Buccal Delivery System

Abstract

A buccal delivery system capable of being blended in a normal dry powder process and compressed using a standard tabletting machine, said buccal delivery system comprising a matrix of: (a) an effective amount of one or more active ingredients; (b) an amount of one or more polyethylene glycols or derivatives thereof having a molecular weight between 1000 to 8000 sufficient to provide the required hardness and time for dissolution of the matrix; (c) 0.05-2% by weight of the total matrix of one or more suspending agents; (d) 0.05-2% by weight of the total matrix of one or more flowing agents; and (e) 0.05-2% by weight of the total matrix of one or more sweeteners.

1 . A buccal delivery system capable of being blended in a normal dry powder process and compressed using a standard tabletting machine, said buccal delivery system comprising a matrix of:
 (a) an effective amount of one or more active ingredients;   (b) an amount of one or more polyethylene glycols or derivatives thereof having a molecular weight between 1000 to 8000 sufficient to provide the required hardness and time for dissolution of the matrix;   (c) 0.05-2% by weight of the total matrix of one or more suspending agents;   (d) 0.05-2% by weight of the total matrix of one or more flowing agents; and   (e) 0.05-2% by weight of the total matrix of one or more sweeteners.   
   
   
       2 . The buccal delivery system according to  claim 1  wherein the effective amount of the active ingredient is an amount up to about 60% by weight of the total matrix. 
   
   
       3 . The buccal delivery system according to  claim 1  wherein the time for dissolution of the matrix is within at least two hours following administration to a patient. 
   
   
       4 . The buccal delivery system according to  claim 3  wherein the time for dissolution of the matrix is within 40 minutes. 
   
   
       5 . The buccal delivery system according to  claim 4  wherein the time for dissolution of the matrix is within 12 to 15 minutes. 
   
   
       6 . The buccal delivery system according to  claim 5  wherein the time for dissolution of the matrix is within 5 minutes. 
   
   
       7 . The buccal delivery system according to  claim 1  wherein the buccal delivery system is suitable for sublingual administration. 
   
   
       8 . The buccal delivery system according to  claim 1  wherein the buccal delivery system is suitable for sustained release administration. 
   
   
       9 . The buccal delivery system according to  claim 1  wherein the polyethylene glycol (PEG) is PEG 1450. 
   
   
       10 . The buccal delivery system according to  claim 1  wherein the polyethylene glycol (PEG) derivative is a PEG-fatty acid ester having surfactant properties. 
   
   
       11 . The buccal delivery system according to  claim 1  wherein the suspending agent is selected from the group consisting of tetragonolobus,  Acacia glaucophylla, Acacia abyssinica, Acacia nilotica, Acacia gummifera, Acacia Arabica , silica gel, kollidon, cremaphor, kollicoat, solutol, ludipress and mixtures thereof. 
   
   
       12 . The buccal delivery system according to  claim 1  wherein the sweetener is selected from the group consisting of sucrose, sucralose; zinc gluconate; ethyl maltitol; glycine; acesulfame-K; aspartame; saccharin; fructose; xylitol; honey; corn syrup, golden syrup, misri, spray dried licorice root; glycerrhizine; dextrose; sodium gluconate; stevia powder; glucono delta-lactone; ethyl vanillin; vanillin; normal and high-potency sweeteners or syrups or salts thereof and mixtures thereof. 
   
   
       13 . The buccal delivery system according to  claim 12  wherein the sweetener is a high-intensity sweetener selected from the group consisting of aspartame, sucralose, and acesulfame-K. 
   
   
       14 . The buccal delivery system according to  claim 1  wherein the active ingredients are selected from the group consisting of anti-infective agents (antibiotics), eye, ear, nose and throat preparations, anti-neoplastic agents including antibody, nanobody, antibody fragment(s), antibody directed enzyme pro-drug therapy (ADEPT), gastrointestinal drugs, respiratory agents, arthritic agents, blood formation and coagulation agents, diagnostic agents, photosensitisers, statins, naproxyn, indole-3-acetic acid, hormones and synthetic substitutes, cardiovascular drugs, skin and mucous membrane preparations, NSAIDs, analgesics, muscle spasm medications, anti-inflammatory agents, central nervous system drugs, dietary supplements, diabetic agents, and electrolyte and water balance agents, mixtures thereof and pro-drugs, drug complexes, drug intermediates, enzyme, vitamins and protein complexes thereof. 
   
