CN111840227B - Oral emulsion of tromethamine and its preparation method - Google Patents
Oral emulsion of tromethamine and its preparation method Download PDFInfo
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Abstract
The invention discloses an oral emulsion of paracetamol and tramadol, which is an oil-in-water emulsion formed by uniformly dispersing an oil solution of paracetamol in an aqueous solution of tramadol hydrochloride; the invention also discloses a preparation method of the oral emulsion of the tromethamine, which comprises the steps of adding the oil phase solution containing the paracetamol into the mixed solution containing the starch sodium octenyl succinate emulsifier, and then adding the mixed solution into the water phase solution containing the tramadol hydrochloride for homogenization. According to the invention, the acetaminophen is coated in the emulsion, so that the degradation and oxidation of the acetaminophen are avoided, the bitter taste of the acetaminophen is covered, the covering effect of the covering agent and the flavoring agent and the cross-linking effect of other components are combined, the bitter taste of tramadol hydrochloride is covered, the stability of the oral emulsion of tramadol hydrochloride is improved, the mouthfeel of the oral emulsion of tramadol hydrochloride is improved, and the bioavailability of the oral emulsion of tramadol hydrochloride is improved; the invention adopts an emulsification coating method to prepare the stable oil-in-water type oral emulsion of the aminophenol tramadol, and the process is simple.
Description
Technical Field
The invention belongs to the technical field of medicines, and particularly relates to an oral emulsion of tromethamine and a preparation method thereof.
Background
In the medication guideline of FDA (united states food and drug administration), the compound combination of nonsteroidal anti-inflammatory analgesic drugs and opioid receptor agonist antagonist analgesic drugs is the development direction of clinical analgesic drugs at present, tramadol hydrochloride is the commonly used opioid receptor agonist analgesic drug, acetaminophen is the nonsteroidal anti-inflammatory analgesic drug, and is commonly used for treating limb pain, headache, fever, and the like caused by cold, the combination of the two has the characteristics of enhancing the analgesic effect and reducing the side effects of the drugs, and is a classic compound preparation combined analgesic drug, and at present, the preparation forms using the combination of acetaminophen (aminophenol) and tramadol hydrochloride (tramadol) as the main drugs include compound oral tablets, chewable tablets, capsules and oral liquids. When pain attacks caused by diseases, particularly acute pain attacks, pain is urgently required to be relieved by using analgesic medicines with quick response, at the moment, the clinical requirements can be quickly met by injecting the analgesic medicines into veins or muscles, the analgesic effect of the oral solid preparation of the analgesic medicines is slow, and the oral solid preparation of the analgesic medicines is used as an oral liquid preparation of the analgesic medicines, has the analgesic effect which is faster than that of the oral solid preparation of the analgesic medicines and slower than that of an injection, and is a good choice when patients suffering from pain who have difficulty in swallowing the oral solid preparation and are inconvenient to take injection at home need to take the medicines for analgesia more quickly. In the patent with the publication number of CN110115708A, glycerin (or propylene glycol), polyethylene glycol and water are used as a mixed solvent system to dissolve the amitraz tramadol into the mixed solvent system to prepare the oral liquid, which solves the problem that some patients have difficulty swallowing common oral solid preparations, but the water in the oral liquid accounts for 39-49% or 39-59%, and because acetaminophen is not a very stable compound, it can be hydrolyzed to generate acetic acid, aminophenol and some oxidation impurities after being placed in an aqueous environment for a long time, resulting in reduced drug effect and increased toxic and side effects of the drug. Therefore, how to solve the problem of drug degradation and keep the drug stable is an important technical problem to be solved by the oral liquid of the tromethamine; meanwhile, aiming at the bitter taste of the tromethamine, the oral liquid system adopts polyethylene glycol coating and a flavoring agent to jointly mask the taste, but the oral liquid is a uniform solution formed by dissolving the tramadol, so the flavoring agent and the polyethylene glycol can only partially mask the bitter taste of the tramadol. In addition, the patent does not mention the use of bacteriostatic preservatives, so that the oral solution preparation of the tromethamine prepared by using glycerin (or propylene glycol), polyethylene glycol and water as a mixed solvent system and adding a flavoring agent can grow bacteria and go bad during the placement process.
