WO2010017053A1 - Solid excipient compositions - Google Patents

Abstract

Excipient blends containing bispyrrolidone butane (BPB) and an excipient are disclosed. Methods for forming the excipient blends and formulations containing the excipient blends are also described.

Description

SOLID EXCIPIENT COMPOSITIONS

BACKGROUND OF THE INVENTION

[0001] The present invention relates to an excipient composition containing bispyrrolidone butane (BPB) and an excipient wherein the excipient blend is in the form of a solid or solid-like composition. The present invention also relates to methods for producing the excipient blend and the use of the excipient blend in pharmaceutical and cosmetic compositions.

[0002] Solid dosage forms are a particularly useful method for administering pharmaceutical and dietary supplements. They can be administered by a variety of routes, including oral, buccal, sublingual, rectal, or intravaginal. Solid dosage forms can assume different materializations- such as tablets, compressed tablets, caplets, capsules, soft gelatin capsules, multi-particulates, granulates, lozenges, pastilles, and troches. These materialization can affect performance attributes, such as active release, physical stability, and ease of handling. Solid dosage forms, together with solid-like dosage forms, differ from non-solid dosage forms, e.g., intravenous drips, in that they do not readily flow.

[0003] Broadly speaking, solid dosage forms typically contain two types of components: The first component comprises one or more active agents, while the second component type comprises non-active ingredients, typically referred to as excipients. The active agents may constitute active pharmaceutical ingredients (API), nutraceutical actives, or other actives of interest, such as dyes, biocides, or fertilizers. Seldom is the case that active agents alone possess suitable compressibility and overall performance attributes that they alone are compressed into a solid dosage form. Consequently, active ingredients are typically formulated with excipients to enable handling, transport, and/or delivery. Excipients may impart a number of desirable properties to the solid dosage form, including: suitable hardness, low friability, size, immediate/delayed/controlled/sustained delivery of the active, and protection of the active.

[0004] Commonly used excipients in solid dosage forms can be generally categorized into various functional purposes: binders, fillers/diluents, disintegrants/disintegrant aides, glidants, lubricants, colors, flavors, and sweeteners. A description of these compositional ingredients may be found in Pharmaceutical Research Development and Training Laboratories, Hands-on Postgraduate Course in Tablet Technology, June 11-16, 2006, Department of Pharmaceutical Sciences, The University of Tennessee, Memphis, Tennessee, the contents of which are hereby incorporated by reference. Another excipient category exists, performance adjuvants, which may alter the performance of the active. Performance adjuvants include surfactants, wetting agents, solubilizers/solvents, and stabilization and sequestering additives. Additionally, solid dosage forms may be coated to provide aesthetic, tastemasking, altered release functionality, or ease-of- use.

SUMMARY OF THE INVENTION

[0005] In accordance with one aspect of the present invention, an excipient blend comprising of (a) bispyrrolidone butane (BPB) and (b) an excipient wherein the excipient blend is in the form of a solid or solid-like composition is provided. In accordance with certain aspects of the present invention, the excipient is a solid excipient. In accordance with the particular aspects of the present invention, the solid excipient may be a disintegrant, a diluent, a filler, a carrier, an adsorbent, or mixtures thereof.

[0006] In accordance with another aspect of the present invention, a method of forming an excipient blend is provided. In accordance with this aspect of the present invention, an excipient blend is formed by blending BPB and an excipient to form a solid or solid-like excipient blend. In accordance with a specific embodiment of the present invention, the components of the excipient blend are prepared as dispersions in a solvent, and then the solvent is removed to provide the solid or solid-like excipient blend.

[0007] In accordance with yet another aspect of the present invention, a method for producing a composition comprising an active ingredient and an excipient blend is provided. In accordance with this aspect of the present invention, the method comprises mixing the active ingredient with an excipient blend wherein the excipient blend comprises (a) bispyrrolidone butane (BPB) and (b) an excipient wherein the excipient blend is in the form of a solid or solid-like composition.

