, ciprofloxacin, cisapride, cetirizine, clarithromycin, clemastine, clomiphene, codeine, coenzyme Q10, cyclosporin, danazol, dantrolene, dexchlorpheniramine, diclofenac, digoxin, dehydrepiandrosterone, dihydroergotamine, dihyrotachysterol, dirithromycin, donepezil, efavirenz, ergocalciferol, ergotamine, essential fatty acid sources, etodolac, etoposide, famotidine, fenofibrate, fentanyl, fexofenadine, finasteride, fluconazole, flurbiprofen, fluvastatin, fosphenytoin, frovatriptan, furazolidone, gabapentin, gemfibrozil, glibenclamide, glipizide, glyburide, glimepiride, griseofulvin, halofantrine, ibuprofen, irinotecan, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lansoprazole, leflunomide, loperamide, loratadine, lovastatin, L-thryroxine, lutein, lycopene, mifepristone, mefloquine, megestrol acetate, methdone, methoxsalen, metronidazole, miconazole, midazolam, miglitol, mitoxantrone, medroxyprogesterone, montelukast, nabumetone, nalbuphine, naratriptan, nelfinavir, nilutanide, nitrofurantoin, nizatidine, omeprazole, oestradiol, oxaprozin, paclitaxel, paracalcitol, pentazocine, pioglitazone, pizofetin, pravastatin, probucol, progesterone, pseudoephedrine, pyridostigmine, rabeprazole, raloxifene, rofecoxib, repaglinide, rifabutine, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sibutramine, sildenafil citrate, simvastatin, sirolimus, spironolactone, sumatriptan, tacrine, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, teniposide, terbinafine, tetrahydrocannabinol, tiagabine, tizanidine, topiramate, topotecan, toremifene, tramadol, tretinoin, troglitazone, trovafloxacin, verteporfin, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, zolpidem, zopiclone, pharmaceutically acceptable salts, isomers and derivatives thereof, and mixtures thereof.

26. The pharmaceutical composition of claim 25, wherein the active ingredient is selected from the group consisting of acetretin, albuterol, aminoglutethimide, amiodarone, amlodipine, amprenavir, atorvastatin, atovaquone, baclofen, benzonatate, bicalutanide, busulfan, calcifediol, calcipotriene, calcitriol, camptothecin, capsaicin, carbamezepine, carotenes, celecoxib, chlorpheniramine, cholecaliferol, cimetidine, cinnarizine, cisapride, citrizine, clemastine, coenzyme Q10, cyclosporin, danazol, dantrolene, dexchlorpheniramine, diclofenac, dehydroepiandrosterone, dihydroergotamine, dihyrotachysterol, efavirenz, ergocalciferol, ergotamine, essential fatty acid sources, etodolac, etoposide, famotidine, fenofibrate, fexofenadine, finasteride, fluconazole, flurbiprofen, fosphenytoin, frovatriptan, furzolidone, glibenclamide, glipizide, glyburide, glymepride, ibuprofen, irinotecan, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lansoprazole, leflunomide, loperamide, loratadine, lovastatin, L-thryroxine, lutein, lycopene, medroxyprogesterone, mifepristone, megestrol acetate, methoxsalen, metronidazole, miconazole, miglitol, mitoxantrone, montelukast, nabumetone, naratriptan, nelfinavir, nilutanide, nitrofurantoin, nizatidine, omeprazole, oestradiol, oxaprozin, paclitaxel, paracalcitol, pioglitazone, pizofetin, pranlukast, probucol, progesterone, pseudoephedrine, rabeprazole, raloxifene, rofecoxib, repaglinide, rifabutine, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sildenafil citrate, simvastatin, sirolimus, tramadol, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, teniposide, terbenafine, tetrahydrocannabinol, tiagabine, tizanidine, topiramate, topotecan, toremifene, tramadol, tretinoin, troglitazone, trovafloxacin, ubidecarenone, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, pharmaceutically acceptable salts, isomers and derivative thereof, and mixtures thereof.

