Chewable composition for rapid buccal absorption

Abstract

The present document describes a buccal delivery dosage form for administration of an active ingredient, including pharmaceutically, pharmacologically, or biologically active ingredients, in the mouth of a subject. The buccal delivery dosage form by-passes the gastrointestinal tract metabolism. The buccal delivery dosage form may comprise chemical permeation enhancers, excipients, texture modulators, and active ingredients.

1 .- 73 . (canceled) 
     
     
         74 . A composition for buccal mucosal absorption of a pharmacologically active ingredient in a subject comprising:
 a particulate amalgam matrix in the form of microspheres, spheres, or spheroids comprising:
 a hydrocolloid base in particulate form; 
 the pharmacologically active ingredient in powder form; and 
 crystalline particles containing entrapped-CO 2  gas, wherein the particles have a diameter between about 0.5 mm and about 1 mm; 
   wherein said chewable composition, is suitable for increasing the absorption of the active ingredient in the buccal mucosa by at least about 2× after being chewed for 30 to 120 seconds as compared to a particulate composition devoid of the sugar particles and modulatory mixture.   
     
     
         75 . The composition of  claim 74 , wherein the hydrocolloid base in particulate form is selected from the group consisting of agar, agarose, alginates, base gum, carrageenan (iota, kappa, lambda), cellulosics, chicle, chitosan, gelatin, gellan gum, guar gum, gum arabic, locust bean gum, pectin, soybean gel, starch, whey protein, and xanthan gum. 
     
     
         76 . The composition of  claim 75 , wherein the hydrocolloid base in particulate form is selected from the group consisting of base gum and chicle. 
     
     
         77 . The composition of  claim 74 , wherein the crystalline particles containing entrapped-gas comprises CO 2 -entrapped in sugar or menthol particles. 
     
     
         78 . The composition of  claim 77 , wherein the CO 2 -entrapped sugar comprises popping sugar. 
     
     
         79 . The composition of  claim 74 , further comprising a modulatory mixture comprising:
 a) a permeation enhancer selected from the group consisting of sodium caprylate, sodium caprate, sodium laurate, lauric acid, oleic acid, lecithin, monoolein, phospholipids and acylcarnitines, and mixtures thereof; and   b) a texture modulator selected from the group consisting of stearic acid, Candelilla and Carnauba wax, and mixtures thereof;   wherein the permeation enhancer and the texture modulator are in a ratio suitable to achieve a melting point of about 36° C.   
     
     
         80 . The composition of  claim 74 , wherein the composition is in particulate form and is compressed to form a chewable dosage form having a Matrix Cohesive Force (MCF) between 2 and 5. 
     
     
         81 . The composition of  claim 74 , wherein the composition comprises 20% to 60% (w/w) of the amalgam matrix. 
     
     
         82 . The composition of  claim 79 , wherein the composition comprises from 0.5 to 15% (w/w) of the phospholipid and from 0.1 to 6% (w/w) of the wax. 
     
     
         83 . The composition of  claim 76 , wherein the composition comprises about 20% w/w to about 90% w/w of the particulate gum base. 
     
     
         84 . The composition of  claim 74 , wherein the particulate amalgam matrix comprises particles having a size greater than about 0.9 mm. 
     
     
         85 . The composition of  claim 77 , wherein the composition comprises about 5% w/w of the CO2-sugar particles. 
     
     
         86 . The delivery dosage form of  claim 75 , wherein the gum base comprises polyols. 
     
