Stability Test of Naomai Xingshen Capsules

Congyan ZENG, Xiaoyan PANG, Yuliang HU, Xiaofang XIN

Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine, Zhongshan 528400, China

Abstract [Objectives] To explore the stability of Naomai Xingshen Capsules. [Methods] Accelerated test and long-term test were carried out to investigate the changes in properties, identification, moisture, disintegration time and microbial limit of Naomai Xingshen Capsules. [Results] There were basically no changes in all indicators for the three batches of samples (after 6-month accelerated test and 24-month long-term test), and they all met the requirements of quality standards. [Conclusions] The preparation of Naomai Xingshen Capsules is stable and reliable, and the stability test provides a reliable basis for its expiration date.

Key words Naomai Xingshen Capsules, Accelerated test, Long-term test, Stability

1 Introduction

Naomai Xingshen Capsules is developed by Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine on the basis of the experience in the treatment of craniocerebral trauma and acute cerebral hemorrhage, according to the theory of traditional Chinese medicine (TCM), and developed on the basis of good clinical application effect. Naomai Xingshen Capsules are mainly consisted of Rhei Radix Et Rhizoma, Persicae Semen, Carthami Flos, Salviae Miltiorrhizae Radix Et Rhizoma, Scutellariae Radix, Gardeniae Fructus, Magnoliae Officinalis Cortex, Pinelliae Rhizoma Praeparatum, Poria, Arisaema Cum Bile, and Bambusae Caulis In Taenias. With functions of activating blood circulation and resolving phlegm, purging fu-organs to eliminate heat, and opening the orifices, it is mainly used for traumatic brain injury, stroke-induced dizziness, dizziness, headache, and constipation, which belong to syndrome of phlegm and heataccumulation[1]. At present, clinical studies have confirmed that Naomai Xingshen Capsules has good effects on acute subdural hematoma in severe craniocerebral injury and acute cerebral edema after hemorrhagic stroke[2-3]. In order to ensure the stability of Naomai Xingshen Capsules during storage, transportation and use, and to ensure the quality of the drug, our team carried out an accelerated stability test and long-term stability test for Naomai Xingshen Capsules with reference to the relevant provisions of 2010 edition of theChinesePharmacopoeia(Volume II)[4]and relevant literature methods[5], and in accordance with the quality standard of Naomai Xingshen Capsules.

2 Instruments and materials

2.1 InstrumentsLHS-150SC laboratory constant temperature and humidity test chamber (Shanghai Yiheng Scientific Instrument Co., Ltd.); Agilent 1260 high performance liquid chromatography system; Chromatographic column: Venusil XBP C18(L) column (250 mm×4.6 mm, 5 μm, Agela Technologies); KQ3200E medical ultrasonic cleaner (Kunshan Ultrasonic Instrument Co., Ltd.); LMQ, C vertical sterilizer (Shandong SHINVA. Shinva Medical Instrument Co., Ltd.); LRH-150B biochemical incubator (Guangdong Medical Equipment Factory); LB-881C six tube disintegration tester (Jiangsu Wuxi Keda Instrument Factory); JA1203 electronic balance (Shanghai Balance Instrument Factory); electric heating constant temperature water bath (Shanghai Hengping Instrument and Meter Factory); silica gel G thin-layer board (Branch Company of Qingdao Ocean Chemical Co., Ltd.).

2.2 MaterialsRhei Radix Et Rhizoma reference crude drug, Scutellariae Radix reference crude drug, Aurantii Fructus Immaturus reference crude drug and Salviae Miltiorrhizae Radix Et Rhizoma reference crude drug, Notoginsenoside R1reference material were provided by China National Institute for the Control of Pharmaceutical and Biological Products (batch No.:121249-201003, 120955-201008, 120936-201005, 120923-201113, 110745-200617); acetonitrile was chromatographically pure, water was double-distilled water, and the rest of the reagents were of analytical grade; Naomai Xinshen Capsules (batch No.:20110113, 20110226, 20110315) were provided by Preparation Laboratory of Zhongshan Hospital of Traditional Chinese Medicine Affiliated to Guangzhou University of Chinese Medicine.

3 Methods and results

3.1 Survey indications and methods

3.1.1Properties. This product is capsule, the content is brownish yellow to tan powder; the odor is slight, the taste is bitter and slightly salty.

3.1.2Identification. With reference to the relevant methods in the registration standard of Naomai Xingshen Capsules[2], we conducted the thin layer chromatography (TLC) identification of Rhei Radix Et Rhizoma, Scutellariae Radix, Aurantii Fructus Immaturus and Miltiorrhizae Radix Et Rhizoma in the preparation.

