수용성 에스테르화된 셀룰로오스 에테르

In the context of the present invention addressed to a cellulose ether carboxylic acid anhydrous glucose unit, writing base nose pie north repeating unit coupled D - β - 1, 4 glycoside has cellulose skeleton. The a cellulose ether is preferably esterified carboxylic acid alkyl cellulose, hydroxyalkyl cellulose or hydroxyalkyl alkyl cellulose are disclosed. This anhydrous glucose unit in a cellulose ether of the present invention is esterified to at least some of the hydroxyl is alkoxylates or hydroxy substituted by a combination of hydroxy alkoxylates or alkoxylates alkoxylates means that other. For hour maul [thok thread hydroxy alkoxylates typically hydroxy, hydroxy or hydroxy and/in at the time of [thok thread [...] group. In at the time of [thok thread and/or hydroxy is preferably hydroxy [...]. Typically 1 or 2 hydroxy cellulose ethers alkoxylates of carboxylic acid is present. Is preferably a single hydroxy to of alkoxylates, more preferably hydroxypropyl-hour pro width thread present. To maul [thok thread typically alkoxylates, [thok thread and/or pro width thread group. Is preferably maul [thok thread. Exemplary said - a cellulose ether is esterified esterified defined alkyl cellulose, e.g. the esterified methyl cellulose, ethyl cellulose, and profile cellulose; the esterified hydroxy alkyl cellulose, e.g. is esterified with hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxy butyl cellulose; and process for hydroxyalkyl alkyl cellulose, such as hydroxy ethyl methyl cellulose is esterified, hydroxymethyl ethyl cellulose, ethyl hydroxyethyl cellulose, hydroxypropyl methyl cellulose, hydroxypropyl ethyl cellulose, hydroxy butyric methyl cellulose, and hydroxy butyl ethyl cellulose; and 2 having at least one hydroxyalkyl groups, such as carboxylic acid hydroxyethyl hydroxypropyl methyl cellulose are disclosed. Most preferably, a cellulose ether carboxylic acid is esterified hydroxy alkyl methyl cellulose, e.g. the esterified hydroxypropyl methyl cellulose are disclosed.

Anhydrous glucose unit hydroxyl group by a group of hydroxy alkoxylates of alkoxylates molar substituted hydroxy substitution is displayed to that excels in MS (hydroxy alkoxylates). MS (hydroxy alkoxylates) esterified hydroxy is a cellulose ether in anhydrous glucose unit of average preparing alkoxylates are disclosed. Hydroxy alkylation reaction of hydroxyl number number alkoxylates coupled to hydroxy cellulose backbone during alkylation, for example methylation number number, and/or hydroxy alkylation can be ether further will be appreciated that the number number should. Anhydrous glucose unit identical to the position of the carbon atoms marked generates the multiple subsequent hydroxy alkylation side chains, the alkoxylates used in multiple hydroxy groups each other by ether linkages, each branched chain alkoxylates substituent hydroxy cellulose backbone generally formed on the substrate.

The term "hydroxy alkoxylates for" is said to any one or fix a single hydroxy alkoxylates as overview and, wherein at least one 2 hydroxy alkoxy units covalently bound to each other by joining the ether, hydroxy alkoxylates of a structural unit for hydroxy as substituent for referring to the MS context of alkoxylates (hydroxy alkoxylates) should interpreted. In hydroxy substituent is hydroxyl end of alkoxylates defined further alkylation, for example methylates and depends whether is it is not as important; and non - alkylated alkylated hydroxy alkoxylates substituent (hydroxy alkoxylates) for both MS for measuring multiple myelomas are included. A cellulose ether of the present invention is esterified generally 0. 05 To 1. 00, Preferably 0. 08 To 0. 90, More preferably 0. 12 To 0. 70, Most preferably 0. 15 To 0. 60, And in particular 0. 20 To 0. 40 Molar substituted hydroxy to from alkoxylates selectivities.

For anhydrous glucose unit alkoxylates, for example a hydroxyl substituted by hydroxyl groups of the average number of substituted alkoxylates that excels in the maul [thok thread, DS (alkoxylates) designated as a substrate. Of a given defined in said - DS, terms "alkoxylates have the same substituted hydroxyl groups" in the present invention is cellulose backbone carbon atoms coupled directly alkylated hydroxyl groups as well as cellulose backbone coupled to hydroxy alkylated hydroxyl groups of alkoxylates substituent including should interpreted. The present invention according to the esterified cellulose ether is preferably 1. 0 To 2. 5, More preferably 1. 1 To 2. 4, Most preferably 1. 2 To 2. 2 And in particular 1. 6 To 2. 05 Has a DS in the range of (alkoxylates).

Most preferably esterified cellulose ether is in the range of said number for the DS and DS (alkoxylates) [...] (maul [thok thread) for said number in the range of to [...] MS MS (hydroxy alkoxylates) having the esterified hydroxypropyl methyl cellulose (hydroxy [...]) are disclosed.

(O)- R - COOH groups of a cellulose ether of the present invention is esterified ester - C type as accuracy, 2 wherein R is a hydrocarbon, e.g. - CH - C (O)₂ - CH₂ - COOH, and optionally for aliphatic 1 is acyl, e.g. acetyl, propionyl, or butyryl, e.g. n - butyryl or i - butyryl among others. Specific examples hydroxypropyl methyl cellulose acetate three sour this [thu a cellulose ether is esterified (HPMCAS), hydroxypropyl cellulose acetate three sour this [thu (HPCAS), hydroxy butyric methyl cellulose propionate (HBMCPrS) three sour this [thu, hydroxyethyl hydroxypropyl cellulose propionate (HEHPCPrS) three sour this [thu, or methyl cellulose acetate three sour this [thu (MCAS) are disclosed. Hydroxypropyl methyl cellulose acetate three sour this [thu esterified (HPMCAS) is most preferably a cellulose ether are disclosed.

The esterified generally at least a cellulose ether 0. 01, Preferably at least 0. 05, And most preferably at least 0. 10 - C (O)- R - COOH type such as 3:00 roh passing of means of substituted selectivities. The esterified cellulose ether generally maximum 0. 90, Preferably maximum 0. 65, And more preferably maximum 0. 50 - R - COOH of formula - C (O) means of substituted selectivities. The esterified cellulose ether generally 0 or at least 0. 05, Preferably at least 0. 10, And more preferably at least 0. 25 To 1 is an aliphatic acyl, e.g. acetyl, propionyl, or butyryl has a degree of. The esterified cellulose ether generally maximum 0. 95, Preferably maximum 0. 80, And more preferably maximum 0. 60 Has a degree of aliphatic 1 is acyl. Total ester substitution generally include at least a 0. 05, Preferably at least 0. 10, And more preferably at least 0. 20 Are disclosed. Total ester substitution generally 1. 0 Hereinafter, preferably 0. 90 Hereinafter, and more preferably 0. 70 Hereinafter are disclosed.