Disclosure of Invention
The technical problem to be solved by the present invention is to provide an oral emulsion of tromethamine. The oral emulsion of the tramadol amitraz is an oil-in-water emulsion, and the acetaminophen is coated in the emulsion, so that the degradation and oxidation of the acetaminophen are avoided, the bitter taste of the acetaminophen is covered, and meanwhile, the covering effect of the covering agent and the flavoring agent and the cross-linking effect of other components and tramadol hydrochloride are combined, the bitter taste of the tramadol hydrochloride is covered in an assisting manner, the stability of the oral emulsion of the tramadol amitraz is improved, and the mouthfeel of the oral emulsion of the tramadol amitraz is improved.
In order to solve the technical problems, the invention adopts the technical scheme that: the oral emulsion of the tromethamine is characterized in that the oral emulsion of the tramadol is an oil-in-water emulsion formed by uniformly dispersing an oil solution of acetaminophen in an aqueous solution of tramadol hydrochloride, the pH value is 6.5-7.5, and the oral emulsion of the tramadol is composed of the following components in percentage by mass: 3.09-3.41 percent of acetaminophen, 0.357-0.394 percent of tramadol hydrochloride, 12.5-13.5 percent of soybean oil, 4002 percent of polyethylene glycol, 0.96-1.05 percent of vitamin E, 0.96-1.05 percent of sodium starch octenyl succinate, 0.097-0.103 percent of potassium cinnamate, 1.17-1.22 percent of xanthan gum, 0.294-0.305 percent of carbomer, 0.5 percent of flavoring agent, 1 percent of oligosaccharide and 75.47-77.07 percent of purified water.
The oral emulsion of the invention is an oil-in-water emulsion of an oil solution of which the water solution of tramadol hydrochloride is emulsified and coated with p-acetaminophenol, wherein sodium starch octenylsuccinate and potassium cinnamate are used as an emulsifier and a stabilizer, so that the formation of the oil-in-water emulsion is effectively ensured, p-acetaminophenol is coated in the emulsion, the contact of the p-acetaminophenol and external phase water is isolated, the degradation and oxidation of p-acetaminophenol are avoided, the stability problem of p-acetaminophenol is solved, and the bitter taste of p-acetaminophenol is covered; meanwhile, the polyethylene glycol 400 in the oral emulsion of the tramadol amnol has the function of masking taste, the bitter taste of the tramadol hydrochloride is masked by combining with the flavoring agents of sucralose and stachyose, polycarboxyl and polyhydroxy in carbomer, xanthan gum, stachyose and polyethylene glycol are mutually crosslinked through hydrogen bonds, and the carboxyl and the hydroxyl are simultaneously crosslinked with the hydroxyl and methylamino in the tramadol hydrochloride, so that the effect of masking the bitter taste of the tramadol amnol is enhanced, and the taste of the oral emulsion of the tramadol amnol can be completely accepted by patients.
The specification of the oral solid preparation of the clinical paracetamol tramadol is that each tablet contains 37.5mg of paracetamol and 325mg of tramadol, the weight of the tablet is 500mg, 1-2 tablets are taken every 4-6 hours, and the maximum dose of the oral solid preparation is not more than 6 tablets every day, so that the oral solid preparation is used for short-term (5 days or shorter) treatment of moderate-to-severe acute pain. The compound preparation of the oral emulsion of the invention is prepared by taking the specifications of the clinically existing oral solid preparation as the basis, designing and preparing a prescription on the premise of not changing the dosage and the administration route, wherein the design specification is that each bottle contains 37.5mg of acetaminophen and 325mg of tramadol, the total weight of the content in the bottle is 10g, and the using method is that 1-2 bottles are taken every 4-6 h, and the number of the bottles is not more than 6 at most every day, so that the compound preparation is used for short-term (5 days or shorter) treatment of moderate-severe acute pain. The oral emulsion of the invention overcomes the difficulty that part of patients swallow solid preparations for taking medicines, solves the technical problems of degradation and oxidation of acetaminophen, bitterness of the tramadol and easy decay and deterioration in the placement process in the existing oral liquid of the tramadol, provides more convenient medication selection for patients to relieve pain, and is a more advanced oral liquid preparation.