     
         87 . The composition of  claim 74 , wherein the active ingredient is selected from the group consisting of
 a) ion channel blockers, reflux suppressants, antiflatulents, antidopaminergics, proton pump inhibitors, H2-receptor antagonists, cytoprotectants, prostaglandin and prostaglandin analogues, laxatives, antispasmodics, antidiarrheals, bile acid sequestrants, opioids, beta-receptor blocker, diuretics, cardiac glycosides, antiarrhythmics, nitrate, antiangials, vasoconstrictor, vasodilators, peripheral activators, ACE inhibitors, angiotensin receptor blockers, alpha-blocker, anticoagulants, heparin, antiplatelet drugs fibrinolytics, anti-hemophilic factors, haemostatic drugs, hypolipidaemic agents, statins, hyphotics, anaesthetics, antipsychotics, antidepressants, antiemetics, anticonvulsants/antiepileptics, anxiolytics, barbiturates, folic acid, phenolic compounds, movement disorder drugs, stimulants, benzodiazepine, cyclopyrrolones, dopamine agonists/antagonists, antihistamines, bromide, scopolamine, cholinergics, anticholinergics, emetics, cannabinoids, 5-HT antagonists, NSAIDs, opioids, paracetamol, muscle relaxant, neuromuscular drugs, anticholinesterases, adrenergic blockers, antibiotics, aminoglycosides, sulfa drugs, fluoroquinolones, antiviral drugs, anti-fungal, corticosteroids, mast cell inhibitors, prostaglandin agonists/inhibitors, steroids, steroids hormone receptor; antiseptics, anesthetics, androgens, antiandrogens, gonadotropin, human growth factor, insulin, antidiabetics, thyroid hormones, antityroid drugs, calcitonin, diphosponate, vasopressin analogues, quinolones, 5-alpha reductase inhibitor, selective alpha-1 blockers, sildenafils, tadalafils, fertility drugs, hormonal contraception, ormeloxifene, antifibrinolytics, follicle stimulating hormone, luteinising hormone, gamolenic acid, gonadotropin release inhibitor, progestin, oestrogen, gonadorelin, clomiphene, tamoxifen, diethyl stilbestrol, antileprotics, antituberculous drugs, antimalarials, anthelmintics, amoebicides, antivirals, antiprotozoals, vaccines, immunoglobulins, immunosuppressants, interferons, monoclonal antibodies, anti-allergics, cytotoxic drugs, therapeutic antibodies, somatostatin inhibitors, recombinant interleukins, G-CSF, erythropoietin, vitamins, antioxidants and combinations thereof;   b) Astaxanthin, Bilobalide, Biotine, Catechine, Choline, Coenzyme Q10, Curcumine, Ginkgolide, Glucosamine, Hypericine, Hyperforin, Silymarine, Silibinin, a Lignan, Diosgenine, hydroxycitric acid, eleutherocide B, Eleutherocide E, L-carnitine, Megastigmane glycoside, Melatonin, Niacinamide, Niacine, Omega-3, Pantothenic acid, a phytosterol, Pinolenic acid, Resveratrol, Riboflavine, Rosiglitazone, Serotonin, Theobromine, Theophylline, Thiamine, g-aminobutyric acid, a saponin, sarsapic acid, Vitamin B12, Yohimbine, gingerol, or combinations thereof; or   c) a plant extract selected from the group consisting of Absinthe ( Artemisia absinthum ), Alfalfa ( Medicago sativa ), Aloe ( Aloe barbadensis ),  Angelica  ( Angelica archangelica  and  sinensis ),  Arnica  ( Arnica montana ), Ashwaganda ( Withania somnifera ),  Astragalus  ( Astragalus membranaceus ), Betony ( Stachys/Betonica officinalis ), Bilberry/Huckleberry ( Vaccinium  spp.), Black cohash ( Cimicifuga racemosa ), Bladderwrack ( Fucus versiculosus ), Blessed thistle ( Cnicus benedictus ), Blue cohosh ( Caulophyllum thalictroides ), Boneset ( Eupatorium perforatum ), Burdock ( Arctium lappa ),  Caesalpinia benthamiana , Calendula ( Calendula officinalis ), California poppy ( Eschscholzia californica ), Caraway ( Carum carvi ), Cardamom ( Elettaria cardamomum ), Cascara ( Rhamnus purshiana ), Catnip ( Nepeta cataria ), Cayenne ( Capsicum frutescens ), Cedar, Western ( Thuja plicata  or  occidentalis ), Chamomile ( Matricaria recutita ), Chaparral ( Larrea mexicana ), Chaste tree berry ( Vitex agnus castus ), Chickweed ( Stellaria media ), Cleavers ( Galium aparine ), Coltsfoot ( Tussilago farfara ), Comfrey ( Symphytum officinalis ), Corn silk ( Zea mays ),  Corynanthe yohimbe , Cramp bark ( Viburnum opulus ), Dandelion ( Taraxacum officinalis ), Devil's club ( Oplopanax horridus ),  Dioscorea villosa , Dong quai ( Angelica sinensis ),  Echinacea  ( Echinacea  spp.), Elder flowers ( Sambucus  spp.), Elecampane ( Inula helenium ), Eyebright ( Euphrasia officinalis ),  Fadogia agrestis , Fennel ( Foeniculum vulgare ), Fenugreek ( Trigonella foenum - graecum ), Feverfew ( Tanacetum parthenium ), Flax seed ( Linum usitatissimum ),  Garcinia Cambogia , Garlic ( Allium sativa ),  Geranium  ( Geranium maculatum ), Ginger ( Zingiber officinalis ), Ginkgo ( Ginkgo biloba ),  Ginseng  ( Panax  spp.), Goldenrod ( Solidago  spp.), Goldenseal ( Hydrastis canadensis ), Gotu kola ( Centella asiatica ), Gravel root ( Eupatorium purpureum ), Hawthorne ( Crataegus  spp.),  Hibiscus subdariffa , Hops ( Humulus lupulus ), Horehound ( Marrubium  vulgaris), Horsetail ( Equisetum arvense ),  Hippophae rhamnoides , Hyssop ( Hyssopus officinalis ), Kava kava ( Piper methysticum ), Lady's mantle ( Alchemilla vulgaris ),  Lepidium meyenii , Linden flower ( Tilia  spp.),  Lobelia  ( Lobelia inflata ), Lomatium ( Lomatium dissectum ), Lungwort ( Sticta pulmonaria ), Marshmallow ( Althea officinalis ),  Massularia acuminate , Meadowsweet ( Filipendula ulmaria ),  Microdesmis keayana , Milk thistle ( Silybum marianum ),  Morinda citrifolia , Motherwort ( Leonurus cardiaca ),  Mucuna pruriens , Mugwort ( Artemisia vulgaris ), Mullein ( Verbascum thapsus ), Myrrh gum ( Commiphora myrrha ), Nettle ( Urtica  spp.), Noni ( Morinda citrifolia ), Nopal ( Opuntia ficus  indica), Oat ( Avena sativa ),  Oenothera biennis , Old man's beard,  Usnea  ( Usnea  spp.), Oregon grape root and barberry ( Mahonia  spp.), Osha ( Ligusticum porteri ), Parsley ( Petroselinum crispum ), Plantain ( Plantago  spp.), Poplar buds ( Populus  spp.), Red clover ( Trifolium pratense ), Red root ( Ceanothus americanus ),  Rhodiola Rosea , Rosemary ( Rosmarinus officinalis ), Sage ( Salvia officinalis ), Saint John's wort ( Hypericum perforatum ), Saw palmetto ( Serenoa repens ), Sea-buckthorn ( Hippophae rhamnoides ), Sesame seed ( Sesamum indicum ), Siberian  ginseng  ( Eleutherococcus senticosus ), Skullcap ( Scutellaria laterifolia ), Slippery elm ( Ulmus  spp. ( rubra, fulva )), Thyme ( Thymus vulgaris ), Triblus  terrestris , Tumeric ( Curcuma longa ), Thuya  occidentalis , Uva  ursi  ( Arctostaphylos uva ursi ), Valerian ( Valeriana officinalis ), Vervain ( Verbena officinalis ), White oak bark ( Quercus alba ), Willow ( Salix  spp.), Yarrow ( Achillea millefolium ), Yellow dock ( Rumex crispus/obtusifolius ) and Guaraná, and combinations thereof.   
     
