Solid Dosage Form

Abstract

The present invention relates to solid dosage forms comprising coatings based on natural ingredients, such as naturally-occuring esterified and non-esterified polyuronic acids, optionally in combination with stabilising lipophilic component(s) (e.g. surfactant(s)) and/or other stabilising components. The inventors have made the surprising discovery that polysaccharide-based coatings can be stabilised, and often imparted with gastric resistant properties, through the inclusion of particular additives and/or additional layers. In particular, polyuronic acid-containing coatings may be stabilised and rendered more robust through the inclusion of a lipophilic component (e.g. surfactant), an esterified polyuronic acid, and/or the deployment of an additional coating layer containing stabilising agents that affect the disintegration and/or dissolution of the polyuronic acid. The polyuronic acid-containing coatings of the invention can exhibit retarded disintegration at gastric pH whilst remaining readily disintegratable at higher pHs. As such, the coatings of the invention provide inter alia promising candidates for enteric coatings.

1 . A solid dosage form comprising a core coated with a coating, wherein the coating comprises:
 a polysaccharide-based layer;   
       wherein:
 the polysaccharide-based layer comprises a polyuronic acid or a salt thereof, and a non-ionic surfactant. 
 
     
     
         2 . The solid dosage form as claimed in  claim 1 , wherein the coating further comprises a non-surfactant hydrophobic compound. 
     
     
         3 . The solid dosage form as claimed in  claim 2 , wherein the non-surfactant hydrophobic compound is a wax. 
     
     
         4 . The solid dosage form as claimed in  claim 3 , wherein the wax is an animal wax, a plant/vegetable wax, a mineral wax, or any combination thereof. 
     
     
         5 . The solid dosage form as claimed in  claim 4 , wherein the wax is selected from the group consisting of beeswax, ceresin wax, carnauba wax, lanolin, and any combination thereof. 
     
     
         6 . The solid dosage form as claimed in  claim 2 , wherein the hydrophobic component comprises or consists of a compound defined by the Formula HC 1 :
   (R a ) a -[L ab ] n -(R b ) b    (Formula HC 1 )
   
       wherein:
 the or each R a  and R b  group are each independently optionally substituted hydrocarbyl groups wherein each hydrocarbyl group comprises a hydrocarbyl moiety of at least 6 carbons; 
 the n L ab  groups are linker moieties which collectively link a R a  groups to b R b  groups, wherein each L ab  group is attached to either: 
 i) at least one R a  group and at least one R b  group; or 
 ii) at least one hydrogen and at least one of either an R a  group or an R b  group; 
 
       wherein each L ab  group is independently selected from the group consisting of —O—, —S—, N, —NR L —, —C(O)—, —OC(O)—, —C(O)O—, —OC(O)O—, —C(O)N(R L )—, —OC(O)N(R L )—, —NR L C(O)O—, —N(R L )C(O)—, N(R L )CON(R L ), —S(O)—, —OS(O)—, —S(O)O—, —S(O) 2 —, —OS(O) 2 —,——S(O) 2 O—, —OS(O)O—, —N(R L )S(O)—, —S(O)N(R L )—, —S(O) 2 —, —N(R L )S(O) 2 —, —S(O) 2 N(R L )—, —N(R L )S(O)N(R L )—, —N(R L )S(O)O—, —OS(O) N(R L )—, —OP(OR L )O—, —OP(O)(OR L )O—, —OP(O)(O—) 2 , wherein each R L  is independently hydrogen or (1-8C)alkyl (suitably 1-3C alkyl);
 a and b are each an integer independently having a value of 1, 2, 3, 4, 5, or 6; 
 n is an integer having a value of 1, 2, 3, 4, 5, or 6. 
 
     
     
         7 . The solid dosage form as claimed in  claim 1 , wherein the non-ionic surfactant is a fatty acid ester of a polyol that exhibits at least one hydrogen-bonding group (suitably at least one hydroxyl group) wherein the non-ionic surfactant comprises one or more fatty acid moieties selected from the group consisting of stearoyl, Capryloyl, Caproyl, Lauroyl, Myristoyl, Palmitoyl, Arachidoyl, Behenoyl, Lignoceroyl, Cerotoyl, Myristoleoyl, Palmitoleoyl, Sapienoyl, Oleoyl, Elaidoyl, Vaccenoyl, Linoleoyl, Linoelaidoyl, α-Linolenoyl, Arachidonoyl, Eicosapentaenoyl, Erucoyl, and Docosahexaenoyl. 
     
     
         8 . The solid dosage form as claimed in  claim 7 , wherein the non-ionic surfactant is glycerol monostearate, glycerol distreate, glycerol trisreate or any combination thereof 
     
     
         9 . The solid dosage form as claimed in  claim 2 , wherein the weight ratio of non-surfactant hydrophobic component to surfactant/emulsifier is 10-60:1-20. 
     