The auxiliary materials adopted in the invention are soybean oil, polyethylene glycol 400, vitamin E, sodium starch octenylsuccinate, potassium cinnamate, xanthan gum, carbomer, flavoring agent and oligosaccharide which are all medicinal grade or food grade, wherein the soybean oil is a refined natural product and is a mixture of triglyceride containing polyunsaturated fatty acid and medium-chain triglyceride, namely triglyceride of caprylic acid and capric acid.
The oral amiloride tramadol emulsion is characterized in that the carbomer is carbomer 940 or carbomer 980.
The oral amitraz emulsion is characterized in that the flavoring agent is sucralose, dipotassium glycyrrhizinate or aspartame.
The oral amitraz emulsion is characterized in that the flavoring agent is sucralose.
The oral emulsion of the tromethamine is characterized in that the oligosaccharide is stachyose or xylooligosaccharide.
The oral emulsion of the tramadol amodiase is characterized in that the oligosaccharide is stachyose.
In addition, the invention also provides a method for preparing the oral emulsion of the amisol tramadol, which is characterized by comprising the following steps:
step one, adding sodium starch octenyl succinate, xanthan gum and carbomer into purified water at the temperature of 25-35 ℃, stirring and dissolving, and cooling to room temperature to obtain a uniform and semitransparent mixed solution;
step two, sequentially adding potassium cinnamate, oligosaccharide, a flavoring agent, polyethylene glycol 400 and tramadol hydrochloride into purified water, and stirring for dissolving to obtain a water-phase solution;
adding acetaminophen into the mixed oil of vitamin E and soybean oil, shearing and stirring to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the water phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 4-5 times to obtain the oral emulsion of the tromethamine.
The invention adopts an emulsification wrapping method, firstly, emulsifier sodium starch octenyl succinate, auxiliary emulsifier, suspending agent xanthan gum and carbomer are added into purified water to form a mixed solution, namely emulsifier solution, main drug paracetamol is dissolved into a mixed oil solvent of vitamin E and soybean oil to obtain oil phase solution, main drug tramadol hydrochloride, auxiliary emulsifier, stabilizer, bacteriostatic preservative potassium cinnamate, flavoring agent stachyose, sucralose and flavor masking polyethylene glycol 400 are added into the purified water to form water phase solution, then the oil phase solution is added into the emulsifier solution to form crude emulsion, then the crude emulsion is added into the water phase solution to be stirred, the emulsifier greatly reduces the tension of an oil/water interface, so that the oil phase solution is sheared, stirred and dispersed into small liquid drops which are uniformly distributed in the water phase solution, and then the oil-in-water system is formed by circulating homogenization, preparing oil-in-water (O/W) oral emulsion of tramadol amonmate.
Compared with the prior art, the invention has the following advantages:
1. the oral emulsion of the invention is oil-in-water emulsion, and the paracetamol is coated in the emulsion, so that the contact between the paracetamol and external phase water is isolated, the degradation and oxidation of the paracetamol are avoided, the stability problem of the paracetamol is solved, and the bitter taste of the paracetamol is covered; meanwhile, the taste masking agent polyethylene glycol 400 in the oral emulsion of the tramadol amonmate, the flavoring agents sucralose and stachyose are combined to mask the bitter taste of the tramadol hydrochloride, and the polycarboxyl and polyhydroxy in the carbomer, the xanthan gum, the oligosaccharide and the polyethylene glycol are mutually crossed through hydrogen bonds and have cross-linking effect with the hydroxyl and methylamino in the tramadol hydrochloride, so that the effect of masking the bitter taste of the tramadol hydrochloride is enhanced, and the taste of the oral emulsion of the tramadol amonmate is improved.