27. The pharmaceutical composition of claim 26, wherein the active ingredient is selected from the group consisting of amlodipine, amprenavir, atorvastatin, atovaquone, celecoxib, cisapride, coenzyme Q10, cyclosporin, famotidine, fenofibrate, fexofenadine, finasteride, ibuprofen, itraconazole, lansoprazole, loratadine, lovastatin, megestrol acetate, montelukast, nabumetone, nizatidine, omeprazole, oxaprozin, paclitaxel, paracalcitol, pioglitazone, pranlukast, progesterone, pseudoephedrine, rabeprazole, rapamycin, rofecoxib, repaglinide, rimexolone, ritanovir, rosiglitazone, saquinavir, sildenafil citrate, simvastatin, sirolimus, tramadol, tacrolimus, tamsulosin, teniposide, terbenafine, tetrahydrocannabinol, tiagabine, tizanidine, tramadol, troglitazone, vitamin A, vitamin D, vitamin E, zafirlukast, zileuton, pharmaceutically acceptable salts, isomers and derivatives thereof, and mixtures thereof.

28. The pharmaceutical composition of claim 1, wherein the active ingredient is selected from the group consisting of progesterone, dehydroepiandrosterone, amiodarone, spironolactone and mixtures thereof.

29. The pharmaceutical composition of claim 1, wherein the active ingredient is selected from the group consisting of clopidogrel, pioglitazone, zafirlukast, sertraline, tramadol, and fentanyl.

30. The pharmaceutical composition of claim 1, wherein the active ingredient is selected from the group consisting of tacrolimus, sirolimus, cilostazol, bicalutaminde, simvastatin, and lovastatin.

31. The pharmaceutical composition of claim 1, wherein the at least one hydrophilic surfactant comprises a non-ionic hydrophilic surfactant.

32. The pharmaceutical composition of claim 31, wherein the non-ionic hydrophilic surfactant has an HLB value of at least about 10.

33. The pharmaceutical composition of claim 31, wherein the non-ionic hydrophilic surfactant is selected from the group consisting of alkylglucosides;

alkylmaltosides;

alkylthioglucosides;

lauryl macrogolglycerides;

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;

polyglycerol fatty acid esters;

polyoxyethylene glycerides;

polyoxyethylene sterols, derivatives, and analogues thereof;

polyoxyethylene vegetable oils;

polyoxyethylene hydrogenated vegetable oils;

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

tocopheryl polyethylene glycol succinates;

sugar esters;

sugar ethers;

sucroglycerides; and

mixtures thereof.

34. The pharmaceutical composition of claim 33, wherein the non-ionic hydrophilic surfactant is a polyoxyethylene sorbitan fatty acid esters.

35. The pharmaceutical composition of claim 34, wherein the polyoxyethylene sorbitan fatty acid ester is PEG-20 sorbitan monooleate.

36. The pharmaceutical composition of claim 33, wherein the non-ionic hydrophilic surfactant is a polyoxyethylene vegetable oil.

37. The pharmaceutical composition of claim 36, wherein the polyoxyethylene vegetable oil is polyethoxylated caster oil.

38. The pharmaceutical composition of claim 37, wherein the polyethoxylated caster oil is PEG-35 caster oil.

39. The pharmaceutical composition of claim 33, wherein the non-ionic hydrophilic surfactant is a polyoxyethylene hydrogenated vegetable oil.

40. The pharmaceutical composition of claim 39, wherein the polyoxyethylene hydrogenated vegetable oil is polyethoxylated hydrogenated caster oil.

41. The pharmaceutical composition of claim 40, wherein the polyethoxylated hydrogenated caster oil is PEG-40 hydrogenated castor oil.

42. The pharmaceutical composition of claim 33, wherein the non-ionic hydrophilic surfactant is a tocopheryl polyethylene glycol succinate.