For vinyl acetate and three sour this [thu a process for content are measured along a synthesized: " Hypromellose Acetate Succinate, United States Pharmacopia and National Formulary, NF 29, pp. 1548 - 1550". Reported value is ("loss on drying" as measured at a certain class of said HPMCAS papers) are corrected for volatile material. The method is propionyl, butyryl content and other a process for measure can be used in a similar manner.

In ether of a cellulose ether is esterified to the nucleotide content measured in the same manner as from those described for S.: "Hypromellose", United States Pharmacopeia and National Formulary, USP 35, pp 3467 - 3469.

Said ester obtained by analysis of content according to individual substituent MS value of DS and boiling water is transformed into a substrate. The may include a cellulose ether ester substituent of a DS and other MS can be used measure in a similar manner.

Typically, weight percent based on the total weight of all forming a repeated unit is mixed with the cellulose weight percentage average are disclosed. To maul [thok thread maul [thok thread of content (i.e., - OCH₃ ) Based on the mass of reporting the with each other. Alkoxylates (i.e., - O - alkylene - OH) to hydroxy content of hydroxy alkoxylates; for example hydroxy [...] (i.e., - O-a CH₂ CH (CH₃ ) - OH) based on the mass of reporting the with each other. The content of aliphatic 1 R is acyl₁ For the 1 is aliphatic, e.g. acetyl (- C (O)- CH₃ ) In - C (O)- R₁ Based on the mass of reporting the with each other. Type - C (O)- R - COOH content of this means of mass, for example [...] (i.e., - CH - C (O)₂ - CH₂ - COOH) based on the mass of reporting the with each other.

A cellulose ether of the present invention is esterified maximum 70,000 Daltons, preferably maximum 60,000 Daltons, weight average molecular weight of 50,000 Daltons or maximum 40,000 Daltons M and more preferably maximum_w The. Generally they are at least 8,000 Daltons, preferably at least 10,000 Daltons, more preferably at least 12,000 Daltons, most preferably the weight average molecular weight of at least 13,000 Daltons M_w The.

2 Generally soluble ester is a cellulose ether. 6 Hereinafter, preferably 2. 1 Hereinafter, more preferably 2. 0 Hereinafter, most preferably 1. 8 Hereinafter, and in some embodiments further 1. 5 Hereinafter by a polydispersity M_w /M_n , I.e., weight average molecular weight M_w To number average molecular weight M_n Of ratio. A polydispersity M_w /M_n At least a conventional 1. 1, Typically at least 1. 2 Or at least 1. 3 Are disclosed. Soluble ester of the cellulose ether is surprisingly low polydispersity low polydispersity is significantly rigid molecular weight distribution index of deformation are desired. Molecular weight distribution (tightness) spacing density steam is, the two individual dosage form increase the interaction of the polymer molecule active ingredient in number about increases the uniformity of therapeutic dosage forms preferably a polymer excipient acting as that number, the dosage forms in the predictability of efficiency to maximize substrate.

M_w And M_n 50 Mm NaH on mobile₂ PO₄ And 0. 1 M NaNO₃ 60 Volume of aqueous buffer containing 40 volume and mixture of acetonitrile using synthesized [Journal of Pharmaceutical and Biomedical Analysis 56 (2011) 743] measured according thereto. The mid is 8. 0 Of pH adjust to. M_w And M_n In measurements of cited in the embodiment being described.

C (O)- R - COOH of neutralization of diagram in a cellulose ether of the present invention is esterified to 0. 4 Hereinafter, preferably 0. 3 Hereinafter, more preferably 0. 2 Hereinafter, most preferably 0. 1 Hereinafter, and in particular 0. 05 Hereinafter or furthermore a 0. 01 Hereinafter are disclosed. Neutralizing diagram further essentially only a little less than or on 0, maximum 10 example^-3 Or further only maximum 10^-4 Are disclosed. As the term is used in the specification is a sum of "neutralizing also" de-protonated carboxyl-de-protonated carboxyl of ratio and proton for defining other. I.e.,

Also neutralizing=[- RCOO - C (O)^- ] / [- C (O)- R-a COO^- + - C (O)- R a-COOH].

Another aspect of the requisite number of characteristic is a cellulose ether of the present invention is esterified - solubility are disclosed. Surprisingly, at least 2 of the present invention is esterified cellulose ether 2 °C. 0 Weight percent of water solubility. I.e., this water in 2 °C at least 2. 0 Weight percent solution, preferably at least 3. 0 Weight percent solution, and more preferably at least 5. 0 Weight percent solution can be dissolved. Generally the temperature of water in a cellulose ether 2 °C maximum 20 weight percent solution of the present invention is esterified or most preferred embodiment further maximum 30 weight percent solution can be dissolved. The terms "water in 2 °C x weight percent solution" as used in the specification of the esterified in a cellulose ether is 2 °C x g (100 - x) g of water soluble in another substrate.

Point of view than the, type - C (O)- R - COOH groups including of the present invention is esterified cellulose ether, a cellulose ether is a cellulose ether carboxylic acid esterified the degree of neutralization of 0. 4 Preferably exceed or said aqueous liquid that does not increase range listed in W hen combined with even, for example, a cellulose ether esterified the only water, even when combined with distilled water deionization or for example, less than 10 °C, more preferably less than 8 °C, further preferably less than 5 °C, and most preferably at a temperature of maximum 3 °C surprisingly been found that soluble in aqueous liquids. This carboxylic acid cellulose ether of the present invention for a variety of purposes, for example, coating and capsule number causes very useful in quiet. The aqueous liquid further comprises a small amount of organic liquid can be dilution number; however, generally the aqueous liquid at least 80 total weight of aqueous liquid, preferably at least 85, more preferably at least at least 90, in particular at least 95 weight percent of water and accomplishing. As used in the specification the terms "organic liquid dilution number" is a mixture of organic solvents at least one organic solvent 2 big. A preferred organic liquid dilution number 1 has at least one heteroatom, such as oxygen, nitrogen or chlorine compounds as polar organic solvent having are disclosed. In a preferred organic liquid dilution number is alcohol, for example a multifunctional alcohol, for example glycerol, or preferably monofunctional alcohol, such as methanol, ethanol, isopropanol or n - propanol; ether, for example tetrahydrofuran, ketones, such as acetone, methyl ethyl ketone, or methyl isobutyl ketone; acetate, such as ethyl acetate; halogenated hydrocarbon, such as methylene chloride; or nitrile, e.g. acetonitrile are disclosed. More preferably organic liquid dilution number is 1 to 6, most preferably 1 to 4 carbon atoms has. The aqueous liquid but basic compound, however the esterified cellulose ether obtained in aqueous liquid of a cellulose ether for - C (O)- R - COOH carboxylic acid formulations particularly 0 diagram. 4 Hereinafter, preferably 0. 3 Or 0. 2 Or 0. 1 Hereinafter, more preferably 0. 05 Or 0. 01 Hereinafter, and most preferably 10^-3 The 10 hereinafter or further^-4 Should is hereinafter. Preferably the aqueous liquid does not comprise a substantial amount of a basic compound. More preferably, a basic compound which does not contain an aqueous liquid. Further preferably, 80 to 100 percent based on the total weight of the aqueous liquid with an aqueous liquid, preferably 85 to 100 percent, more preferably 90 to 100 percent and most preferably 95 to 100 percent of water, and 0 to 20 percent, preferably 0 to 15 percent, more preferably 0 to 10 percent, and most preferably 0 to 5 percent of organic liquid dilution number without using a tool. Most preferably the aqueous liquid water, for example, consists of deionization or the reservoir.