2. The oily solvent component vitamin E in the oral emulsion of the invention also serves as an antioxidant to ensure that the acetaminophen is prevented from being oxidized and degraded, the flavoring agent stachyose also serves as a prebiotic, probiotics in intestinal tracts can be rapidly propagated after oral administration, and micromolecular organic acid is generated by degradation to promote small intestine peristalsis, so that the side effect of constipation caused by taking the oral emulsion of the amitradol is greatly relieved, and the potassium cinnamate serves as an emulsion stabilizer and a bacteriostatic agent, so that the stability of the oral emulsion of the amitradol is enhanced, the putrefaction caused by breeding of bacteria is prevented, and the shelf life of the oral emulsion of the amitra is prolonged.
3. The soybean oil and the vitamin E in the oral emulsion of the invention also have certain fat emulsion nutritive value as fat-soluble solvents, thus providing nutrition for human body.
4. The pH value of the oral emulsion of the invention is 6.5-7.5, which is basically consistent with the pH value of human intestinal tract, so the oral emulsion is easy to be transmitted to absorption parts through a hydration layer of the gastrointestinal wall after being taken, overcomes the first pass effect of the medicament to a certain extent, is widely distributed in various places of the gastrointestinal tract, is easier to be absorbed by the intestinal tract while being absorbed by the stomach, and improves the bioavailability.
5. Compared with common tablets, capsule preparations, chewable tablets and other dosage forms, the oral emulsion of the invention overcomes the defect that part of patients are difficult to swallow by taking common solid preparations, and has almost no bitter taste, good mouthfeel, easy administration and quick response.
6. The invention adopts an emulsification wrapping method, under the action of an emulsifier, an oil phase solution is uniformly dispersed and uniformly distributed in an aqueous phase solution, and simultaneously, the xanthan gum and carbomer are combined to thicken and float to form a stable oil-in-water type system, so that the oil-in-water (O/W) oral emulsion of the tromethamine is prepared.
The technical solution of the present invention is further described in detail by examples below.
Detailed Description
Example 1
The oral emulsion of the tromethamine hydrochloride of the present embodiment is an oil-in-water emulsion in which an oil solution of acetaminophen is uniformly dispersed in an aqueous solution of tramadol hydrochloride, and the pH of the emulsion is 7.0, and the oral emulsion of the tramadol hydrochloride comprises the following components by mass percent: 3.25% of acetaminophen, 0.375% of tramadol hydrochloride, 13% of soybean oil, 4002% of polyethylene glycol, 1% of vitamin E, 1% of starch sodium octenylsuccinate, 0.1% of potassium cinnamate, 1.2% of xanthan gum, 9400.3% of carbomer, 0.5% of sucralose, 1% of stachyose and 76.275% of purified water.
The preparation method of the oral emulsion of the amisol tramadol of the embodiment comprises the following steps:
step one, 100g of sodium starch octenylsuccinate, 120g of xanthan gum and 30g of carbomer 940 are added into 6000g of purified water at the temperature of 25-35 ℃ and stirred to be dissolved, and a uniform and semitransparent mixed solution is obtained after the mixture is cooled to room temperature;
step two, sequentially adding 10g of potassium cinnamate, 100g of stachyose, 50g of sucralose, 200g of polyethylene glycol 400 and 37.5g of tramadol hydrochloride into 1627.5g of purified water, and stirring for dissolving to obtain an aqueous phase solution;
step three, adding 325g of acetaminophen into mixed oil of 100g of vitamin E and 1300g of soybean oil, and shearing and stirring at the speed of 1200r/min to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring at a speed of 1500r/min until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the aqueous phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 4 times to obtain 10000g of the oral emulsion of the aminophenol tramadol.
The oral emulsion of tramadol amodiae prepared in this example was divided into 950 bottles to obtain 10 g/bottle of oral emulsion of tramadol amodiae.
