喷雾干燥法制备阿司匹林固体分散体及其胶囊制备与体外特性研究_

1、20148318 Chin J Mod Appl Pharm, 2014 August, Vol.31 No.8 g 973g, 1983, 27(1: 15-19.3LI L Z, ZHU H Y, SHI J S, et al. Chemical composition and pharmacological activities of Crotalaria linn. plants J. Nat Prod Res Dev(, 2007, 19(4: 724-730, 670.4HAN D, WANG C J, ZHANG C L, et al. Comprehensive treatme

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3、435.7ZHANG S J, LIU N, DAI X M, et al. Construction of animal model of skin squamous cell carcinoma J. Acad J Kunming Med Coll(, 2009(3B: 75-79.8WANG S M, RUAN J S. Inhibition of Sceptridium ternatum on papillomas of the skin of mice J. J Chin Med Mater(, 2008, 3(31: 418-420.9 GE H B, FU Z D, SUN Z,

4、 et al. Effect of spirulina platensis onthe prevention of chemically induced skin tumors of mice J. Beijing J Stomatol(, 2004, 12(3: 135-137. 10 SHEN X M, YAO H, ZHOU Z T. Chemopreventive effect ofDongju compound against DMBA/Croton oil induced skin papillomagenesis in mice J. J Clin Stomat(, 2009,

5、25(10: 579-581.2013-10-03©1221,2*(1. 3120002. 312000 (PVP K 30 X-(SEM 16l 63.230 min99.8% X- R943 B 1007-7693(201408-0973-05 DOI: 10.13748/ki.issn1007-7693.2014.08.016Preparation of Aspirin Solid Dispersions by Spray Drying and Characterization of Its Capsules in VitroZHANG Kai 1, WANG Lihong 2

6、, GUAN Yongjun 2, YANG Qun 1,2*(1.Taiji Group Zhejiang East Pharmaceutical Co.,Ltd, Shaoxing 312000, China; 2.Shaoxing University, Yuanpei College, Shaoxing 312000, ChinaABSTRACT: OBJECTIVE To prepare aspirin solid dispersion(SD and capsules, and to improve its dissolution. METHODS Using polyvi-nylp

7、yrrolidone(PVP K 30 as carrier, aspirin SD was prepared by spray-drying method. The dissolution in vitro was determined. X-ray diffractometer and Scanning electron microscope were used to investigate the dispersion status of aspirin in the carriers, and specific surface area was determined. Aspirin

8、solid dispersion capsules were prepared, the dissolution in vitro of aspirin SD and capsules were investigated. RESULTS The solubility of aspirin in aspirin SD was significantly increased compared with raw material and aspirin-carrier physical mixture. The higher the proportion of carrier, the rapid

9、er drug was dissolved. When the ratio of drug to carrier was above 16, the increase of dissolution was no longer significant. Aspirin were highly dispersed in the carrier in amorphous or molecular form. Compared with raw material, the specific surface area of aspirin SD with drug-carrier ratio of 16

10、 increased by 3.2 folds; the cumulative release of aspirin in aspirin SD capsule achieved about 99.8% within 30 min. CONCLUSION The preparation technology of SD is feasible, and the quality of capsules is controllable. KEY WORDS: aspirin; solid dispersion; spray-drying method; capsules; dissolution;

11、 X-ray diffraction; scanning electron mieroscope Tel:E-mail: zhangkai3328 * Tel:E-mail: yangqun5818g 974gChin J Mod Appl Pharm, 2014 August, Vol.31 No.8 20148318.1(solid dispersion 23-56X-X7-10©©(PVP K30 © 1 1.1 AR2130(- UV-2102PCS ( ZRC-8ST ( JSM-840(JEOL D/

12、MAX2500X ( GP-01( JW-04( 1.2 PVP K 30(õP130104006-1 +(100113-20060399.5%+(1001106-20030399.9%(11121799%2 2.1 111213141516171819110PVP K 30 20 g10-PVP K 30©©( 120 20 mL·min10.5 MPa 7080 ©© 2.2 PVP K 30© 2.3 2.3.1 +5 mg(24 mL1 000 mL 20 min100 mL10 mL100 mL+PVP K 303