[0008] Yet another aspect of the present invention relates to a pharmaceutical or cosmetic composition comprising a pharmaceutical or cosmetic active ingredient admixed with a pre- mixed excipient blend wherein the pre-mixed excipient blend comprises (a) bispyrrolidone butane (BPB) and (b) an excipient wherein the excipient blend is in the form of a solid or solid- like composition.

DETAILED DESCRIPTION OF THE INVENTION

[0009] The present invention relates to solid or solid-like excipient compositions comprising a blend of (a) bispyrrolidone butane (BPB) and (b) an excipient and the use of the solid excipient blend in the formulation of cosmetic and pharmaceutical compositions.

[0010] The term "comprising" encompasses the more restrictive terms "consisting essentially of and "consisting of."

[0011] The phrase "excipient blend" refers to a composition containing bispyrrolidone butane (BPB) and at least one excipient. In accordance with certain embodiments, the at least one excipient is solid such that the resulting blend is a solid or solid-like composition. As used herein the term "solid" in reference to the form of an excipient or the excipient blend means a body of matter having a definable shape, existing before, and being recovered after, the application of a stress less than its ultimate stress. A solid body fractures when the applied stress exceeds its ultimate stress and the original shape is not recovered. A solid-like body flows when the applied stress exceeds its ultimate stress and the original shape is not recovered.

[0012] In accordance with certain embodiments of the present invention, the excipient blend may be in the form of a solid dispersion or solid solution. In accordance with the present invention, the excipient blend itself is free of active ingredients although excipient blends and active ingredients can be combined to form active containing compositions.

[0013] The term "solid dispersion" as used herein refers to a system in a solid state comprising at least two components, wherein one component is dispersed evenly throughout the other component or components. The term "solid dispersion" includes systems having small particles either completely crystalline, completely amorphous or any state in between, typically less than about 1 μm in diameter, of one phase dispersed in another phase. [0014] The term "solid solution" as used herein refers to a type of solid dispersion wherein one component is molecularly dispersed throughout another component such that the system is chemically and physically uniform and homogeneous throughout. These systems do not contain any significant amounts of active ingredients in their crystalline or microcrystalline state as evidenced by thermal analysis or X-ray diffraction.

[0015] All percentages, ratios and proportions used herein are by weight unless otherwise specified.

[0016] Bispyrrolidone butane (BPB) is a 1, 3-bis-(n-lactamyl) propane that provides excellent dissolving capabilities for a number of active ingredients. BPB and the preparation thereof is described in U.S. Patent Numbers 3,872,100 and 6,497,886. BPB is miscible with many pharmaceutically-approved solvents and exhibits good physiological tolerability.

[0017] In accordance with one aspect of the present invention, solid compositions comprising composites of BPB are described. The term "composite" refers to a composition containing two or more materials, at least one of which is BPB. These compositions exhibit solid or solid-like characteristics, meaning they possess a defined shape, existing before and recovered after the application of a stress less than its ultimate stress. Upon the application of a stress greater than the ultimate stress, solid compositions fracture whereas solid-like compositions flow.

[0018] Various methods may be utilized to produce solid and solid-like compositions in accordance with various aspects of the present invention. The following methods represent a sampling of the methods that may be used:

• granulation methods, including wet and dry high-shear granulation,

• evaporation methods, including vacuum evaporation, rotary evaporation, and spray drying from aqueous and non-aqueous solutions, dispersions, and emulsions, t melt operations, including melt congelation and hot melt extrusion,

• fluid bed operations, including top- and bottom-spray methods

• lyophilization,

• mixing methods, including tumble blending, co-mingling, stirring, and blending, and

• milling operations, including ballmilling and cryogenic milling. [0019] The excipient blends as described herein contain BPB and at least one excipient, typically a solid excipient. Notably, the excipient blend does not contain an active ingredient. The excipient blend can be used as a pre-mix that facilitates handling and processing as compared to the normally viscous BPB. The excipient blend can be mixed with an active ingredient to produce a pharmaceutical or cosmetic composition.