Example 2
The oral emulsion of the tromethamine hydrochloride of the present embodiment is an oil-in-water emulsion in which an oil solution of acetaminophen is uniformly dispersed in an aqueous solution of tramadol hydrochloride, and the pH of the emulsion is 6.95, and the oral emulsion of the tramadol hydrochloride comprises the following components by mass percent: 3.41% of acetaminophen, 0.394% of tramadol hydrochloride, 13.5% of soybean oil, 4002% of polyethylene glycol, 1.05% of vitamin E, 1.05% of sodium starch octenylsuccinate, 0.103% of potassium cinnamate, 1.22% of xanthan gum, 9400.305% of carbomer, 0.5% of sucralose, 1% of stachyose and 75.468% of purified water.
The preparation method of the oral emulsion of the amisol tramadol of the embodiment comprises the following steps:
step one, adding 105g of sodium starch octenyl succinate, 122g of xanthan gum and 30.5g of carbomer 940 into 6000g of purified water at the temperature of 25-35 ℃, stirring and dissolving, and cooling to room temperature to obtain a uniform and semitransparent mixed solution;
step two, sequentially adding 10.3g of potassium cinnamate, 100g of stachyose, 50g of sucralose, 200g of polyethylene glycol 400 and 39.4g of tramadol hydrochloride into 1546.8g of purified water, stirring and dissolving to obtain an aqueous phase solution;
step three, adding 341g of acetaminophen into mixed oil of 105g of vitamin E and 1350g of soybean oil, and shearing and stirring at the speed of 1200r/min to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring at a speed of 1500r/min until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the aqueous phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 5 times to obtain 10000g of the oral emulsion of the aminophenol tramadol.
The oral emulsion of tramadol amodiae prepared in this example was divided into 950 bottles to obtain 10 g/bottle of oral emulsion of tramadol amodiae.
Example 3
The oral emulsion of the tromethamine hydrochloride of the present embodiment is an oil-in-water emulsion in which an oil solution of acetaminophen is uniformly dispersed in an aqueous solution of tramadol hydrochloride, and the pH of the emulsion is 7.0, and the oral emulsion of the tramadol hydrochloride comprises the following components by mass percent: 3.095% of acetaminophen, 0.357% of tramadol hydrochloride, 12.5% of soybean oil, 4002% of polyethylene glycol, 0.96% of vitamin E, 0.96% of sodium starch octenyl succinate, 0.097% of potassium cinnamate, 1.17% of xanthan gum, 9400.294% of carbomer, 0.5% of sucralose, 1% of stachyose and 77.067% of purified water.
The preparation method of the oral emulsion of the amisol tramadol of the embodiment comprises the following steps:
step one, adding 96g of sodium starch octenyl succinate, 117g of xanthan gum and 29.4g of carbomer 940 into 6100.5g of purified water at the temperature of 25-35 ℃, stirring and dissolving, and cooling to room temperature to obtain a uniform and semitransparent mixed solution;
step two, sequentially adding 9.7g of potassium cinnamate, 100g of stachyose, 50g of sucralose, 200g of polyethylene glycol 400 and 35.7 g of tramadol hydrochloride into 1606.7g of purified water, and stirring for dissolving to obtain an aqueous phase solution;
step three, adding 309g of acetaminophen into mixed oil of 96g of vitamin E and 1250g of soybean oil, and shearing and stirring at the speed of 1200r/min to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring at a speed of 1500r/min until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the aqueous phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 4 times to obtain 10000g of the oral emulsion of the aminophenol tramadol.
The oral emulsion of tramadol amodiae prepared in this example was divided into 950 bottles to obtain 10 g/bottle of oral emulsion of tramadol amodiae.
