CN113081996A - Simvastatin capsule and preparation method thereof - Google Patents
Simvastatin capsule and preparation method thereof Download PDFInfo
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- CN113081996A CN113081996A CN202110353800.1A CN202110353800A CN113081996A CN 113081996 A CN113081996 A CN 113081996A CN 202110353800 A CN202110353800 A CN 202110353800A CN 113081996 A CN113081996 A CN 113081996A
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Abstract
The application discloses a preparation method of a simvastatin capsule and the simvastatin capsule. Selecting simvastatin mixture particles with the particle size of less than 20 meshes, respectively limiting the content of the simvastatin mixture particles with the particle size range of 20-60 meshes, and facilitating dissolution in a human body, so that long-term stable dissolution of the capsule in the human body is guaranteed, adding auxiliary materials of croscarmellose sodium, silicon dioxide and magnesium stearate which are sieved by a 60-mesh sieve, adding the simvastatin mixture particles, the croscarmellose sodium, the silicon dioxide, the magnesium stearate and the simvastatin mixture particles into a mixer in sequence for mixing, facilitating acceleration of dissolution of simvastatin, and guaranteeing high dissolution rate of simvastatin. Therefore, the dissolution rate of the simvastatin capsule can be improved by selecting proper auxiliary materials and adjusting the placing sequence and mixing time of the medicinal materials, the simvastatin capsule with high dissolution rate is prepared, and the technical problem of low dissolution rate of the existing simvastatin capsule is solved.
Description
Technical Field
The application relates to the technical field of medicines, in particular to a simvastatin capsule and a preparation method thereof.
Background
With the continuous development of society, the living standard and working rhythm of people are increasing, patients with cardiovascular and cerebrovascular diseases are increasing, and the cardiovascular and cerebrovascular diseases are also called "hypertension, hyperlipidemia and hyperglycemia" of "riches and honour disease", which refer to diseases of heart ischemia or hemorrhage caused by the sclerosis of heart and artery blood vessels, and comprise symptoms of coronary heart disease, angina pectoris, hypertension, arrhythmia, myocardial infarction, cerebral infarction and the like. Cardiovascular and cerebrovascular diseases are always threatening the health of human beings, and hypertension, hyperlipidemia, coronary heart disease and diabetes become epidemic of the times.
According to statistics, 40-45% of people over 60 years old suffer from hypertension and hyperglycemia or hyperlipidemia, and about 50% of diabetes patients are complicated with various senile diseases such as hypertension and hyperlipidemia. The cardiovascular and cerebrovascular diseases have the characteristics of high morbidity, high disability rate, high mortality, high recurrence rate and more complications, namely high morbidity, high morbidity and high mortality, the first onset age of patients with the cardiovascular and cerebrovascular diseases is below 60 years old, the morbidity of the patients with the cardiovascular and cerebrovascular diseases is 13.6 percent, and the patients with the cardiovascular and cerebrovascular diseases are gradually increased at the speed of twenty thousand persons every day; the death rate is up to 45 percent and accounts for 50 percent of the total death number; the disability rate of patients with cerebral apoplexy is up to 75 percent, and patients with coronary heart disease become half-labor; the recurrence rate is high and the recurrence rate of cardiovascular and cerebrovascular diseases (myocardial infarction and cerebral infarction) is as high as 42 percent within five years; many diseases of respiratory system, digestive system, urinary system, etc. are caused by cardiovascular and cerebrovascular accidents. Hyperlipidemia is one of representative diseases of cardiovascular and cerebrovascular diseases.
Hyperlipidemia is a common disease, and is a high incidence among the middle-aged and elderly people, and in recent years, the disease begins to be "favored" by a young white-collar family. The blood fat is too high, which easily causes 'blood viscosity', deposits on the vessel wall and forms atherosclerosis. These deposits build up and grow, gradually blocking the blood vessels, slowing blood flow, and in severe cases, blood flow is interrupted. This condition, if it occurs in the heart, causes coronary heart disease; if it occurs in the kidney, it causes renal arteriosclerosis and renal failure; when it occurs in the lower limbs, symptoms such as necrosis and ulceration of the limbs occur. In addition, hyperlipidemia can cause hypertension, induce gallstone and pancreatitis, and aggravate hepatitis, leading to male sexual dysfunction and senile dementia. Therefore, hyperlipidemia is not only a little higher problem of blood lipid, and its severity cannot be ignored absolutely.
