Preparation and in vitro release studies of azithromycin losartan gastric Floating Sustained Release Tablets

[Abstract] Objective the the wet granulation Aziz Chastain gastric floating sustained-release tablets and its release evaluation method to release single factor experiment investigated prescription HPMC specifications and usage as index bicarbonate The amount of sodium and low-substituted hydroxypropylcellulose in an amount of the prepared tablets (high temperature, excessive light, humidity) investigated the influence factors results the optimal prescription HPMCK100M dosage of 110mg / sheet, in an amount of sodium bicarbonate 200 mg / tablet, and low-substituted hydroxypropylcellulose in an amount of 100 mg / tablet. average release rate was 88.2%, holding the drift time of 7.5H. Factors Affecting test the stability of the tablet are preferably Conclusion each of the indexes compliance, the prescription process is reliable.

[Keywords] Aziz Chastain Floating Sustained preparation in vitro release

[ABSTRACT] OBJECTIVE Azilsartan Floating Sustained Release Tablets were prepared by granulation method, and the in vitro release was studied. METHODS The formulation of Azilsartan Floating Sustained Tablets was optimized by One-factor experimental design using the in vitro release as the main evaluation parameter.The amount of HPMCK100M, sodium bicarbonate and low-substituted hydroxypropyl cellulose were used as factors. The influencing factors (high temperature, high light, and high moisturewere investigated as well. RESULTS The optimized formulation of Azilsartan Floating Sustained Tablets was as follows: HPMCK100M 110mg/tablet, sodium bicarbonate 200 mg / tablet, and L-HPC 100 mg / tablet. The drug release was 88.2%, and floating time was 7.5h. In the influencing factor test, the tablets were stable. CONCLUSION Each index of the prescription of Azilsartan Floating Sustained Release Tablets meet requirements.The technology is stable and reliab1e.

[Key Words] Azilsartan Floating Sustained Release Tablets Preparation In vitro release

Aziz Chastain is a new generation of selective AT1 subtype angiotensin II receptor blockers (ARBs class of anti-hypertensive drugs with angiotensin-converting enzyme inhibitors (ACEI) class of antihypertensive drugs, compared with a smooth drop pressure does not cause the advantages of a dry cough. listed multiple ARBs, but for many patients, only inhibition of the renin - aldosterone system (RAS activity is not sufficient to control blood pressure and reduce the risk of cardiovascular disease and diabetes. research shows , Aziz Chastain as the new generation of dual-function ARBs antagonize angiotensin II type 1 receptor (AT1 receptor, through a variety of mechanisms may also reduce the risk of cardiovascular disease and diabetes [1,2] .2010 April 28, Japan's Takeda Pharmaceutical Company (Takeda completed Phase III clinical trials of the drug. clinical trials to prove that the goods have a good effect, and a lower incidence of adverse effects and better compliance. gastric Floating Retention sustained release tablets [3] is a special kind of sustained release formulations after oral administration, floats on top of the gastric juice, while slow release, thereby extending the residence time of the drug in the stomach, so that the absorption rate of the drug in the upper end of the stomach and small intestine not yet See Chastain stomach Aziz floating sustained-release tablets reported this experiment were prepared using wet granulation azithromycin losartan gastric Floating Sustained Release Tablets, a preliminary evaluation of the quality of its in vitro dissolution preparations.

1 Materials

1.1 Instrument

TDP single punch tablet machine (Shanghai Tianfan machine factory) PYC-A-type tablet hardness tester (Shanghai Huanghai drug test instrument factory) 2RS-8G Intelligent Dissolution Tester (Tianjin Sea Star Technology Co., Ltd., UV- 2450 UV spectrophotometer (Shimadzu Corporation, Japan

1.2 Reagents

Aziz Chastain (Zhejiang Taizhou Baolong Chemical Co., Ltd., Hypromellose HPMC MethocelK4M, K15M, K100M, Shanghai Colorcon Coating Technology Co., Ltd.), low-substituted hydroxypropyl cellulose (L-HPC, Anhui province Pharmaceutical Excipients Co., Ltd., magnesium stearate (Hunan Kang Pharmaceutical Corporation, sodium bicarbonate (Hubei Hing Galaxy Chemical Co., Ltd.).

2 Methods and Results

2.1 preparation process of the raw materials, HPMC, L-HPC and sodium bicarbonate, respectively, through a 100 mesh sieve, France Mix sliding scale by an equal amount, with 80% ethanol solution as a binder, using a 30-mesh granulation, 60 ℃ dried 4 h, the whole, adding magnesium stearate and mixing, tabletting, hardness control in 10-12 kg.