Example 4
The oral emulsion of the tromethamine hydrochloride of the present embodiment is an oil-in-water emulsion in which an oil solution of acetaminophen is uniformly dispersed in an aqueous solution of tramadol hydrochloride, and the pH of the emulsion is 7.1, and the oral emulsion of the tramadol hydrochloride comprises the following components by mass percent: 3.19% of acetaminophen, 0.368% of tramadol hydrochloride, 12.74% of soybean oil, 4002% of polyethylene glycol, 0.98% of vitamin E, 0.98% of sodium starch octenylsuccinate, 0.098% of potassium cinnamate, 1.18% of xanthan gum, 9400.296% of carbomer, 0.5% of sucralose, 1% of stachyose and 76.668% of purified water.
The preparation method of the oral emulsion of the amisol tramadol of the embodiment comprises the following steps:
step one, adding 98g of sodium starch octenylsuccinate, 118g of xanthan gum and 29.6g of carbomer 940 into 6050g of purified water at the temperature of 25-35 ℃, stirring and dissolving, and cooling to room temperature to obtain a uniform and semitransparent mixed solution;
step two, sequentially adding 9.8g of potassium cinnamate, 100g of stachyose, 50g of sucralose, 200g of polyethylene glycol 400 and 36.8g of tramadol hydrochloride into 1616.8g of purified water, stirring and dissolving to obtain an aqueous phase solution;
step three, adding 319g of acetaminophen into mixed oil of 98g of vitamin E and 1274g of soybean oil, and shearing and stirring at the speed of 1300r/min to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring at a speed of 1450r/min until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the aqueous phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 4 times to obtain 10000g of the oral emulsion of the aminophenol tramadol.
The oral emulsion of tramadol amodiae prepared in this example was divided into 950 bottles to obtain 10 g/bottle of oral emulsion of tramadol amodiae.
Example 5
The oral emulsion of the tromethamine hydrochloride of the present embodiment is an oil-in-water emulsion in which an oil solution of acetaminophen is uniformly dispersed in an aqueous solution of tramadol hydrochloride, and the pH of the emulsion is 7.1, and the oral emulsion of the tramadol hydrochloride comprises the following components by mass percent: 3.32% of acetaminophen, 0.383% of tramadol hydrochloride, 13.26% of soybean oil, 4002% of polyethylene glycol, 1.02% of vitamin E, 1.02% of sodium starch octenylsuccinate, 0.101% of potassium cinnamate, 1.215% of xanthan gum, 9400.307% of carbomer, 0.5% of sucralose, 1% of stachyose and 75.874% of purified water.
The preparation method of the oral emulsion of the amisol tramadol of the embodiment comprises the following steps:
step one, 102g of sodium starch octenyl succinate, 122.5g of xanthan gum and 30.7g of carbomer 940 are added into 6099g of purified water at the temperature of 25-35 ℃ and stirred for dissolution, and the mixture is cooled to room temperature to obtain a uniform and semitransparent mixed solution;
step two, sequentially adding 10.1g of potassium cinnamate, 100g of stachyose, 50g of sucralose, 200g of polyethylene glycol 400 and 38.3g of tramadol hydrochloride into 1487.4g of purified water, stirring and dissolving to obtain an aqueous phase solution;
step three, adding 332g of acetaminophen into mixed oil of 102g of vitamin E and 1326g of soybean oil, and shearing and stirring at a speed of 1250r/min to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring at a speed of 1500r/min until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the aqueous phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 5 times to obtain 10000g of the oral emulsion of the aminophenol tramadol.
The oral emulsion of tramadol amodiae prepared in this example was divided into 950 bottles to obtain 10 g/bottle of oral emulsion of tramadol amodiae.
In the embodiments 1 to 5 of the present invention, carbomer 940 in the oral emulsion of the aminophenol tramadol may be replaced by carbomer 980, sucralose as a flavoring agent may be replaced by dipotassium glycyrrhizinate or aspartame, and stachyose as an oligosaccharide may be replaced by xylo-oligosaccharide.
In addition, the pH range of the oral amitraz emulsion in the embodiments 1 to 5 can be expanded to 6.5 to 7.5.
The above description is only for the preferred embodiment of the present invention, and is not intended to limit the present invention in any way. Any simple modification, change and equivalent changes of the above embodiments according to the technical essence of the invention are still within the protection scope of the technical solution of the invention.
