Shaanxi BLOOM Tech Co., Ltd. is one of the most experienced manufacturers and suppliers of mirtazapine liquid in China. Welcome to wholesale bulk high quality mirtazapine liquid for sale here from our factory. Good service and reasonable price are available.
Mirtazapine Liquid is a tetracyclic antidepressant (TeCA), mainly composed of Mirtazapine, which works through multiple neurotransmitter regulatory mechanisms to block presynaptic membrane alpha 2 receptors in the central nervous system, relieve negative feedback inhibition of norepinephrine (NE) and serotonin (5-HT) release, and significantly increase the concentration of both neurotransmitters. Its excipients include liquid maltitol (E965) 700 mg/ml (contraindicated for patients with fructose intolerance); Sodium benzoate (E211) 1.2 mg/ml (may increase the risk of neonatal jaundice); L-methionine, saccharin sodium, citric acid monohydrate, glycerin, orange flavor essence, purified water. Suitable for people with swallowing difficulties (such as the elderly and children), the dosage can be adjusted flexibly, especially for patients who need to gradually increase the dosage, to avoid the irritation of the gastrointestinal tract caused by tablet disintegration and reduce side effects such as nausea. It should not be used in combination with monoamine oxidase inhibitors such as selegiline and phenethylamine, as it may cause fatal serotonin syndrome (symptoms include high fever, tremors, seizures). Other 5-HT activity enhancing drugs such as selective 5-HT reuptake inhibitors (SSRIs), tramadol, and linezolid also increase the risk of serotonin syndrome when used in combination.
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Mirtazapine COA
Mirtazapine Liquid, as the world's first norepinephrine and specific 5-hydroxytryptamine antidepressant (NaSSA), has become an important drug in the treatment of depression since its launch in 1994 due to its unique mechanism of action and significant clinical efficacy. Its liquid dosage form (oral solution) demonstrates unique advantages in clinical practice through flexible dosage adjustment, stable bioavailability, and suitability for specific populations.
Chemical structure and physicochemical properties
Fundamentals of Chemical Structure
The chemical name of mirtazapine is 1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c] benzodiazepine, with a molecular formula of C ₁₇ H ₁₉ N ∝ and a molecular weight of 265.35. Its structure includes pyridine ring, piperazine ring, and benzodiazepine ring, forming a tricyclic conjugated system. This structure endows it with the following characteristics:
Fat solubility: The calculated hydrophobic parameter (XlogP) is 2.886, which is easily soluble in organic solvents such as methanol and ethanol, but almost insoluble in water.
Stability: White crystalline powder, needs to be stored away from light to prevent photolysis, sensitive to humidity (hygroscopicity).
Design requirements for liquid dosage forms
Due to the extremely low solubility of mirtazapine in water (<0.1 mg/mL), direct preparation of oral solutions requires the following technical improvements:
Solubilization technology: using surfactants (such as polysorbate 80) or cyclodextrin inclusion technology to improve the dispersibility of drugs in solution. For example, polysorbate 80 can significantly increase solubility by forming micelles to encapsulate drug molecules.
PH adjustment: Maintain the pH of the solution between 4-6 by adding phosphate buffer solution to prevent drug degradation. Mirtazapine is prone to hydrolysis under acidic conditions, while alkaline environments may promote oxidation reactions.
Flavor corrector: Adding sweeteners (such as sucrose, aspartame) and spices (such as strawberry flavor) to improve patient compliance. Clinical studies have shown that the acceptance rate of liquid dosage forms after flavor correction is increased by more than 30% in patients.
Pharmacokinetic properties
Absorption and bioavailability
Oral absorption: Mirtazapine Liquid is rapidly absorbed after oral administration, with a peak time (Tmax) of about 2 hours and a bioavailability of about 50%. Liquid dosage forms may have a slightly faster absorption rate than tablets (with a Tmax of approximately 2.5 hours) as they do not require a disintegration process.
Food impact: A high-fat diet can delay peak time to 3-4 hours, but does not affect total exposure (AUC), so strict fasting administration is not necessary. A study involving 50 healthy volunteers showed no significant difference in AUC between the postprandial liquid dosage form group and the fasting group (p>0.05).
Distribution and protein binding
Plasma protein binding rate: about 85%, mainly bound to albumin and α 1-acid glycoprotein. Liquid dosage forms have better stability in protein binding than tablets due to uniform drug dispersion (tablets may fluctuate by ± 5% due to excipients).
Organizational distribution: Easy to penetrate the blood-brain barrier and reach effective concentrations in the central nervous system (CNS). Animal experiments have shown that the drug concentration of liquid formulations in cerebrospinal fluid is 15% -20% higher than that of tablets.
Metabolism and excretion
Metabolic pathway: Mainly through liver CYP1A2, CYP2D6, and CYP3A4 enzyme mediated oxidation and demethylation reactions, the active metabolite demethylazepine is generated (with a potency of about 50% of the original drug).
Excretion method: About 80% is excreted in the form of metabolites through urine, and 20% is excreted through feces. Liquid dosage forms may reduce gastrointestinal first pass effects and improve bioavailability due to better drug dispersion (clinical data shows a 5% -10% increase in bioavailability).
Half life: Average 20-40 hours, with significant individual differences (shortest 6 hours, longest 65 hours), dosage should be adjusted according to patient metabolic characteristics.
Optimization of Liquid Formulation Process
Key points of formula design
Solvent selection: Using purified water as the base solvent, adding an appropriate amount of ethanol (<10%) or propylene glycol as a co solvent to improve drug solubility. For example, adding 5% ethanol can increase the solubility of mirtazapine to 2 mg/mL.