When measuring the solubility as described class in the embodiment, of the present invention is esterified a cellulose ether is preferably, at least 80 wt. %, Typically at least 85 wt. %, More typically at least 90 wt. %, And often at least in the case of 95 wt. % Of a cellulose ether is 2 °C is esterified in 2. 5 Parts by weight of the esterified cellulose ether 97. 5 Parts by weight of soluble in a mixture of solubility properties. Typically the degree of solubility in 5 or 10 parts by weight of the esterified cellulose ether 2 °C 95 or 90 parts by weight of a mixture of 20 parts by weight of the esterified cellulose ether in the 2 °C or further a mixture of 80 parts by weight of observed in addition in 2000.

A cellulose ether of the present invention is esterified in generally 20 °C 0. 43 Wt. In the esterified of the cellulose ether 2 -% aqueous NaOH. 0 Wt. DIN 53211 maximum 100 mpa -% solution, s, preferably maximum 50 mpa, s, and more preferably maximum 5. 0 Mpa, having a viscosity of s has. Generally viscosity 20 °C in 0. 43 Wt. In the esterified of the cellulose ether 2 -% aqueous NaOH. 0 Wt. DIN 53211 at least 1 -% solution. 2 Mpa, s, more typically at least 1. 8 Mpa, s, and more typically at least 2. 4 Mpa, s, and most typically at least 2. 8 Mpa, s are disclosed. The esterified cellulose ether 2. 0 Weight % solution is as described for the nucleotide number bath and, then DIN 51562 - 1:1999 - 01 (January 1999) it has been determined that the viscosity with right bell: " Hypromellose Acetate Succinate, United States Pharmacopeia and National Formulary, NF 29, pp. 15481550.

In addition, among acetone in a cellulose ether of the present invention is esterified has surprisingly even in the heavily doped and soluble in low viscosity. A cellulose ether of the present invention generally 10 wt of the cellulose ether carboxylic acid is esterified in acetone in a 20 °C. -% Solution DIN 53211, only maximum 13 mpa, s, preferably maximum 10 mpa, s, and more preferably maximum 6 mpa, having a viscosity of s has. A cellulose ether of the present invention is esterified in the 20 °C 10 wt of the cellulose ether carboxylic acid in acetone. -% Solution DIN 53211, typically 2. 0 Mpa, s or more, more typically 3. 0 Mpa, has a viscosity of s or more. A cellulose ether of the present invention is esterified in the 20 °C generally 20 wt of the cellulose ether carboxylic acid in acetone. -% Solution DIN 53211, only maximum 40 mpa, s, more preferably only maximum 30 mpa, s, and most preferably furthermore only 25 mpa, s has to viscosity. A cellulose ether of the present invention is esterified in the 20 °C 20 wt of the cellulose ether carboxylic acid in acetone. -% Solution DIN 53211, typically 6 mpa, s or more, more typically 10 mpa, has a viscosity of s or more. The preparation of a very low viscosity cellulose ether with a station number patent application WO2014/137777 call call and WO2014/137778 is esterified with acetone disclosure with each other. However, these patent Official Gazette esterified to the disclosure a cellulose ether water-soluble endured. In addition, station call number patent application WO2014/137777 disclosure so that cost is a cellulose ether esterified call and WO2014/137778 - depolymerization and discoloration of the cellulose ether during intermediate wall influenced by viscosity cellulose ethers are vlps extremely vigorous depolymerization process which has been subjected.

A wide range of - C (O)- R - COOH inventor patent application during the study groups is esterified including publicly known type are lower than a cellulose ether is a cellulose ether molecule portion the esterified as defined in combination with said aqueous liquid formulation temperature of 10 °C and is less than, preferably less than 8 °C, more preferably less than 5 °C, below the temperature of aqueous liquids and in particular 3 °C or dissolved found surprisingly that can be performed. The esterified non - 10 °C higher molecules portion is a cellulose ether dissolved molecules of less than 2000. When the temperature of the combination temperature of 10 °C or more, the partial dissolution is not field-of-view. In particular - C (O)- R - COOH groups is esterified at room temperature type including publicly known a cellulose ether a significant extent does not dissolving in water.

The, formula - C (O)- R - COOH groups of a cellulose ether soluble ester of the present invention is described including said - fractionation can be esterified to a process produced a cellulose ether, the process comprises a) said aqueous liquid and a type - C (O)- R - COOH groups such as described in the specification including a cellulose ether is esterified combining 10 °C and is below the temperature of said aqueous liquid formulation is esterified in a cellulose ether dissolve a portion of said setting step, b) said residue from said blend is dissolved and a cellulose ether is esterified - piece of c) recovering said esterified cellulose ether dissolved in said aqueous liquid comprising the following steps.

Step a) number used for the temperature of the high pressure liquid coolant combination in aqueous liquid preferably 0 °C or more, typically 1 °C or greater than. Step a) the temperature of the maximum 20 °C typically used in aqueous liquid, preferably less than 10 °C, more preferably less than 8 °C, further preferably less than 5 °C, maximum 3 °C and most preferably are disclosed. Generally to parts by weight of a cellulose ether of at least 5 parts by weight of a cellulose ether is esterified, preferably at least 10 parts by weight, and more preferably at least 20 parts by weight, and often maximum 100 parts by weight, preferably maximum 60 parts by weight, more preferably maximum 40 parts by weight of aqueous liquid in combination with substrate.

Step a) compound obtained in temperature less than 10 °C, preferably less than 8 °C, more preferably 5 °C less than, and most preferably 3 °C or less would significantly affect a fractionation process set in inside of the pipe. Formulations generally include at least a minus 2 °C obtained temperature, typically 0 °C or more, and more typically selected to 1 °C or more. The temperature of the aqueous liquid is esterified in combination with a cellulose ether is adjusted before every few minutes after every few minutes does not necessarily disclosed. Preferably said maximum blend week, more preferably maximum 72 time, said - temperature and more preferably maximum 24 referred period of time being maintained. Preferably said combination comprises at least 10 minutes, preferably at least 30 minutes, and more preferably at least 2 said - period of time mentioned temperature being maintained.