     
         88 . The composition of  claim 87 , wherein the active ingredient is selected from the group consisting of Guaraná, Black cohash ( Cimicifuga racemosa ),  Ginseng  ( Panax  spp.), Hops ( Humulus lupulus ),  Rhodiola Rosea , Tumeric ( Curcuma longa ), Astaxanthin, Coenzyme Q 10 , Curcumine, Glucosamine, Melatonin, Resveratrol, gingerol, diosgenine, bras sicasterol, campesterol, 5α-cholestane, β-sitosterone, β-sitosterol and stigmasterol, and combinations thereof. 
     
     
         89 . The composition of  claim 87 , wherein the active ingredient is selected from the group consisting of NSAIDs; Beta-receptor blockers; Vasodilators; Antiarrhytmics; Antibiotics; Ion channel blockers; Antispasmodics; Anaesthetics; Diphosphonates; Diuretics; Stimulants; Antihistamines; Angiotensin-Converting Enzyme (ACE) Inhibitors; Antiviral drugs; Antiemetics; Vasoconstrictors; Dopamine agonists/antagonists; Proton pump inhibitors; Antidiabetics; H2 receptor antagonists; Antidepressants; 5-HT antagonists; Anxiolytics; Hypnotics; Muscle relaxants; Anticholinergics; Somatostatine inhibitors; Antioxidants; Angiotensin receptor blockers; Steroids hormone receptor; Oestrogens; and Statins; and combination thereof. 
     
     
         90 . The composition of  claim 89 , wherein the stimulant is caffeine. 
     
     
         91 . The composition of  claim 87 , wherein the active ingredient is  Rodiola Rosea.    
     
     
         92 . The composition of  claim 87 , wherein the active ingredient is melatonin.