Hydroxypropyl methylcellulose (HPMC)
Category: coating materials; Membrane material; Speed-controlled polymer materials for slow-release preparations; Stabilizing agent; Suspension aid, tablet adhesive; Reinforced adhesion agent.
1. Product introduction
This PRODUCT IS A NON-IONIC CELLULOSE ETHER, externally observed as a white powder, odorless and tasteless, soluble in water and most polar organic solvents, swelling in cold water to clear or slightly turBIdized colloidal solution. The aqueous solution has surface activity, high transparency and stable performance. HPMC has the property of hot gel. After heating, the product aqueous solution forms gel precipitation, and then dissolves after cooling. The gel temperature of different specifications is different. Solubility changes with viscosity, viscosity zhao low, the greater the solubility, different specifications of HPMC properties have some differences, HPMC dissolved in water is not affected by pH value.
The spontaneous combustion temperature, loose density, true density and glass transition temperature were 360℃, 0.341g/cm3, 1.326g/cm3 and 170 ~ 180℃, respectively. After heating, it turns brown at 190 ~ 200 ° C and burns at 225 ~ 230 ° C.
HPMC is almost insoluble in chloroform, ethanol (95%), and diethyl ether, and dissolved in a mixture of ethanol and methylene chloride, a mixture of methanol and methylene chloride, and a mixture of water and ethanol. Some levels of HPMC are soluble in mixtures of acetone, methylene chloride, and 2-propanol, as well as in other organic solvents.
Table 1: Technical indicators
project
Gauge,
60 gd (2910).
65GD(2906)
75GD(2208)
Methoxy %
28.0-32.0
27.0-30.0
19.0-24.0
Hydroxypropoxy %
7.0-12.0
4.0-7.5
4.0-12.0
Gel temperature ℃
56-64.
62.0-68.0
70.0-90.0
Viscosity mpa s.
3,5,6,15,50,4000
50400 0
100400 0150 00100 000
Dry weight loss %
5.0 or less
Burning residue %
1.5 or less
pH
4.0-8.0
Heavy metal
20 or less
arsenic
2.0 or less
2. Product features
2.1 Hydroxypropyl methylcellulose is dissolved in cold water to form a viscous colloidal solution. As long as it is added to cold water and slightly stirred, it can be dissolved into a transparent solution. On the contrary, it is basically insoluble in hot water above 60℃ and can only swell. In the preparation of hydroxypropyl methicellulose aqueous solution, it is best to add part of hydroxypropyl methicellulose in a certain amount of water, stir vigorously, heated to 80 ~ 90℃, and then add the remaining hydroxypropyl methicellulose, and finally use cold water to supplement to the required amount.
2.2 Hydroxypropyl methylcellulose is a non-ionic cellulose ether, its solution does not carry ionic charge, does not interact with metal salts or ionic organic compounds, so as to ensure that HPMC does not react with other raw materials and excipients in the process of preparation production.
2.3 Hydroxypropyl methylcellulose has strong anti-sensitivity, and with the increase of substitution degree in molecular structure, the anti-sensitivity is also enhanced. Drugs using HPMC as excipients have more stable quality within the effective period than drugs using other traditional excipients (starch, dextrin, powdered sugar).
2.4 Hydroxypropyl methylcellulose is metabolically inert. As a pharmaceutical excipient, it is not metabolized or absorbed, so it does not provide heat in drugs and food. It has unique applicability to low calorific value, salt-free, non-allergenic drugs and food for diabetics.
2.5HPMC is relatively stable to acids and bases, but if the pH exceeds 2 ~ 11 and is affected by higher temperature or longer storage time, it will reduce the degree of ripenness.
2.6 Hydroxypropyl methylcellulose aqueous solution can provide surface activity, showing moderate surface and interfacial tension values. It has an effective emulsification in the two-phase system and can be used as an effective stabilizer and protective colloid.
2.7 Hydroxypropyl methylcellulose aqueous solution has excellent film-forming properties, and is a good coating material for tablets and pills. The membrane formed by it is colorless and tough. If glycerol is added, its plasticity can be increased. After surface treatment, the product is dispersed in cold water, and the dissolution rate can be controlled by changing the pH environment. It is used in slow-release preparations and enteric-coated preparations.
3. Product application
3.1. Used as adhesive and disintegrating agent
HPMC is used to promote the drug dissolution and the degree of release applications, can be directly dissolved in solvent as adhesive, low viscosity of HPMC dissolved in water to form transparent to ivory sticky colloid solution, tablets, pills, granules on the adhesive and disintegrating agent, and the high viscosity for glue, only use owing to the different type and different requirements, the general is 2% ~ 5%.