43. The pharmaceutical composition of claim 42, wherein the tocopheryl polyethylene glycol succinate is tocopheryl PEG-1000 succinate.

44. The pharmaceutical composition of claim 33, wherein the non-ionic hydrophilic surfactant is a polyoxyethylene glyceride.

45. The pharmaceutical composition of claim 44, wherein the polyoxyethylene glyceride is a PEG-8 caprylic/capric glyceride.

46. The pharmaceutical composition of claim 31, wherein the non-ionic hydrophilic surfactant is selected from the group consisting of lauryl macrogol glycerides and stearoyl macrogol glycerides.

47. The pharmaceutical composition of claim 46, wherein the non-ionic hydrophilic surfactant is a lauryl macrogol glyceride.

48. The pharmaceutical composition of claim 47, wherein the lauryl macrogol glyceride is lauryl macrogol-32 glyceride.

49. The pharmaceutical composition of claim 46, wherein the non-ionic hydrophilic surfactant is a stearoyl macrogol glyceride.

50. The pharmaceutical composition of claim 1, wherein the at least one hydrophilic surfactant comprises an ionic surfactant.

51. The pharmaceutical composition of claim 50, wherein the ionic surfactant is selected from the group consisting of alkyl ammonium salts;

bile acids and salts, analogues, and derivatives thereof;

fatty acid derivatives of amino acids, camitines, oligopeptides, and polypeptides;

glyceride derivatives of amino acids, oligopeptides, and polypeptides;

acyl lactylates;

mono- and di-acetylated tartaric acid esters of mono- and di-glycerides;

succinylated monoglycerides;

citric acid esters of mono- and di-glycerides;

alginate salts;

propylene glycol alginate;

lecithins and hydrogenated lecithins;

lysolecithin and hydrogenated lysolecithins, lysophospholipids and derivatives thereof;

phospholipids and derivatives thereof;

salts of alkylsulfates;

salts of fatty acids;

sodium docusate; and

mixtures thereof.

52. The pharmaceutical composition of claim 1, wherein the solid carrier comprises a bead, a beadlet, a granule, a spherule, a pellet, a microcapsule, a microsphere, a nanosphere, a film, a wafer, a sprinkle, an implant, a troche, a lozenge, a platelet, a nanocapsule or a strip.

53. The pharmaceutical composition of claim 1, wherein the solid carrier is enteric coated, coated for fast disintegration, seal coated, film coated, barrier coated, compress coated, or coated with an enzyme-degradable coating.

54. The pharmaceutical composition of claim 1, wherein the composition is encapsulated, extruded, compressed, pelletized, coated, mixed, granulated, crystallized, lyophilized or molded.

55. The pharmaceutical composition of claim 1, wherein the composition is prepared by spheronization.

56. The pharmaceutical composition of claim 1, wherein the composition is prepared by compression.

57. The pharmaceutical composition of claim 1, wherein the composition is prepared by extrusion.

58. The pharmaceutical composition of claim 1, in the form of a capsule, a tablet, an ovule, a suppository, a wafer, a chewable tablet, a buccal tablet, a sublingual tablet, a quick-dissolve tablet, an effervescent tablet, a granule, a pellet, a bead, a pill, a sachet, a sprinkle, a film, a dry syrup, a reconstitutable solid, a suspension, a lozenge, a troche, an implant, a powder, a triturate, a platelet, or a strip.

59. The pharmaceutical composition of claim 1, wherein the composition is formulated for controlled release.

60. The pharmaceutical composition of claim 59, wherein the controlled release is immediate release, pulsatile release, extended release, delayed release, targeted release, targeted delayed release, or mixtures thereof.

61. The pharmaceutical composition of claim 1, wherein the composition is formulated for oral, nasal, ocular, urethral, buccal, transmucosal, vaginal, topical or rectal delivery.

62. A method of administering an active ingredient to a mammalian patient, the method comprising administering the pharmaceutical composition of claim 1 to the patient.