[0020] In accordance with one aspect of the present invention, the excipient blend is produced by forming a dispersion of BPB and the excipient(s) in a solvent and then removing the solvent to produce a solid or solid-like composition. Spray drying is a particularly effective method of producing the excipient blend. Solvents useful in forming the dispersion are not particularly limited and may be readily selected by one of ordinary skill in the art.

[0021] Excipients useful in forming the excipient blend include those excipients typically used in the art such as disintegrants, diluents, fillers, carriers, and/or adsorbents. A descriptive summary of potential excipients is provided in the Handbook of Pharmaceutical Excipients, Fifth Edition, 2005 (ISBN: 0853696187), the contents of which are hereby incorporated by reference.

[0022] Disintegrants may aide in the disintegration of solid dosage forms, and may be classified as being water-soluble and water-insoluble. Examples of water-soluble disintegrants include, without limitation, starches (e.g., maize starch, potato starch, rice starch, tapioca starch, wheat starch, and pregelatinized starch), cellulose derivatives (e.g., low-substituted hydroxypropylcellulose, carboxymethylcellulose sodium), and guar gum. Examples of water- insoluble disintegrants include, without limitation, starch derivatives, (e.g., sodium starch glycolate), and crossHnked polymers (e.g., crosslmked polyvinyl pyrrolidone and crosslinked sodium carboxymethylcellulose).

[0023] Examples of fillers that may be used in forming the excipient blend include, without limitation, lactose, calcium, hydrogen phosphate, microcrystalline cellulose, silicates, talc, starch, and isomalt. Examples of diluents that can be used in creating the excipient blend include, without limitation, calcium phosphates (e.g., calcium phosphate dibasic dihydrate), celluloses (e.g., powdered), cellulose derivatives (e.g., hydroxypropylcellulosε), lactoses (e.g., monohydrate, amorphous), sugars, including reducing sugars (e.g., glucose) and non-reducing sugars (e.g., trehalose).

[0024] Examples of adsorbents that can be used in forming the BPB excipient blend include, without limitation, purified clay constituents (e.g., attapuigite, bentonϊte, kaolin), microcrystalline celluloses, silicon dioxides (including colloidal silicon dioxide), and silicates (e.g., aluminum silicate, magnesium aluminum silicate),

[0025] Excipient blends prepared in accordance with the present invention typically contain from about 0.1% to about 99.0% by weight BPB, more particularly from about 1% to about 70%, and in accordance with certain embodiments from about 2% to about 50%, and more particularly in accordance with certain embodiments from about 3% to about 20%. The excipient blends typically contain from about 1% to about 99.9% by weight excipient, more particularly from about 30% to about 99%, and in accordance with certain embodiments from about 50% to about 98%, and more particularly in accordance with certain embodiments from about 80% to about 97%. Percentages set forth herein with respect to the amounts of BPB and excipient in the excipient blend are based on the total weight of the BPB (on a neat basis) and the excipient (on a dry weight basis).

[0026] Other components in addition to the BPB and the excipient may be present in the excipient blend in amounts from about 99.9% to about 1.0%, more particularly from about 99.9% to about 30% and in accordance with certain embodiments from about 99% to about 80%. Percentages set forth in this paragraph are based on the total weight of the excipient blend and express the non-BPB excipient component(s) on a dry weight basis and BPB on a neat basis (since BPB exists as a viscous liquid at standard room temperature).

[0027] Active ingredients capable of being formulated with the excipient blend described herein are not particularly limited.