   
       15 . The buccal delivery system according to  claim 14  wherein the active ingredients are hormones of natural or synthetic origin selected from the group consisting of insulin, triamcinolone, testosterone, levonorgestrel, estradiol, phytoestrogen, estrone, dexamethasone, ethynodiol, prednisone, desogestrel, cyproterone, norethindrone, megestrol, hydrocortisone, danazol, cortisone acetate, aviane, nandrolone, fluoxymesterone, fludrocortisone, fluoxymesterone dexamethasone levora fludrocortisone low-ogestrel methylprednisolone, necon, levonorgestrel, estropipate, levoxyl, methimazole, propylthiouracil desmopressin, prednisolone orgestrel norethindrone triamcinolone trivora zovia gestodene, alfacalcidol, 1,25-dihydroxyvitamin D3, clomiphene, finasteride and tibolone or any biologically relevant intermediate or combination thereof and mixtures thereof. 
   
   
       16 . The buccal delivery system according to  claim 1  wherein the active ingredient is a bisphosphonic acid or a bisphosphonate salt selected from the group consisting of alendronate, etidronate, pamidronate, tiludronate and risedronate compounds and mixtures thereof. 
   
   
       17 . The buccal delivery system according to  claim 16  wherein the bisphosphonate is an alendronate selected from the group consisting of anhydrous alendronate, hydrated alendronate salts and mixtures thereof. 
   
   
       18 . The buccal delivery system according to  claim 17  wherein the bisphosphonate is sodium alendronate. 
   
   
       19 . The buccal delivery system according to  claim 16  further comprising one or more hormones used in hormone replacement therapy. 
   
   
       20 . The buccal delivery system according to  claim 19  wherein the hormones are selected from the group consisting of estradiol, progesterone, testosterone, dehydroepiandrosterone (DHEA) and mixtures thereof. 
   
   
       21 . The buccal delivery system according to  claim 1  further comprising one or more other pharmaceutically acceptable carriers and/or excipients. 
   
   
       22 . The buccal delivery system according to  claim 21  wherein the pharmaceutically acceptable carriers and/or excipients are selected from the group consisting of binding agents, flavouring agents, lubricants, colouring agents, solubility enhancers, disintegrants, fillers, proteins, co-factors, emulsifiers, solubilising agents, complexing agents and mixtures thereof. 
   
   
       23 . The buccal delivery system according to  claim 1  wherein the flowing agent is magnesium stearate. 
   
   
       24 . The buccal delivery system according to  claim 1  further comprising a binding and gelling agent. 
   
   
       25 . The buccal delivery system according to  claim 24  wherein the binding and gelling agent is hydroxypropyl methocellulose. 
   
   
       26 . A dry process prepared buccal formulation comprising a matrix of:
 (a) an effective amount of one or more active ingredients;   (b) an amount of one or more polyethylene glycols or derivatives thereof having a molecular weight between 1000 to 8000 sufficient to provide the required hardness and time for dissolution of the matrix;   (c) 0.05-2% by weight of the total matrix of one or more suspending agents;   (d) 0.05-2% by weight of the total matrix of one or more flowing agents; and   (e) 0.05-2% by weight of the total matrix of one or more sweeteners.   
   
   
       27 . A method of manufacturing a dosage formulation capable of delivering one or more active ingredients across one or more membranes within the buccal cavity, said method comprising the steps of:
 (a) preparing a matrix by blending
 (i) an effective amount of one or more active ingredients; 
 (ii) an amount of one or more polyethylene glycols or derivatives thereof having a molecular weight between 1000 to 8000 sufficient to provide the required hardness and time for dissolution of the matrix; 
 (iii) 0.05-2% by weight of the total matrix of one or more suspending agents; 
 (iv) 0.05-2% by weight of the total matrix of one or more flowing agents; and 
 (v) 0.05-2% by weight of the total matrix of one or more sweeteners. 
   (b) compressing the matrix into a suitable tablet format for administration to the one or more membranes in the buccal cavity;   wherein the ratio of active ingredients and excipients enables dissolution and absorption of the active ingredient within a desired time period.