Formulations

Abstract

The present invention relates to a formulation comprising a pharmaceutically active ingredient and a coating. The invention also relates to the use of the formulation in the treatment and prevention of disorders of the gastrointestinal tract. Also disclosed are methods for preparing the formulations.

1 - 2 . (canceled) 
     
     
         3 . A pharmaceutical formulation comprising a core, a first coating and a second coating outside the first coating, wherein the core comprises a hydrogel forming polymer matrix and a pharmaceutically active ingredient comprising cyclosporin A, wherein the first coating comprises a water-soluble cellulose ether and the first coating has a thickness of from 10 μm to 100 μm, wherein the second coating comprises a single polymer, wherein the polymer is a delayed release pH independent polymer and the first coating is present in an amount to provide a higher % release of the pharmaceutically active ingredient from the pharmaceutical formulation than a corresponding pharmaceutical formulation without the first coating at 12 hours from the start of a dissolution test. 
     
     
         4 - 113 . (canceled) 
     
     
         114 . The pharmaceutical formulation of  claim 3 , wherein the first coating has a thickness of from 10 μm to 50 μm. 
     
     
         115 . The pharmaceutical formulation of  claim 3 , wherein the first coating is present in an amount corresponding to a weight gain due to the coating of from 1% to 9% by weight of the core. 
     
     
         116 . The pharmaceutical formulation of  claim 3 , wherein the first coating is present in an amount corresponding to a weight gain due to the coating of from 8% to 20%. 
     
     
         117 . The pharmaceutical formulation of  claim 3 , wherein the first coating comprising a water-soluble cellulose ether is in contact with the core. 
     
     
         118 . The pharmaceutical formulation of  claim 3 , wherein the second coating is in contact with the first coating comprising a water-soluble cellulose ether. 
     
     
         119 . The pharmaceutical formulation of  claim 3 , wherein the second coating is present in an amount corresponding to a weight gain due to the additional coating of from 2% to 40%. 
     
     
         120 . The pharmaceutical formulation of  claim 3 , wherein the delayed release polymer is water-soluble or water-permeable in an aqueous medium with a pH greater than 6.5. 
     
     
         121 . The pharmaceutical formulation of  claim 3 , wherein the delayed release polymer comprises ethyl cellulose. 
     
     
         122 . The pharmaceutical formulation of  claim 3 , wherein the water-soluble cellulose ether is selected from any one or a combination of: methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxyethyl methylcellulose and hydroxypropylmethyl cellulose. 
     
     
         123 . The pharmaceutical formulation of  claim 122 , wherein the water-soluble cellulose ether is hydroxypropylmethyl cellulose. 
     
     
         124 . The pharmaceutical formulation of  claim 3 , wherein the first coating is present in an amount corresponding to a weight gain due to the coating of from 0.5% to 20% by weight of the core. 
     
     
         125 . The pharmaceutical formulation of  claim 3 , wherein the first coating is present in an amount corresponding to a weight gain due to the coating in a range selected from: 0.5% to 15%; 1% to 15%; 1% to 12%; 1% to 10%; 1% to 8%; 1% to 6%; 1% to 4%, 2% to 10%; 2% to 8%; 2% to 6%; 2% to 4%; 4% to 8%; 4% to 7%, 5% to 7%; 7% to 20%; 7% to 16%; 9% to 20%; 9% to 16%; 10% to 15%; or 12% to 16%. 
     
     
         126 . The pharmaceutical formulation of  claim 3 , wherein the hydrogel forming polymer matrix comprises a hydrocolloid, a non-hydrocolloid gum or chitosan. 
     
     
         127 . The pharmaceutical formulation of  claim 3 , wherein the hydrogel forming polymer matrix comprises gelatin, agar, a polyethylene glycol, starch, casein, chitosan, soya bean protein, safflower protein, alginates, gellan gum, carrageenan, xanthan gum, phthalated gelatin, succinated gelatin, cellulosephthalate-acetate, oleoresin, polyvinylacetate, polymerisates of acrylic or methacrylic esters and polyvinylacetate-phthalate and any derivative of any of the foregoing; or a mixture of one or more such a hydrogel forming polymer. 
     
     
         128 . The pharmaceutical formulation of  claim 3 , wherein the hydrogel forming polymer matrix comprises a hydrocolloid selected from carrageenan, gelatin, agar and pectin, or a combination thereof. 
     
     
         129 . The pharmaceutical formulation of  claim 3 , wherein the hydrogel forming polymer matrix further comprises a plasticiser. 
     
     
         130 . The pharmaceutical formulation of  claim 3 , wherein the hydrogel forming polymer matrix encapsulates the active ingredient. 
     
     
         131 . The pharmaceutical formulation of  claim 3 , wherein the core is in the form of a solid colloid, the colloid comprising a continuous phase and a disperse phase, wherein the continuous phase comprises the hydrogel forming polymer matrix. 
     
     
         132 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises a hydrophobic phase. 
     
     
         133 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises a liquid lipid. 
     
     
         134 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises a glyceride composition. 
     