Fractionation process steps b) is esterified in a cellulose ether - dissolved portion of publicly known way, for example by filtration or centrifuging a tilting or separation can be separated from the rest of the blend by precipitation. This object can be used for publicly known. As a blend at temperatures less than said 10 °C from the remainder is esterified after separation of a cellulose ether, a cellulose ether comprising the remainder surprisingly still dissolved in the blend is esterified. Esterified carboxylic acid dissolved in a cellulose ether portion of the total weight of a cellulose ether generally at least 1 percent, typically at least 5 percent, and often maximum 70 percent, 50 percent maximum typically are disclosed. A cellulose ether esterified shows no visual is dissolved.

Fractionation process steps c) esterified dissolved aqueous liquids in a cellulose ether for example, at least 30 °C, preferably at least 45 °C and more preferably at least 60 °C, and most preferably at least 80 °C temperature dissolved in the esterified cellulose ether is mixed with an aqueous liquid including withdrawn by heating. Typically dissolved the esterified cellulose ether is mixed aqueous liquid including maximum 98 °C, maximum 95 °C more typically heated to a temperature of substrate. This temperature dissolved in a cellulose ether carboxylic acid precipitated as follows. The publicly known way a cellulose ether precipitated is esterified, for example by filtration or centrifuging or inclined base member can be separated from the aqueous liquid precipitation. Heating a cellulose ether is esterified by-number of observed the royal favor to do - reversible insoluble are disclosed. Separated aqueous liquids at temperatures less than 10 °C esterified cellulose ether soluble are disclosed. Alternatively, a cellulose ether esterified drying aqueous liquids dissolved refrigeration - fractionation process steps c) withdrawn in.

Soluble ester of the present invention is a method for recovering said - a cellulose ether is esterified cellulose ethers are corrected to regenerate a cellulose ether can be integrated. Therefore, one of the steps are a) type - C (O)- R - COOH groups including the esterified cellulose ether is mixed to produce a mixture including aliphatic carboxylic acid reaction product for the presence of the aliphatic carboxylic acid anhydrides in dicarboxylic acid anhydride or dicarboxylic acid anhydride and reacting the combination of cellulose ether, a cellulose ether esters from precipitating reaction product mixture, a cellulose ether can be prepared aqueous liquid and an aqueous liquid and a precipitated is esterified in a cellulose ether is esterified to dissolve a portion of less than 10 °C compound obtained by setting the temperature, b) the blend from the rest of the esterified - a cellulose ether dissolved portion of said step of separating, and c) a cellulose ether esterified recovering dissolved aqueous liquids comprising the following steps.

The esterified cellulose ether is mixed to produce a mixture including aliphatic carboxylic acid reaction product for the presence of the aliphatic carboxylic acid anhydrides in dicarboxylic acid anhydride or dicarboxylic acid anhydride and combination of the cellulose ether reaction is publicly known manner, for example call and number 4,226,981 call number 3,435,027 U.S. patent number, station number patent application WO 2005/115330 WO2013/148154 mobile wireless call, or can be performed as described in European patent application EP 0 219 426.

A cellulose ether is esterified reaction product mixture is obtained, typically aliphatic carboxylic acid is used as a reaction medium, typically reaction catalyst, e.g. alkali metal carboxylate, typically 1 residual amount of esterification of at least one number number and by-products, such as dicarboxylic acid anhydride and optionally includes the amount of the aliphatic carboxylic anhydride. Reaction product mixture is generally 3 to 60 weight percent, typically 7 to 35 weight percent of a cellulose ether is esterified, generally 10 to 95 weight percent, typically 20 to 70 weight percent of aliphatic carboxylic acid, generally 1 to 50 weight percent, typically 5 to 30 weight percent of a reaction catalyst, e.g. alkali metal carboxylate, and generally 0. 1 To 50, typically 2 to 40 weight percent of small quantities component, such as non - under - the amount of the aliphatic carboxylic anhydride reacted dicarboxylic acid anhydride and reacted and, automaton based on the total weight percentage of all reaction product mixture. The esterified cellulose ether including reaction product mixture is generally 60 °C or more, typically 75 °C or more, and often maximum 110 °C, typically of temperature of the maximum 90 °C.

Upon completion of the esterification reaction product obtained from a mixture precipitation of cellulose ether is esterified. The esterified cellulose ether has a publicly known manner, for example American patent number number 4,226,981 call, station number patent application WO 2005/115330 call, mobile wireless terminal station number patent application WO2013/148154 precipitate from the reaction mixture as described in European patent application EP 0 219 426 can be.

An aqueous-based liquid esterified precipitated a cellulose ether is then cleaned. In addition to suitable aqueous liquid hchk1. above. In combination with a cellulose ether with an aqueous liquid are esterified in the three cleaning step; preferably 2 to 400 parts by weight of the cellulose ether is esterified with parts by weight, more preferably 3 to 300 parts by weight, and most preferably 4 to 150 parts by weight of aqueous liquid are used. Cleaning step once or several times, preferably 5 times to once can be. Surprisingly, precipitated a cellulose ether portion of the esterified esterified description less than 10 °C a cellulose ether and aqueous liquid, preferably less than 8 °C, more preferably 5 °C less than, and most preferably 3 °C or cleaning purposes can be performed below the temperature of that used dissolved aqueous liquids has been found.

Production process steps b) - dissolved portion of a cellulose ether in the esterified, i.e., 10 °C is esterified at temperatures less than a cellulose ether and aqueous liquid combination of a cellulose ether is esterified to give the part of the fractionation process steps b) as described in the specification can be separated from the rest of said in the blend.

Production process steps c) dissolved aqueous liquids in a cellulose ether esterified fractionation process steps c) as said in a withdrawn. In addition to such characteristics as described in the specification of the present invention said having a cellulose ether is esterified production process steps c) obtained in

Another aspect of the present invention dissolved in aqueous dilution number a of the present invention said liquid composition including at least one of a cellulose ether esterified. The specification the term "liquid composition" as used in the liquid composition 25 °C and at atmospheric pressure. Aqueous dilution number is desirably water alone or mixed with a small quantity of water and an organic liquid such as dilution number said described in the specification are disclosed. In one implementation of the present invention composition comprises liquid dilution number and water based on a total weight greater than 50, preferably at least 65, and more preferably at least 80, most preferably at least at least 90, in particular at least 95 weight percent of water and less than 50, preferably maximum 35, more preferably maximum 20, most preferably 10 maximum, in particular organic liquid comprising the following dilution number and maximum 5 weight percent. Basic compound is aqueous dilution number but, the esterified cellulose ether obtained in aqueous liquid of a cellulose ether for - C (O)- R - COOH carboxylic acid formulations particularly 0 diagram. 4 Hereinafter, preferably 0. 3 Or 0. 2 Or 0. 1 Hereinafter, more preferably 0. 05 Or 0. 01 Hereinafter, and most preferably 10^-3 10 Hereinafter or further^-4 Hereinafter should then. Preferably aqueous dilution number is does not comprise a substantial amount of a basic compound. More preferably, does not contain an aqueous dilution number is a basic compound. Liquid composition may be preferably at least 5 wt based on total weight of the liquid composition. -%, More preferably at least 10 wt. -%, And more preferably at least 15 wt. M0 -% of a cellulose ether of the present invention is esterified. Liquid compositions will generally comprise up to 20 wt based on total weight of the liquid composition. Maximum 30 wt -% or in a preferred embodiment further. M0 -% of a cellulose ether of the present invention is esterified. A cellulose ether of the present invention is esterified to the less than 10 °C - 2 °C, preferably less than 0 °C to 8 °C, more preferably 0. Less than 5 °C to 5 °C, and most preferably 0. 5 °C to 3 °C temperature by cooling the liquid composition can be a solution.