Simvastatin is an HMG-COA (β -hydroxy and β -methyl-glutaryl-COA) reductase inhibitor that reduces cholesterol biosynthesis and regulates blood lipids by competitively inhibiting an early rate-limiting enzyme (HMG-COA reductase) in cholesterol anabolism. Simvastatin can reduce the content of Total Cholesterol (TC), low-density lipoprotein (LDL-C) and very low-density lipoprotein cholesterol (VLDC-C), slightly increase high-density lipoprotein cholesterol (HDL-C) and reduce plasma Triglyceride (TG), simvastatin has high selectivity to liver after being orally taken, the concentration of simvastatin in liver is obviously higher than that of other non-target tissues, most of simvastatin is absorbed by liver tissues and converted into an active metabolite, namely an e-hydroxy acid structure, can reduce the synthesis of liver cholesterol and regulate low-density lipoprotein receptor, promotes the clearance of low-density lipoprotein to reduce the level of intracellular cholesterol, reduces the level of moderate serum triglyceride and increases the level of blood high-density lipoprotein, and mainly plays a role in the liver and is then excreted from bile. Simvastatin has the advantages of strong pertinence, obvious curative effect, small toxic and side effects, good tolerance and the like, and is one of the best medicines for treating hypercholesterolemia.
Currently, the simvastatin capsule sold in the market has the problem of large individual dissolution difference, the auxiliary material is magnesium stearate which is used as a lubricant, and due to the hydrophobic property of the magnesium stearate, the dissolution rate of the simvastatin capsule can be reduced, so that the requirement of people cannot be met.
Disclosure of Invention
The embodiment of the application provides a preparation method of a simvastatin capsule, which is used for solving the technical problems that the existing simvastatin capsule has large individual dissolution rate difference, influences the dissolution rate of the simvastatin capsule and can not meet the requirements of people.
In view of the above, the present application provides a method for preparing simvastatin capsules, comprising the steps of:
s1: preparing an adhesive, namely dissolving hydroxypropyl methylcellulose with a formula amount into an ethanol solution to prepare a hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: simvastatin, and the auxiliary materials comprise: croscarmellose sodium, silicon dioxide and magnesium stearate;
s3: sieving, and respectively sieving adjuvants including croscarmellose sodium, silicon dioxide and magnesium stearate with 60 mesh sieve;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, granulating through a 0.8mm screen to obtain simvastatin mixture particles, sucking the prepared simvastatin mixture particles into a ternary rotary vibration sieve through a vacuum feeding machine, removing coarse particles through a 20-mesh screen, removing fine particles through a 60-mesh screen, repeatedly finishing coarse particles, and collecting heavy powder particles;
s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 10-30 minutes, and mixing at a constant speed to obtain an intermediate product;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, and generating a production instruction according to the filling amount to control a full-automatic capsule filling machine to prepare the simvastatin capsule.
Optionally, the mass concentration of the ethanol solution is 45-55%, and the mass concentration of the hydroxypropyl methyl cellulose ethanol solution adhesive is 1.5-2.5%.
Optionally, the temperature of sieving, weighing, dosing, granulating, mixing, filling and packaging is 18 ℃ to 26 ℃.
Optionally, the humidity of sieving, weighing, dosing, granulating, mixing, filling and packaging is 45-65%.
Optionally, in step S5, the pressure of the dry granulator is 8 to 10MPa, and the gap between the rollers is 0.6 to 0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min.
Optionally, in step S6, the raw and auxiliary materials are added to the mixer in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate, and simvastatin mixture granules, and the mixing time is set to 10-25 minutes.
Optionally, in step S6, the raw and auxiliary materials are added to the mixer in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate, and simvastatin mixture granules, and the mixing time is set to 10-20 minutes.