[0028] Examples of pharmaceutically active ingredients and nutraceutically active ingredients include: abacavir sulfate, acebutolol, acetaminophen, acemetacin acetylcysteine, acetylsalicylic acid, acyclovir, adefovir dipivoxil, alprazolam, albumin, alfacalcidol, allantoin, allopurinol, ambroxol, amikacin, amiloride, aminoacetic acid, amiodarone, amitriptyline, amlodipine, amoxicillin, amoxicillin trihydrate, amiodarone hydrochloride, amphotericin B, ampicillin amprenavir, aprepitant, anastrozole, ascorbic acid, aspartame, astemizole, atazanavir sulfate, atenolol, atorvastatin calcium, azathioprine, azithromycin, azithromycin dihydride, beclomethasone, benserazide, benzalkonium hydroxide, benzocaine, benzoic acid, betametasone, bezafibrate, bicalutamide, biotin, biperiden, bisoprolol, bosentan, bromazepam, bromhexine, bromocriptine, budesonide, bufexamac, buflomedil, buspirone, caffeine, camphor, candesartan cilexetil, captopril, carbamazepine, carbidopa, carboplatin, carvedilol, cefachlor, cefalexin, cefadroxil, cefazolin, cefdinir, cefixime, cefotaxime, ceftazidime, ceftriaxone, cefuroxime, celecoxib, chloramphenicol, chlorhexidine, chlorpheniramine, chlortalidone, choline, cilastatin, cilostazol, cimetidine, ciprofloxacin, cisapride, cisplatin, citalopram hydrobromide, clarithromycin, clavulanic acid, clomipramine, clonazepam, clonidine, clopidogrel bisulfate, clotrimazole, clozapine, codeine, colestyramine, coenzyme QlO, cromoglycic acid, cyanocobalamin, cyclosporin, cyproterone, danazole, delavirdine mesylate, desipramine, desloratadine, desmopressin, desogestrel, dexamethasone, dexpanthenol, dextromethorphan, dextropropoxiphene, diazepam, diclofenac, digoxin, dihydrocodeine, dihydroergotamine, diltiazem, diphenhydramine, dipyridamole, dipyrone, disopyramide, docetaxel, domperidone, dopamine, doxycycline, doxorubicin hydrochloride, dronabinol, dutasteride, efavirenz, eletriptan hydrobromide, emtricitabine, enalapril, eπrofloxacin, entacapone, ephedrine, epinephrine, eplerenone, eprosartan mesylate, ergocalciferol, ergoloid mesylate, ergotamine tartrate, erythromycin, escitalopram oxalate, estradiol, etbinylestradiol, etoposide, exemestane, ezetimibe, famotidine, felodipine, fenofibrate, fenoterol, fentanyl, fexofenadine hydrochloride, finasteride, flavin mononucleotide, fluconazole, flunarizine, fluorouracil, fluoxetine, flurbiprofen, fluphenazine hydrochloride, flutamide, fluticasone propionate, fluvastatin, fosamprenavir, fosamprenavir calcium, furosemide, gabapentin, galantamine hydrobromide, ganciclovir, gemfibrozil, gentamicin, ginkgo biloba, glibenclamide, glimepiride, glipizide, Glycyrrhiza Glabra, glyburide, guaifenesin, guanabenz, haloperidol, heparin, hyaluronic acid, hydrochlorothiazide, hydrocodone, hydrocortisone, hydromorphone, hydroxytetracycline, ipratropium hydroxide, ibuprofen, idarubicin, imipenem, imipramine hydrochloride, indinavir sulfate, indomethacin, iohexol, iopamidol, irinotecan, isosorbide dinitrate, irbesartan, isosorbide mononitrate, isotretinoin, isradipine, itraconazole, kεtotifen, ketoconazole, ketoprofen, ketorolac, labetalol, lactulose, lamivudine, lamotrigine, lansoprazole, lecithin, levetiracetam, levocaπύtine, Ievodopa, levoglutamide, levonorgestrel, levothyroxine, lidocaine, lipase, lisinopril, loperamide, lopinavir, loratadine, lorazepam, lovastatin, medroxyprogesterone, meloxicam, melphalan, menthol, mercaptopurine, raesalamine, methotrexate methyldopa, N-methylephedrine, methylprednisolone, metoclopramide, metolazone, metoprolol, miconazole, midazolam, minocycline, minoxidil, misoprostol, mitotane, modafanil, mometasone, moφhine, mosapride, multivitamins and minerals, nabumetone, nadolol, naftidrofuryl, naproxen, nefazodone, nelfmavir mesylate, neomycin, nevirapine, nicardipine hydrochloride,, nicergoline, nicotinamide, nicotine, nicotinic acid, nifedipine, nimodipine, nisoldipine, nitrendipine, nizatidine, norethisterone, norfloxacin, norgestrel, nortriptyline, nystatin, ofloxacin, olanzepine, olmesartan medoxomil, omeprazole, ondansetron, orlistat, oxcarbazepine, paclitaxel, pancreatin, panthenol, pantoprazole, pantothenic acid, paracetamol, paroxetine hydrochloride, penicillin G, penicillin V, perphenazine, phenobarbital, phenylephrine, phenylpropanolamine, phenytoin, pimecrolimus, pimozide, pioglitazone hydrochloride, piroxicam, polymyxin B, povidone-iodine, pravastatin sodium, prazepam, prazosin, prednisolone, prednisone, proglumetacin, propafenone hydrochloride, propranolol, propofol, pseudoephedrine, pyridoxine, quinaprile hydrochloride, quinidine, raloxifme hydrochloride, ramipril, ranitidine, reserpine, resveratrol, resveratrol- analogues, retinol, ribavirin, riboflavin, rifampicin, risperidone, ritonavir , rosuvastatin calcium, rutoside, saccharin, salbutamol, salcatonin, salicylic acid, salmetrol xinafoate, saquinavir, sertaline, sildenafil citrate, simvastatin, sirolimus, somatropin, sotalol, spironolactone, stavudine, sucralfate, sulbactam, sulfamethoxazole, sulphasalazine, sulpiride, tacrolimus, tadalafil, tamoxifen, tamsulosin hydrochloride, tegafur, tenofovir disoproxil fumarate, tenoxicam, teprenone, terazosin, terbinafine hydrochloride, tegaserod maleate, telmisartan, terbutaline, terfenadine, thalidomide, theophylline, thiamine, tiaprofenic acid, ticlopidine, timolol, tizanidine hydrochloride, topiramate, trandolapril, tranexatnic acid, tretinoin, triamcinolone acetonide, triamterene, triazolam, trimethoprim, troxerutin, uracil, valdecoxib, valgancyclovir hydrochloride, valproic acid, valrubicin, valsartan, vancomycin, verapamil, vardenafil hydrochloride, vitamin E, zafirlukast, zalcitabine, zalephon, zidovudine, ziprasidone, Zolpidem tartrate, zonisamide, and zotepine.