A aqueous dilution number and said pin including at least one of a cellulose ether esterified liquid composition including contacting a number of capsules of the bath dipped liquid composition useful in particular. The esterified affecting a cellulose ether enteric properties can be a cellulose ether is esterified partial neutralizing would not be required disclosed. Furthermore, the bath at room temperature can be about further provides a capsule number, reduction of energy results in substrate. Typically having a temperature of 10 °C liquid aqueous composition contains at least 15 °C, preferably at least 20 °C, more preferably at least 30 °C and maximum 95 °C, preferably maximum 70 °C, and more preferably maximum 60 °C of dipped has at contacting pins with each other. The capsule is enteric properties.

Dissolved in said aqueous dilution number therein and a liquid composition including at least one of a cellulose ether esterified in addition dosage forms, for example positive number, granules, pellets, elliptical dragee, the percentage, suppository, or implantable dosage forms 7.4. lung frost coating.

Another aspect of the present invention said organic dilution number including at least one of a cellulose ether of the present invention and a carboxylic acid wash. Organic liquid composition may be present alone or mixed with water dilution number can be. In one implementation of the present invention compositions are preferably organic liquid based on the total weight and dilution number at least 50, more preferably at least 65, most preferably at least 75, in particular at least 90 weight percent and preferably maximum 50 on organic liquid dilution number, more preferably maximum 35, most preferably maximum 25, and in particular comprising maximum 10 weight percent of water. Most preferably organic dilution number and including at least one of a cellulose ether of the present invention is esterified said a substantial amount of liquid composition does not include water. A preferred organic dilution number is in addition to said hchk1. In the dilution number 20 °C at high concentrations of the present invention is esterified with an organic liquid, for example soluble in acetone are disclosed. High-concentration solution, for example 10 to 20 weight percent or further more has low viscosity even in. Liquid composition preferably contains at least 5 wt based on total weight of the liquid composition. -%, More preferably at least 10 wt. -%, And more preferably at least 15 wt. M0 -% of a cellulose ether of the present invention is esterified. Liquid compositions will generally comprise up to 20 wt based on total weight of the liquid composition. Maximum 30 wt -% or in a preferred embodiment further. M0 -% of a cellulose ether of the present invention is esterified. The present invention is useful in particular embodiments of the present invention including active ingredients when receiving [...] if this invention.

A liquid dilution number and said one or more excipients including of the present invention for a cellulose ether esterified antagonism number system useful in addition and in particular active ingredient, such as fertilizer, or insecticidal number number number seconds, or biologically active components, such as vitamin, herbal and mineral supplement excipients in drug number system useful as an intermediate for the number and high pressure liquid coolant. The, at least one active ingredient of the present invention compositions are preferably 1, most preferably 1 comprises at least one drug. The term "drug" animal, in particular beneficial prophylactic and/or therapeutic properties when administered to a human to general compound by a goniophotometer. Of the present invention liquid composition preferably contains 1 to 40 percent, more preferably 5 to 35 percent, further preferably 7 to 30 percent, most preferably 10 to 25 percent of said species is esterified at least 1 such as described in the specification a cellulose ether and 40 to 99 percent, more preferably 50 to 94. 9 Percent, further preferably 65 to 92. 5 Percent and most preferably 70 to 89 percent of said further to comprise a liquid dilution number. Furthermore, the total weight of the composition of the present invention liquid compositions will generally comprise 0 to 40 percent, more preferably 0. 1 To 40 percent, further preferably 0. 5 To 25 percent, and most preferably 1 to 15 percent of active component. 20 °C in 10 wt in acetone. 20 Wt % or further. Measured % solution, 10 °C below the temperature of water in a cellulose ether is esterified low viscosity and high solubility of the cellulose ether is esterified with the incorporation of a cellulose ether is esterified at a high concentration, i.e., a cellulose ether liquid ratio while still allowing dilution number is esterified liquid composition viscosity number significantly high specific of [...] substrate. This is esterified in a cellulose ether solid dispersions of active ingredients can be used to produce two method: 1. The ratio of active ingredient a cellulose ether is esterified/publicly known, dilution than the same compositions as in being maintained. In this case, stabilization of the cellulose ether in a concentration above the liquid composition active ingredients in higher concentration, the solid dispersion in the production of active ingredients leading to increased throughput while, holds the same stability of active ingredients. 2. Alternatively, only the liquid composition within the increased concentration of a cellulose ether is esterified only the concentration of the agent is not increased. This would reduce the rate of processing of active ingredients without liquid dilution number number of stabilization of the cellulose ether matrix/active ingredient leads to improved stabilizing a cellulose ether is esterified leads to high specific active ingredients therein. This protrusion is elder brother character number of active ingredients in order to achieve pharmaceutically active amorphous improved stabilization of active ingredients like a chlorohydrin content - - liquid number without the need higher content of operating in a cellulose ether is esterified switched to each other. The high load of active ingredients of the present invention is esterified in a cellulose ether liquid composition while still allowing solid dispersions used number tank achieves significantly high throughput rates.

Liquid composition of the present invention in another aspect of the present invention at least 1 species active ingredient such as a drug, such as described in the at least 1 species is esterified to produce a cellulose ether and optionally including at least one oh [cyu half [thu 1 solid dispersions are used. The liquid from the solid dispersions preferably comprise a composition produced by a high dilution number number are disclosed. The lower viscosity of the cellulose ether carboxylic acid in acetone or another organic solvent allows the incorporation of a cellulose ether is esterified at a high concentration, the significantly low viscosity liquid composition while still maintaining a high concentration into the composition allows the incorporation of drug. This liquid composition or in the esterified cellulose ether is used in a coating including an active ingredient and the esterified cellulose ether is for example high pressure liquid coolant spray - dried solid dispersions including number for when high throughput rates achieves a very advantageous disclosed. In addition, said active ingredient is esterified to a cellulose ether as a high signal-to-liquid number may be spray drying furnace number 1308. elder brother anger. A cellulose ether is esterified to active ingredient hardly soluble active principles of high ratio increases which are supersaturated for holding the bioavailability of desired.