Optionally, in step S8, the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute.
Optionally, the method further comprises the following steps:
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
On the other hand, the invention also provides a simvastatin capsule prepared by the preparation method of the simvastatin capsule, which comprises the following components in parts by weight:
according to the technical scheme, the embodiment of the application has the following advantages:
the application provides a preparation method of a simvastatin capsule, which comprises the following steps: s1: preparing an adhesive, namely dissolving hydroxypropyl methylcellulose with a formula amount into an ethanol solution to prepare a hydroxypropyl methylcellulose ethanol solution adhesive; s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: simvastatin, and the auxiliary materials comprise: croscarmellose sodium, silicon dioxide and magnesium stearate; s3: sieving, and respectively sieving adjuvants including croscarmellose sodium, silicon dioxide and magnesium stearate with 60 mesh sieve; s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking; s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, granulating through a 0.8mm screen to obtain simvastatin mixture particles, sucking the prepared simvastatin mixture particles into a ternary rotary vibration sieve through a vacuum feeding machine, removing coarse particles through a 20-mesh screen, removing fine particles through a 60-mesh screen, repeatedly finishing coarse particles, and collecting heavy powder particles; s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 10-30 minutes, and mixing at a constant speed to obtain an intermediate product; s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified; s8: filling, and generating a production instruction according to the filling amount to control a full-automatic capsule filling machine to prepare the simvastatin capsule.
The simvastatin capsule provided by the application comprises the following components in parts by weight: 10-80 parts of simvastatin, 5-15 parts of croscarmellose sodium, 2-7 parts of silicon dioxide, 3-9 parts of magnesium stearate and 10-18 parts of hydroxypropyl methylcellulose.
The application provides a preparation method of simvastatin capsules, which comprises the steps of dissolving hydroxypropyl methylcellulose in a prescription amount in an ethanol solution to prepare a hydroxypropyl methylcellulose ethanol solution adhesive, preparing raw materials simvastatin and auxiliary materials of croscarmellose sodium, silicon dioxide and magnesium stearate, respectively sieving the auxiliary materials of the croscarmellose sodium, the silicon dioxide and the magnesium stearate with a 60-mesh sieve, weighing the simvastatin, the croscarmellose sodium, the silicon dioxide and the magnesium stearate according to the prescription amount, marking, weighing the simvastatin and the hydroxypropyl methylcellulose ethanol solution adhesive in the prescription amount, mixing the simvastatin and the hydroxypropyl methylcellulose ethanol solution adhesive in a mixer to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-process granulator, granulating through a 0.8mm sieve to obtain simvastatin mixture granules, sucking the prepared simvastatin mixture granules into a three-way rotary vibration sieve through a vacuum feeding machine, removing coarse particles by using a 20-mesh screen, removing fine particles by using a 60-mesh screen, repeatedly finishing the coarse particles to obtain heavy powder particles, selecting simvastatin mixture particles with the particle size of less than 20 meshes, respectively limiting the content of the simvastatin mixture particles with the particle size range of 20-60 meshes, and facilitating dissolution in a human body, thereby ensuring long-term and stable dissolution of capsules in the human body, adding raw and auxiliary materials into a mixing machine according to the sequence of the simvastatin mixture particles, crosslinked sodium carboxymethylcellulose, silicon dioxide, magnesium stearate and the simvastatin mixture particles, closing a feeding port, setting the mixing time to be 10-30 minutes, mixing at a constant speed, facilitating accelerated dissolution of simvastatin, ensuring higher dissolution rate of simvastatin, obtaining an intermediate product, detecting properties, identification, moisture, dissolution rate and content of the intermediate product, calculating the filling amount according to the content after the intermediate product is qualified, the simvastatin capsule is prepared by controlling a full-automatic capsule filling machine according to a filling amount generation production instruction, so that a dissolution rate of the simvastatin capsule can be improved by selecting appropriate auxiliary materials and adjusting the placing sequence and mixing time of medicinal materials, and the technical problem that the existing simvastatin capsule has large individual dissolution rate difference, influences the dissolution rate of the simvastatin capsule and cannot meet the requirements of people is solved.