     
         10 . The solid dosage form as claimed in  claim 2 , wherein the polysaccharide-based coating layer/composition comprises:
 30-70 parts by weight (pbw) non-esterified polyuronic acid;   20-40 pbw non-surfactant hydrophobic compound; and   5-15 pbw surfactant.   
     
     
         11 . The solid dosage form as claimed in  claim 1 , wherein the non-esterified polyuronic acid and/or a salt thereof is an aliginate compound. 
     
     
         12 . The solid dosage form as claimed in  claim 10 , wherein the weight ratio of the alginate compound to the non-ionic surfactant is between 50:1 and 2:1. 
     
     
         13 . The solid dosage form as claimed in  claim 1 , wherein the coating comprises a stabilising layer, the stabilising layer comprising a stabilising component and optionally either or both a lipophilic component (and/or an esterified polyuronic acid or a salt thereof. 
     
     
         14 . The solid dosage form as claimed in  claim 13 , wherein the stabilising component of the stabilising layer is a compound which promotes precipitation or otherwise reduces the solubility of the non-esterified polyuronic acid or a salt thereof when mixed therewith in water. 
     
     
         15 . The solid dosage form as claimed in  claim 14 , wherein the stabilising component is an acid component selected from the group consisting of: fumaric acid, citric acid, tartaric acid, malic acid, maleic acid, malonic acid, glutaric acid, adipic acid, sorbic acid, pimelic acid, suberic acid, succinic acid, glutaconic acid, muconic acid, glutinic acid, citraconic acid, mesaconic acid, tartronic acid, arabinaric acid, saccharic acid, and/or a derivative and/or acceptable salt thereof 
     
     
         16 . The solid dosage form as claimed  claim 1 , wherein the solid dosage form is a delayed-release nutraceutical and/or a dietary supplement dosage form. 
     
     
         17 . The solid dosage form as claimed  claim 1 , wherein the core is a tablet, capsule, or lozenge without a coating, and the core comprises a nutraceutically and/or dietarily active substance. 
     
     
         18 . The solid dosage form as claimed in  claim 1 , wherein the core is itself an immediate-release dosage form at a pH between pH 5 and pH 7.4. 
     
     
         19 . The solid dosage form as claimed in  claim 1 , wherein:
 the core is in the form of a tablet, capsule, or lozenge and comprises a nutraceutically and/or dietarily active substance, and the core is itself an immediate-release dosage form at a pH between pH 5 and pH 7.4;   the solid dosage form is a delayed-release nutraceutical and/or a dietary supplement dosage form; and   the polysaccharide-based layer comprises:
 an aliginate compound; 
 a non-ionic surfactant that is a fatty acid ester of a polyol that exhibits at least one free hydroxyl; and 
 a wax selected from the group consisting of an animal wax, a plant/vegetable wax, a mineral wax, or any combination thereof 
   
     
     
         20 . The solid dosage form as claimed in  claim 19 , wherein the polysaccharide-based coating layer comprises:
 30-70 parts by weight (pbw) alginate compound;   20-40 pbw wax; and   5-15 pbw non-ionic surfactant, suitably glyceryl monostearate.   
     
     
         21 . A polysaccharide coating layer composition comprising a non-esterified polyuronic acid and/or a salt thereof as defined in  claim 1 , a non-ionic surfactant as defined in  claim 1 , and optionally further comprises a non-surfactant hydrophobic compound. 
     
     
         22 . The polysaccharide coating layer composition of  claim 21 , wherein the ingredients are dissolved in or emulsified within a solvent system comprising water and ethanol. 
     
     
         23 . A method of preparing a solid dosage form according to  claim 1 , the method comprising:
 i) providing a core; and   ii) coating the core with:
 a polysaccharide coating layer composition comprising a non-esterified polyuronic acid and/or a salt thereof as defined in  claim 1 , a non-ionic surfactant as defined in  claim 1 , and optionally further comprises a non-surfactant hydrophobic compound; and 
   iii) drying, curing, cooling, congealing and/or further processing the solid dosage form.   
     
     
         24 . (canceled) 
     
     
         25 . A solid dosage form as claimed in  claim 1 , wherein any one or more of the coating layers or coating compositions comprises a bulking agent or a mixture of bulking agents. 
     
     
         26 . A solid dosage form as claimed in  claim 1 , wherein any one or more coating layers or coating compositions further comprises one or more of a colouring agent, an opacifier, a sweetener, a flavourant, or any combination thereof 
     
     
         27 . A solid dosage form as claimed in  claim 1 , wherein an outer polysaccharide-based layer surrounds, and is optionally in contact with, a lipophilic coating layer. 
     
     
         28 . The solid dosage form of  claim 27 , wherein the liophilic coating layer surrounds, and is optionally in contact with, a further inner polysaccharide-based layer. 
     
     
         29 . The solid dosage form of  claim 28 , wherein the lipophilic coating layer consists of wax, and both inner and out polysaccharide-based layers comprise a polyuronic acid or a salt thereof and a non-ionic surfactant.