63. The method of claim 62, wherein the mammal is a human.

77. The pharmaceutical composition of claim 61, wherein the composition is prepared by spheronization, pelletization, coating, balling, extrusion, spray congealing, nanoencapsulation, super critical fluid processes, cryopelletization, mixing, molding, compression, granulation, lyophilization, chilling, agglomeration, congealing, drying, melt extrusion, crystallization, coacervation, and combinations thereof.

2. A pharmaceutical composition in the form of a solid carrier comprising an admixture of:

(a) a pharmaceutical active ingredient;

(b) an effective solubilizing amount of at least one hydrophilic surfactant selected from the group consisting of (i) polyoxyethylene sorbitan fatty acid esters, (ii) polyoxyethylene-polyoxypropylene block copolymers, (iii) polyglycerol fatty acid esters, (iv) polyoxyethylene glycerides, (v) polyoxyehtylene sterols, deriviatives, and analogues thereof, (vi) polyoxyehtylene vegetable oils, (vii) polyoxyethylene hydrogenated vegetable oils, (viii) reaction mixtures of polyols and at least one member of the group consisting of fatty acids, glycerides, vegetable oils, hydrogenated vegetable oils, and sterols (ix) tocopheryl polyethylene glycol succinates, (x) sugar esters, (xi) sugar ethers, (xii) sucroglycerides, and (xiii) mixtures thereof; and

(c) an additive to provide for controlled release of the active ingredient following administration to a patient, said additive selected from the group consisting of polyvinylpyrrolidone, polyethylene glycol, hydroxypropyl methylcellulose, hyrosypropyl cellulose and other cellulose derivatives and mixtures thereof.

64. The pharmaceutical composition of claim 2, wherein the active ingredient is selected from the group consisting of analgesics, anti-inflammatory agents, antihelminthics, anti-arrhythmic agents, anti-bacterial agents, anti-viral agents, anti-coagulants, anti-depressants, anti-diabetics, anti-epileptics, anti-fungal agents, anti-gout agents, anti-hypertensive agents, anti-malarials, anti-migraine agents, anti-muscarinic agents, anti-neoplastic agents, erectile dysfunction improvement agents, immunosuppressants, anti-protozoal agents, anti-thyroid agents, anxioytic agents, sedatives, hypnotics, neuroleptics, β

-blockers, cardiac inotropic agents, corticosteroids, diuretics, anti-parkinsonian agents, gastro-intestinal agents, histamine receptor antagonists, kerarolytics, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, nutritional agents, opioid analgesics, protease inhibitors, sex hormones, stimulants, muscle relaxants, anti-osteoperosis agents, anti-obesity agents, cognition enhancers, anti-urinary incontinence agents, nutritional oils, anti-benign prostate hypertrophy agents, essential fatty acids, non-essential fatty acids, and mixtures thereof.

65. The pharmaceutical composition of claim 64, wherein the effective solubilizing amount of the hydrophilic surfactant is an amount effective to facilitate sustained solubilization of the active ingredient upon administration.

66. The pharmaceutical composition of claim 64, wherein the effective solubilizing amount of the hydrophilic surfactant is an amount effective to partially or fully solubilize the active ingredient in the solid carrier.

67. The pharmaceutical composition of claim 64, wherein the effective solubilizing amount of the hydrophilic surfactant is an amount effective to facilitate rapid dispersion of the active ingredient upon administration.

68. The pharmaceutical composition of claim 67, wherein the rapid dispersion comprises micellization and/or emulsification.

69. The pharmaceutical composition of claim 64, wherein the hydrophilic surfactant is PEG-20 sorbitan monooleate.

70. The pharmaceutical composition of claim 64, wherein the hydrophilic surfactant is selected from the group consisting of PEG-35 caster oil, PEG-40 hydrogenated castor oil, and mixtures thereof.

71. The pharmaceutical composition of claim 64, wherein the hydrophilic surfactant is tocopheryl PEG-1000 succinate.

72. The pharmaceutical composition of claim 64, wherein the hydrophilic surfactant is selected from the group consisting of lauryl macrogols-32 glyceride, stearoyl macrogols glyceride and mixtures thereof.