2.2 Determination of quality evaluation of the right amount of the original drug, wavelength selection accurately weighed hydrochloric acid plus 0.1 mol · ml-1 to 0.1 mol · ml-1 hydrochloric acid blank, in the wavelength range 200-400 nm scan at 240 nm, the maximum absorption peak, and accessories without interference, so choose a 240 nm UV detection wavelength.

2.3 floating properties in vitro experiments using the second method of Chinese Pharmacopoeia 2010 edition Appendix XC device Aziz Chastain gastric floating sustained-release tablets at 37 ℃ 0.1 mol · ml-1 hydrochloric acid in 900 ml, speed 50 r · min-1 observed sustained-release tablets from the drift time and held the drift time T. system tablet can rapidly within 10 min from the bleaching, bleaching time the prescription, as detailed below.

2.4 release test

2.4.1 standard curve accurately weighed Aziz Chastain reference substance 10.51 mg, accurately weighed, set 100 ml volumetric flask, and dissolved in 0.1 mol · ml-1 hydrochloric acid and dilute to the mark, shake, as solution I. Precision Measure the solution I 2 ml, 4 ml, 5 ml, 6 ml, 7 ml, set 100 ml volumetric flask, diluted with 0.1 mol · ml-1 hydrochloric acid to the mark, as the test solution, according to the UV - visible spectrophotometry (Chinese Pharmacopoeia 2010 edition two Appendix IVA absorbance was measured at 240 nm wavelength in a concentration C (μg ml-1 as abscissa, absorbance A longitudinal coordinates, linear regression. The test results are shown in Table 1.

2.4.2 recoveries reference solution: accurately weighed reference substance 10.53 mg of azithromycin losartan set 100 ml volumetric flask, add hydrochloric acid appropriate amount of 0.1 mol · ml-1, shaking Aziz losartan dissolved, add 0.1 mol · ml-1 diluted hydrochloric acid to the mark, shake, the precise amount of filtrate added 5 ml set 100ml volumetric flask, diluted with 0.1 mol · ml-1 hydrochloric acid to the mark, shake, as the reference solution.

2.4.3, respectively, for the test solution by prescribing the amount of 80%, 100%, 120% accurately weighed reference substance about 8.0 mg of azithromycin losartan, 10.0 mg, 12.0 mg, 3 copies of each concentration, 9, set 100 ml volumetric flask, respectively, joined by prescription accessories, hydrochloric acid 0.1 mol · ml-1, plus the right amount, shaking Aziz losartan dissolved, add 0.1 mol · ml-1 hydrochloric acid diluted to the mark, shake, filtration, The precise amount of the filtrate 5 ml, set 100 ml volumetric flask, diluted with 0.1 mol · ml-1 solution of hydrochloric acid to the mark, shake, as the test solution.

Were taken of the reference solution and the test solution, according to spectrophotometry (Chinese Pharmacopoeia 2010 edition two Appendix Ⅳ A absorbance was measured at the wavelength of 240 nm. Calculation of recovery test results are shown in Table 1.

2.4.4 precision take the linear relationship between the test under a concentration of 5.255 μg · ml-1 solution, as the test solution, according to spectrophotometry (Chinese Pharmacopoeia 2010 edition two Appendix Ⅳ A continuously measured at the wavelength of 240 nm absorbent degrees 6 and recorded, and the test results are shown in Table 1.

2.4.5 solution stability to take the the dissolution determination under the solution, respectively 0,1,2,4 hours determined by dissolution method to examine the stability of solution

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results show that good this Act linearity, precision, recovery and stability of solution.
2.4.6 Method for determination to take this product, according to the release assay (Chinese Pharmacopoeia 2010 edition two Appendix Ⅹ C law, speed 50 r · min-1, 900 mL of 0.1 mol · ml-1 hydrochloric acid for a medium temperature 37 ℃. operating in accordance with the law, the sampling timing (while complementing the same temperature and the same amount of the corresponding media), the precise amount of filtrate added 5ml, home 50ml volumetric flask, dilute to the mark with the dissolution medium, shake as the test solution, and the other precision Weigh Aziz Chastain appropriate reference and diluted per 1ml about containing 4μg solution. taken the two solutions with 0.1 mol · ml-1 hydrochloric quantitative, according to ultraviolet - visible spectrophotometry (Chinese Pharmacopoeia 2010 edition Ministry Appendix Ⅳ A, the absorbance was measured at 240nm wavelength, respectively, were calculated at different times of the cumulative release.

