Key words valsartan dispersible tablets;,, orthogonal design;,, high-performance liquid chromatography
Abstract: Objective To develop a valsartan tablet and carry out determination. Method of orthogonal design method was optimized using the best conditions for preparation. High-performance liquid chromatography in different batches of Valsartan Dispersible Tablets. The results of the goods in the total collapse within 1 min and the determination of stability. Conclusion preferred prescription tablet valsartan prepared by the collapse of quick, uniformly dispersed and the results comply with the limits of determination of requirements.
Keywords: Valsartan tablet; orthogonal design; high-performance liquid chromatography
Preparation and Content Determination of Valsartan Dispersible Tablets
Abstract: ObjectiveTo study the preparation of valsartan dispersible tablets and to determine valsartan content in the formulation.MethodsThe conditions for preparation were optimized by orthogonal design and the determination of valsartan was studied with a HPLC method. ResultsThe tablets could completely disintegrate within 1 min. ConclusionThe dispersible tablets prepared in optimum condition were rapid in disintegration and homogenous in dispersal with a stable content.
Key words: Valsartan dispersible tablet; Orthogonal design; HPLC
Valsartan (Valsartan, VAL) for the angiotensin �� (Ang ��) receptor AT1 blockers, which can prevent the Ang �� and tighten the blood vessels caused by the release of aldosterone, to mild to moderate essential hypertension antihypertensive effect of significant no less favorable than the existing antihypertensive drugs, but also reverse cardiac hypertrophy caused by high pressure, and fewer adverse reactions . In order to facilitate swallowing difficulties in infants and young children and in patients taking , we have developed a valsartan tablet and carry out determination.
1 Materials and methods
1.1 Drugs and reagents Valsartan API (Shanghai sine laboratory, batch number 020,916); Valsartan reference substance (Changzhou Kangli Livzon Pharmaceutical Group Co., Ltd.); valsartan tablet (self-made, 80 mg / film); accessories are used in pharmaceutical excipients; the reagents were analytical pure.
1.2 Instrument ZRS8 Intelligent Dissolution Tester (Tianjin University Precision Instrument Factory); high-performance liquid chromatography (Shimadzu Corporation); electronic balance (Shanghai Precision Instrument Factory); tablets with four detector (Shanghai Yellow doping Instrument Factory) ; Shan Chong profiled sheeting machine (Shanghai Pharmaceutical Machinery 3 plant).
1.3 Preparation of dispersible tablets
1.3.1 Prescription and preparation process of Valsartan and microcrystalline cellulose (MCC), carboxymethyl starch sodium (CMSNa), sodium lauryl sulfate (SLS), magnesium stearate, lactose are over 100 mesh sieve, After mixing with the amount of 2% PVP aqueous solution system of soft material, with 40 mesh nylon net granulation, was inside the oven (60 �� 2) �� temperature drying 6 h, 30 mesh sieve Whole, by adding agents and Mixed collapse lubricant, mixed evenly, placing sealed container, after passing inspection tablet derived.
1.3.2 to determine the best prescription by orthogonal experiments, may disintegrating agents and swelling ratio of excipients to filter. After pre-test to determine the effects of the preparation of dispersible tablets main factors for the A (lactose), B (MCC), C (CMS-Na), D (SLS), sub-3 levels of each factor, according to L9 (34) orthogonal experiment table design experimental program factor level in Table 1, to in vitro dissolution of the indexes.
Table 1 experimental factor level (abbreviated)
1.4 Analysis of the establishment
1.4.1 Determination of the wavelength determine the amount of valsartan reference substances and by prescribing the ratio of full-accessories were added to the flask with 0.1 mol / L hydrochloric acid solution to dissolve scale, respectively, in the 200 ~ 400 nm wavelength range for purple outside the scan. The results showed that: valsartan in 0.1 mol / L hydrochloric acid in the maximum absorption wavelength of 270 nm, and accessories at this wavelength was not absorbed.
1.4.2 Chromatographic conditions for the choice of column Nucleosil C18 column (4.6 mm �� 250 mm, 5 ��m), mobile phase of acetonitrile: water: acetic acid (48:52:0.1), flow rate 1.0 ml / min, Determination of wavelength of 270 nm, column temperature at room temperature.
1.4.3 Standard curve said precision reference substance is about taking valsartan 80 mg, buy 100 ml flask, add the amount of mobile phase, ultrasound 15 min allows the dissolved, diluted to the scale, shake, sophisticated take the amount of 4 ml to 50 ml Liang Ping, the constant volume, precision capacity to take 1,3,5,7,9 ml to 10 ml Liang Ping, add the mobile phase was diluted to scale, take 20 ml into the chromatograph, respectively, on the peak area of drug the concentration of linear regression. The results showed that: valsartan in 6.4 ~ 57.6 ��g / ml concentration range of the regression equation: A = 12 200C-5 654.9, a good linear relationship (r = 0.999 9).