73. The pharmaceutical composition of claim 64, wherein the hydrophilic surfactant is PEG-8 caprylic/capric glyceride.

74. The pharmaceutical composition of claim 64, wherein the hydrophilic surfactant is a poloxamer.

75. The pharmaceutical composition of claim 64, wherein the controlled release is immediate release, extended release, delayed release, pulsatile release, targeted release or mixtures thereof.

76. The pharmaceutical composition of claim 64, wherein the solid carrier is provided with one or more coatings.

78. The pharmaceutical composition of claim 64, wherein the active ingredient is selected from the group consisting of analgesics, anti-bacterial agents, anti-viral agents, anti-inflammatory agents, anti-depressants, anti-diabetics, anti-epileptics, anti-hypertensive agents, anti-migraine agents, immunosupressants, anxiolytic agents, sedatives, hypnotics, neuroleptics, β

-blockers, gastro-intestinal agents, lipid regulating agents, anti-anginal agents, Cox-2 inhibitors, leukotriene inhibitors, macrolides, muscle relaxants, opioid analgesics, protease inhibitors, sex hormones, cognition enhancers, anti-urinary incontinence agents, and mixtures thereof.

79. The pharmaceutical composition of claim 78, wherein the effective solubilizing amount of the hydrophilic surfactant is an amount effective to partially or fully solubilize the active ingredient in the solid carrier.

80. The pharmaceutical composition of claim 78, wherein the effective solubilizing amount of the hydrophilic surfactant is an amount effective to facilitate rapid dispersion of the active ingredient upon administration.

81. The pharmaceutical composition of claim 80, wherein the rapid dispersion comprises micellization and/or emulsification.

82. The pharmaceutical composition of claim 2, wherein the active ingredient is selected from the group consisting of acetretin, albendazole, albuterol, aminoglutethimide, amiodarone, amlodipine, amphetamine, amphotericin B, atorvastatin, atovaquone, azithromycin, baclofen, beclomethasone, benezepril, benzonatate, betamethasone, bicalutanide, budesonide, bupropion, busulfan, butenafine, calcifediol, calcipotriene, calcitriol, camptothecin, candesartan, capsaicin, carbamezepine, carotenes, celecoxib, cerivastatin, cetirizine, chlorpheniramine, cholecalciferol, cilostazol, cimetidine, cinnarizine, ciprofloxacin, cisapride, clarithromycin, clemastine, clomiphene, clomipramine, clopidogrel, codeine, coenzyme Q10, cyclobenzaprine, cyclosporin, danazol, dantrolene, dexchlorpheniramine, diclofenac, dicoumarol, digoxin, dehydroepiandrosterone, dihydroergotamine, dihydotachysterol, dirithromycin, donezepil, efavirenz, eprosartan, ergocalciferol, ergotamine, essential fatty acid sources, etodolac, etoposide, famotidine, fenofibrate, fentanyl, fexofenadine, finasteride, fluconazole, flurbiprofen, fluvastatin, fosphenytoin, frovatriptan, furazolidone, gabapentin, gemfibrozil, glibenclamide, glipizide, glyburide, glimepiride, griseofulvin, halofantrine, ibuprofen, irbesartan, irinotecan, isosorbide dinitrate, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lansoprazole, leflunomide, lisinopril, loperamide, loratadine, lovastatin, L-thyroxine, lutein, lycopene, medroxyprogesterone, mifepristone, mefloquine, megestrol acetate, methadone, methoxsalen, metronidazole, miconazole, midazolam, miglitol, minoxidil, mitoxantrone, montelukast, nabumetone, nalbuphine, naratriptan, nelfinavir, nifedipine, nilsolidipine, nilutanide, nitrofurantoin, nizatidine, omeprazole, oprevelkin, oestradiol, oxaprozin, paclitaxel, paracalcitol, paroxetine, pentazocine, pioglitazone, pizofetin, pravastatin, prednisolone, probucol, progesterone, pseudoephedrine, pyridostigmine, rabeprazole, raloxifene, rofecoxib, repaglinide, rifabutine, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sertraline, sibutramine, sildenafil citrate, simvastatin, sirolimus, spironolactone, sumatriptan, tacrine, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, telmisartan, teniposide, terbinafine, terazosin, tetrahydrocannabinol, tiagabine, ticlopidine, tirofibran, tizanidine, topiramate, topotecan, toremifene, tramadol, tretinoin, troglitazone, trovafloxacin, ubidecarenone, valsartan, venlafaxine, verteporfin, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, zolpidem, zopiclone, pharmaceutically acceptable salts, isomers, and derivatives thereof, and mixtures thereof.

