CN113209017A - Paroxetine hydrochloride suspension and preparation method thereof - Google Patents
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Abstract
Translated fromChinese
Description
Technical Field
The invention belongs to the technical field of pharmaceutical preparations, and particularly relates to a paroxetine hydrochloride suspension and a preparation method thereof, in particular to a paroxetine hydrochloride suspension with good drug stability, high drug loading capacity and good compliance and a preparation method thereof.
Background
Paroxetine Hydrochloride (PX) is a novel antidepressant drug of 5-hydroxytryptamine reuptake blocker (SSRI), and is mainly used for treating major depression, obsessive compulsive disorder, panic disorder, social anxiety disorder, post-traumatic stress disorder and the like. Compared with the traditional tricyclic and monoamine oxidase inhibitor antidepressant, the paroxetine hydrochloride has stronger selectivity and less adverse reactions, and has good organism tolerance and high therapeutic index. Paroxetine hydrochloride exerts its therapeutic effect by inhibiting 5-hydroxytryptamine reuptake by the presynaptic membrane of neurons in the central nervous system, thereby enhancing the impulse transmission of central 5-hydroxytryptamine-capable nerves. The paroxetine hydrochloride has the following structural formula:
the molecular formula is C19H20FNO3HCl; the molecular weight is 374.84; white or off-white crystalline powder; no odor; is easy to dissolve in methanol, dissolve in ethanol, slightly dissolve in acetone and dissolve in water to a minimum extent; it is almost insoluble in a 0.1mol/L hydrochloric acid solution. The specific rotation degree is-88 to-91 degrees; melting point is 129-131 ℃; the partition coefficient log P (octanol/water) was 3.95. The absorption maxima are at the wavelength of 235nm, 265nm, 271nm and 295 nm; belongs to BCS I class medicine.
Paroxetine hydrochloride is almost completely absorbed by gastrointestinal tract after oral administration, and reaches peak plasma concentration 5-8 hours after oral administration. The distribution in the body is wide, and the plasma protein binding rate of paroxetine at a treatment concentration is about 95 percent. Less than 1% of the total drug recovered in the feces indicates that paroxetine is almost completely absorbed, the mean elimination half-life of paroxetine is about 24 hours (9 to 30 hours), the plasma concentration of paroxetine is increased in elderly patients with depression, patients with severe renal failure and patients with liver cirrhosis, and the final elimination half-life is prolonged. Less than 5% of the parent compound is excreted intact and ineffective polar metabolites are excreted in urine (65%) and feces (25%).
Dosage forms and preparations suitable for patients of special populations such as children and the old are very limited, and due to the difference of physiological functions of the patients and the adults, besides the difference of administration dosage, the requirements on dosage forms and the compliance of administration are also different, and solid preparations such as oral tablets or capsules are often inconvenient to take because of the problems of uncomfortable taste, difficulty in dividing the dosage and the like, and the completion of a normal treatment scheme and the exertion of the drug effect are influenced. Compared with the conventional preparations, such as tablets, capsules and the like, the oral liquid suspension has good absorption after oral administration; the dosage is convenient for patients to take in divided doses, and can be adjusted according to different types and courses of depression treatment; the liquid preparation is easier to swallow, thereby solving the problem that the medicine is difficult to swallow, improving the medicine taking compliance of patients and the like. However, paroxetine hydrochloride has strong bitter taste, and is obviously bitter when being prepared into a common oral liquid preparation, and is difficult to swallow for patients.
CN108926529A discloses a paroxetine hydrochloride oral suspension and a preparation process thereof, wherein the paroxetine hydrochloride oral suspension is prepared by sieving and premixing a raw material drug and a suspending agent silicon dioxide, dispersing the raw material drug and the suspending agent silicon dioxide into propylene glycol, adding a prescription amount of double distilled water, glycerol, a preservative, a taste bud paralytic agent, a sweetening agent, a coloring agent and a pH regulator, regulating the pH of the solution to 3-7, uniformly stirring by magnetic force, carrying out high-pressure homogenization by a micro-jet high-pressure homogenizer, and finally adding a defoaming agent and an essence. The oral suspension covers the bitter and numb feeling of the medicine and is easier to be accepted by patients, wherein a micro-jet high-pressure homogenizer is adopted for high-pressure homogenization, and the prepared suspension has larger sedimentation volume and is stable. The paroxetine hydrochloride oral suspension improves the compliance of patients, is convenient for children and adults with difficulty in swallowing oral solid preparations, ensures the accuracy of the administration dosage and improves the safety and the effectiveness of the medicine.