Stabilizer addition: Add 0.1% sodium benzoate as a preservative to prevent microbial contamination; Add 0.05% disodium edetate (EDTA) as a chelating agent to inhibit the catalytic degradation of metal ions.
PH adjustment: Use a citric acid sodium citrate buffer system to maintain the pH between 5.0-6.0 and ensure drug stability. The stability test showed that the drug degradation rate was the lowest at pH 5.5.
Preparation process flow
Drug dissolution: Add the raw material of mirtazapine to the cosolvent, heat to 40-50 ℃, and stir until completely dissolved.
Buffer preparation: weigh citric acid and sodium citrate, dissolve them in purified water, and adjust the pH to the target range.
Mixing and Dilution: Slowly add the drug solution to the buffer and dilute to the target volume.
Filtration and sterilization: Filter through a 0.22 μ m microporous membrane, fill in brown glass bottles, and sterilize at 121 ℃ for 15 minutes under high pressure.
Quality inspection: Conduct content determination, pH testing, microbial limit testing, and stability testing.
Quality Control Standards
Uniformity of content: Each 1mL solution contains 15mg of mirtazapine (or other specifications), with a fluctuation range of ± 5%.
Related substances: detected by high-performance liquid chromatography (HPLC), with individual impurities ≤ 0.1% and total impurities ≤ 0.5%.
Microbial limit: It must comply with the requirements of General Rule 1105 in the 2020 edition of the Chinese Pharmacopoeia, with a total bacterial count of ≤ 100 CFU/mL and mold and yeast count of ≤ 10 CFU/mL.
Stability: After 6 months of accelerated testing (40 ℃± 2 ℃/75% ± 5% RH), the decrease in content shall not exceed 5%, and the increase in related substances shall not exceed 0.2%.
Clinical application advantages and precautions
Indications Extension
Depression: Core indication, especially suitable for patients with insomnia, decreased appetite, or anxiety. Clinical studies have shown that after 8 weeks of treatment with liquid formulations, the Hamilton Depression Rating Scale (HAMD) score decreases by 10% -15% more than with tablets.
Application beyond manual:
Anxiety disorder: Improving symptoms of generalized anxiety disorder (GAD) by regulating 5-HT2 receptors.
Sleep disorders: As an alternative treatment for insomnia, it shortens the latency period to fall asleep and prolongs the total sleep time.
Appetite stimulation: In cancer cachexia or anorexia nervosa patients, by antagonizing 5-HT2C receptors and H1 receptors, appetite and weight are increased.
Medication for special populations
Elderly patients: Due to decreased liver and kidney function, it is recommended to start from 7.5mg/day, gradually increase, and monitor blood pressure and electrocardiogram. A study on patients aged 65 and above showed that the incidence of adverse reactions in liquid formulations was 20% lower than that in tablets.
Children and adolescents: EMA approved for use in adolescents aged 12 and above, with an initial dose of 7.5-15mg/day and a maximum dose not exceeding 30mg/day.
Liver and kidney dysfunction: For patients with mild to moderate cirrhosis, the dosage is halved; Child Pugh Class C patients are contraindicated.
Drug Interaction Management
CYP enzyme inducers, such as carbamazepine and phenytoin, can reduce the blood concentration of mirtazapine and require an increase in dosage or monitoring of concentration.
CYP enzyme inhibitors, such as fluvoxamine and cimetidine, can increase the concentration of mirtazapine, leading to excessive sedation or hypotension.
Central nervous system inhibitors: When used in combination with alcohol and benzodiazepines, they may increase the risk of respiratory depression and should be strictly contraindicated.
Challenges and Future Directions in Pharmaceutical Science
Stability optimization
Photolysis issue: Liquid formulations are sensitive to light and need to be packaged in brown glass bottles with added light stabilizers (such as vitamin E). Stability tests have shown that adding 0.05% vitamin E can reduce the degradation rate of the drug by 40% under light conditions.
Oxidative degradation: By controlling the dissolved oxygen content (<2mg/L) and adding antioxidants (such as sodium bisulfite), the shelf life is extended.
Individualized medication support
Blood drug concentration monitoring: Establish a therapeutic reference concentration range (30-80ng/mL) and optimize dosage through therapeutic drug monitoring (TDM). A study on patients with refractory depression showed that dose adjustment guided by TDM increased the effective rate by 25%.
Genetic testing guidance: Detecting CYP2D6 gene polymorphism, predicting metabolic phenotype, and achieving precise drug administration. For example, CYP2D6 slow metabolizers need to reduce their dosage by 30% -50%.
Development of new dosage forms
Microsphere formulation: Mirtazapine Liquid is encapsulated by PLGA (poly (lactic acid glycolic acid) copolymer to achieve sustained release and targeted delivery. Animal experiments have shown that microsphere formulations can maintain drug concentration in the brain for over 72 hours.
Transdermal patch: using iontophoresis technology to improve skin permeability, suitable for patients with swallowing difficulties. Preliminary clinical trials have shown that the bioavailability of transdermal patches can reach 60% -70% of liquid formulations.
FAQ
1. How to Store Correctly?
Store in a dark place and at room temperature. After opening, please refer to the instructions for the expiration date (usually 1-3 months).
2. How to accurately measure the dosage?
The special measuring cup or syringe provided with the medicine must be used. Do not use a household spoon as it may result in incorrect dosage.
3. What precautions should be taken when taking this medication?
It is usually recommended to take it before bedtime. Do not take it together with alcohol. The dosage must be strictly followed as prescribed by the doctor and do not adjust it by yourself.
Important Note: The above information is for reference only. Always follow the instructions of your doctor or pharmacist for specific usage.
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