83. The pharmaceutical composition of claim 82, wherein the active ingredient is selected from the group consisiting of acetretin, albendazole, albuterol, aminoglutethimide, amiodarone, amlodipine, amphetamine, amphotericin B, atorvastatin, atovaquone, azithromycin, baclofen, benzonatate, bicalutanide, busulfan, butenafine, calcifediol, calcipotriene, calcitriol, camptothecin, capsaicin, carbamezepine, carotenes, celecoxib, cerivastatin, chlorpheniramine, cholecaliferol, cimetidine, cinnarizine, ciprofloxacin, cisapride, cetirizine, clarithromycin, clemastine, clomiphene, codeine, coenzyme Q10, cyclosporin, danazol, dantrolene, dexchlorpheniramine, diclofenac, digoxin, dehydrepiandrosterone, dihydroergotamine, dihyrotachysterol, dirithromycin, donepezil, efavirenz, ergocalciferol, ergotamine, essential fatty acid sources, etodolac, etoposide, famotidine, fenofibrate, fentanyl, fexofenadine, finasteride, fluconazole, flurbiprofen, fluvastatin, fosphenytoin, frovatriptan, furazolidone, gabapentin, gemifibrozil, glibenclamide, glipizide, glyburide, glimepiride, griseofulvin, halofantrine, ibuprofen, irinotecan, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lansoprazole, leflunomide, loperamide, loratadine, lovastatin, L-thryroxine, lutein, lycopene, mifepristone, mefloquine, megestrol acetate, methdone, methoxsalen, metronidazole, miconazole, midazolam, miglitol, mitoxantrone, medroxyprogesterone, montelukast, nabumetone, nalbuphine, naratriptan, nelfinavir, nilutanide, nitrofurantoin, nizatidine, omeprazole, oestradiol, oxaprozin, paclitaxel, paracalcitol, pentazocine, pioglitazone, pizofetin, pravastatin, probucol, progesterone, pseudoephedrine, pyridostigmine, rabeprazole, raloxifine, rofecoxib, repaglinide, rifabutine, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sibutramine, sildenafil citrate, simvastatin, siroliumus, spironolactone, sumatriptan, tacrine, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, teniposide, terbinafine, tetrahydrocannabinol, tiagabine, tizanidine, topiramate, topotecan, toremifene, tramadol, tretinoin, troglitazone, trovafloxacin, verteporfin, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, zolpidem, zopiclone, pharmaceutically acceptable salts, isomers and derivatives thereof, and mixtures thereof.