However, the types of paroxetine hydrochloride oral suspensions disclosed in the prior art are still very limited and it would therefore be of great interest to develop alternative paroxetine hydrochloride formulations suitable for administration to the elderly, children and patients with dysphagia.
Disclosure of Invention
Aiming at the defects of the prior art, the invention aims to provide a paroxetine hydrochloride suspension and a preparation method thereof, and particularly provides a paroxetine hydrochloride suspension with good drug stability, high drug loading and good compliance and a preparation method thereof.
In order to achieve the purpose, the invention adopts the following technical scheme:
in a first aspect, the invention provides a paroxetine hydrochloride suspension, which is prepared from the following raw materials: paroxetine hydrochloride, cation exchange resin, impregnant and pharmaceutic adjuvant; the cation exchange resin is composed of a strong-acid cation exchange resin and a weak-acid cation exchange resin.
The paroxetine hydrochloride suspension related by the invention creatively adopts the cation exchange resin consisting of the strong acid cation exchange resin and the weak acid cation exchange resin as the carrier of the paroxetine hydrochloride, and the drug is loaded on the resin material, so that the bitter taste of the drug can be covered, and the paroxetine hydrochloride suspension is easier to swallow by patients; meanwhile, the drug loading rate of the paroxetine hydrochloride is improved, and the stability, the redispersibility and the drug release behavior are further improved.
Preferably, the mass ratio of the strongly acidic cation exchange resin to the weakly acidic cation exchange resin is 1 (2-8), such as 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, and the like, and other specific values in the value range can be selected, which is not described in detail herein. Preferably 1 (5-8).
When the strong-acid cation exchange resin and the weak-acid cation exchange resin are matched according to the mass ratio of 1 (2-8), the paroxetine hydrochloride has the best comprehensive performance in drug loading, stability and redispersibility. Wherein 1 (5-8) is a range in which the overall effect is further remarkable.
Preferably, the mass ratio of the cation exchange resin to the paroxetine hydrochloride is (1-5):1, such as 1:1, 2:1, 3:1, 4:1, 5:1, and the like, and other specific values in the value range can be selected, and are not described in detail herein. Preferably, (1-2) 1.
The mass ratio of the cation exchange resin to the paroxetine hydrochloride is specifically selected to be (1-5):1, because if the relative mass of the cation exchange resin is too high, the drug loading is too low, and if the relative mass of the cation exchange resin is too low, the utilization rate of the drug is too low, which causes the waste of the drug. On the other hand, (1-2):1 is the range where the effect is most excellent.
Preferably, the strong acid cation exchange resin comprises Amberlite IRP 69.
Preferably, the weakly acidic cation exchange resin comprises Amberlite IRP88 and/or Amberlite IRP64, preferably a combination of Amberlite IRP88 and Amberlite IRP 64.
Further, the invention finds that the combination of Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 is used as a carrier, and the effect is optimal in the aspects of optimizing drug loading capacity, stability, redispersibility and drug release behavior of the preparation.
Preferably, the impregnating agent comprises polyethylene glycol.
The invention can effectively prevent the swelling of the resin by using the polyethylene glycol as the impregnant. And the combination of polyethylene glycol 4000 and polyethylene glycol 3350 is used as the impregnant of the invention, which can help to improve the stability of the paroxetine hydrochloride suspension to a certain extent.
Preferably, the impregnating agent is polyethylene glycol 4000 and/or polyethylene glycol 3350, preferably a combination of polyethylene glycol 4000 and polyethylene glycol 3350.