Drawings
In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings needed to be used in the description of the embodiments are briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments described in the present invention, and it is obvious for those skilled in the art to obtain other drawings according to these drawings.
Fig. 1 is a schematic flow chart of a preparation method of a simvastatin capsule provided in the examples of the present application.
Detailed Description
In order to make those skilled in the art better understand the technical solutions of the present invention, the following embodiments of the present invention are clearly and completely described, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention. Unless otherwise specifically stated, various raw materials, reagents, instruments, equipment and the like used in the present invention are commercially available or can be prepared by existing methods.
Example 1
For easy understanding, please refer to fig. 1, which provides an example of a simvastatin capsule preparation method and a simvastatin capsule, and a simvastatin capsule preparation method, comprising the following steps:
s1: preparing an adhesive, namely dissolving 18 parts by weight of hydroxypropyl methylcellulose in an ethanol solution to prepare the hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: 80 parts by weight of simvastatin, and the auxiliary materials comprise: 10 parts by weight of croscarmellose sodium, 5 parts by weight silicon dioxide and 5 parts by weight magnesium stearate;
s3: sieving, namely respectively sieving the auxiliary materials of the croscarmellose sodium, the silicon dioxide and the magnesium stearate through a 60-mesh sieve at the temperature of 18-26 ℃ and the humidity of 45-65%;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking at the temperature of 18-26 ℃ and the humidity of 45-65%;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, and granulating through a 0.8mm screen to obtain simvastatin mixture granules, wherein the pressure of a compression roller of the dry-method granulator is 8-10 MPa, and the gap between the compression rollers is 0.6-0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min, the finished simvastatin mixture particles are sucked into the ternary rotary vibration sieve through a vacuum feeding machine, coarse particles are removed through a 20-mesh screen, fine particles are removed through a 60-mesh screen, the coarse particles are finished repeatedly, and heavy powder particles are obtained, wherein the temperature is 18-26 ℃, and the humidity is 45-65%;
s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 10 minutes, and mixing at a constant speed to obtain an intermediate product, wherein the temperature is 18-26 ℃, and the humidity is 45-65%; preferably, the simvastatin mixture particles added first are half of the prescribed amount, and the simvastatin mixture particles added later are the other half of the prescribed amount;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, wherein a production instruction is generated according to the filling amount to control a full-automatic capsule filling machine to obtain the simvastatin capsule, the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute, the temperature is 18-26 ℃, and the humidity is 45-65%, so that the simvastatin capsule is prepared;
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
Example 2
A preparation method of simvastatin capsules comprises the following steps:
s1: preparing an adhesive, namely dissolving 18 parts by weight of hydroxypropyl methylcellulose in an ethanol solution to prepare the hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: 80 parts by weight of simvastatin, and the auxiliary materials comprise: 10 parts by weight of croscarmellose sodium, 5 parts by weight silicon dioxide and 5 parts by weight magnesium stearate;
s3: sieving, namely respectively sieving the auxiliary materials of the croscarmellose sodium, the silicon dioxide and the magnesium stearate through a 60-mesh sieve at the temperature of 18-26 ℃ and the humidity of 45-65%;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking at the temperature of 18-26 ℃ and the humidity of 45-65%;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, and granulating through a 0.8mm screen to obtain simvastatin mixture granules, wherein the pressure of a compression roller of the dry-method granulator is 8-10 MPa, and the gap between the compression rollers is 0.6-0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min, the finished simvastatin mixture particles are sucked into the ternary rotary vibration sieve through a vacuum feeding machine, coarse particles are removed through a 20-mesh screen, fine particles are removed through a 60-mesh screen, the coarse particles are finished repeatedly, and heavy powder particles are obtained, wherein the temperature is 18-26 ℃, and the humidity is 45-65%;