A preferred method to produce a solid dispersion is spray - drying substrate. The terms "spray - drying" small droplets (atomized) liquid mixture comprising a strong propulsion force for evaporation of solvent from the droplets of liquid breaks with spray - drying device quickly solvent from a mixture in a stand-alone number refer to process. Spray - drying process and spray [Perry's Chemical Engineers' Handbook, pages 20 - 54 to 20 - 57 (Sixth Edition 1984)] - conditioner generally synthesized to hchk1. Spray - drying process and plant is a more details the synthesized [Marshall, "Atomization and Spray-a Drying," 50 Chem. Eng. Prog. Monogr. Series 2 (1954), and Masters, Spray Drying Handbook (Fourth Edition 1985)] described by. The line 34 - 35 25 - 7 call in the queue number patent application WO 2005/115330 useful spray drying station is disclosed. Solid dispersions of the present invention alternatively i) a) defined said at least 1 species is esterified a cellulose ether, b) at least one active ingredient and 1 c) at least one optionally an additive number 1 dietary, and ii) blend by extrusion to number bath 1308. The terms "extrusion" specification as used in injection molding, molten casting and compression molding process by means of publicly known. Example drug active ingredient composition including extrusion, preferably the synthesized by extruding molten - techniques [Joerg Breitenbach, Melt extrusion]: a drug delivery techniques, document [European Journal OfPharmaceuticsAndBiopharmaceutics 54 (2002) 107 - 117] Or European patent application EP 0 872 233 call from a publicly known and described. A solid dispersion of the present invention is esterified preferably include a cellulose ether) as active component b) based on the total weight of a) 20 to 99. 9 Percent, more preferably 30 to 98 percent, and most preferably 60 to 95 percent of said carboxylic acid such as described in the specification a cellulose ether, and b) preferably 0. 1 To 80 percent, more preferably 2 to 70 percent, and most preferably 5 to 40 percent of active component. The esterified cellulose ether a) and active ingredient b) a metered quantity is preferably at least 70 percent by weight based on the total combination of solid dispersion, more preferably at least 80 percent, and most preferably at least 90 percent are disclosed. If, the balance c) consists of one or more adjuvants such as described below. A solid dispersion comprises at least a cellulose ether is esterified), one or more active ingredient b), and optionally one or more adjuvant c) but include, but are into a generally referred to the total amount of said -. Once a cellulose ether at least 1 species is esterified at least 1 species of active principles including solid dispersions once formed, can be dispersed in an incorporation of dosage forms can be used hereinafter for the several processing operation. These processing operation drying, granulation, and milling comprises. The dosage form composition embedded in solid dispersions a selective oh [cyu half [thu number can be useful for elder brother anger. Solid dispersions of the present invention in various forms, such as stranded, pellets, granules, pills, positive number, elliptical dragee, extra-particle, capsule or injection molded filling of capsules be in the form of powder, film, paste, cream, suspension or the form of a slurry can be.

Of the present invention liquid composition and solid dispersions preferably comprise a further optionally an additive number, e.g. colored number, pigment, opaque body, flavor number number and mouthfeel enhancer, antioxidant number, and their comprising any combination of can. Optionally an additive number is desirably about number dermatologically acceptable disclosed. 1 Selective oh [cyu half [thu at least one publicly known techniques of the present invention is a useful amount and types have the intended end uses and liquid composition or solid dispersion depends on the other.

In the embodiment of the present invention will to some embodiments detailed number is described.

In the embodiment

Not alternatively referred, and percentages are all due to the weight body. Test procedure is provided which in the embodiment are used.

Ester of content

1. A cellulose ether is esterified to the nucleotide content of ether in the same manner as measured substrate: "Hypromellose", United States Pharmacopeia and National Formulary, USP 35, pp 3467 - 3469.

For acetyl (- CO-a CH₃ ) To the ester substituted and [...] (- CO-a CH₂ - CH₂ - COOH) are measured along the ester substituted is a synthesized: Hypromellose Acetate Succinate, United States Pharmacopia and National Formulary, NF 29, pp. 15481550. Ester substituted report in to the values (as measured at a certain class of said HPMCAS papers "loss on drying") are corrected for volatile material.

Solubility - be

Qualitative measurement: 2 Wt HPMCAS and water. Percent mixture vigorous stirring in 0. 5 °C 98 16 in time. 0G water, based on the dry weight of 2. 0G HPMCAS number bath by mixing take place. The temperature of the mixture of HPMCAS and then 5 °C been increased. Receiving a cellulose ether is esterified [...] been measured by visual inspection. In a process for determination of the HPMCAS is 2% soluble in water is under 5 °C whether does not been. ". ". "". "Example 2% soluble in water -" said procedure is obtained without sediments solution was an other. ". ". "". "2% Soluble in water - no" is 98 according to said procedure. 0G water, based on the dry weight of 2. 0G HPMCAS when forming a precipitate of insoluble harmful HPMCAS mixing and that the remaining at least passes is big. ". ". "". "2% Soluble in water - partially" is 98 according to said procedure. 0G water, based on the dry weight of 2. 0G HPMCAS when only a small portion of mixing and forming a precipitate that the remaining insoluble harmful HPMCAS is big.

Quantitative measurement: Based on dry weight of 2. 5 Parts by weight of HPMCAS is 2 °C having temperature of 97. 5 Parts by weight of deionized water was then added to 2 °C then the stir 6 hours 16 hours 2 °C has been stored. A metered amount of a mixture of a metered centrifuge vial hit; g weight is a mixture of M1 has been moved to display. HPMCAS is movement of weight (g/100 g * 2 weight of mixture. 5G) has been calculated based on the. Mixture is 60 minutes 5000 rpm (2823 xg, it buys fick slang mote (Thermo Scientific) transmitting from the [su sprout toss excellent bio fugitive (Biofuge Stratos) centrifuge) 2 °C in centrifugal in have been isolated. After centrifuging and volatile liquid phase number aliquots from dried metered vial hit. Recording the weight M3 has been shifted g aliquots. The aliquots 105 °C been dried in 12 hours. It has been recorded to the remainder of the metered M4 g g HPMCAS after drying.

Below table 2 terms in " 2. In % 5% water-soluble " is 2. 5 Parts by weight of HPMCAS and 97. 5 Parts by weight of deionized water in a mixture of HPMCAS dissolved in the number chamber a percentage of phenoxyethanol. This (g HPMCAS/centrifuge vial in liquid aliquots shifted g HPMCAS) * (g/g mixture after separation centrifuge vial shifted centrifugal liquid aliquots) corresponding to (M4/M2) * (M1/M3)* 100) are calculated.