Preferably, the mass ratio of the impregnant to the cation exchange resin is 1 (0.3-1), such as 1:0.3, 1:0.4, 1:0.5, 1:0.6, 1:0.7, 1:0.8, 1:0.9, 1:1, and the like, and other specific values in the numerical range can be selected, so that the details are not repeated.
In the present invention, the pharmaceutical excipients include any one or a combination of at least two of a dispersing agent, a humectant, a sweetener, a flavoring agent, a coloring agent, a thickener, a preservative, a pH adjuster, or a defoaming agent.
The combination of at least two of the above components, such as the combination of a dispersing agent and a humectant, the combination of a sweetener, a flavoring agent and a coloring agent, the combination of a thickener and a preservative, and the like, can be selected in any combination manner, and thus, the details are not repeated.
Preferably, the dispersant comprises any one of propylene glycol, polyethylene glycol 200 or polyethylene glycol 400 or a combination of at least two thereof; the combination of at least two of the above-mentioned compounds, such as the combination of propylene glycol and polyethylene glycol 200, the combination of polyethylene glycol 200 and polyethylene glycol 400, the combination of propylene glycol and polyethylene glycol 400, etc., can be selected in any other combination manner, and are not repeated herein.
Preferably, the humectant comprises glycerin.
Preferably, the thickener comprises any one of Avicel RC 591, Avicel CL 611 or Keltrol or a combination of at least two thereof. The combination of at least two of the above-mentioned combinations, for example, the combination of Avicel RC 591 and Avicel CL 611, the combination of Avicel CL 611 and Keltrol, etc., may be selected in any other combination manner, and thus, the details thereof are not repeated herein.
Preferably, the preservative comprises any one or a combination of at least two of methylparaben, ethylparaben, propylparaben, or sodium benzoate. The combination of at least two of the above-mentioned compounds, such as methyl hydroxybenzoate and ethyl hydroxybenzoate, ethyl hydroxybenzoate and propyl hydroxybenzoate, propyl hydroxybenzoate and sodium benzoate, can be selected in any combination manner, and will not be described herein again.
Preferably, the defoamer comprises a silicone defoamer and/or a polysiloxane defoamer.
Preferably, the sweetener comprises any one of sucrose, sorbitol or sodium saccharin or a combination of at least two of these.
Preferably, the flavoring agent comprises any one of or a combination of at least two of orange essence, lemon essence, or orange essence.
Preferably, the colorant comprises FD & C yellow No. 6.
In a second aspect, the present invention provides a process for the preparation of a paroxetine hydrochloride suspension as defined in the first aspect, said process comprising the steps of:
(1) mixing paroxetine hydrochloride and cation exchange resin to prepare a drug-loaded resin compound;
(2) impregnating the drug-loaded resin compound obtained in the step (1) with an impregnant to obtain an impregnated drug-loaded resin compound;
(3) and (3) mixing the impregnated drug-loaded resin compound obtained in the step (2) with a pharmaceutic adjuvant and water to obtain the paroxetine hydrochloride suspension.
The preparation process of the paroxetine hydrochloride suspension is relatively simple and easy to operate, and is very suitable for large-scale industrial production.
The drug-loaded resin composite can be prepared in the following two ways by way of example:
the preparation method of the drug-loaded resin compound comprises the following steps: mixing cation exchange resin with water, mixing with paroxetine hydrochloride, washing with water when the concentration of the drug in the solution does not change with time, and drying to obtain the final product;
or mixing cation exchange resin with water, placing into a chromatographic column, adding paroxetine hydrochloride solution into the chromatographic column for chromatography, washing with water when the concentrations of the added solution and the effluent are the same, and drying.
Preferably, the drying temperature is 40-60 ℃, for example, 40 ℃, 42 ℃, 45 ℃, 48 ℃, 50 ℃, 52 ℃, 55 ℃, 58 ℃, 60 ℃ and the like, and other specific values in the numerical range can be selected, which is not described in detail herein.