13、200400 nm275 nm304 nmPVP K 302275304 nm2.3.2 10 mg100 mL (24 mL1 000 mL 20 min 0246810 mL10 mL275 nm (A (CA =7.120 0C +0.007 4(r =0.999 9600.1 mg·mL1+15 mg0.51.02.03.05.07.0 mL50 mL304 nm (A (C A =0.042 09C +0.001 07r =0.999 971.521 µg·mL1 2.4 20148318 Chin J Mod Appl Pharm, 2014 Augu

14、st, Vol.31 No.8 g 975g(0.1 g(2010XC 11(10%24 mL 1 000 mL 1 000 mL100 r·min1(37f 0.5 51015304560 min10 mL(10 mL 0.45 µm8 mL275304 nm1.3041231 -PVP K 30Fig. 1 Dissolution curves of aspirin and aspirin-PVP K 30physical mixture2 Fig. 2 Dissolution curves of aspirin and its solid dispersion1230

15、 min16PVP K30163 cFig. 3 The content of salicylic acid in solid dispersion, physical mixtures and raw medicine360 min21.48 µg·mL115 min 60 min 60 min 3.79 µg·mL-12.5 2.5.1 X- PVP K 30X-X Cu-Ka 40 mA40 kV(20.026°5°50°44 X-AJ111213141516171819110K PVP K 30L MV1112131

16、41516171819110Fig. 4 X-ray diffraction patternA J solid dispersion 11, 12, 13, 14, 15, 16, 17, 18,19, 110; K-PVP K 30; Laspirin; MV physical mixture 11, 12, 13, 14, 15, 16, 17, 18, 19, 110. g 976gChin J Mod Appl Pharm, 2014 August, Vol.31 No.8 2014831847.73°15.56°16.74°18.11°20.5

17、8°22.64°23.15°27.04°28.84°29.50°31.34°32.54°33.83°PVP 5°50°-PVP K 30PVP 2.5.2 11 111515110110PVP K 30 55 A B PVP K30C 11D 11E 15F 15G 110H 110Fig. 5 Scanning electron micrographA asiprin; B PVP K 30; C physical mixture 11; D solid dispersion 11;

18、 E physical mixture 15; F solid dispersion 15; G physical mixture 110; Hsolid dispersion 110.5PVP K-30PVP K 30©2.5.3 29 30 min BET (16 4.23.2Noyes-Whitney d c /dt =KS (C S C C0dc/dt = KSCS dc/dt(S 3.22.6 2.6.1 162.1-PVP K 30181%12(tan=h /r 0.1%0.2%0.3%0.4%0.5%0.8%1.0%C n/C =n/a+1/aba b(ab a b 0

19、.2%a 0.1b 1.3 2.6.2 l 62.1-PVP K 30180.2%11110.292 g f 1.9%20148318 Chin J Mod Appl Pharm, 2014 August, Vol.31 No.8 g 977g30 min99.8% 3 ©X-X©©©©6PVP K 30REFERENCES1LI J T, LI Z S, LIU H H, et al. Clinical analysis of non-steroidal anti-inflammatory drugs induced upper gastro

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21、ss, 2003: 31.4 LOU S L, WU L W. The clinical application of theory of aspirin J. Heilongjiang Med J(, 2010, 23(2: 255-257.5REDONDO S, SANTOS-GALLEGO C G, GANADO P, et al. Acetylsalicylic acid inhibits cell proliferation by involving transforming growth factor-beta J. Circulation, 2003, 107(4: 626-629.6 CUI F D. Pharmaceutics( M. Vol 7. Beijing: People's Medical Publishing House, 2011: 347-348, 352.7 ZOU Y, HUANG H. Progress of preparation of solid dispersion J. Chin J Pharm(, 2005, 36(10