HydroxypropylMethyl Cellulose acetate Three sour this [thu (HPMCAS) Viscosity

0. 43 Wt. In 2% aqueous NaOH of HPMCAS. 0 Weight % solution as described for the nucleotide number bath and, then DIN 51562 - 1:1999 - 01 (January 1999) it has been determined that in accordance with right bell 20 °C viscosity: " Hypromellose Acetate Succinate, United States Pharmacopia and National Formulary, NF 29, pp. 1548 - 1550".

10 Wt of HPMCAS in acetone. 90 -% Solution under vigorous stirring at room temperature. 0G based on dry weight of acetone and 10. 0G HPMCAS number bath by mixing take place. The mixture includes from about 24 hours are rolling on roller mixer. (Heraeus Holding) commercially available from right [su [...] GmbH of Germany solution is excellent holding 1 fugitive in the magazine. 0 Lever 3 minutes using centrifugal in 2000 rpm have been isolated. DIN 51562 - 1:1999 - 01 (January 1999) viscosity measurement is performed in accordance with right bell been. 20 °C measurement has been performed.

20 Wt of HPMCAS in acetone. 80 -% Solution under vigorous stirring at room temperature. 0G based on dry weight of acetone and 20. 0G HPMCAS number bath by mixing take place. The mixture includes from about 24 hours are rolling on roller mixer. Solution is commercially available from right [su excellent holding GmbH of Germany [...] 1 mega fugitive (Megafuge). 0 Lever 3 minutes using centrifugal in 2000 rpm have been isolated. DIN 51562 - 1:1999 - 01 (January 1999) viscosity measurement is performed in accordance with right bell been. 20 °C measurement has been performed.

M_w and M_n Measuring

M_w And M_n Not synthesized [Journal of Pharmaceutical and Biomedical Analysis 56 (2011) 743 - 747] referred to are otherwise determined according to other. The mid 50 mm NaH₂ PO₄ And 0. 1M NaNO₃ 60 Volume of aqueous buffer containing 40 volume mixture of acetonitrile by number tank and mixing take place. The furnace 8. 0 Of pH has been adjusted. Cellulose ether ester solution is 0. HPLC vial has been filtered through the filter 45 μm pore size syringe.

More specifically, chemical and solvent used as follows:

The California standard polyethylene oxide (PEOX 20 K and PEOX 30 K is provided to) it will beat with [ayl the toe (Agilent Technologies, Inc.) purchased from material excellent in the diketide [...] oh quality [len, catalog number PL2083 provided 1005 and been PL2083-a 2005.

Acetonitrile (HPLC grade ≥ 99. 9%, CHROMASOL plus), catalog number 34998, sodium hydroxide (semiconductor grade, 99. 99%, Trace metal substrate), catalog number 306576, water (HPLC grade, CHROMASOLV plus) catalog number 34877 and sodium nitrate (99,995%, trace metal substrate) was purchased from sigma (SigmaAldrich) the [tu reach which it will know the catalog number 229938 Switzerland - excellent.

2 Sodium hydrogen phosphate (≥ 99. 999% TraceSelect) catalog number has been purchase from 71492 excellent car proofing of Switzerland.

5 Mg/mL PEOX20 K to automatic solution, 2 mg/mL PEOX30 K to standard solution, the sample solution is a metered amount of polymer HPMCAS and 2 mg/mL vial within a variable volume measured by adding the moving hearth reducing furnace dissolve and remove same number bath take place. PTFE - all solution is coated stirring bar magnets 24 hours at room temperature with stirring to dissolve in the capped vial in using his.

Normalization solution (PEOX 20k, single tank number article, N) and standard solution (PEOX30 K, double tank number article, S1 and S2) is 0. 02 Μm pore size and 25 mm diameter syringe filter (25 top of drug away watts (Whatman Anatop), catalog number 6809 - 2002), it is distant watts through HPLC was filtered into a vial.

(HPMCAS, becoming trillion, doubly number, T1, T2) and standard laboratory test sample solution (HPMCAS, single tank number article, LS) is 0. 45 Μm pore size syringe filter (nylon, for example arc furnace disk (Acrodisc) 13 mm VWR catalog number 514 - 4010) was filtered through into HPLC vial.

Chromatography conditions and execution order document [Chen, R. Et al. ; Journal of Pharmaceutical and Biomedical Analysis 56 (2011) 743748)] been the application management described in the specification. It will beat with [ayl the toe California (Agilent Technologies, Inc.) oh quality [len material excellent [...] SEC provided MALLS device settings from the diketide HP1100 HPLC system; (Wyatt Technologies, Inc.) is an excellent material from both of short California bhabha y crooked diketide [...] each laser light scattering detector and refractive index detector was OPTILAB rex DAWN Heleos II 18. Analytical size times number column (TSK-a GEL®GMPWXL, 300 × 7. 8 Mm) between the [su which freezes the toe show (Tosoh Bioscience) was purchased from bio. And DAWN OPTILAB been operating in both 35 °C. Analytical SEC column at room temperature (24 ± 5 °C) has been operating. The mid 40 volume of acetonitrile and below 50 mm NaH prepared by the number as₂ PO₄ And 0. 1M NaNO₃ 60 Volume containing a mixture of aqueous buffer was:

Aqueous buffer: 7. 20G sodium hydrogen phosphate and 10 2. 2G sodium nitrate is dissolved under stirring until clean 2L in glass bottle 1. 2L number positive number has been added.

A furnace: 1 prepared by the number of said to 800 ml of acetonitrile. 2L added to aqueous buffer material has been achieved then the stir until temperature equilibrium mixture to ambient temperature.

10M NaOH 8 into the furnace. 0 Adjusted to pH 0. 2M nylon was filtered through a membrane filter. De gas continuous flow rate is 0. Was 5 ml/min. 100 Μl injection capacity is 35 been fluorescence and analyzing time is continuous.

Data is collected for 0 MALLS HPMCAS. (Refractive index increment) dn/dc value of 120 ml/g using Wyatt ASTRA software (version 5. 3. 4. 20) Been processed by. Detector number 14, 17, and 18) light scattering signal calculating molecular weight used yet. A representative chromatography under the execution sequence given other: B, N, LS, S1 (5x), S2, T1 (2x), T2 (2x), T3 (2x), T4 (2x), S2, T5 (2x), such as, S2, LS, W, wherein, B represents the mid blank scanning, N1 represents the normalization solution; LS represents laboratory standard HPMCAS is; S1 and S2 represents each one and two standard solution; T1, T2, T3, T4, and T5 represents the test sample solution, and W comprises water injection by a goniophotometer. (2X) and (5x) have the same number of solutions injection exhibits.

OPTILAB and DAWN both number of recommended procedures and been correcting periodically bath according to use frequency. 5 Mg/mL standard polyethylene oxide (PEOX20 K) 100 μl of each executing on the presentation order 90° implantation normalizing all detector each light scattering detector has been used.