Preferably, the impregnation method in step (2) is as follows: mixing the medicine-carrying resin compound with the impregnant solution, stirring, drying and sieving.
Preferably, the stirring temperature is 55-65 ℃, for example 55 ℃, 58 ℃, 60 ℃, 62 ℃ or 65 ℃, and the time is 20-40min, for example 20min, 25min, 30min, 35min, 40min, and other specific values within the above numerical range can be selected, and are not described herein again.
Preferably, the drying temperature is 40-60 ℃, for example, 40 ℃, 42 ℃, 45 ℃, 48 ℃, 50 ℃, 52 ℃, 55 ℃, 58 ℃, 60 ℃ and the like, and other specific values in the numerical range can be selected, which is not described in detail herein.
Compared with the prior art, the invention has the following beneficial effects:
the paroxetine hydrochloride suspension related by the invention creatively adopts the cation exchange resin consisting of the strong acid cation exchange resin and the weak acid cation exchange resin as the carrier of the paroxetine hydrochloride, and the drug is loaded on the resin material, so that the bitter taste of the drug can be covered, and the paroxetine hydrochloride suspension is easier to swallow by patients; meanwhile, the drug loading rate of the paroxetine hydrochloride is improved, and the stability, the redispersibility and the drug release behavior are further improved.
Drawings
FIG. 1 is a graph of the in vitro release of paroxetine hydrochloride from example 1.
Detailed Description
The technical solution of the present invention is further explained by the following embodiments. It should be understood by those skilled in the art that the examples are only for the understanding of the present invention and should not be construed as the specific limitations of the present invention.
The following examples and comparative examples relate to the following raw material source information:
example 1
This example provides a paroxetine hydrochloride suspension (10mL specification) comprising the following starting materials:
the preparation method comprises the following steps:
(1) amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 were mixed with water and then with paroxetine hydrochloride, sampled periodically and the concentration of drug in the solution was determined. When the drug concentration in the solution is not changed along with the time, the drug concentration reaches the balance, deionized water is used for washing away the drug which is not combined on the surface of the resin, and the drug-loaded resin compound is obtained after drying at 50 ℃;
(2) adding the drug-loaded resin compound obtained in the step (1) into aqueous solution of PEG4000 (10%) and PEG3350 (15%), stirring for 30min at 60 ℃, and drying at 50 ℃ to obtain an impregnated drug-loaded resin compound;
(3) and (3) uniformly mixing the impregnated drug-loaded resin compound obtained in the step (2) with all the pharmaceutic adjuvants and water in the table above to obtain the paroxetine hydrochloride suspension.
Example 2
This example provides a paroxetine hydrochloride suspension (10mL specification) comprising the following starting materials:
the preparation method comprises the following steps:
(1) mixing Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 with water, placing the mixture into a chromatographic column, adding paroxetine hydrochloride solution into the chromatographic column for chromatography, sampling at regular time, balancing when the concentrations of the added liquid and the effluent liquid are the same, washing away the unbound medicine on the surface of the resin by deionized water, and drying at 45 ℃ to obtain a medicine-carrying resin compound;
(2) adding the drug-loaded resin compound obtained in the step (1) into aqueous solution of PEG4000 (15%) and PEG3350 (10%), stirring for 40min at 55 ℃, and drying at 45 ℃ to obtain an impregnated drug-loaded resin compound;
(3) and (3) uniformly mixing the impregnated drug-loaded resin compound obtained in the step (2) with all the pharmaceutic adjuvants and water in the table above to obtain the paroxetine hydrochloride suspension.
Example 3
This example provides a paroxetine hydrochloride suspension (10mL specification) comprising the following starting materials:
the preparation method comprises the following steps:
(1) mixing Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 with water, placing the mixture into a chromatographic column, adding paroxetine hydrochloride solution into the chromatographic column for chromatography, sampling at regular time, balancing when the concentrations of the added liquid and the effluent liquid are the same, washing away the unbound medicine on the surface of the resin by deionized water, and drying at 60 ℃ to obtain a medicine-carrying resin compound;
(2) adding the drug-loaded resin compound obtained in the step (1) into aqueous solution of PEG4000 (15%) and PEG3350 (10%), stirring for 20min at 65 ℃, and drying at 60 ℃ to obtain an impregnated drug-loaded resin compound;
(3) and (3) uniformly mixing the impregnated drug-loaded resin compound obtained in the step (2) with all the pharmaceutic adjuvants and water in the table above to obtain the paroxetine hydrochloride suspension.