84. The pharmaceutical composition of claim 83, wherein the active ingredient is selected from the group consisting of acetretin, albuterol, aminoglutethimide, amiodarone, amlodipine, amprenavir, atorvastatin, atovaquone, baclofen, benzonatate, bicalutanide, busulfan, calcifediol, calcipotriene, calcitrol, camptothecin, capsaicin, carbamezepine, carotenes, celecoxib, chlorpheniramine, cholecaliferol, cimitidine, cinnarizine, cisapride, citrizine, clemastine, coenzyme Q10, cyclosporin, danazol, dantrolene, dexchlorpheniramine, diclofenac, dehydroepiandrosterone, dihydroergotamine, dihyrotachysterol, efavirenz, ergocalciferol, ergotamine, essential fatty acid sources, etodolac, etoposide, famotidine, fenofibrate, fexofenadine, finasteride, fluconazole, flurbiprofen, fosphenytoin, frovatriptan, flurzolidone, glibenclamide, glipizide, glyburide, glymepride, ibuprofen, ironotecan, isotretinoin, itraconazole, ivermectin, ketoconazole, ketorolac, lamotrigine, lansoprazole, leflunomide, loperamide, loratadine, lovastatin, L-thyroxine, lutien, lycopene, medroxyprogesterone, mifepristone, megestrol acetate, methoxsalen, metronidazole, miconazole, miglitol, mitoxantrone, montelukast, nabumetone, naratriptan, nelfinavir, nilutanide, nitrofurantoin, nizatidine, omeprazole, oestradiol, oxaprozin, paclitaxel, paracalcitol, pioglitazone, pizofetin, pranlukast, probucol, progesterone, pseudophedrine, raberprazole, raloxifene, rofecoxib, repaglinide, rifabutine, rifapentine, rimexolone, ritanovir, rizatriptan, rosiglitazone, saquinavir, sildenafil citrate, simvastatin, sirolimus, tramadol, tacrolimus, tamoxifen, tamsulosin, targretin, tazarotene, teniposide, terbenafine, tetrahydrocannabinol, tiagabine, tizanidine, topiramate, topotecan, toremifine, tramadol, tretinoin, troglitazone, trovafloxacin, ubidecarenone, vigabatrin, vitamin A, vitamin D, vitamin E, vitamin K, zafirlukast, zileuton, zolmitriptan, pharmaceutically acceptable salts, isomers and derivative thereof, and mixtures thereof.

85. The pharmaceutical composition of claim 84, wherein the active ingredient is selected from the group consisting of amlodipine, amprenavir, atorvastatin, atovaquone, celecoxib, cisapride, coenzyme Q10, cyclosporin, famotidine, fenofibrate, fexofenadine, finasteride, ibuprofen, itraconazole, lansoprazole, loratadine, lovastatin, megestrol acetate, montelukast, nebumetone, nizatidine, omeprazole, oxaprozin, paclitaxel, paracalcitol, pioglitazone, pranlukast, progesterone, pseudoephedrine, rabeprazole, rapamycin, rofecoxib, repaglinide, rimexolone, ritanovir, rosiglitazone, saquinavir, sildenafil citrate, simvastatin, sirolimus, tramadol, tacrolimus, tamsulosin, teniposide, terbenafine, tetrahydrocannabinol, tiagabine, tizanidine, tramadol, trogliazone, vitamin A, vitamin D, vitamin E, zafirlukast, zileuton, pharmaceutically acceptable salts, isomers and derivatives thereof, and mixtures thereof.

86. The pharmaceutical composition of claim 2, wherein the active ingredient is selected from the group consisting of progesterone, dehydroepiandrosterone, amiodarone, spironolactone and mixtures thereof.

87. The pharmaceutical composition of claim 2, wherein the active ingredient is selected from the group consisting of clopidogrel, pioglitazone, zafirlukast, sertraline, tramadol, and fentanyl.

88. The pharmaceutical composition of claim 2, wherein the active ingredient is selected from the group consisting of tacrolimus, sirolimus, cilostazol, bicalutaminde, simvastatin, and lovastatin.

22. A pharmaceutical composition in the form of a solid carrier comprising a substrate and an encapsulation coat on the substrate, wherein the encapsulation coat comprises a therapeutically effective amount of a hydrophobic pharmaceutical active ingredient and an effective solubilizing amount of at least one hydrophilic surfactant, wherein the effective solubilizing amount of the at least one hydrophilic surfactant is an amount effective to facilitate sustained solubilization of the active ingredient upon administration.