s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 20 minutes, and mixing at a constant speed to obtain an intermediate product, wherein the temperature is 18-26 ℃, and the humidity is 45-65%; preferably, the simvastatin mixture particles added first are half of the prescribed amount, and the simvastatin mixture particles added later are the other half of the prescribed amount;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, wherein a production instruction is generated according to the filling amount to control a full-automatic capsule filling machine to obtain the simvastatin capsule, the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute, the temperature is 18-26 ℃, and the humidity is 45-65%, so that the simvastatin capsule is prepared;
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
Example 3
A preparation method of simvastatin capsules comprises the following steps:
s1: preparing an adhesive, namely dissolving 18 parts by weight of hydroxypropyl methylcellulose in an ethanol solution to prepare the hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: 80 parts by weight of simvastatin, and the auxiliary materials comprise: 10 parts by weight of croscarmellose sodium, 5 parts by weight silicon dioxide and 5 parts by weight magnesium stearate;
s3: sieving, namely respectively sieving the auxiliary materials of the croscarmellose sodium, the silicon dioxide and the magnesium stearate through a 60-mesh sieve at the temperature of 18-26 ℃ and the humidity of 45-65%;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking at the temperature of 18-26 ℃ and the humidity of 45-65%;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, and granulating through a 0.8mm screen to obtain simvastatin mixture granules, wherein the pressure of a compression roller of the dry-method granulator is 8-10 MPa, and the gap between the compression rollers is 0.6-0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min, the finished simvastatin mixture particles are sucked into the ternary rotary vibration sieve through a vacuum feeding machine, coarse particles are removed through a 20-mesh screen, fine particles are removed through a 60-mesh screen, the coarse particles are finished repeatedly, and heavy powder particles are obtained, wherein the temperature is 18-26 ℃, and the humidity is 45-65%;
s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 30 minutes, and mixing at a constant speed to obtain an intermediate product, wherein the temperature is 18-26 ℃, and the humidity is 45-65%; preferably, the simvastatin mixture particles added first are half of the prescribed amount, and the simvastatin mixture particles added later are the other half of the prescribed amount;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, wherein a production instruction is generated according to the filling amount to control a full-automatic capsule filling machine to obtain the simvastatin capsule, the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute, the temperature is 18-26 ℃, and the humidity is 45-65%, so that the simvastatin capsule is prepared;
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
Example 4
A preparation method of simvastatin capsules comprises the following steps:
s1: preparing an adhesive, namely dissolving 18 parts by weight of hydroxypropyl methylcellulose in an ethanol solution to prepare the hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: 80 parts by weight of simvastatin, and the auxiliary materials comprise: 15 parts by weight of croscarmellose sodium, 9 parts by weight silicon dioxide and 7 parts by weight magnesium stearate;
s3: sieving, namely respectively sieving the auxiliary materials of the croscarmellose sodium, the silicon dioxide and the magnesium stearate through a 60-mesh sieve at the temperature of 18-26 ℃ and the humidity of 45-65%;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking at the temperature of 18-26 ℃ and the humidity of 45-65%;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, and granulating through a 0.8mm screen to obtain simvastatin mixture granules, wherein the pressure of a compression roller of the dry-method granulator is 8-10 MPa, and the gap between the compression rollers is 0.6-0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min, the finished simvastatin mixture particles are sucked into the ternary rotary vibration sieve through a vacuum feeding machine, coarse particles are removed through a 20-mesh screen, fine particles are removed through a 60-mesh screen, the coarse particles are finished repeatedly, and heavy powder particles are obtained, wherein the temperature is 18-26 ℃, and the humidity is 45-65%;
s6: mixing, namely adding simvastatin mixture granules, croscarmellose sodium, silicon dioxide and magnesium stearate which are raw and auxiliary materials into a mixer, closing a feeding port, setting the mixing time to be 10 minutes, and mixing at a constant speed to obtain an intermediate product, wherein the temperature is 18-26 ℃, and the humidity is 45-65%; preferably, the simvastatin mixture particles added first are half of the prescribed amount, and the simvastatin mixture particles added later are the other half of the prescribed amount;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, wherein a production instruction is generated according to the filling amount to control a full-automatic capsule filling machine to obtain the simvastatin capsule, the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute, the temperature is 18-26 ℃, and the humidity is 45-65%, so that the simvastatin capsule is prepared;