Example 4
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: the mass of Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 was 10mg, 20mg and 10mg respectively, and all other conditions were kept unchanged. The preparation process was identical to example 1.
Example 5
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: the mass of Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 was 20mg, 10mg and 10mg respectively, and all other conditions were kept unchanged. The preparation process was identical to example 1.
Example 6
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: the mass of Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 was 10mg, 40mg and 30mg respectively, and all other conditions were kept unchanged. The preparation process was identical to example 1.
Example 7
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: the mass of Amberlite IRP69, Amberlite IRP88 and Amberlite IRP64 was 15mg, 60mg and 45mg respectively, and all other conditions were kept unchanged. The preparation process was identical to example 1.
Example 8
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: amberlite IRP88 was not included and the mass of Amberlite IRP64 was 35mg, all other conditions remaining unchanged. The preparation process was identical to example 1.
Example 9
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: amberlite IRP64 was not included and the mass of Amberlite IRP88 was 35mg, all other conditions remaining unchanged. The preparation process was identical to example 1.
Example 10
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: no peg4000 was included and the mass of peg3350 was mg, all other conditions remaining unchanged. The preparation process was identical to example 1.
Example 11
This example provides a paroxetine hydrochloride suspension (10mL _ standard) which differs from example 1 only in the preparation starting materials: no polyethylene glycol 3350 was included, and the mass of polyethylene glycol 4000 was mg, all other conditions remaining unchanged. The preparation process was identical to example 1.
Comparative example 1
This comparative example provides a paroxetine hydrochloride suspension (10mL _ scale) which differs from example 1 only in the preparation starting materials: the Amberlite IRP69 was not contained, and the mass of Amberlite IRP88 and Amberlite IRP64 was 23mg and 17mg, respectively, all other conditions were kept unchanged. The preparation process was identical to example 1.
Comparative example 2
This comparative example provides a paroxetine hydrochloride suspension (10mL _ scale) which differs from example 1 only in the preparation starting materials: amberlite IRP88 and Amberlite IRP64 were not included, and the mass of Amberlite IRP69 was 40mg each, all other conditions remaining unchanged. The preparation process was identical to example 1.
Comparative example 3
This comparative example provides a paroxetine hydrochloride suspension (10mL _ scale) which differs from example 1 only in the preparation starting materials: amberlite IRP69 and Amberlite IRP64 were not included, and the mass of Amberlite IRP88 was 40mg each, all other conditions remaining unchanged. The preparation process was identical to example 1.
Evaluation test:
(1) in vitro release assay
An in vitro release test was performed on the paroxetine hydrochloride suspension prepared in example 1, with the specific operating method: adopting an RCZ-8 medicine dissolution instrument, taking 900mL artificial gastric juice (taking 2g sodium chloride and 7mL hydrochloric acid, putting in 1000mL water) (without protease) as a release medium; the rotating speed is 100 revolutions per minute; and (3) taking 5mL of solution at the temperature of 37 ℃ at 10min, 20min, 30min and 45min respectively, filtering, simultaneously supplementing release media with the same temperature and the same volume, precisely taking 20 mu L of subsequent filtrate, injecting into HPLC, recording peak area, calculating the drug concentration at each time point according to a standard curve, and observing the relation between the accumulative release amount of the drug within 45min and time. The results are shown in FIG. 1, and it can be seen from FIG. 1 that: the paroxetine hydrochloride suspension has high in-vitro release rate, and the accumulated release amount within 45min can reach 80-95%.