1.4.4 recovery and precision were given valsartan precision that is about 64,80,96 mg buy 100 ml Liang Ping, press the prescription ratio, add the appropriate accessories, and each with an appropriate mobile phase, ultrasound allows the dissolved, Canada The mobile phase was diluted to scale, shake, filter, take home 50ml Liangping added 2ml filtrate, add the mobile phase was diluted to scale, take 20ml solution into the chromatograph analysis. Low, middle and high concentrations of valsartan in three different samples of the average recoveries were (99.5 �� 1.0)%, (98.5 �� 1.3)%, (101.5 �� 0.8)% (n = 5), low, middle and high 3 different concentrations of Valerian Chastain sample precision RSD were 1.17%, 1.23%, 0.89% (n = 5). Reposted elsewhere in the paper for free download http://www.hi138.com
1.5 Determination of 10 to take this product, and research small, sophisticated take that amount of powder (equivalent to valsartan is about 80 mg), set 100 ml Liang Ping, add the amount of mobile phase, ultrasound 15 min allows the dissolved, add liquidity phase was diluted to scale, shake, filter, precision volume of 2 ml continued to take home the filtrate 50 ml Liang Ping, add the mobile phase was diluted to scale, take 20 ml solution into the chromatograph analysis; valsartan reference substance with an alternative method measured by external standard method to calculate the peak area indicated the average amount of dispersible tablets.
1.6 disintegration properties of check "Chinese Pharmacopoeia" 2000 version of "disintegration agents check the item" states: the collapse of medium temperature control (20 �� 2) ��, check the dispersible tablet disintegration time should be less than 3 min and the collapse of solution after the particles should all through the 710 ��m sieve. The results showed that three groups dispersible tablets complete disintegration time were 1 min, the dispersed particles all passed 710 ��m sieve, in line with the collapse of dispersible tablets duration and dispersion uniformity requirements.
1.7 weight difference between 3 groups of valsartan dispersible tablets sample test results are in line with the provisions under the relevant .
2.1 Orthogonal experimental design results according to L9 (34) orthogonal experimental table design experimental programs to study the in vitro dissolution of indicators, their programs and results of orthogonal experiment in Table 2.
Table 2 L9 (34) orthogonal experimental results (omitted)
As can be seen from Table 1 data, the impact of tablet excipients on the order: C> D> A> B; the best prescription for: A2B3C2D1. Accordingly, the self-preparation in the 3 groups of valsartan tablet samples, obtained by smoothing the appearance of the tablet, dissolution characteristics of a good.
2.2 Determination of three batches of samples results in Table 3.
Table 33 batches of samples by HPLC results (omitted)
3 groups of valsartan tablet samples using high performance liquid measured by external standard method to calculate peak area of the labeled amount of dispersible tablets, the average (103.52 �� 0.15)% (n = 3).
Dispersible by at least one kinds of disintegrating agents and in contact with water to form a high viscosity of the swelling of accessories which are made to change the composition of prescription accessories can be adjusted within a certain range tablet disintegration time limit to conform to the requirements of dispersible tablets . Valsartan dispersible tablets and the disintegration of the tablets difference is illustrated together "Chinese Pharmacopoeia" requirement, other items attached to associates, internal control standards; its analysis studies have shown that: HPLC determination of content is simple, fast and accurate, re - is good and feasible, be able to more accurately determine the content of valsartan. Of sodium carboxymethyl starch study the impact of the collapse, carboxymethyl starch sodium for fast disintegrating agent, 1% ~ 10% by adding the amount of controlled trials showed that: 1% ~ 2% of the impact of the collapse was not significant (1.6 ~ 1.8 min); 3% ~ 7% significantly accelerated the collapse of (0.6 ~ 0.7 min), 8% ~ 10% but delayed by the collapse of (1.1 ~ 1.7 min), probably because of partial hydrolysis of sodium carboxymethyl starch, resulting from plastic -like substance induced. As the cited carboxymethyl wet, 6% or more by adding the amount of tablets obtained were significantly absorb moisture, become soft phenomena. Different concentrations of PVP on the tablet has a great impact on the collapse. With 5% PVP aqueous solution of different concentrations of ethanol as a binder, anhydrous ethanol, the disintegration time of 5.8min, with the reduction in the proportion of ethanol, collapse accelerated, to the aqueous solution to achieve the fastest time (1.0 min). With different concentrations of PVP aqueous solution as adhesive, 10% disintegration time of 5.2 min, with the reduction in the proportion of PVP, collapse accelerated; 1% to 2% concentration difference was not significant (0.9 ~ 1 min), and compare the adhesive 2% PVP aqueous solution and 2% starch slurry, examine the tablet disintegration time, experimental results show that with 2% PVP solution as the glue better. The preparation with 2% PVP aqueous solution as adhesive, can increase the hydrophilic to accelerate collapse. Examine the impact of increased volume of solvent, in order to further shorten the disintegration time and increase dissolution, adjust by adding commonly used surfactant (sodium lauryl sulfate, SLS) to increase the amount of drugs can change the wettability and solubility of valsartan in the water-miscible uniformity, to increase drug dissolution in the gastric juice. Good selection of compressibility microcrystalline cellulose, increase the availability of medicines in compressibility; use lactose because of its better appearance to help collapse the role and tablet forms and finish are good, and further enhance the disintegration of the dispersible tablets speed.
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