     
         135 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises an oil phase selected from caprylic/capric triglyceride; caprylic/capric/linoleic triglyceride; caprylic/capric/succinic triglyceride; and propylene glycol dicaprylate/dicaprate. 
     
     
         136 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises an oil phase selected from linoleoyl macrogolglycerides (polyoxylglycerides) and caprylocaproyl macrogolglycerides. 
     
     
         137 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase further comprises a solvent, wherein the solvent is miscible with the disperse phase and water. 
     
     
         138 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises an oil phase which represents 10-85% by dry weight of the core. 
     
     
         139 . The pharmaceutical formulation of  claim 131 , wherein the active ingredient is in solution or suspended in the continuous phase or the disperse phase. 
     
     
         140 . The pharmaceutical formulation of  claim 139 , wherein the active ingredient is:
 a. in solution in the disperse phase;   b. in solution in the continuous phase;   c. suspended in the disperse phase; or   d. suspended in the continuous phase.   
     
     
         141 . The pharmaceutical formulation of  claim 131 , wherein the core further comprises an anionic surfactant present in at least the continuous phase, the anionic surfactant having an HLB value of at least 10. 
     
     
         142 . The pharmaceutical formulation of  claim 131 , wherein the continuous phase comprises a hydrogel forming polymer matrix and the disperse phase comprises an oil phase comprising an oil wherein the oil has an HLB in the range 0-10. 
     
     
         143 . The pharmaceutical formulation of  claim 142 , wherein the oil has an HLB of 1-5. 
     
     
         144 . The pharmaceutical formulation of  claim 142 , wherein the oil phase comprises a triglyceride. 
     
     
         145 . The pharmaceutical formulation of  claim 131 , wherein the disperse phase comprises an oil phase selected from caprylic/capric triglyceride; caprylic/capric/linoleic triglyceride; caprylic/capric/succinic triglyceride; and propylene glycol dicaprylate/dicaprate; and a polyethoxylated castor oil. 
     
     
         146 . The pharmaceutical formulation of  claim 137 , wherein the solvent is 2-(2-ethoxyethoxy)ethanol. 
     
     
         147 . The pharmaceutical formulation of  claim 131 ,
 wherein the disperse phase comprises:
 a pharmaceutically active ingredient comprising cyclosporin A; 
 a medium chain mono- di- or tri-glyceride; and 
 a solvent, and 
   wherein the continuous phase comprises:
 an anionic surfactant, 
 a hydrogel forming polymer matrix which comprises a hydrocolloid selected from carrageenan, gelatin, agar and pectin, or a combination thereof; and 
 optionally a plasticiser. 
   
     
     
         148 . The pharmaceutical formulation of  claim 3 , wherein the core comprises a hydrogel forming polymer comprising gelatin in an amount of 300 to 700 mg/g, the core further comprising medium chain mono, di or tri-glycerides in an amount of 20 to 200 mg/g, and the pharmaceutical formulation further comprises the following components:
 co-solvent in an amount of 150 to 250 mg/g; and   anionic surfactant in an amount of 15 to 50 mg/g.   
     
     
         149 . The pharmaceutical formulation of  claim 3 , wherein the formulation is in the form of a minibead. 
     
     
         150 . The pharmaceutical formulation of  claim 3 , wherein the largest cross sectional dimension of a core is from about 0.01 mm to about 5 mm. 
     
     
         151 . A pharmaceutical formulation comprising a multiplicity of minibeads of  claim 149 . 
     
     
         152 . The pharmaceutical formulation of  claim 3 , wherein the formulation is for oral administration. 
     
     
         153 . The pharmaceutical formulation of  claim 3 , the core having the characteristics of a core formed by mixing a disperse phase with a continuous phase to form a colloid, wherein the continuous phase is an aqueous phase comprising hydrogel forming polymer and the disperse phase is a hydrophobic phase, wherein the pharmaceutically active ingredient is in the continuous phase or the disperse phase, wherein the colloid is gelled to form the core. 
     
     
         154 . The pharmaceutical formulation of  claim 153 , wherein the continuous phase further comprises an anionic surfactant. 
     
     
         155 . The pharmaceutical formulation of  claim 153 , wherein the core comprises a hydrogel forming polymer matrix and a hydrophobic phase dispersed in the a hydrogel forming polymer matrix, wherein the core comprises gelatin, SDS, sorbitol, polyethoxylated castor oil, caprylic/capric triglyceride, and 2-(ethoxyethoxy)ethanol; wherein the aqueous phase comprises gelatin, sorbitol and SDS; and the disperse phase comprises polyethoxylated castor oil, caprylic/capric triglyceride, 2-(ethoxyethoxy)ethanol and cyclosporin A. 
     
     
         156 . The pharmaceutical formulation of  claim 3 , formulated into a unit dosage form for oral administration comprising from 0.1 mg to 1000 mg of the active ingredient. 
     
     
         157 . The pharmaceutical composition of  claim 3 , wherein the second coating further comprises at least one excipient. 
     
     
         158 . The pharmaceutical composition of  claim 157 , wherein the at least one excipient is selected from a plasticizer and/or a glidant.