(2) Evaluation of stability
The paroxetine hydrochloride suspensions prepared in examples 1 to 11 and comparative examples 1 to 3 were subjected to stability evaluation under conditions of high temperature, light and air exposure (specifically, as shown in table 1 below), and tests were performed according to the relevant methods in the 2020 edition of chinese pharmacopoeia, and the stability of each suspension was evaluated by using the content, the drug leakage, the release rate, the sedimentation volume ratio, and the redispersibility as indices. The changes of the drug content, drug leakage and release rate with time under the conditions of high temperature and light are shown in Table 2.
TABLE 1
TABLE 2
As can be seen from the data in Table 2: compared with example 1, comparative examples 1 to 3 have larger leakage amount and content change of the drug under high temperature and strong light conditions than example 1, and the in vitro release rate of comparative example 2 at high temperature for 10 days is compared with that of the sample at 0 day, and f2<50, the in vitro release behavior is not similar. But none of the traits changed significantly.
The specific operation method for the redispersibility evaluation is as follows: taking the suspension which is kept still for 3 hours under an appropriate sedimentation volume ratio experimental item, centrifuging the suspension in a centrifugal tube at normal temperature for 10 minutes in a high-speed refrigerated centrifuge under the condition of the rotating speed of 500r/min, taking out the suspension, performing turnover shaking at the same speed, recording the turnover frequency when the suspension reaches a uniform dispersion system again, and evaluating the results to be good, common and poor (the uniform dispersion is good when the time is not more than 12, the uniform dispersion is good when the time is required to be 12-60, the uniform dispersion is common when the time is more than 60, and the uniform dispersion cannot be uniform when the time is not more than 60). The results are shown in Table 3, and it can be seen from the data in Table 3 that: in addition to examples 6 and 7, the other examples and comparative examples all had better redispersibility.
The specific operation method of the sedimentation volume ratio comprises the following steps: the prepared suspension was placed in a 50mL stoppered cylinder and the height of the suspension at that time (H) was recorded0) After 3H at 25 ℃, the final height (H) of the sediment was recorded and the sedimentation volume ratio was calculated (F ═ H/H)0). The results are shown in Table 3, and it can be seen from the data in Table 3 that: in addition to examples 6 and 7, other examples and comparative examples have better sedimentation volume ratios.
(3) Drug loading of drug-loaded resin composites
The calculation of the drug-loaded capacity of the drug-loaded resin composite prepared in the step (1) of the examples 1 to 11 and the comparative examples 1 to 3 comprises the following specific operation methods: determining the initial concentration of paroxetine hydrochloride and the drug concentration in the solution after drug loading balance according to the formula Qt ═ C0-Ct)V/WRCalculation of C0(mg·mL-1) Is the initial concentration of the drug; ct(mg·mL-1) Is the concentration of drug in solution at time t; v (mL) is the volume of the solution; wR(mg) is the mass of the resin; qt(mg·mg-1) The drug loading of the resin at time t is shown. The results are shown in Table 3, and it can be seen from the data in Table 3 that: compared with a comparative example, the paroxetine hydrochloride suspension has a remarkably high drug loading rate.
(4) Evaluation of mouthfeel
The paroxetine hydrochloride suspensions prepared in examples 1 to 11 and comparative examples 1 to 3 were subjected to taste evaluation by a conventional subjective evaluation method. The results are shown in Table 3, and it can be seen from the data in Table 3 that: the mouthfeel of all examples and comparative examples was sweet with an aromatic smell.
TABLE 6
The applicant states that the invention is illustrated by the above examples to describe a paroxetine hydrochloride suspension and a method of making the same, but the invention is not limited to the above examples, which means that the invention must not be relied upon to practice the invention. It should be understood by those skilled in the art that any modification of the present invention, equivalent substitutions of the raw materials of the product of the present invention, addition of auxiliary components, selection of specific modes, etc., are within the scope and disclosure of the present invention.
The preferred embodiments of the present invention have been described in detail, however, the present invention is not limited to the specific details of the above embodiments, and various simple modifications may be made to the technical solution of the present invention within the technical idea of the present invention, and these simple modifications are within the protective scope of the present invention.