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
Example 5
A preparation method of simvastatin capsules comprises the following steps:
s1: preparing an adhesive, namely dissolving 18 parts by weight of hydroxypropyl methylcellulose in an ethanol solution to prepare the hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: 80 parts by weight of simvastatin, and the auxiliary materials comprise: 15 parts by weight of croscarmellose sodium, 9 parts by weight silicon dioxide and 7 parts by weight magnesium stearate;
s3: sieving, namely respectively sieving the auxiliary materials of the croscarmellose sodium, the silicon dioxide and the magnesium stearate through a 60-mesh sieve at the temperature of 18-26 ℃ and the humidity of 45-65%;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking at the temperature of 18-26 ℃ and the humidity of 45-65%;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, and granulating through a 0.8mm screen to obtain simvastatin mixture granules, wherein the pressure of a compression roller of the dry-method granulator is 8-10 MPa, and the gap between the compression rollers is 0.6-0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min, the finished simvastatin mixture particles are sucked into the ternary rotary vibration sieve through a vacuum feeding machine, coarse particles are removed through a 20-mesh screen, fine particles are removed through a 60-mesh screen, the coarse particles are finished repeatedly, and heavy powder particles are obtained, wherein the temperature is 18-26 ℃, and the humidity is 45-65%;
s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 10 minutes, and mixing at a constant speed to obtain an intermediate product, wherein the temperature is 18-26 ℃, and the humidity is 45-65%; preferably, the simvastatin mixture particles added first are half of the prescribed amount, and the simvastatin mixture particles added later are the other half of the prescribed amount;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, wherein a production instruction is generated according to the filling amount to control a full-automatic capsule filling machine to obtain the simvastatin capsule, the filling speed of the full-automatic capsule filling machine is 2000-2500 granules/minute, the temperature is 18-26 ℃, and the humidity is 45-65%, so that the simvastatin capsule is prepared;
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
Example 6
The dissolution rate test method comprises the following steps: taking a simvastatin capsule sample prepared in the examples 1-6, according to a dissolution test method (appendix XC first method), using 900mL of water as a solvent, wherein the temperature of the solvent is (37 +/-0.5) DEG C, and the rotating speed: 100r/min, operating according to the method for 45min, taking a proper amount of solution, filtering through a 0.45-micron filter membrane, precisely taking a proper amount of subsequent filtrate, diluting the filtrate with a solvent to obtain a solution containing about 130 mug of solution in each 1mlL, and measuring the absorbance at the wavelength of 272nm by an ultraviolet-visible spectrophotometry (appendix IV A); taking the contents with different loading amounts, mixing uniformly, precisely weighing a proper amount (about equal to the average loading amount), adding a dissolution medium according to the marked amount to dissolve and dilute the dissolution medium into a solution containing about 130 mug per 1mL, filtering, taking the subsequent filtrate as a control solution, measuring by the same method, and calculating the dissolution amount of each granule. The limit is 80%, which should be met.
Comparison group: according to the preparation method of simvastatin capsules in the prior art, 10g of simvastatin, 140g of starch, 8g of carboxymethyl starch sodium, 0.8g of tert-butyl-4-hydroxyanisole, 23g of starch slurry and 0.8g of aerosil are taken to prepare simvastatin capsules as comparative examples, and the results are as follows: the dissolution rate of the simvastatin capsule is 98.69%.
A first group: taking 80 parts by weight of simvastatin as raw materials, taking 10 parts by weight of croscarmellose sodium, 5 parts by weight of silicon dioxide and 5 parts by weight of magnesium stearate as auxiliary materials, adding the raw materials into a mixing machine according to the preparation method of the simvastatin capsule in the embodiment 1 in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, mixing for 10 minutes to prepare the simvastatin capsule, carrying out dissolution rate measurement on the simvastatin capsule, comparing the measurement result with the dissolution rate of the simvastatin capsule in a comparison group, wherein the dissolution rate of the simvastatin capsule is higher than that of the simvastatin capsule in the comparison group.