[0029] Examples of cosmetic active ingredients include: acetylsalicylic acid, alkyl resorcinols (and derivatives), allantoin, alpha lipoic acid, alpha lipoic acid, aluminum chlorohydrates and mixtures thereof, aluminum zirconium, chlorhydrates and mixtures thereof, arbutin, ascorbic acid (including L-ascorbic acid), ascorbyl palmitate, bentazone, benzalkonium chloride, benzethonium chloride, benzocaine, benzophenones (including benzophenone 3, benzophenonε 4, benzophenone-4-octyl methoxy cinnamate, and benzophenone 8), benzoyl peroxide, bis- ethylhexyloxyphenol methoxyphenyl triazine, butyl methoxydibenzoylrnethane, butylated hydroxyanisole, butylated hydroxytoluene, caffeic acid, calamine, camphorated metacresol, camphorated phenol, carboxin, carotenes, carotenoids, chlorogenic acid, 2-CME, coal tar, coenzyme QlO (ubiquinone), coffeic acid, corticosteroids, dexpanthenol, dimethylpabaimidopropyl laurdimonium tosylate-benzophenone-3, dipropyl , isocinchomeronate, ellagic acid, eucalyptol, eugenol, ferrulic acid, genistein, 1-3-beta-l- 6-D- glucan, glucosamine, glycyrrhetinic acid, gycyrrhizic acid, hexylresorcinol, hydroquinone, icotinamide, iodine, kaolin, kinetin, kojic acid, lidocaine, lutein, luteoiin, lycopene, magnesium L-2 phosphate, menthol, methyl salicylate, methylbenzethonium chloride, N-acetylcysteine, niacinamide, oxybenzone, phenol, phenylbenzimidazole, sulfonic acid, phytosterols, povidone- iodine, prilocaine, procaine, propyl paraben, resorcinol, resorcϊnol monoacetate, resveratrol, retinol, retinol palmitate, rosmeranic acid, salicylic acid, slenium sulfide, sodium ascorbate, sodium L-2 phosphate, soy isoflavones, stearyl glycyrrhetinate, sulfanilamide, sulfur, thymol, titanium dioxide, tocopherol, tocopheryl acetate, tocopheryl esters, tocopheryl linoleate, 2-4-6- trianilϊno-p-(carbo-2-ethylhexyl-l-oxi)- 1-3 -5 -triazine, triclosan, trolamine saliclylate, vanillic acid, vitamine A esters, zinc acetate, zinc carbonate, zinc oxide, and zinc pyrithione.