It should be noted that the various technical features described in the above embodiments can be combined in any suitable manner without contradiction, and the invention is not described in any way for the possible combinations in order to avoid unnecessary repetition.
Claims (10)
1. A paroxetine hydrochloride suspension is characterized in that the paroxetine hydrochloride suspension is prepared from the following raw materials: paroxetine hydrochloride, cation exchange resin, impregnant and pharmaceutic adjuvant; the cation exchange resin is composed of a strong-acid cation exchange resin and a weak-acid cation exchange resin.
2. Paroxetine hydrochloride suspension of claim 1, wherein the mass ratio of strong acid cation exchange resin to weak acid cation exchange resin is 1 (2-8), preferably 1 (5-8);
preferably, the mass ratio of the cation exchange resin to the paroxetine hydrochloride is (1-5):1, preferably (1-2): 1.
3. The paroxetine hydrochloride suspension of claim 1 or 2, wherein the strong acid cation exchange resin comprises Amberlite IRP 69;
preferably, the weakly acidic cation exchange resin comprises Amberlite IRP88 and/or Amberlite IRP64, preferably a combination of Amberlite IRP88 and Amberlite IRP 64.
4. The paroxetine hydrochloride suspension of any one of claims 1 to 3, wherein the steeping agent comprises polyethylene glycol;
preferably, the impregnating agent is polyethylene glycol 4000 and/or polyethylene glycol 3350, preferably a combination of polyethylene glycol 4000 and polyethylene glycol 3350;
preferably, the mass ratio of the impregnant to the cation exchange resin is 1 (0.3-1).
5. The paroxetine hydrochloride suspension of any one of claims 1 to 4, wherein the pharmaceutical excipients comprise any one or a combination of at least two of a dispersing agent, a humectant, a sweetener, a flavoring agent, a coloring agent, a thickening agent, a preservative, a pH adjusting agent or an antifoaming agent.
6. The paroxetine hydrochloride suspension of claim 5, wherein the dispersing agent comprises any one or a combination of at least two of propylene glycol, polyethylene glycol 200, or polyethylene glycol 400;
preferably, the humectant comprises glycerin;
preferably, the thickener comprises any one of Avicel RC 591, Avicel CL 611 or Keltrol or a combination of at least two thereof;
preferably, the preservative comprises any one or a combination of at least two of methylparaben, ethylparaben, propylparaben, or sodium benzoate;
preferably, the defoamer comprises a silicone defoamer and/or a polysiloxane defoamer.
7. The process for the preparation of a paroxetine hydrochloride suspension of any one of claims 1 to 6, wherein the process comprises the steps of:
(1) mixing paroxetine hydrochloride and cation exchange resin to prepare a drug-loaded resin compound;
(2) impregnating the drug-loaded resin compound obtained in the step (1) with an impregnant to obtain an impregnated drug-loaded resin compound;
(3) and (3) mixing the impregnated drug-loaded resin compound obtained in the step (2) with a pharmaceutic adjuvant and water to obtain the paroxetine hydrochloride suspension.
8. The preparation method of paroxetine hydrochloride suspension of claim 7, wherein the drug-loaded resin complex is prepared by the following steps: mixing cation exchange resin with water, mixing with paroxetine hydrochloride, washing with water when the concentration of the drug in the solution does not change with time, and drying to obtain the final product;
or mixing cation exchange resin with water, placing into a chromatographic column, adding paroxetine hydrochloride solution into the chromatographic column for chromatography, washing with water when the concentrations of the added solution and the effluent are the same, and drying.
9. The process for preparing a paroxetine hydrochloride suspension of claim 8, wherein the drying temperature is from 40 ℃ to 60 ℃.
10. The process for preparing a paroxetine hydrochloride suspension of any one of claims 7 to 9, wherein the impregnation of step (2) is by: mixing the medicine-carrying resin compound with the impregnant solution, stirring, drying and sieving;
preferably, the stirring temperature is 55-65 ℃ and the stirring time is 20-40 min;
preferably, the temperature of the drying is 40-60 ℃.
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