Second group: taking 80 parts by weight of simvastatin as raw materials, taking 10 parts by weight of croscarmellose sodium, 5 parts by weight of silicon dioxide and 5 parts by weight of magnesium stearate as auxiliary materials, adding the raw materials into a mixing machine according to the preparation method of the simvastatin capsule in the embodiment 1 in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, mixing for 20 minutes to prepare the simvastatin capsule, carrying out dissolution rate measurement on the simvastatin capsule, comparing the measurement result with the dissolution rate of the simvastatin capsule in a comparison group, wherein the dissolution rate of the simvastatin capsule is higher than that of the simvastatin capsule in the comparison group.
Third group: taking 80 parts by weight of simvastatin as raw materials, taking 10 parts by weight of croscarmellose sodium, 5 parts by weight of silicon dioxide and 5 parts by weight of magnesium stearate as auxiliary materials, adding the raw materials into a mixing machine according to the preparation method of the simvastatin capsule in the embodiment 1 in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, mixing for 30 minutes to prepare the simvastatin capsule, carrying out dissolution rate determination on the simvastatin capsule, comparing the determination result with the dissolution rate of the simvastatin capsule in a comparison group, wherein the dissolution rate of the simvastatin capsule is higher than that of the simvastatin capsule in the comparison group.
And a fourth group: taking 80 parts by weight of simvastatin as raw materials, taking 15 parts by weight of croscarmellose sodium, 9 parts by weight of silicon dioxide and 7 parts by weight of magnesium stearate as auxiliary materials, adding the simvastatin mixture granules, the croscarmellose sodium, the silicon dioxide and the magnesium stearate into a mixing machine according to the preparation method of the simvastatin capsule in the embodiment 1, mixing for 10 minutes to prepare the simvastatin capsule, carrying out dissolution rate determination on the simvastatin capsule, comparing the determination result with the dissolution rate of the simvastatin capsule in a comparison group, wherein the dissolution rate of the simvastatin capsule is lower than that of the simvastatin capsule in the comparison group.
And a fifth group: taking 80 parts by weight of simvastatin as raw materials, taking 15 parts by weight of croscarmellose sodium, 9 parts by weight of silicon dioxide and 7 parts by weight of magnesium stearate as auxiliary materials, adding the raw materials into a mixing machine according to the preparation method of the simvastatin capsule in the embodiment 1 in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, mixing for 10 minutes to prepare the simvastatin capsule, carrying out dissolution rate determination on the simvastatin capsule, comparing the determination result with the dissolution rate of the simvastatin capsule in a comparison group, wherein the dissolution rate of the simvastatin capsule is higher than that of the simvastatin capsule in the comparison group.
Table of dissolution test of the product:
and (4) conclusion: as can be seen from the table, the first, second and third groups had a mixing time within a certain range, and the smaller the mixing time, the higher the dissolution rate, compared with the control group.
And compared with the first group, the simvastatin capsules prepared by putting the auxiliary materials into the mixing machine out of sequence and mixing the auxiliary materials into the mixing machine in sequence have low dissolution rate.
In the first group and the fifth group, compared with the fifth group, the auxiliary material is in a certain amount range, and the larger the amount of the auxiliary material is, the higher the dissolution rate of the simvastatin capsule is.
The above embodiments are only used for illustrating the technical solutions of the present application, and not for limiting the same; although the present application has been described in detail with reference to the foregoing embodiments, it should be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions in the embodiments of the present application.