HPMC aqueous solution and a certain concentration of ethanol to make a composite binder; Example: 2%HPMC aqueous solution mixed with 55% ethanol solution was used for the pelleting of amoxicillin capsules, so that the average dissolution of amoxicillin capsules increased from 38% to 90% without HPMC.
HPMC can be made of composite adhesive with different concentration of starch slurry after dissolution; The dissolution of erythromycin enteric-coated tablets increased from 38.26% to 97.38% when 2% HPMC and 8% starch were combined.
2.2. Make film coating material and film forming material
HPMC as a water-soluble coating material has the following characteristics: moderate solution viscosity; The coating process is simple; Good film forming property; Can keep the shape of the piece, writing; Can be moistureproof; Can color, correction flavor. This PRODUCT IS USED AS WATER-SOLUBLE FILM COATING FOR TABLETS AND PILLS WITH LOW VISCOSITY, AND FOR NON-WATER-BASED FILM COATING WITH HIGH VISCOSITY, THE USAGE AMOUNT IS 2%-5%.
2.3, as a thickening agent and colloidal protection glue
HPMC used as thickening agent is 0.45% ~ 1.0%, can be used as eye drops and artificial tear thickening agent; Used to increase the stability of hydrophobic glue, prevent particle coalescence, precipitation, the usual dosage is 0.5% ~ 1.5%.
2.4, as a blocker, slow release material, controlled release agent and pore agent
HPMC high viscosity model is used to prepare the blockers and controlled release agents of mixed material skeleton sustained release tablets and hydrophilic gel skeleton sustained release tablets. The low-viscosity model is a pore-inducing agent for sustained-release or controlled-release tablets so that the initial therapeutic dose of such tablets is rapidly obtained, followed by sustained-release or controlled-release to maintain effective concentrations in blood.
2.5. Gel and suppository matrix
Hydrogel suppositories and gastric adhesive preparations can be prepared by using the characteristic of hydrogel formation commonly used by HPMC in water.
2.6 Biological adhesive materials
Metronidazole was mixed with HPMC and polycarboxylethylene 934 in a mixer to make bioadhesive controlled release tablets containing 250mg. In vitro dissolution test showed that the preparation rapidly swelled in water, and the drug release was controlled by diffusion and carbon chain relaxation. Animal implementation showed that the new drug release system had significant biological adhesion properties to bovine sublingual mucosa.
2.7, as suspension aid
The HIGH viscosity of this product is a good suspension aid for suspension liquid preparations, its usual dosage is 0.5% ~ 1.5%.
4. Application examples
4.1 Film coating solution: HPMC 2kg, talc 2kg, castor oil 1000ml, Twain -80 1000ml, propylene glycol 1000ml, 95% ethanol 53000ml, water 47000ml, pigment appropriate amount. There are two ways to make it.
4.1.1 Preparation of soluble pigment coated clothes liquid: Add the prescribed amount of HPMC into 95% ethanol, soak it overnight, dissolve another pigment vector in water (filter if necessary), combine the two solutions and stir evenly to form a transparent solution. Mix 80% of the solution (20% for polishing) with the prescribed amount of castor oil, Tween-80, and propylene glycol.
4.1.2 Preparation of insoluble pigment (such as iron oxide) coating liquid HPMC was soaked in 95% ethanol overnight, and water was added to make 2%HPMC transparent solution. 20% of this solution was taken out for polishing, and the remaining 80% solution and iron oxide were prepared by liquid grinding method, and then the prescription amount of other components were added and mixed evenly for use. The coating process of the coating liquid: pour the grain sheet into the sugar coating pot, after rotation, the hot air preheats to 45℃, you can spray feeding coating, flow control in 10 ~ 15ml/min, after spraying, continue to dry with hot air for 5 ~ 10min can be out of the pot, put in the dryer to dry for more than 8h.
4.2α-interferon eye membrane 50μg of α-interferon was dissolved in 10ml0.01ml hydrochloric acid, mixed with 90ml ethanol and 0.5GHPMC, filtered, coated on a rotating glass rod, sterilized at 60℃ and dried in air. This product is made into film material.
4.3 Cotrimoxazole tablets (0.4g±0.08g) SMZ (80 mesh) 40kg, starch (120 mesh) 8kg, 3%HPMC aqueous solution 18-20kg, magnesium stearate 0.3kg, TMP (80 mesh) 8kg, the preparation method is to mix SMZ and TMP, and then add starch and mix for 5min. With prefabricated 3%HPMC aqueous solution, soft material, with 16 mesh screen granulation, drying, and then with 14 mesh screen whole grain, add magnesium stearate mix, with 12mm round with word (S.M.Zco) stamping tablets. This product is mainly used as a binder. The dissolution of the tablets was 96%/20min.