3.1.3Moisture. Took 2-5 g of the content of the test product and measured it using the moisture determination method [Appendix IX H of theChinesePharmacopoeia(2010 edition)], and the moisture should not exceed 9.0%.

3.1.4Loading difference. Took 10 capsules of the test product, and checked using the loading difference method under the capsule item [Appendix I L ofChinesePharmacopoeia(2010 edition)]. The limit of the loading difference should be within ±10% of the labeled volume.

3.1.5Disintegration time. Took 6 capsules of the test product and checked according to the disintegration time method [Appendix XII A ofChinesePharmacopoeia(2010 edition)], all capsules should be disintegrated and pass through the screen within 30 min.

3.1.6Microbial limit test. Took the capsules and checked using the microbial limit test method [Appendix XIII C ofChinesePharmacopoeia(2010 edition)]. The count of bacteria, mold and yeast should not exceed 10 pieces/g, andEscherichiacoli,Salmonella, and live mites should not be detected, and should comply with relevant regulations.

3.1.7Content determination. With reference to the method for the determination of the content of Notoginsenoside R1in Naomai Xinshen Capsules previously studied by our team[5], we determined the content of Notoginsenoside R1in the preparation.

3.2 Stability test

3.2.1Accelerated test. We took three batches of samples (batch No.:20110113, 20110226, 20110315) with the market package and placed them in a test box with constant temperature (40±2) ℃ and relative humidity (75±5)% for 6 months. We conducted sampling in the end of 0, 1, 2, 3 and 6 months, respectively, and tested according to the quality standard of this product. Through comparing the test results with those in 0 month, we found that all of the three batches of samples at 0, 1, 2, 3 and 6 months met the requirements of the quality standard in terms of properties, thin layer identification, moisture, disintegration time, and microbial limit, and the content of Nodoginsenoside R1did not change significantly compared with the initial value, indicating that the stability of Naomai Xinshen Capsules in the accelerated test meets the requirements. The specific results are listed in Table 1. The TLC identification is shown in Fig.1 to Fig.4.

Table 1 Accelerated test results of Naomai Xinshen Capsules

3.2.2Long-term stability test. We took three batches of samples (batch No.:20110113, 20110226, 20110315) with the market package and placed them in a test box with temperature (25±2) ℃ and relative humidity (60±10)%. We conducted sampling in the end of 0, 1, 2, 3, 6, 9, 12, 18 and 24 months, respectively, tested according to the quality standard of this product. We found that all of the three batches of samples in the end of 0, 1, 2, 3, 6, 9, 12, 18 and 24 months met the requirements of the quality standard in terms of properties, thin layer identification, moisture, disintegration time, and microbial limit, and the content of Nodoginsenoside R1did not change significantly compared with the initial value, indicating that the stability of Naomai Xinshen Capsules in the long-term stability test meets the requirements. The specific results are listed in Table 2. The TLC identification is shown in Fig.1 to Fig.4.

Note: 1-3: Accelerated stability test sample; 4-6: Room temperature stability test sample; 7: Rhei Radix Et Rhizoma reference crude drug.

Note: 1-3: Accelerated stability test sample; 4-6: Room temperature stability test sample; 7: Scutellariae Radix reference crude drug.

Note: 1-3: Accelerated stability test sample; 4-6: Room temperature stability test sample; 7: Aurantii Fructus Immaturus reference crude drug.

Note: 1-3: Accelerated stability test sample; 4-6: Room temperature stability test sample; 7: Miltiorrhizae Radix Et Rhizoma reference crude drug.

From Table 2, it can be known that the samples were placed in an environment of (25 ± 2) ℃ and relative humidity of (60±10)% for 12 months, and all the investigation indicators of Naomai Xingshen Capsules did not change significantly, which met the quality requirements. In other words, the quality of Naomai Xinshenshen Capsule is stable within 12 months.

Table 2 Long-term stability test results of Naomai Xinshen Capsules

4 Discussion

Both the accelerated test and long-term stability test show that samples of Naomai Xingshen Capsules were placed in an environment of (40±2) ℃ and relative humidity of (75±5)% for 3 months and the environment of (25±2) ℃ and relative humidity of (60±10)% for 24 months, the appearance, identification, moisture, disintegration time limit and microbial limit test results have not changed significantly, and all indicators meet the quality standards of Naomai Xingshen Capsules, and the content of its indicator component, Nodoginsenoside R1, has no significant change. Therefore, it can be preliminarily determined that its validity period is 2 years. The results of the stability test show that the production process of Naomai Xingshen Capsules is reasonable. The drug quality can be guaranteed under the current packaging and storage conditions, and the safety and efficacy of the preparation can be guaranteed during the tentative validity period of 2 years.