The 2.5 different factors on the tablet vitro release and floating performance
The size selection 2.5.1 HPMC tablet is prepared using "2.1 Preparation Process" under process, were investigated to HPMCK4M (4000 mPa · s), K15M (15000 mPa · s), K100M (100000 mPa · s) as a skeleton material on vitro release dosage was 110 mg / piece, the results shown in Figure 1.

Figure 1 HPMC different specifications (n ​​= 3

The results showed that HPMC viscosity increases the release rate slows with increasing viscosity, plus floating slightly enhanced performance, to improve sustained release and floating effect, choose the specifications for K100M skeleton material.

The choice selection specifications 2.5.2 HPMC K100M dosage the K100M skeleton materials were investigated tablets 90mg / tablets 110mg / 130mg / tablets of different dosage release, the results shown in Figure 2.

Figure 2 HPMC K100M influence of the amount (n = 3
With the increased use of HPMCK100M, slow down the release rate and the amount of 3 significant difference (P> 0.05). The floating performance study show that, when K100M with increase in volume drift time of 110mg / films held about the above results, for 7.5 h, considering the preparation process to control the amount of HPMC K100M 110mg / tablets.

2.5.3 Sodium bicarbonate dosage release regulating the amount of sodium bicarbonate prescription for tablets 150mg / 200mg / tablets, 250mg / tablets, other accessories and the same preparation, Compare tablets in vitro release (Figure 3).

Figure 3 sodium bicarbonate amount of release (n = 3
The results indicate that the selected amount of 3 significant difference (P> 0.05). The floating performance study shows that sodium bicarbonate increased use of floating performance to continuously enhance the selected amount of 3 significant difference (P> 0.05) , 150mg / sheet holding drift time T at 5.3 h, this may be because of the low amount of sodium bicarbonate used in an amount easily depleted sake Preparation process control sodium bicarbonate used in an amount of 200mg / sheet.

2.5.4 low-substituted hydroxypropylcellulose dosage effect on the release of the prescription of low-substituted hydroxypropyl cellulose was adjusted to be used in an amount of 50mg / tablets, 100 mg / tablet, 150 mg / tablet, and other excipients and the same method, compare tablets in vitro release (see Figure 4).

Figure 4 low-substituted hydroxypropyl cellulose of the amount of release (n = 3
The results show that the low-substituted hydroxypropylcellulose to cause the accelerated release rate with increase in volume and Assembly, the preparation process control low-substituted hydroxypropyl cellulose used in an amount of 100mg / sheet.

2.5.5 tablet prescription determine

The prescription 2.1 of said tableting floating properties in vitro assay showed that after about 1min tablet surface layer of gel barrier is formed, and holding the tablet shape, floating on the liquid surface. Tablet volume gradually increases with time, but still maintaining the integrity of the sheet-shaped holding the drift time of 7.2 h.

3 Factors Influencing the use of aluminum-plastic composite film packaging, the the homemade sample piece placed directly under the following conditions: 60 ° C (high temperature), 92.5% relative humidity (high humidity), illumination 4500 lx (light). Respectively 0 5,10 d sampling, test results in Table 2.

Table 2, the factor influencing the experimental results (n = 3


Tab2 Results of stability experiments of sample

Light, high temperature (60 ° C and high humidity (92.5% The results showed that the high temperature (60 ° C and high humidity (92.5% 5 days 10 days Appearance, release content substantially no change 10 days related substances of the high temperature is slightly elevated , illumination test the indexes are obvious changes. Therefore, in order to ensure the stability of this product, double-sided plastic composite film packaging.

4 Discussion In this study, wet granulation tablet prescription HPMC hydrophilic matrix material, water can form a gel layer play a sustained release sodium bicarbonate case of acid (gastric juice can react quickly to produce carbon dioxide play drift from the drug to maintain a slow release in the stomach, the present prescription, low-substituted hydroxypropyl cellulose as disintegrating agent, to promote tablet release plays a good regulation. this experiment, the choice of the traditional process, the cost low, easy to implement industrial production.

References

[1] Kathy Zaiken, PharmD, Judy WM Cheng etc. Azilsartan Medoxomil: A New Angiotensin Receptor Blocker. Clinical Therapeutics, 2011,33 (11) :1577-1589
[2] Keiji Kusumoto, Hideki Igata, Mami Ojima etc. Antihypertensive, insulin-sensitising and renoprotective effects of a novel, potent and long-acting angiotensin II type 1 receptor blocker, azilsartan medoxomil, in rat and dog models. European Journal of Pharmacology , 2011,669 (1-3) :84-93
[3] Yang Xun, Hu Liandong. Ciprofloxacin hydrochloride floating sustained-release tablets and in vitro release of Chinese medicine industry magazine, 2007,38 (11:776-779

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