Claims (7)
1. The oral emulsion of the tromethamine is characterized in that the oral emulsion of the tramadol is an oil-in-water emulsion formed by uniformly dispersing an oil solution of acetaminophen in an aqueous solution of tramadol hydrochloride, the pH value is 6.5-7.5, and the oral emulsion of the tramadol is composed of the following components in percentage by mass: 3.09-3.41 percent of acetaminophen, 0.357-0.394 percent of tramadol hydrochloride, 12.5-13.5 percent of soybean oil, 4002 percent of polyethylene glycol, 0.96-1.05 percent of vitamin E, 0.96-1.05 percent of sodium starch octenyl succinate, 0.097-0.103 percent of potassium cinnamate, 1.17-1.22 percent of xanthan gum, 0.294-0.305 percent of carbomer, 0.5 percent of flavoring agent, 1 percent of oligosaccharide and 75.47-77.07 percent of purified water.
2. The oral emulsion of claim 1, wherein the carbomer is carbomer 940 or carbomer 980.
3. The oral emulsion of claim 1, wherein the flavoring agent is sucralose, dipotassium glycyrrhizinate, or aspartame.
4. The oral emulsion of claim 3, wherein the flavoring agent is sucralose.
5. The oral emulsion of claim 1, wherein the oligosaccharide is stachyose or xylo-oligosaccharide.
6. The oral emulsion of claim 5, wherein the oligosaccharide is stachyose.
7. A process for the preparation of an oral emulsion of the aminophenol tramadol according to any one of claims 1 to 6, comprising the steps of:
step one, adding sodium starch octenyl succinate, xanthan gum and carbomer into purified water at the temperature of 25-35 ℃, stirring and dissolving, and cooling to room temperature to obtain a uniform and semitransparent mixed solution;
step two, sequentially adding potassium cinnamate, oligosaccharide, a flavoring agent, polyethylene glycol 400 and tramadol hydrochloride into purified water, and stirring for dissolving to obtain a water-phase solution;
adding acetaminophen into the mixed oil of vitamin E and soybean oil, shearing and stirring to obtain an oil phase solution;
step four, under the conditions of stirring and nitrogen protection, slowly adding the oil phase solution obtained in the step three into the mixed solution obtained in the step one at a constant speed, and then shearing and stirring until a uniform coarse emulsion is formed;
and step five, slowly adding the crude emulsion obtained in the step four into the water phase solution obtained in the step two at a constant speed under the stirring condition, then stirring to form uniform emulsion, transferring the emulsion into a circulating nano sand mill homogenizer for circulating and homogenizing for 4-5 times to obtain the oral emulsion of the tromethamine.
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Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3326651A1 (en) * | 2016-11-23 | 2018-05-30 | Bora Pharmaceuticals Co., Ltd. | Acetaminophen and tramadol compound oral solution |
| US20180286505A1 (en) * | 2017-04-04 | 2018-10-04 | Children's Hospital Medical Center | Drug dosage alerts and related methods and media |
| WO2019174755A1 (en) * | 2018-03-14 | 2019-09-19 | Laboserve Pharmaceutical Company S.A. | Oral solutions comprising tramadol and acetaminophen |
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| DE102010015143A1 (en) * | 2010-04-16 | 2011-10-20 | Cts Chemical Industries Ltd. | Stable liquid oily ready-to-use formulations, preparation thereof and use thereof |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP3326651A1 (en) * | 2016-11-23 | 2018-05-30 | Bora Pharmaceuticals Co., Ltd. | Acetaminophen and tramadol compound oral solution |
| US20180286505A1 (en) * | 2017-04-04 | 2018-10-04 | Children's Hospital Medical Center | Drug dosage alerts and related methods and media |
| WO2019174755A1 (en) * | 2018-03-14 | 2019-09-19 | Laboserve Pharmaceutical Company S.A. | Oral solutions comprising tramadol and acetaminophen |
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