[0030] The active ingredients typically will be present in an amount sufficient to provide the desired function of the composition. Pharmaceutical active ingredients are typically present in an amount sufficient to exert a local or systematic effect Amounts can vary significantly depending on the particular active, formulation, form of the composition, administration, etc.

[0031] Composition in accordance with the present invention may also include other components including, without limitation, solvents, additional actives, liquid excipients, and other conventional formulating or processing ingredients.

[0032] The present invention is further illustrated by the following, non-limiting examples.

[0033] Example 1 1. Dispersions were created containing ethanol (190-proof), bispyrrolidone butane (BPB), and crospovidone (POLYPLASDONE^® XL-IO) at 10% total solids. These dispersions contain increasing amounts of BPB (Table 1).

2. The alcohol dispersions were dried to a solvent-free state using an infrared moisture balance (Ohaus MB45, Ohaus Corporation).

3. The dried dispersions of crospovidone : BPB were characterized based on their tackiness at room temperature and their resistance to flow.

[0034] Table 1 : Characteristics of crospovidone : BPB compositions.

[0035] Example 2

1. Two dispersions were prepared in ethanol (190-proof) : a. The first dispersion contained only crospovidone (Polypi asdone XL-10) at 10% solids. b. The second dispersion contained 90% crospovidone (Poiyplasdone XL-10) and 10% bispyrrolidone butane again at 10% total solids

2. These dispersions were spray dried on a PSD-I spray dryer (Niro Inc.) using a two-fluid nozzle with the following operating conditions: a. inlet temperature: 190⁰C, b. outlet temperature: 90⁰C, c. solution-dispersion feed rate: 3.5 kg/h, d. nitrogen process gas flow rate: 90 kg/h

3. Powder products were collected in the spray dryer cyclone jar from each spray dried I dispersion. The powders were free-flowing and did not exhibit tackiness at room I temperature.

[0036] Example 3

1. A dispersion, was prepared in ethanol (190-proof) containing 80% crospovidone (Polyplasdone XL-10) and 20% bispyrrolidone butane.

2. The dispersion was spray dried using the experimental set-up as described in Example 2.

3. A powder product collected in the spray dryer cyclone jar. Unlike the products of Example 2, this powder was slightly tacky. Distinct and non-bridging particles were created, which exhibited a tendency to stick to neighboring particles at room temperature.

[0037] Example 4

1. A dispersion was prepared in ethanol (190-proof) containing 79.6% crospovidone (Polyplasdone XL-10), 20% bispyrrolidone butane, and 0.4% fumed silica (Cabosil M5P).