Claims (10)
1. The preparation method of the simvastatin capsule is characterized by comprising the following steps of:
s1: preparing an adhesive, namely dissolving hydroxypropyl methylcellulose with a formula amount into an ethanol solution to prepare a hydroxypropyl methylcellulose ethanol solution adhesive;
s2: preparing raw materials and auxiliary materials, wherein the raw materials comprise: simvastatin, and the auxiliary materials comprise: croscarmellose sodium, silicon dioxide and magnesium stearate;
s3: sieving, and respectively sieving adjuvants including croscarmellose sodium, silicon dioxide and magnesium stearate with 60 mesh sieve;
s4: weighing and proportioning, weighing simvastatin, croscarmellose sodium, silicon dioxide and magnesium stearate according to the prescription amount, and marking;
s5: granulating, namely weighing simvastatin and a hydroxypropyl methyl cellulose ethanol solution adhesive in a prescription amount, placing the simvastatin and the hydroxypropyl methyl cellulose ethanol solution adhesive in a mixer, mixing to obtain a simvastatin mixture, adding the simvastatin mixture into a dry-method granulator, granulating through a 0.8mm screen to obtain simvastatin mixture particles, sucking the prepared simvastatin mixture particles into a ternary rotary vibration sieve through a vacuum feeding machine, removing coarse particles through a 20-mesh screen, removing fine particles through a 60-mesh screen, repeatedly finishing coarse particles, and collecting heavy powder particles;
s6: mixing, namely adding the raw and auxiliary materials into a mixer according to the sequence of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate and simvastatin mixture granules, closing a feeding port, setting the mixing time to be 10-30 minutes, and mixing at a constant speed to obtain an intermediate product;
s7: inspecting the intermediate product, taking the intermediate product to detect the character, identification, moisture, dissolution and content, and calculating the filling amount according to the content after the intermediate product is qualified;
s8: filling, and generating a production instruction according to the filling amount to control a full-automatic capsule filling machine to prepare the simvastatin capsule.
2. The preparation method of simvastatin capsule as claimed in claim 1, wherein the mass concentration of the ethanol solution is 45-55%, and the mass concentration of the hydroxypropyl methylcellulose ethanol solution adhesive is 1.5-2.5%.
3. The method for preparing simvastatin capsules according to claim 1, wherein the temperature for sieving, weighing, blending, granulating, mixing, filling and packaging is 18-26 ℃.
4. The preparation method of simvastatin capsules according to claim 1, wherein the humidity of the sieving, the weighing and the batching, the granulating, the mixing, the filling and the packaging is 45% -65%.
5. The method for producing simvastatin capsules according to claim 1, wherein in step S5, the pressure of the dry granulator is 8 to 10MPa, and the gap between rollers is 0.6 to 0.9 mm; the rotating speed of the press roll is 15-20 r/min; the rotating speed of the ternary rotary vibration sieve is 100-120 r/min.
6. The method for producing simvastatin capsules according to claim 1, wherein in step S6, the raw and auxiliary materials are added to the mixer in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate, and simvastatin mixture granules, and the mixing time is set to 10 to 25 minutes.
7. The method for producing simvastatin capsules according to claim 1, wherein in step S6, the raw and auxiliary materials are added to the mixer in the order of simvastatin mixture granules, croscarmellose sodium, silicon dioxide, magnesium stearate, and simvastatin mixture granules, and the mixing time is set to 10 to 20 minutes.
8. The method for producing simvastatin capsules according to claim 1, wherein in step S8, the filling speed of the fully automatic capsule filling machine is 2000-2500 granules/min.
9. The method of preparing simvastatin capsules according to claim 1, further comprising the steps of:
s9: packaging, loading PVC and aluminum foil, debugging normally, confirming the aluminum-plastic plate, printing the valid period on the aluminum foil, printing the batch number in the middle of the lower end of the aluminum-plastic plate without reticulate pattern, checking the sealing performance of the aluminum-plastic plate, and feeding aluminum and plastic after the aluminum-plastic plate is qualified.
10. A simvastatin capsule prepared by the method for preparing the simvastatin capsule according to any one of claims 1-9, comprising the following components in parts by weight:
10-80 parts by weight of simvastatin
5-15 parts by weight of croscarmellose sodium
2-7 parts by weight of silicon dioxide
3-9 parts by weight of magnesium stearate
10-18 parts of hydroxypropyl methyl cellulose.
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| CN115282160A (en) * | 2022-07-04 | 2022-11-04 | 滨海宇美科技有限公司 | Compound simvastatin sodium chondroitin sulfate capsule and preparation method thereof |
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