In addition OPTILAB DAWN - mono polymer dispersion can be counted and the use of standard volume of delay between when the, light scattering signal refractive index signal the proper alignment or the like. This provides a weight average molecular weight (Mw)- slice data required for calculating disclosed.

In the embodiment 1: Water-soluble HPMCASNumber of bath

Listed in table 1 below (HPMCAS) of the present invention is hydroxypropyl methyl cellulose acetate three sour this [thu having properties for producing water-soluble HPMCAS disclosure material are used. 750G having temperature of 2 °C in temperature of 20 °C of HPMCAS is 2 meat and mixing with 4. 6 Liter 880 in suspension in water and 3 °C 12 been stored for time. HPMCAS and water having a temperature of 3 °C blend was obtained. The portion of the blend at a temperature of 3 °C HPMCAS has been dissolved. The blend is part of the liquid at a temperature of 1 °C then centrifuge (micro fugitive (Microfuge) 1. 0, Heraeus, 10000 rpm, 20 minutes) have been isolated from suspended by HPMCAS.

RNA replicases are listed in table 1 below the characteristics of water-soluble HPMCAS HPMCAS disclosure material. In addition to the properties listed in table 1 below, water-soluble in acetone 20 wt of HPMCAS. -% Where the viscosity of the solution was measured. It is 22. 8 Mpa, s been.

WO 2014/137777 As described in Comparison exampleCE-11 To CE-16, CEOf HPMCAS CE provided E - D and

Comparison example to example CE provided 11 station number patent application number WO 2014/137777 CE provided D CE provided 16 and comparison in the embodiment 11 - 16 and comparison example D and E and CE provided E is call corresponding to the substrate. For its production number patent application WO 2014/137777 call the station 22 and 23 detailed hchk1.

WOSuch as described/2014/031422 Comparison exampleCE- C of HPMCAS

The station number patent application WO/2014/031422 call corresponding to comparison example comparison example CE provided C C 2000. For its production number patent application WO/2014/031422 hchk1. detailed call the station 25.

Comparison exampleCE- H to CE- J

Comparison example number patent application number WO 2014/137777 comparison example H to J station is CE a-H to CE provided J corresponding to other calls. Station number patent application WO 2014/137777 call number patent application WO 2011/159626 call 1 and 2 surface 24 surface and station as disclosure, the HPMCAS [...] chemical [...] american mote [tu (Shin a-Etsu Chemical Co. , Ltd.) (Japanese toe [khyo) and current from commercially available, to brand "AQOAT" been publicly known. In shoes [chu enteric protection having substituents at the level number [...] various pH levels of different combinations of three grades of AQOAT polymeric having AS a-L, AS provided M, and AS a-H number and a high pressure liquid coolant, typically designated call "F" or "G" for fine, e.g. AS provided LF or AS-a LG is along. The table of the size specification of WO 2011/159626 call 2 1 24 and to the WO 2014/137777 call are listed. It is sour with the [pu "Shin a-Etsu AQOAT Enteric Coating Agent" plate 04 is in shoes [chu techniques. 9 05. 2/500 According to, but soluble in 10% NaOH in positive number be insoluble in all grade AQOAT polymer are disclosed. Table 2 analysis of sample data to the WO 2011/159626 call all grade polymer AQOAT 13 disclosure in the nanometer range.

Comparison example CE provided 11 to CE provided 16, CE provided C, CE provided D, 1 under the table of characteristics of HPMCAS CE provided E and CE a-H to CE provided J listed with each other. Abbreviation " n. a. "is" not evaluated " means other.

N. M. : Not measured

In the embodiment 2: Water-soluble From HPMCAS Capsule number bath

In obtained according procedure in the embodiment 1 of 25 wt soluble HPMCAS. An aqueous solution obtained by dissolving in deionized water at a temperature of 2 °C -% by number of HPMCAS bath take place.

5 °C capsule sheath has at each of HPMCAS solution into 21 °C, temperature of 30 °C and 55 °C metal pin 29 has been produced by immersion. Pin is then aqueous HPMCAS is volatile and film formation on a shaping pin number from solution. Capsule shell has been formed on each these temperatures are a pin lead-in. Room temperature (21 °C) was dried at room temperature having a pin formed on the capsule shell, formed on the first conductive capsule sheath 30 °C temperature of 30 °C in a too soon, and temperature of 55 °C in a capsule shell has been formed on the first conductive 55 °C.

On solubility in order to test a capsule in an acidic environment of the shell, wherein the first surface 0 capsule shell is unformed. 1 N HCl immersion into take place. 12 Hours at a temperature of 21 °C capsule piece is been left there. These time capsule piece 12 0. Is not dissolved in 1N HCl. These entire capsule piece 12 time 0. 1N HCl were non-protected eye are observed. Also 1a, 2a and 3a is 0. In capsule shell non - 1N HCl dissolved piece shown substrate. Room temperature is also 1a having pin on of the shell capsule prepared by the number and is exemplified piece, 1b also includes a first conductive sheath piece is exemplified and temperature of 30 °C on capsule prepared by the number, the number of the shell temperature of 55 °C 1c is also on capsule prepared by the first conductive piece is exemplified substrate.

Neutral environment of the shell capsule in order to test a solubility, 0. It pours out, within 1N HCl capsule and the capsule piece piece is 6. 8 PH of having been located in pulse the vane which will grow buffer solution (containing the resulting [thu loom monophosphate and citric acid). All capsule of the shell piece is about 60 minutes after pH 6. 8 Of buffer clear solution had been completely dissolved. Also 1b, 2b and 3b is also 1a, 2a and 3a are shown in the capsule shell of pH 6 - dissolved piece is located. 8 Part of the description and of pulse the vane which will grow buffer solution; pH 6 all pieces of the shell capsule. 8 Pulse the vane which will grow buffer solution of dissolved with each other.

In the embodiment 2 of the present invention is a cellulose ether is esterified water at a high concentration, for example, 25 wt. May be dissolved in at a concentration of -% that is exemplified substrate. A cellulose ether solution in water of the present invention is esterified fillers and ability to produce the capsule shell or coating is esterified [...] number from a cellulose ether or a cellulose ether drug solid dispersion stabilization high throughput rates effective environment-friendly and allows producing process. The esterified cellulose ether enteric properties may affect neutralizing partial would not be required disclosed. In addition, the capsules in the embodiment 2 can be negative number even at room temperature bath to exemplify the each other.

In addition, table 1 of the present invention even high concentrations of low viscosity of the cellulose ether is esterified with acetone in said example as follows. In a cellulose ether of the present invention is esterified [...] fillers and organic solvent e.g. acetone solution number ability from a cellulose ether is esterified capsule or coating to produce a cellulose ether or high throughput rates and stabilization process with which to produce the solid dispersion causes effective medication.