2. The dispersion was spray dried using the experimental set-up as described in Example 2.

3. A powder product collected in the spray dryer cyclone jar. Unlike the products of Example 2, this powder was slightly tacky. Distinct and non-bridging particle were created, which exhibited a tendency to stick to neighboring particles at room temperature.

[0038] Example 5

1. The following properties were measured for powder products from Examples 2-4: a. residual moisture (loss on drying, LOD)-MB 45 (Ohaus Corporation) b. bulk density-Tap Density Tester TD2 (Sotax AG) c. tap density (1250 taps>-Tap Density Tester TD2 (Sotax AG) d. particle size distribution-Mastersizer 2000 with Scirocco 2000M dry feeder (Malvern Instruments Ltd.) e. glass transition temperature-QlOOO (TA Instruments) f. particle morphology (AA-x)-Olympus BX-51 (Olympus America, Inc.) 4. Properties are presented in Table 2.

[0039] Table 2: Properties of solid materials comprising bispyrrolidone butane

What is claimed is:

Claims

1. An excipient blend comprising:

(a) blspyrrolidone butane (BPB) and

(b) one or more excipient(s) wherein said excipient blend is in the form of a solid or solid-like composition.

2. An excipient blend in accordance with claim 1 wherein the excipient is selected from the group consisting of a disintegrant, a diluent, a filler, a carrier, an adsorbent, and mixtures thereof.

3. An excipient blend in accordance with claim 1 wherein the excipient comprises a disintegrant.

4. An excipient blend in accordance with claim 3 wherein said disintegrant is crosslinked polyvinylpyrrolidone.

5. An excipient blend in accordance with claim 1 wherein the excipient blend comprises about 0.1% to about 50% (a) and about 99.9% to about 50% (b) based on the total weight of (a) and (b).

6. An excipient blend in accordance with claim 1 wherein the excipient blend is in the form of a solid composition.

7. A method of forming an excipient blend comprising:

blending (a) bispyrrolidone butane and (b) an excipient to form a solid or solid-like excipient blend.

8. The method of claim 7 further comprising forming a dispersion of (a) and (b) in a solvent and then removing the solvent to form the excipient blend.

9. The method of claim 7 wherein the excipient blend is in the form of a solid dispersion,

10. The method of claim 8 wherein the step of removing the solvent comprises spray drying the dispersion of (a) and (b).

11. A method for producing a composition comprising an active ingredient and an excipient blend comprising:

mixing the active ingredient with an excipient blend wherein the excipient blend comprises (a) bispyrrolidone butane and (b) an excipient wherein the excipient blend is in the form of a solid or solid-like composition.

12. The method of claim 11 wherein the excipient is a solid excipient.

13. The method of claim 11 wherein the active ingredient is a pharmaceutical active ingredient, a nutraceutical active ingredient, or a cosmetic active ingredient.

14. The method of claim 11 wherein the excipient blend comprises a disintegrant.

15. The method of claim 14 wherein the disintegrant is crosslinked polyvinylpyrrolidone,

16. A pharmaceutical, nutraceutical, or cosmetic composition comprising a pharmaceutical, nutraceutical, or cosmetic active ingredient admixed with a pre-mixed excipient blend wherein the pre-mixed excipient blend is in the form of a solid or solid-like composition and comprises (a) bispyrrolidone butane and (b) an excipient.

17. A pharmaceutical, nutraceutical, or cosmetic composition in accordance with claim 16 wherein the excipient is selected from the group consisting of a disintegrant, a diluent, a filler, a carrier, an adsorbent and mixtures thereof.

18. A pharmaceutical, nutraceutical, or cosmetic composition in accordance with claim 16 wherein the excipient comprises crosslinked polyvinylpyrrolidone.

19. A pharmaceutical, nutraceutical, or cosmetic composition in accordance with claim 16 wherein the excipient is a solid excipient.