4.4 Piperate tablets (0.25g) piperate 80 mesh 25kg, starch (120 mesh) 2.1kg, magnesium stearate appropriate amount. Its production method is to mix pipeoperic acid, starch, HPMC evenly, with 20% ethanol soft material, 16 mesh screen granulate, dry, and then 14 mesh screen whole grain, plus vector magnesium stearate, with 100mm circular belt word (PPA0.25) stamping tablets. With starch as disintegrating agent, the dissolution rate of this tablet is not less than 80%/2min, which is higher than similar products in Japan.
4.5 Artificial tear HPMC-4000, HPMC-4500 or HPMC-5000 0.3g, sodium chloride 0.45g, potassium chloride 0.37g, borax 0.19g, 10% ammonium chlorbenzylammonium solution 0.02ml, water added to 100ml. Its production method is HPMC placed in 15ml water, at 80 ~ 90℃ full water take a, add 35ml water, and then containing the remaining components of 40ml aqueous solution mixed evenly, add water to the full amount, then mixed evenly, stand overnight, gently pour filtration, filtrate into the container sealed, sterilized at 98 ~ 100℃ for 30min, that is, The pH ranges from 8.4 ° C to 8.6 ° C. This PRODUCT IS USED FOR TEAR DEFICIENCY, IS A GOOD SUBSTITUTE FOR TEAR, WHEN used FOR ANTERIOR chamber microscopy, can be APPROPRIATELY INCREASED THE DOSAGE OF THIS PRODUCT, 0.7% ~ 1.5% is APPROPRIATE.
4.6 Meththorphan controlled release tablets meththorphan resin salt 187.5mg, lactose 40.0mg, PVP70.0mg, vapor silica 10mg, 40.0 mGHPMC-603, 40.0mg ~ microcrystalline cellulose phthalate-102 and magnesium stearate 2.5mg. It is prepared as tablets by normal method. This product is used as controlled release material.
4.7 For avantomycin ⅳ tablets, 2149g avantomycin ⅳ monohydrate and 1000ml isopropyl water mixture of 15% (mass concentration) eudragitL-100 (9:1) were stirred, mixed, granulated, and dried at 35℃. The dried granules 575g and 62.5g hydroxypropylocellulose E-50 were thoroughly mixed, and then 7.5g stearic acid and 3.25g magnesium stearate were added to the tablets to obtain continuous release of vanguard mycin ⅳ tablets. This product is used as slow release material.
4.8 Nifedipine sustained-release granules 1 part nifedipine, 3 parts hydroxypropyl methyl cellulose and 3 parts ethyl cellulose were mixed with mixed solvent (ethanol: methylene chloride = 1:1), and 8 parts corn starch was added to produce granules by medium-soluble method. The drug release rate of the granules was not affected by the change of environmental pH and was slower than that of commercially available granules. After 12 hours of oral administration, the human blood concentration was 12mg/ml, and there was no individual difference.
4.9 Propranhaol hydrochloride sustained release capsule Propranhaol hydrochloride 60kg, microcrystalline cellulose 40kg, adding 50L water to make granules. HPMC1kg and EC 9kg were mixed in the mixed solvent (methylene chloride: methanol =1:1) 200L to make the coating solution, with a flow rate of 750ml/min spray on the rolling spherical particles, coated particles through the pore size of 1.4mm screen whole particles, and then filled into the stone capsule with ordinary capsule filling machine. Each capsule contains 160mg of propranolol hydrochloride spherical particles.
4.10 Naprolol HCL skeleton tablets were prepared by mixing naprolol HCL :HPMC: CMC-NA at the ratio of 1:0.25:2.25. The drug release rate was close to zero order within 12 hours.
Other drugs can also be made of mixed skeleton materials, such as metoprolol: HPMC: CMC-NA according to: 1:1.25:1.25; Allylprolol :HPMC according to 1:2.8:2.92 ratio. The drug release rate was close to zero order within 12 hours.
4.11 Skeleton tablets of mixed materials of ethylaminosine derivatives were prepared by normal method using a mixture of micro powder silica gel: CMC-NA :HPMC 1:0.7:4.4. The drug could be released for 12h both in vitro and in vivo, and the linear release pattern had a good correlation. The results of the accelerated stability test according to FDA regulations predict that the storage life of this product is up to 2 years.
4.12 HPMC (50mPa·s) (5 parts), HPMC (4000 mPa·s) (3 parts) and HPC1 were dissolved in 1000 parts of water, 60 parts acetaminophen and 6 parts silica gel were added, stirred with a homogenizer, and spray dried. This product contains 80% of main medicine.
4.13 Theophylline hydrophilic gel skeleton tablets were calculated according to the total tablet weight, 18%-35% theophylline, 7.5%-22.5% HPMC, 0.5% lactose, and an appropriate amount of hydrophobic lubricant were normally prepared into controlled release tablets, which could maintain the effective blood concentration of human body for 12h after oral administration.
Post time: Sep-20-2022